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Экспериментальная и клиническая гастроэнтерология

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НАРУШЕНИЯ МИКРОБНОГО И ЭНДОГЕННОГО МЕТАБОЛИЗМА ПРИ ЯЗВЕННОМ КОЛИТЕ И ЦЕЛИАКИИ: МЕТАБОЛОМНЫЙ ПОДХОД К ВЫЯВЛЕНИЮ ПОТЕНЦИАЛЬНЫХ БИОМАРКЕРОВ ХРОНИЧЕСКОГО ВОСПАЛЕНИЯ В КИШЕЧНИКЕ, СВЯЗАННОГО С ДИСБИОЗОМ

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Аннотация

Цель исследования: выявление потенциальных биомаркеров язвенного колита и целиакии путем изучения метаболома сыворотки крови. Материалы и методы: В исследование было включено 125 пациентов: 40 пациентов с язвенным колитом, 43 пациента с целиакией и 42 практически здоровых добровольца. Состав метаболома сыворотки крови определялся с помощью метода газовой хроматографии - масс-спектрометрии (ГХ-МС). Результаты: Из 93 идентифицированных соединений, общих для всех пациентов, 28 метаболитов имели микробное происхождение. У пациентов с язвенным колитом концентрации молочной, 2-гидроксимасляной, 3-гидроксиизомасляной, 2-гидроксиизовалериановой, 3-гидроксикоричной, янтарной, бензойной и парагидроксифенилуксусной кислот в сыворотке крови были значимо повышены по сравнению со здоровыми. В свою очередь, уровни капроновой, линолевой и эйкозадиеновой кислот при язвенном колите были значимо ниже, чем в группе здоровых. Концентрации 2-гидроксимасляной и 2-гидроксиизовалериановой кислот у больных язвенным колитом были значимо повышены и по сравнению с пациентами с целиакией. Концентрации капроновой, линолевой и гликолевой кислот при язвенном колите были значимо ниже, чем в группе целиакии. У пациентов с целиакией концентрации стеариновой, 2-гидроксиизовалериановой, янтарной, фумаровой и бензойной кислот были значимо повышены по сравнению со здоровыми добровольцами, а уровень арахидоновой кислоты был значимо повышен только по сравнению с больными язвенным колитом. Липогенный индекс (C16:0/C 18:2n-6) был значимо повышен у пациентов с язвенным колитом по сравнению как со здоровыми добровольцами, так и с больными целиакией. Индекс активности элонгазы ELOVL6 (C18:0/C16:0) и отношение уровня стеариновой кислоты к уровню линолевой кислоты (C18:0/C18:2n-6) у пациентов с язвенным колитом были значимо повышены по сравнению со здоровыми. Отношение уровня арахидоновой кислоты к уровню эйкозадиеновой кислоты (C20:4n-6/C20:2n-6) было повышено в обеих группах больных. На фоне дополнительного применения масляной кислоты в комбинации с инулином отмечалось значимое понижение сывороточных концентраций провоспалительных метаболитов микробного происхождения - янтарной кислоты (как у больных язвенным колитом, так и у пациентов с целиакией) и 2-гидроксиизовалериановой кислоты (у больных целиакией). Кроме того, у пациентов с язвенным колитом значимо повышался уровень линолевой и эйкозадиеновой кислот. Выводы: Как при язвенном колите, так и при целиакии наблюдаются значимые изменения сывороточных концентраций метаболитов микробного и эндогенного происхождения, отражающие нарушения в соответствующих метаболических путях (гликолиз, цикл Кребса, окисление и биосинтез жирных кислот, метаболизм кетоновых тел, метаболизм триптофана, фенилаланина и тирозина, микробный метаболизм). По результатам ROC-анализа, некоторые из этих метаболитов (преимущественно микробного или смешанного происхождения), а также новый метаболомный индекс (отношение уровня арахидоновой кислоты к уровню эйкозадиеновой кислоты), отражающий баланс между провоспалительными и противовоспалительными компонентами пула ω-6-ПНЖК, могут рассматриваться как потенциальные биомаркеры хронического воспаления в кишечнике. Снижение уровня провоспалительных метаболитов микробного происхождения в сыворотке крови свидетельствует о возможности эффективной коррекции метаболического дисбиоза с помощью метабиотиков при обоих заболеваниях.

Об авторах

С. И. Ситкин
Гос. НИИ ОЧБ ФМБА России; СЗГМУ им. И. И. Мечникова Минздрава России
Россия


Т. Я. Вахитов
Гос. НИИ ОЧБ ФМБА России
Россия


Е. И. Ткаченко
Военно-медицинская академия имени С. М. Кирова
Россия


Л. Б. Лазебник
МГМСУ им. А. И. Евдокимова Минздрава России
Россия


Л. С. Орешко
СЗГМУ им. И. И. Мечникова Минздрава России
Россия


Т. Н. Жигалова
СЗГМУ им. И. И. Мечникова Минздрава России
Россия


В. Г. Радченко
СЗГМУ им. И. И. Мечникова Минздрава России
Россия


Е. Б. Авалуева
СЗГМУ им. И. И. Мечникова Минздрава России
Россия


П. В. Селиверстов
СЗГМУ им. И. И. Мечникова Минздрава России
Россия


В. А. Утсаль
Институт токсикологии ФМБА России
Россия


Э. В. Комличенко
НМИЦ им. В. А. Алмазова Минздрава России
Россия


Список литературы

1. Vancamelbeke M, Vermeire S. The intestinal barrier: a fundamental role in health and disease. Expert Rev Gastroenterol Hepatol. 2017 Jun 26:1-14. doi: 10.1080/17474124.2017.1343143.

2. Wapenaar MC, Monsuur AJ, van Bodegraven AA, Weersma RK, Bevova MR, Linskens RK, Howdle P, Holmes G, Mulder CJ, Dijkstra G, van Heel DA, Wijmenga C. Associations with tight junction genes PARD 3 and MAGI2 in Dutch patients point to a common barrier defect for coeliac disease and ulcerative colitis. Gut. 2008 Apr;57(4):463-7. doi: 10.1136/gut.2007.133132.

3. Miner-Williams WM, Moughan PJ. Intestinal barrier dysfunction: implications for chronic inflammatory conditions of the bowel. Nutr Res Rev. 2016 Jun;29(1):40-59. doi: 10.1017/S 0954422416000019.

4. Pastorelli L, De Salvo C, Mercado JR, Vecchi M, Pizarro TT. Central role of the gut epithelial barrier in the pathogenesis of chronic intestinal inflammation: lessons learned from animal models and human genetics. Front Immunol. 2013 Sep 17;4:280. doi: 10.3389/fimmu.2013.00280.

5. McCole DF. IBD candidate genes and intestinal barrier regulation. Inflamm Bowel Dis. 2014 Oct;20(10):1829-49. doi: 10.1097/MIB.0000000000000090.

6. Pascual V, Dieli-Crimi R, López-Palacios N, Bodas A, Medrano LM, Núñez C. Inflammatory bowel disease and celiac disease: overlaps and differences. World J Gastroenterol. 2014 May 7;20(17):4846-56. doi: 10.3748/wjg.v20.i17.4846.

7. Meddings J. The significance of the gut barrier in disease. Gut. 2008 Apr;57(4):438-40. doi: 10.1136/gut.2007.143172.

8. Swidsinski A, Loening-Baucke V, Herber A. Mucosal flora in Crohn's disease and ulcerative colitis - an overview. J Physiol Pharmacol. 2009 Dec;60 Suppl 6:61-71.

9. Chen SJ, Liu XW, Liu JP, Yang XY, Lu FG. Ulcerative colitis as a polymicrobial infection characterized by sustained broken mucus barrier. World J Gastroenterol. 2014 Jul 28;20(28):9468-75. doi: 10.3748/wjg.v20.i28.9468.

10. Hering NA, Fromm M, Schulzke JD. Determinants of colonic barrier function in inflammatory bowel disease and potential therapeutics. J Physiol. 2012 Mar 1;590(Pt 5):1035-44. doi: 10.1113/jphysiol.2011.224568.

11. Круис В., Ситкин С. И. Заживление слизистой оболочки при воспалительных заболеваниях кишечника: Влияние месалазина и различных механизмов его действия на заживление слизистой оболочки кишечника при язвенном колите. - М.: Форте принт, 2013. - 36 с.

12. Neurath MF. Cytokines in inflammatory bowel disease. Nat Rev Immunol. 2014 May;14(5):329-42. doi: 10.1038/nri3661.

13. Matsuoka K, Kanai T. The gut microbiota and inflammatory bowel disease. Semin Immunopathol. 2015 Jan;37(1):47-55. doi: 10.1007/s00281-014-0454-4.

14. Sartor RB, Wu GD. Roles for Intestinal Bacteria, Viruses, and Fungi in Pathogenesis of Inflammatory Bowel Diseases and Therapeutic Approaches. Gastroenterology. 2017 Feb;152(2):327-339.e4. doi: 10.1053/j.gastro.2016.10.012.

15. Duboc H, Rajca S, Rainteau D, Benarous D, Maubert MA, Quervain E, Thomas G, Barbu V, Humbert L, Despras G, Bridonneau C, Dumetz F, Grill JP, Masliah J, Beaugerie L, Cosnes J, Chazouillères O, Poupon R, Wolf C, Mallet JM, Langella P, Trugnan G, Sokol H, Seksik P. Connecting dysbiosis, bile-acid dysmetabolism and gut inflammation in inflammatory bowel diseases. Gut. 2013 Apr;62(4):531-9. doi: 10.1136/gutjnl-2012-302578.

16. Meisel M, Mayassi T, Fehlner-Peach H, Koval JC, O'Brien SL, Hinterleitner R, Lesko K, Kim S, Bouziat R, Chen L, Weber CR, Mazmanian SK, Jabri B, Antonopoulos DA. Interleukin-15 promotes intestinal dysbiosis with butyrate deficiency associated with increased susceptibility to colitis. ISME J. 2017 Jan;11(1):15-30. doi: 10.1038/ismej.2016.114.

17. Корниенко Е. А. Роль кишечной микробиоты в развитии целиакии // Медицинский совет. - 2013. - № 1. - С. 44-51.

18. Verdu EF, Galipeau HJ, Jabri B. Novel players in coeliac disease pathogenesis: role of the gut microbiota. Nat Rev Gastroenterol Hepatol. 2015 Sep;12(9):497-506. doi: 10.1038/nrgastro.2015.90.

19. De Palma G, Nadal I, Collado MC, Sanz Y. Effects of a gluten-free diet on gut microbiota and immune function in healthy adult human subjects. Br J Nutr. 2009 Oct;102(8):1154-60. doi: 10.1017/S 0007114509371767.

20. Brown K, DeCoffe D, Molcan E, Gibson DL. Diet-induced dysbiosis of the intestinal microbiota and the effects on immunity and disease. Nutrients. 2012 Aug;4(8):1095-119. doi: 10.3390/nu4081095.

21. Ситкин С. И., Вахитов Т. Я., Ткаченко Е. И., Орешко Л. С., Жигалова Т. Н., Радченко В. Г., Селиверстов П. В., Авалуева Е. Б., Суворова М. А., Комличенко Э. В. Микробиота кишечника при язвенном колите и целиакии // Экспериментальная и клиническая гастроэнтерология. - 2017. - № 1 (137). - С. 8-30.

22. Ситкин С. И., Ткаченко Е. И., Вахитов Т. Я. Метаболический дисбиоз кишечника и его биомаркеры // Экспериментальная и клиническая гастроэнтерология. - 2015. - № 12 (124). - С. 6-29.

23. Huda-Faujan N, Abdulamir AS, Fatimah AB, Anas OM, Shuhaimi M, Yazid AM, Loong YY. The impact of the level of the intestinal short chain fatty acids in inflammatory bowel disease patients versus healthy subjects. Open Biochem J. 2010 May 13;4:53-8. doi: 10.2174/1874091X01004010053.

24. Romagnoli PA, Shenk GK, Pham QM, Maher L, Khanna KM. Commensal metabolite indol-3-propionic acid promotes gut barrier function by regulating IL-22 production during intestinal inflammatory conditions. J Immunol. 2016 May 1;196(1) Suppl 67.10.

25. Sitkin S., Vakhitov T., Tkachenko E., Oreshko L., Zhigalova T. Metabolic dysbiosis concept and its biomarkers in ulcerative colitis and celiac disease. J Crohns Colitis. 2015;9(Suppl 1): S 437. doi: 10.1093/ecco-jcc/jju027.829.

26. Nicholson JK, Holmes E, Kinross J, Burcelin R, Gibson G, Jia W, Pettersson S. Host-gut microbiota metabolic interactions. Science. 2012 Jun 8;336(6086):1262-7. doi: 10.1126/science.1223813.

27. Verbeke KA, Boobis AR, Chiodini A, Edwards CA, Franck A, Kleerebezem M, Nauta A, Raes J, van Tol EA, Tuohy KM. Towards microbial fermentation metabolites as markers for health benefits of prebiotics. Nutr Res Rev. 2015 Jun;28(1):42-66. doi: 10.1017/S 0954422415000037.

28. Vernocchi P, Del Chierico F, Putignani L. Gut Microbiota Profiling: Metabolomics Based Approach to Unravel Compounds Affecting Human Health. Front Microbiol. 2016 Jul 26;7:1144. doi: 10.3389/fmicb.2016.01144.

29. Patti GJ, Yanes O, Siuzdak G. Innovation: Metabolomics: the apogee of the omics trilogy. Nat Rev Mol Cell Biol. 2012 Mar 22;13(4):263-9. doi: 10.1038/nrm3314.

30. Zhang A., Sun H, Wang X. Serum metabolomics as a novel diagnostic approach for disease: a systematic review. Anal Bioanal Chem. 2012 Sep;404(4):1239-45. doi: 10.1007/s00216-012-6117-1.

31. De Preter V, Verbeke K. Metabolomics as a diagnostic tool in gastroenterology. World J Gastrointest Pharmacol Ther. 2013 Nov 6;4(4):97-107. doi: 10.4292/wjgpt.v4.i4.97.

32. De Preter V. Metabolomics in the Clinical Diagnosis of Inflammatory Bowel Disease. Dig Dis. 2015 Sep 14;33 Suppl 1:2-10. doi: 10.1159/000437033.

33. Zhang A, Sun H, Yan G, Wang P, Wang X. Mass spectrometry-based metabolomics: applications to biomarker and metabolic pathway research. Biomed Chromatogr. 2016 Jan;30(1):7-12. doi: 10.1002/bmc.3453.

34. Ooi M, Nishiumi S, Yoshie T, Shiomi Y, Kohashi M, Fukunaga K, Nakamura S, Matsumoto T, Hatano N, Shinohara M, Irino Y, Takenawa T, Azuma T, Yoshida M. GC/MS-based profiling of amino acids and TCA cycle-related molecules in ulcerative colitis. Inflamm Res. 2011 Sep;60(9):831-40. doi: 10.1007/s00011-011-0340-7.

35. Vigsnaes LK, van den Abbeele P, Sulek K, Frandsen HL, Steenholdt C, Brynskov J, Vermeiren J, van de Wiele T, Licht TR. Microbiotas from UC patients display altered metabolism and reduced ability of LAB to colonize mucus. Sci Rep. 2013;3:1110. doi: 10.1038/srep01110.

36. Novak EA, Mollen KP. Mitochondrial dysfunction in inflammatory bowel disease. Front Cell Dev Biol. 2015 Oct 1;3:62. doi: 10.3389/fcell.2015.00062.

37. Heller S, Penrose HM, Cable C, Biswas D, Nakhoul H, Baddoo M, Flemington E, Crawford SE, Savkovic SD. Reduced mitochondrial activity in colonocytes facilitates AMPKα2-dependent inflammation. FASEB J. 2017 May;31(5):2013-2025. doi: 10.1096/fj.201600976R.

38. Bernini P, Bertini I, Calabrò A, la Marca G, Lami G, Luchinat C, Renzi D, Tenori L. Are patients with potential celiac disease really potential? The answer of metabonomics. J Proteome Res. 2011 Feb 4;10(2):714-21. doi: 10.1021/pr100896s.

39. Calabrò A, Gralka E, Luchinat C, Saccenti E, Tenori L. A metabolomic perspective on coeliac disease. Autoimmune Dis. 2014;2014:756138. doi: 10.1155/2014/756138.

40. Белобородова Н. В., Ходакова А. С., Байрамов И. Т., Оленин А. Ю. Микробный путь образования фенилкарбоновых кислот в организме человека // Биохимия. - 2009. - Т. 74, вып. 12. - С. 1657-1663.

41. Осипов Г. А., Зыбина Н. Н., Родионов Г. Г. Опыт применения масс-спектрометрии микробных маркеров в лабораторной диагностике // Медицинский алфавит. - 2013. - Том 1, № 3 (193). - С. 64-67.

42. DuPont AW, DuPont HL. The intestinal microbiota and chronic disorders of the gut. Nat Rev Gastroenterol Hepatol. 2011 Aug 16;8(9):523-31. doi: 10.1038/nrgastro.2011.133.

43. Belcheva A, Irrazabal T, Martin A. Gut microbial metabolism and colon cancer: can manipulations of the microbiota be useful in the management of gastrointestinal health? Bioessays. 2015 Apr;37(4):403-12. doi: 10.1002/bies.201400204.

44. Undseth R, Jakobsdottir G, Nyman M, Berstad A, Valeur J. Low serum levels of short-chain fatty acids after lactulose ingestion may indicate impaired colonic fermentation in patients with irritable bowel syndrome. Clin Exp Gastroenterol. 2015 Nov 27;8:303-8. doi: 10.2147/CEG.S 94084.

45. Chang C, Lin H. Dysbiosis in gastrointestinal disorders. Best Pract Res Clin Gastroenterol. 2016 Feb;30(1):3-15. doi: 10.1016/j.bpg.2016.02.001.

46. Hold GL. Gastrointestinal Microbiota and Colon Cancer. Dig Dis. 2016;34(3):244-50. doi: 10.1159/000443358.

47. Ahmed I, Roy BC, Khan SA, Septer S, Umar S. Microbiome, Metabolome and Inflammatory Bowel Disease. Microorganisms. 2016 Jun 15;4(2). pii: E 20. doi: 10.3390/microorganisms4020020.

48. Ситкин С. И., Вахитов Т. Я., Ткаченко Е. И., Орешко Л. С., Жигалова Т. Н., Радченко В. Г., Селиверстов П. В., Авалуева Е. Б., Суворова М. А., Утсаль В. А. Дисбиоз кишечника при язвенном колите и целиакии и его терапевтическая коррекция с помощью масляной кислоты в комбинации с инулином // Экспериментальная и клиническая гастроэнтерология. - 2017. - № 6 (142). - С. 77-98.

49. Nachman F, del Campo MP, González A, Corzo L, Vázquez H, Sfoggia C, Smecuol E, Sánchez MI, Niveloni S, Sugai E, Mauriño E, Bai JC. Long-term deterioration of quality of life in adult patients with celiac disease is associated with treatment noncompliance. Dig Liver Dis. 2010 Oct;42(10):685-91. doi: 10.1016/j.dld.2010.03.004.

50. Лохов П. Г., Арчаков А. И. Масс-спектрометрические методы в метаболомике // Биомедицинская химия. - 2008. - Том 54, № 5. - С. 497-511.

51. Гладилович В. Д., Подольская Е. П. Возможности применения метода ГХ-МС (обзор) // Научное приборостроение. - 2010. - Том 20, № 4. - C. 36-49.

52. Lei Z, Huhman DV, Sumner LW. Mass spectrometry strategies in metabolomics. J Biol Chem. 2011 Jul 22;286(29):25435-42. doi: 10.1074/jbc.R 111.238691.

53. Вирюс Э. Д., Иванов А. В., Лузянин Б. П., Пальцын А. А., Кубатиев А. А. Масс-спектрометрия в биологии и медицине ХХI века // Патологическая физиология и экспериментальная терапия. - 2013. - № 4. - С. 68-75.

54. Kohashi M., Nishiumi S, Ooi M, Yoshie T, Matsubara A, Suzuki M, Hoshi N, Kamikozuru K, Yokoyama Y, Fukunaga K, Nakamura S, Azuma T, Yoshida M. A novel gas chromatography mass spectrometry-based serum diagnostic and assessment approach to ulcerative colitis. J Crohns Colitis. 2014 Sep;8(9):1010-21. doi: 10.1016/j.crohns.2014.01.024.

55. van Hees NJ, Giltay EJ, Geleijnse JM, Janssen N, van der Does W. DHA serum levels were significantly higher in celiac disease patients compared to healthy controls and were unrelated to depression. PLoS One. 2014 May 19;9(5): e97778. doi: 10.1371/journal.pone.0097778.

56. Мороз В. В., Белобородова Н. В., Бедова А. Ю., Ревельский А. И., Гецина М. Л., Осипов А. А., Саршор Ю. Н., Бучинская А. А., Оленин А. Ю. Разработка и адаптация к условиям клинической лаборатории методик газохроматографического определения фенилкарбоновых кислот в сыворотке крови // Журнал аналитической химии. - 2015. - Том 70, № 4. - С. 418-425. - DOI: 10.7868/S 004445021504012X.

57. Wiese DM, Horst SN, Brown CT, Allaman MM, Hodges ME, Slaughter JC, Druce JP, Beaulieu DB, Schwartz DA, Wilson KT, Coburn LA. Serum Fatty Acids Are Correlated with Inflammatory Cytokines in Ulcerative Colitis. PLoS One. 2016 May 26;11(5): e0156387. doi: 10.1371/journal.pone.0156387.

58. Babushok VI, Linstrom PJ, Reed JJ, Zenkevich IG, Brown RL, Mallard WG, Stein SE. Development of a database of gas chromatographic retention properties of organic compounds. J Chromatogr A. 2007 Jul 20;1157(1-2):414-21. doi: 10.1016/j.chroma.2007.05.044.

59. Psychogios N, Hau DD, Peng J, Guo AC, Mandal R, Bouatra S, Sinelnikov I, Krishnamurthy R, Eisner R, Gautam B, Young N, Xia J, Knox C, Dong E, Huang P, Hollander Z, Pedersen TL, Smith SR, Bamforth F, Greiner R, McManus B, Newman JW, Goodfriend T, Wishart DS. The human serum metabolome. PLoS One. 2011 Feb 16;6(2): e16957. doi: 10.1371/journal.pone.0016957.

60. Wishart DS, Jewison T, Guo AC, Wilson M, Knox C, Liu Y, Djoumbou Y, Mandal R, Aziat F, Dong E, Bouatra S, Sinelnikov I, Arndt D, Xia J, Liu P, Yallou F, Bjorndahl T, Perez-Pineiro R, Eisner R, Allen F, Neveu V, Greiner R, Scalbert A. HMDB 3.0-The Human Metabolome Database in 2013. Nucleic Acids Res. 2013 Jan;41(Database issue): D 801-7. doi: 10.1093/nar/gks1065.

61. Osipov GA, Verkhovtseva NV. Study of human microecology by mass spectrometry of microbial markers. Benef Microbes. 2011 Mar;2(1):63-78. doi: 10.3920/BM2010.0017.

62. Ktsoyan ZA, Beloborodova NV, Sedrakyan AM, Osipov GA, Khachatryan ZA, Kelly D, Manukyan GP, Arakelova KA, Hovhannisyan AI, Olenin AY, Arakelyan AA, Ghazaryan KA, Aminov RI. Profiles of Microbial Fatty Acids in the Human Metabolome are Disease-Specific. Front Microbiol. 2011 Jan 20;1:148. doi: 10.3389/fmicb.2010.00148.

63. Гржибовский А. М. Типы данных, проверка распределения и описательная статистика // Экология человека. - 2008. - № 1. - С. 52-58.

64. Банержи A. Медицинская статистка понятным языком: вводный курс / пер. с англ. под ред. В. П. Леонова. - М.: Практическая медицина, 2014. - 287 с.

65. Гржибовский А. М. Анализ количественных данных для двух независимых групп // Экология человека. - 2008. - № 2. - С. 54-61.

66. Наследов А. SPSS 19: профессиональный статистический анализ данных. - СПб.: Питер, 2011. - 400 с.

67. Гржибовский А. М. Анализ трех и более независимых групп количественных данных // Экология человека. - 2008. - № 3. - С. 50-58.

68. Гржибовский А. М. Одномерный анализ повторных измерений // Экология человека. - 2008. - № 4. - С. 51-60.

69. Гржибовский А. М. Корреляционный анализ // Экология человека. - 2008. - № 9. - С. 50-60.

70. Гржибовский А. М. Анализ номинальных данных (независимые наблюдения) // Экология человека. - 2008. - № 6. - С. 58-68.

71. Леонов В. П. Логистическая регрессия и ROC-анализ [Электронный ресурс]. - Режим доступа: http://www.biometrica.tomsk.ru/logit_4.htm.

72. Nishiumi S, Shinohara M, Ikeda A, Yoshie T, Hatano N, Kakuyama S, Mizuno S, Sanuki T, Kutsumi H, Fukusaki E, Azuma T, Takenawa T, Yoshida M. Serum metabolomics as a novel diagnostic approach for pancreatic cancer. Metabolomics. 2010;6(4): 518-28. doi: 10.1007/s11306-010-0224-9.

73. Dibner JJ, Buttin P. Use of organic acids as a model to study the impact of gut microflora on nutrition and metabolism. J Appl Poult Res. 2002;11(4):453-63. doi: 10.1093/japr/11.4.453.

74. Белобородова Н. В. Интеграция метаболизма человека и его микробиома при критических состояниях // Общая реаниматология. - 2012. - Т. VIII, № 4. - С. 42-54.

75. Sharon G, Garg N, Debelius J, Knight R, Dorrestein PC, Mazmanian SK. Specialized metabolites from the microbiome in health and disease. Cell Metab. 2014 Nov 4;20(5):719-30. doi: 10.1016/j.cmet.2014.10.016.

76. Richards JL, Yap YA, McLeod KH, Mackay CR, Mariño E. Dietary metabolites and the gut microbiota: an alternative approach to control inflammatory and autoimmune diseases. Clin Transl Immunology. 2016 May 13;5(5): e82. doi: 10.1038/cti.2016.29.

77. Руденко А. О., Карцова Л. А., Снарский С. И. Определение важнейших аминокислот в сложных объектах биологического происхождения методом обращенно-фазовой ВЭЖХ с получением фенилтиогидантоинов аминокислот // Сорбционные и хроматографические процессы. 2010. Т. 10. Вып. 2. - С. 223-230.

78. Fekkes D. Automated analysis of primary amino acids in plasma by high-performance liquid chromatography. Methods Mol Biol. 2012;828:183-200. doi: 10.1007/978-1-61779-445-2_16.

79. Kumps A, Duez P, Mardens Y. Metabolic, nutritional, iatrogenic, and artifactual sources of urinary organic acids: a comprehensive table. Clin Chem. 2002 May;48(5):708-17.

80. Вахитов Т. Я. Регуляторные функции бактериальных экзометаболитов на внутрипопуляционном и межвидовом уровнях: Автореф. дис. … д-ра биол. наук: 03.00.23 - биотехнология. - СПб., 2007-40 с.

81. Dai ZL, Wu G, Zhu WY. Amino acid metabolism in intestinal bacteria: links between gut ecology and host health. Front Biosci (Landmark Ed). 2011 Jan 1;16:1768-86.

82. Белобородова Н. В., Байрамов И. Т., Оленин А. Ю., Федотчева Н. И. Экзометаболиты некоторых анаэробных микроорганизмов микрофлоры человека // Биомедицинская химия. - 2011. - Т. 57, № 1. - С. 95-105.

83. Russell WR, Hoyles L, Flint HJ, Dumas ME. Colonic bacterial metabolites and human health. Curr Opin Microbiol. 2013 Jun;16(3):246-54. doi: 10.1016/j.mib.2013.07.002.

84. Вахитов Т. Я., Петров Л. Н. Регуляторные функции экзометаболитов бактерий // Микробиология. - 2006. - Т. 75, № 4. - С. 483-488.

85. Lord RS, Bralley JA. Clinical applications of urinary organic acids. Part 2. Dysbiosis markers. Altern Med Rev. 2008 Dec;13(4):292-306.

86. Полевая Е. В., Вахитов Т. Я., Яковлева Е. П. Штаммоспецифические особенности в составе и динамике карбоновых кислот при выращивании бактерий Escherichia coli и Salmonella enteritidis // Научный журнал КубГАУ. - 2012. - № 3 (77).

87. Захарова Ю. В., Сухих А. С. Хроматографический анализ жирных кислот клеточных стенок бифидобактерий с различной гидрофобностью // Сорбционные и хроматографические процессы. - 2015. - Т. 15, № 6. - С. 776-783.

88. Yoshida M, Hatano N, Nishiumi S, Irino Y, Izumi Y, Takenawa T, Azuma T. Diagnosis of gastroenterological diseases by metabolome analysis using gas chromatography-mass spectrometry. J Gastroenterol. 2012 Jan;47(1):9-20. doi: 10.1007/s00535-011-0493-8.

89. De Preter V, Machiels K, Joossens M, Arijs I, Matthys C, Vermeire S, Rutgeerts P, Verbeke K. Faecal metabolite profiling identifies medium-chain fatty acids as discriminating compounds in IBD. Gut. 2015 Mar;64(3):447-58. doi: 10.1136/gutjnl-2013-306423.

90. Uttley L, Whiteman BL, Woods HB, Harnan S, Philips ST, Cree IA; Early Cancer Detection Consortium. Building the Evidence Base of Blood-Based Biomarkers for Early Detection of Cancer: A Rapid Systematic Mapping Review. EBioMedicine. 2016 Aug;10:164-73. doi: 10.1016/j.ebiom.2016.07.004.

91. Lamaziere A, Wolf C, Quinn PJ. Perturbations of lipid metabolism indexed by lipidomic biomarkers. Metabolites. 2012 Jan 4;2(1):1-18. doi: 10.3390/metabo2010001.

92. Gaber T, Strehl C, Buttgereit F. Metabolic regulation of inflammation. Nat Rev Rheumatol. 2017 May;13(5):267-279. doi: 10.1038/nrrheum.2017.37.

93. Белобородова Н. В., Белобородов С. М. Метаболиты анаэробных бактерий (летучие жирные кислоты) и реактивность макроорганизма // Антибиотики и химиотерапия. - 2000. - Том 45, № 2. - С. 28-36.

94. Безрукова С. А. Карбоновые кислоты и их функциональные производные: практическое руководство. - Северск: Изд-во СТИ НИЯУМИФИ, 2011. - 34 с.

95. Zheng X, Qiu Y, Zhong W, Baxter S, Su M, Li Q, Xie G, Ore BM, Qiao S, Spencer MD, Zeisel SH, Zhou Z, Zhao A, Jia W. A targeted metabolomic protocol for short-chain fatty acids and branched-chain amino acids. Metabolomics. 2013 Aug 1;9(4):818-827. doi: 10.1007/s11306-013-0500-6.

96. Tan J, McKenzie C, Potamitis M, Thorburn AN, Mackay CR, Macia L. The role of short-chain fatty acids in health and disease. Adv Immunol. 2014;121:91-119. doi: 10.1016/B 978-0-12-800100-4.00003-9.

97. Shetty SA, Marathe NP, Lanjekar V, Ranade D, Shouche YS. Comparative genome analysis of Megasphaera sp. reveals niche specialization and its potential role in the human gut. PLoS One. 2013 Nov 18;8(11): e79353. doi: 10.1371/journal.pone.0079353.

98. Zhu X, Tao Y, Liang C, Li X, Wei N, Zhang W, Zhou Y, Yang Y, Bo T. The synthesis of n-caproate from lactate: a new efficient process for medium-chain carboxylates production. Sci Rep. 2015 Sep 25;5:14360. doi: 10.1038/srep14360.

99. Bäckhed F, Ley RE, Sonnenburg JL, Peterson DA, Gordon JI. Host-bacterial mutualism in the human intestine. Science. 2005 Mar 25;307(5717):1915-20. doi: 10.1126/science.1104816.

100. Домарадский И. В., Хохоев Т. Х., Кондракова О. А., Дубинин А. В., Вострухов С. В., Бабин В. Н. Противоречивая микроэкология // Рос. хим. ж. (Ж. Рос. хим. об-ва им. Д. И. Менделеева). - 2002. - Т. XLVI, № 3. - С. 80-89.

101. Mar Rodríguez M, Pérez D, Javier Chaves F, Esteve E, Marin-Garcia P, Xifra G, Vendrell J, Jové M, Pamplona R, Ricart W, Portero-Otin M, Chacón MR, Fernández Real JM. Obesity changes the human gut mycobiome. Sci Rep. 2015 Oct 12;5:14600. doi: 10.1038/srep14600.

102. Huang CB, Alimova Y, Myers TM, Ebersole JL. Short- and medium-chain fatty acids exhibit antimicrobial activity for oral microorganisms. Arch Oral Biol. 2011 Jul;56(7):650-4. doi: 10.1016/j.archoralbio.2011.01.011.

103. Garner CE, Smith S, de Lacy Costello B, White P, Spencer R, Probert CS, Ratcliffe NM. Volatile organic compounds from feces and their potential for diagnosis of gastrointestinal disease. FASEB J. 2007 Jun;21(8):1675-88. doi: 10.1096/fj.06-6927com.

104. Narayanan A, Baskaran SA, Amalaradjou MA, Venkitanarayanan K. Anticarcinogenic properties of medium chain fatty acids on human colorectal, skin and breast cancer cells in vitro. Int J Mol Sci. 2015 Mar 5;16(3):5014-27. doi: 10.3390/ijms16035014.

105. Вахитов Т. Я., Чалисова Н. И., Ситкин С. И., Салль Т. С., Шалаева О. Н., Демьянова Е. В., Моругина А. С., Виноградова А. Ф., Петров А. В., Ноздрачев А. Д. Низкомолекулярные компоненты метаболома крови регулируют пролиферативную активность в клеточных и бактериальных культурах // Доклады Академии наук. - 2017. - Том 472, № 4. - С. 491-493. - DOI: 10.7868/S 0869565217040284.

106. Vakhitov TY, Chalisova NI, Sitkin SI, Sall TS, Shalaeva ON, Demyanova EV, Morugina AS, Vinogradova AF, Petrov AV, Nozdrachev AD. Low-molecular-weight components of the metabolome control the proliferative activity in cellular and bacterial cultures. Dokl Biol Sci. 2017 Jan;472(1):8-10. doi: 10.1134/S 0012496617010069.

107. Scher JU, Ubeda C, Artacho A, Attur M, Isaac S, Reddy SM, Marmon S, Neimann A, Brusca S, Patel T, Manasson J, Pamer EG, Littman DR, Abramson SB. Decreased bacterial diversity characterizes the altered gut microbiota in patients with psoriatic arthritis, resembling dysbiosis in inflammatory bowel disease. Arthritis Rheumatol. 2015 Jan;67(1):128-39. doi: 10.1002/art.38892.

108. Di Cagno R, De Angelis M, De Pasquale I, Ndagijimana M, Vernocchi P, Ricciuti P, Gagliardi F, Laghi L, Crecchio C, Guerzoni ME, Gobbetti M, Francavilla R. Duodenal and faecal microbiota of celiac children: molecular, phenotype and metabolome characterization. BMC Microbiol. 2011 Oct 4;11:219. doi: 10.1186/1471-2180-11-219.

109. Терешина Е. В. Роль жирных кислот в развитии возрастного окислительного стресса. Гипотеза // Успехи геронтологии. - 2007. - Том 20, № 1. - С. 59-65.

110. Brolinson A. Regulation of Elovl and fatty acid metabolism. Doctoral thesis from the department of Physiology, The Wenner-Gren Institute, Stockholm University. Stockholm 2009. 58 p.

111. Matsuzaka T, Shimano H. Elovl6: a new player in fatty acid metabolism and insulin sensitivity. J Mol Med (Berl). 2009 Apr;87(4):379-84. doi: 10.1007/s00109-009-0449-0.

112. Diet, nutrition and the prevention of chronic diseases. World Health Organ Tech Rep Ser. 2003;916: i-viii, 1-149.

113. Valli A, Rodriguez M, Moutsianas L, Fischer R, Fedele V, Huang HL, Van Stiphout R, Jones D, Mccarthy M, Vinaxia M, Igarashi K, Sato M, Soga T, Buffa F, Mccullagh J, Yanes O, Harris A, Kessler B. Hypoxia induces a lipogenic cancer cell phenotype via HIF1α-dependent and -independent pathways. Oncotarget. 2015 Feb 10;6(4):1920-41. doi: 10.18632/oncotarget.3058.

114. Wei X, Yang Z, Rey FE, Ridaura VK, Davidson NO, Gordon JI, Semenkovich CF. Fatty acid synthase modulates intestinal barrier function through palmitoylation of mucin 2. Cell Host Microbe. 2012 Feb 16;11(2):140-52. doi: 10.1016/j.chom.2011.12.006.

115. Shores DR, Binion DG, Freeman BA, Baker PR. New insights into the role of fatty acids in the pathogenesis and resolution of inflammatory bowel disease. Inflamm Bowel Dis. 2011 Oct;17(10):2192-204. doi: 10.1002/ibd.21560.

116. Lands B. Benefit-Risk Assessment of Fish Oil in Preventing Cardiovascular Disease. Drug Saf. 2016 Sep;39(9):787-99. doi: 10.1007/s40264-016-0438-5.

117. Uusitalo L, Nevalainen J, Salminen I, Ovaskainen ML, Kronberg-Kippilä C, Ahonen S, Niinistö S, Alfthan G, Simell O, Ilonen J, Veijola R, Knip M, Virtanen SM. Fatty acids in serum and diet - a canonical correlation analysis among toddlers. Matern Child Nutr. 2013 Jul;9(3):381-95. doi: 10.1111/j.1740-8709.2011.00374.x.

118. Ramsden CE, Ringel A, Feldstein AE, Taha AY, MacIntosh BA, Hibbeln JR, Majchrzak-Hong SF, Faurot KR, Rapoport SI, Cheon Y, Chung YM, Berk M, Mann JD. Lowering dietary linoleic acid reduces bioactive oxidized linoleic acid metabolites in humans. Prostaglandins Leukot Essent Fatty Acids. 2012 Oct-Nov;87(4-5):135-41. doi: 10.1016/j.plefa.2012.08.004.

119. Tjonneland A, Overvad K, Bergmann MM, Nagel G, Linseisen J, Hallmans G, Palmqvist R, Sjodin H, Hagglund G, Berglund G, Lindgren S, Grip O, Palli D, Day NE, Khaw KT, Bingham S, Riboli E, Kennedy H, Hart A. (IBD in EPIC Study Investigators) Linoleic acid, a dietary n-6 polyunsaturated fatty acid, and the aetiology of ulcerative colitis: a nested case-control study within a European prospective cohort study. Gut. 2009 Dec;58(12):1606-11. doi: 10.1136/gut.2008.169078.

120. Johnson GH, Fritsche K. Effect of dietary linoleic acid on markers of inflammation in healthy persons: a systematic review of randomized controlled trials. J Acad Nutr Diet. 2012 Jul;112(7):1029-41, 1041.e1-15. doi: 10.1016/j.jand.2012.03.029.

121. Liou YA, Innis SM. Dietary linoleic acid has no effect on arachidonic acid, but increases n-6 eicosadienoic acid, and lowers dihomo-gamma-linolenic and eicosapentaenoic acid in plasma of adult men. Prostaglandins Leukot Essent Fatty Acids. 2009 Apr;80(4):201-6. doi: 10.1016/j.plefa.2009.02.003.

122. Poudel-Tandukar K, Nanri A, Matsushita Y, Sasaki S, Ohta M, Sato M, Mizoue T. Dietary intakes of alpha-linolenic and linoleic acids are inversely associated with serum C-reactive protein levels among Japanese men. Nutr Res. 2009 Jun;29(6):363-70. doi: 10.1016/j.nutres.2009.05.012.

123. Weigert C, Brodbeck K, Staiger H, Kausch C, Machicao F, Häring HU, Schleicher ED. Palmitate, but not unsaturated fatty acids, induces the expression of interleukin-6 in human myotubes through proteasome-dependent activation of nuclear factor-kappaB. J Biol Chem. 2004 Jun 4;279(23):23942-52. doi: 10.1074/jbc.M312692200.

124. Kaska L, Mika A, Stepnowski P, Proczko M, Ratnicki-Sklucki K, Sledzinski T, Goyke E, Swierczynski J. The relationship between specific Fatty acids of serum lipids and serum high sensitivity C- reactive protein levels in morbidly obese women. Cell Physiol Biochem. 2014;34(4):1101-8. doi: 10.1159/000366324.

125. de Mello VD, Paananen J, Lindström J, Lankinen MA, Shi L, Kuusisto J, Pihlajamäki J, Auriola S, Lehtonen M, Rolandsson O, Bergdahl IA, Nordin E, Ilanne-Parikka P, Keinänen-Kiukaanniemi S, Landberg R, Eriksson JG, Tuomilehto J, Hanhineva K, Uusitupa M. Indolepropionic acid and novel lipid metabolites are associated with a lower risk of type 2 diabetes in the Finnish Diabetes Prevention Study. Sci Rep. 2017 Apr 11;7:46337. doi: 10.1038/srep46337.

126. Banni S. Conjugated linoleic acid metabolism. Curr Opin Lipidol. 2002 Jun;13(3):261-6.

127. Coakley M, Ross RP, Nordgren M, Fitzgerald G, Devery R, Stanton C. Conjugated linoleic acid biosynthesis by human-derived Bifidobacterium species. J Appl Microbiol. 2003;94(1):138-45.

128. Ogawa J, Kishino S, Ando A, Sugimoto S, Mihara K, Shimizu S. Production of conjugated fatty acids by lactic acid bacteria. J Biosci Bioeng. 2005 Oct;100(4):355-64. doi: 10.1263/jbb.100.355.

129. Macouzet M, Lee BH, Robert N. Production of conjugated linoleic acid by probiotic Lactobacillus acidophilus La-5. J Appl Microbiol. 2009 Jun;106(6):1886-91. doi: 10.1111/j.1365-2672.2009.04164.x.

130. Bassaganya-Riera J, Viladomiu M, Pedragosa M, De Simone C, Carbo A, Shaykhutdinov R, Jobin C, Arthur JC, Corl BA, Vogel H, Storr M, Hontecillas R. Probiotic bacteria produce conjugated linoleic acid locally in the gut that targets macrophage PPAR γ to suppress colitis. PLoS One. 2012;7(2): e31238. doi: 10.1371/journal.pone.0031238.

131. Devillard E, McIntosh FM, Duncan SH, Wallace RJ. Metabolism of linoleic acid by human gut bacteria: different routes for biosynthesis of conjugated linoleic acid. J Bacteriol. 2007 Mar;189(6):2566-70. doi: 10.1128/JB.01359-06.

132. O'Shea EF, Cotter PD, Stanton C, Ross RP, Hill C. Production of bioactive substances by intestinal bacteria as a basis for explaining probiotic mechanisms: bacteriocins and conjugated linoleic acid. Int J Food Microbiol. 2012 Jan 16;152(3):189-205. doi: 10.1016/j.ijfoodmicro.2011.05.025.

133. Aydin R. Conjugated linoleic acid: chemical structure, sources and biological properties. Turk J Vet Anim Sci. 2005;29:189-95.

134. Dilzer A, Park Y. Implication of conjugated linoleic acid (CLA) in human health. Crit Rev Food Sci Nutr. 2012;52(6):488-513. doi: 10.1080/10408398.2010.501409.

135. Iwanaga K, Nakamura T, Maeda S, Aritake K, Hori M, Urade Y, Ozaki H, Murata T. Mast cell-derived prostaglandin D 2 inhibits colitis and colitis-associated colon cancer in mice. Cancer Res. 2014 Jun 1;74(11):3011-9. doi: 10.1158/0008-5472.CAN-13-2792.

136. Stenson WF. The universe of arachidonic acid metabolites in inflammatory bowel disease: can we tell the good from the bad? Curr Opin Gastroenterol. 2014 Jul;30(4):347-51. doi: 10.1097/MOG.0000000000000075.

137. Brash AR. Arachidonic acid as a bioactive molecule. J Clin Invest. 2001 Jun;107(11):1339-45. doi: 10.1172/JCI13210.

138. de Silva PS, Luben R, Shrestha SS, Khaw KT, Hart AR. Dietary arachidonic and oleic acid intake in ulcerative colitis etiology: a prospective cohort study using 7-day food diaries. Eur J Gastroenterol Hepatol. 2014 Jan;26(1):11-8. doi: 10.1097/MEG.0b013e328365c372.

139. Quehenberger O, Armando AM, Brown AH, Milne SB, Myers DS, Merrill AH, Bandyopadhyay S, Jones KN, Kelly S, Shaner RL, Sullards CM, Wang E, Murphy RC, Barkley RM, Leiker TJ, Raetz CR, Guan Z, Laird GM, Six DA, Russell DW, McDonald JG, Subramaniam S, Fahy E, Dennis EA. Lipidomics reveals a remarkable diversity of lipids in human plasma. J Lipid Res. 2010 Nov;51(11):3299-305. doi: 10.1194/jlr.M009449.

140. Tanaka T, Uozumi S, Morito K, Osumi T, Tokumura A. Metabolic conversion of C20 polymethylene-interrupted polyunsaturated fatty acids to essential fatty acids. Lipids. 2014 May;49(5):423-9. doi: 10.1007/s11745-014-3896-5.

141. Huang YS, Huang WC, Li CW, Chuang LT. Eicosadienoic acid differentially modulates production of pro-inflammatory modulators in murine macrophages. Mol Cell Biochem. 2011 Dec;358(1-2):85-94. doi: 10.1007/s11010-011-0924-0.

142. Idborg H, Olsson P, Leclerc P, Raouf J, Jakobsson PJ, Korotkova M. Effects of mPGES-1 deletion on eicosanoid and fatty acid profiles in mice. Prostaglandins Other Lipid Mediat. 2013 Dec;107:18-25. doi: 10.1016/j.prostaglandins.2013.07.004.

143. Forouhi NG, Imamura F, Sharp SJ, Koulman A, Schulze MB, Zheng J, Ye Z, Sluijs I, Guevara M, Huerta JM, Kröger J, Wang LY, Summerhill K, Griffin JL, at all Association of Plasma Phospholipid n-3 and n-6 Polyunsaturated Fatty Acids with Type 2 Diabetes: The EPIC-InterAct Case-Cohort Study. PLoS Med. 2016 Jul 19;13(7): e1002094. doi: 10.1371/journal.pmed.1002094.

144. Drbal A. Studies on bioactive lipid mediators involved in brain function and neurodegenerative disorders: the effect of ω-3PUFA supplementation and lithium treatment on rat brain sphingomyelin species and endocannabinoids formation: changes in oxysterol profiles in blood of ALS patients and animal models of ALS. University of Bradford Doctoral Thesis (Ph.D.) 2013. EThOS ID: uk.bl.ethos.600435.

145. Raouf J, Idborg H, Olsson P, Jakobsson PJ, Lundberg IE, Korotkova M. Altered Serum Fatty Acid Profiles in Patients with Polymyositis or Dermatomyositis Compared to Healthy Individuals and in Relation to Immunosuppressive Treatment [abstract]. Arthritis Rheumatol. 2015; 67 Suppl 10.

146. Wang Y, Liu D, Li Y, Guo L, Cui Y, Zhang X, Li E. Metabolomic analysis of serum from obese adults with hyperlipemia by UHPLC-Q-TOF MS/MS. Biomed Chromatogr. 2016 Jan;30(1):48-54. doi: 10.1002/bmc.3491.

147. Tanaka T, Shen J, Abecasis GR, Kisialiou A, Ordovas JM, Guralnik JM, Singleton A, Bandinelli S, Cherubini A, Arnett D, Tsai MY, Ferrucci L. Genome-wide association study of plasma polyunsaturated fatty acids in the InCHIANTI Study. PLoS Genet. 2009 Jan;5(1): e1000338. doi: 10.1371/journal.pgen.1000338.

148. Li SW, Wang J, Yang Y, Liu ZJ, Cheng L, Liu HY, Ma P, Luo W, Liu SM. Polymorphisms in FADS 1 and FADS 2 alter plasma fatty acids and desaturase levels in type 2 diabetic patients with coronary artery disease. J Transl Med. 2016 Mar 22;14:79. doi: 10.1186/s12967-016-0834-8.

149. Mocking RJ, Lok A, Assies J, Koeter MW, Visser I, Ruhé HG, Bockting CL, Schene AH. Ala54Thr fatty acid-binding protein 2 (FABP2) polymorphism in recurrent depression: associations with fatty acid concentrations and waist circumference. PLoS One. 2013 Dec 10;8(12): e82980. doi: 10.1371/journal.pone.0082980.

150. Pereira DM, Correia-da-Silva G, Valentão P, Teixeira N, Andrade PB. Anti-inflammatory effect of unsaturated fatty acids and Ergosta-7,22-dien-3-ol from Marthasterias glacialis: prevention of CHOP-mediated ER-stress and NF-κB activation. PLoS One. 2014 Feb 13;9(2): e88341. doi: 10.1371/journal.pone.0088341.

151. Ma Y, Liu W, Peng J, Huang L, Zhang P, Zhao X, Cheng Y, Qin H. A pilot study of gas chromatograph/mass spectrometry-based serum metabolic profiling of colorectal cancer after operation. Mol Biol Rep. 2010 Mar;37(3):1403-11. doi: 10.1007/s11033-009-9524-4.

152. Zhang Y, He C, Qiu L, Wang Y, Qin X, Liu Y, Li Z. Serum Unsaturated Free Fatty Acids: A Potential Biomarker Panel for Early-Stage Detection of Colorectal Cancer. J Cancer. 2016 Jan 29;7(4):477-83. doi: 10.7150/jca.13870.

153. Urayama S, Zou W, Brooks K, Tolstikov V. Comprehensive mass spectrometry based metabolic profiling of blood plasma reveals potent discriminatory classifiers of pancreatic cancer. Rapid Commun Mass Spectrom. 2010 Mar 15;24(5):613-20. doi: 10.1002/rcm.4420.

154. Xue R, Lin Z, Deng C, Dong L, Liu T, Wang J, Shen X. A serum metabolomic investigation on hepatocellular carcinoma patients by chemical derivatization followed by gas chromatography/mass spectrometry. Rapid Commun Mass Spectrom. 2008 Oct;22(19):3061-8. doi: 10.1002/rcm.3708.

155. Poudel-Tandukar K, Sato M, Ejima Y, Nanri A, Matsushita Y, Imaizumi K, Mizoue T. Relationship of serum fatty acid composition and desaturase activity to C-reactive protein in Japanese men and women. Atherosclerosis. 2012 Feb;220(2):520-4. doi: 10.1016/j.atherosclerosis.2011.11.012.

156. Jia HJ, Zhang PJ, Liu YL, Jiang CG, Zhu X, Tian YP. Relationship of serum polyunsaturated fatty acids with cytokines in colorectal cancer. World J Gastroenterol. 2016 Feb 28;22(8):2524-32. doi: 10.3748/wjg.v22.i8.2524.

157. Liu J, Mazzone PJ, Cata JP, Kurz A, Bauer M, Mascha EJ, Sessler DI. Serum free fatty acid biomarkers of lung cancer. Chest. 2014 Sep;146(3):670-9. doi: 10.1378/chest.13-2568.

158. Rodríguez-Carrio J, Alperi-López M, López P, Ballina-García FJ, Suárez A. Non-Esterified Fatty Acids Profiling in Rheumatoid Arthritis: Associations with Clinical Features and Th1 Response. PLoS One. 2016 Aug 3;11(8): e0159573. doi: 10.1371/journal.pone.0159573.

159. Fritsche KL. Too much linoleic acid promotes inflammation-doesn't it? Prostaglandins Leukot Essent Fatty Acids. 2008 Sep-Nov;79(3-5):173-5. doi: 10.1016/j.plefa.2008.09.019.

160. Hokari R, Matsunaga H, Miura S. Effect of dietary fat on intestinal inflammatory diseases. J Gastroenterol Hepatol. 2013 Dec;28 Suppl 4:33-6. doi: 10.1111/jgh.12252.

161. Honda KL, Lamon-Fava S, Matthan NR, Wu D, Lichtenstein AH. Docosahexaenoic acid differentially affects TNFα and IL-6 expression in LPS-stimulated RAW 264.7 murine macrophages. Prostaglandins Leukot Essent Fatty Acids. 2015 Jun;97:27-34. doi: 10.1016/j.plefa.2015.03.002.

162. Le Loupp AG, Bach-Ngohou K, Bettan A, Denis M, Masson D. Dual role for prostaglandin D 2 in intestinal epithelial homeostasis. Med Sci (Paris). 2015 Jun-Jul;31(6-7):617-21. doi: 10.1051/medsci/20153106014.

163. Esteve-Comas M, Ramírez M, Fernández-Bañares F, Abad-Lacruz A, Gil A, Cabré E, González-Huix F, Moreno J, Humbert P, Guilera M, Boix J, Gassull MA. Plasma polyunsaturated fatty acid pattern in active inflammatory bowel disease. Gut. 1992 Oct;33(10):1365-9.

164. Esteve-Comas M, Núñez MC, Fernández-Bañares F, Abad-Lacruz A, Gil A, Cabré E, González-Huix F, Bertrán X, Gassull MA. Abnormal plasma polyunsaturated fatty acid pattern in non-active inflammatory bowel disease. Gut. 1993 Oct;34(10):1370-3.

165. Figler M, Gasztonyi B, Cseh J, Horváth G, Kisbenedek AG, Bokor S, Decsi T. Association of n-3 and n-6 long-chain polyunsaturated fatty acids in plasma lipid classes with inflammatory bowel diseases. Br J Nutr. 2007 Jun;97(6):1154-61. doi: 10.1017/S 0007114507682956.

166. Socha P, Ryzko J, Koletzko B, Celinska-Cedro D, Woynarowski M, Czubkowski P, Socha J. Essential fatty acid depletion in children with inflammatory bowel disease. Scand J Gastroenterol. 2005 May;40(5):573-7. doi: 10.1080/00365520510012136.

167. Karrasch T, Obermeier F, Straub RH. Systemic metabolic signaling in acute and chronic gastrointestinal inflammation of inflammatory bowel diseases. Horm Metab Res. 2014 Jun;46(6):445-51. doi: 10.1055/s-0034-1374587.

168. Romanato G, Scarpa M, Angriman I, Faggian D, Ruffolo C, Marin R, Zambon S, Basato S, Zanoni S, Filosa T, Pilon F, Manzato E. Plasma lipids and inflammation in active inflammatory bowel diseases. Aliment Pharmacol Ther. 2009 Feb 1;29(3):298-307. doi: 10.1111/j.1365-2036.2008.03886.x.

169. Masoodi M, Pearl DS, Eiden M, Shute JK, Brown JF, Calder PC, Trebble TM. Altered colonic mucosal Polyunsaturated Fatty Acid (PUFA) derived lipid mediators in ulcerative colitis: new insight into relationship with disease activity and pathophysiology. PLoS One. 2013 Oct 18;8(10): e76532. doi: 10.1371/journal.pone.0076532.

170. Solakivi T, Kaukinen K, Kunnas T, Lehtimäki T, Mäki M, Nikkari ST. Serum fatty acid profile in celiac disease patients before and after a gluten-free diet. Scand J Gastroenterol. 2009;44(7):826-30. doi: 10.1080/00365520902912589.

171. Riezzo G, Ferreri C, Orlando A, Martulli M, D'Attoma B, Russo F. Lipidomic analysis of fatty acids in erythrocytes of coeliac patients before and after a gluten-free diet intervention: a comparison with healthy subjects. Br J Nutr. 2014 Dec 14;112(11):1787-96. doi: 10.1017/S 0007114514002815.

172. Pan DA, Lillioja S, Milner MR, Kriketos AD, Baur LA, Bogardus C, Storlien LH. Skeletal muscle membrane lipid composition is related to adiposity and insulin action. J Clin Invest. 1995 Dec;96(6):2802-8. doi: 10.1172/JCI118350.

173. Devillard E, McIntosh FM, Duncan SH, Wallace RJ. Metabolism of linoleic acid by human gut bacteria: different routes for biosynthesis of conjugated linoleic acid. J Bacteriol. 2007 Mar;189(6):2566-70. doi: 10.1128/JB.01359-06.

174. Martinelli N, Girelli D, Malerba G, Guarini P, Illig T, Trabetti E, Sandri M, Friso S, Pizzolo F, Schaeffer L, Heinrich J, Pignatti PF, Corrocher R, Olivieri O. FADS genotypes and desaturase activity estimated by the ratio of arachidonic acid to linoleic acid are associated with inflammation and coronary artery disease. Am J Clin Nutr. 2008 Oct;88(4):941-9.

175. Hodson L, Skeaff CM, Fielding BA. Fatty acid composition of adipose tissue and blood in humans and its use as a biomarker of dietary intake. Prog Lipid Res. 2008 Sep;47(5):348-80. doi: 10.1016/j.plipres.2008.03.003.

176. Kishino S, Takeuchi M, Park SB, Hirata A, Kitamura N, Kunisawa J, Kiyono H, Iwamoto R, Isobe Y, Arita M, Arai H, Ueda K, Shima J, Takahashi S, Yokozeki K, Shimizu S, Ogawa J. Polyunsaturated fatty acid saturation by gut lactic acid bacteria affecting host lipid composition. Proc Natl Acad Sci U S A. 2013 Oct 29;110(44):17808-13. doi: 10.1073/pnas.1312937110.

177. Druart C, Neyrinck AM, Vlaeminck B, Fievez V, Cani PD, Delzenne NM. Role of the lower and upper intestine in the production and absorption of gut microbiota-derived PUFA metabolites. PLoS One. 2014 Jan 27;9(1): e87560. doi: 10.1371/journal.pone.0087560.

178. Zhang LS, Davies SS. Microbial metabolism of dietary components to bioactive metabolites: opportunities for new therapeutic interventions. Genome Med. 2016 Apr 21;8(1):46. doi: 10.1186/s13073-016-0296-x.

179. Guillou H, Zadravec D, Martin PG, Jacobsson A. The key roles of elongases and desaturases in mammalian fatty acid metabolism: Insights from transgenic mice. Prog Lipid Res. 2010 Apr;49(2):186-99. doi: 10.1016/j.plipres.2009.12.002.

180. Hudgins LC, Hellerstein M, Seidman C, Neese R, Diakun J, Hirsch J. Human fatty acid synthesis is stimulated by a eucaloric low fat, high carbohydrate diet. J Clin Invest. 1996 May 1;97(9):2081-91. doi: 10.1172/JCI118645.

181. Chong MF, Hodson L, Bickerton AS, Roberts R, Neville M, Karpe F, Frayn KN, Fielding BA. Parallel activation of de novo lipogenesis and stearoyl-CoA desaturase activity after 3 d of high-carbohydrate feeding. Am J Clin Nutr. 2008 Apr;87(4):817-23.

182. Bäckhed F, Ding H, Wang T, Hooper LV, Koh GY, Nagy A, Semenkovich CF, Gordon JI. The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A. 2004 Nov 2;101(44):15718-23. doi: 10.1073/pnas.0407076101.

183. Muccioli GG, Naslain D, Bäckhed F, Reigstad CS, Lambert DM, Delzenne NM, Cani PD. The endocannabinoid system links gut microbiota to adipogenesis. Mol Syst Biol. 2010 Jul;6:392. doi: 10.1038/msb.2010.46.

184. Dahiya DK, Renuka, Puniya M, Shandilya UK, Dhewa T, Kumar N, Kumar S, Puniya AK, Shukla P. Gut Microbiota Modulation and Its Relationship with Obesity Using Prebiotic Fibers and Probiotics: A Review. Front Microbiol. 2017 Apr 4;8:563. doi: 10.3389/fmicb.2017.00563.

185. Kersten S. Mechanisms of nutritional and hormonal regulation of lipogenesis. EMBO Rep. 2001 Apr;2(4):282-6. doi: 10.1093/embo-reports/kve071.

186. Consolazio A, Alò PL, Rivera M, Iacopini F, Paoluzi OA, Crispino P, Pica R, Paoluzi P. Overexpression of fatty acid synthase in ulcerative colitis. Am J Clin Pathol. 2006 Jul;126(1):113-8. doi: 10.1309/PUBV-QNDN-VQKJ-VC8M.

187. Cruz MD, Wali RK, Bianchi LK, Radosevich AJ, Crawford SE, Jepeal L, Goldberg MJ, Weinstein J, Momi N, Roy P, Calderwood AH, Backman V, Roy HK. Colonic mucosal fatty acid synthase as an early biomarker for colorectal neoplasia: modulation by obesity and gender. Cancer Epidemiol Biomarkers Prev. 2014 Nov;23(11):2413-21. doi: 10.1158/1055-9965.EPI-14-0026.

188. Matsuo S, Yang WL, Aziz M, Kameoka S, Wang P. Fatty acid synthase inhibitor C75 ameliorates experimental colitis. Mol Med. 2014 Jan 17;20:1-9. doi: 10.2119/molmed.2013.00113.

189. Angeles TS, Hudkins RL. Recent advances in targeting the fatty acid biosynthetic pathway using fatty acid synthase inhibitors. Expert Opin Drug Discov. 2016 Dec;11(12):1187-1199. doi: 10.1080/17460441.2016.1245286.

190. Wang R, Gu X, Dai W, Ye J, Lu F, Chai Y, Fan G, Gonzalez FJ, Duan G, Qi Y. A lipidomics investigation into the intervention of celastrol in experimental colitis. Mol Biosyst. 2016 Apr 26;12(5):1436-44. doi: 10.1039/c5mb00864f.

191. Martinelli N, Consoli L, Olivieri O. A 'desaturase hypothesis' for atherosclerosis: Janus-faced enzymes in omega-6 and omega-3 polyunsaturated fatty acid metabolism. J Nutrigenet Nutrigenomics. 2009;2(3):129-39. doi: 10.1159/000238177.

192. Yang K, Li H, Dong J, Dong Y, Wang CZ. Expression profile of polyunsaturated fatty acids in colorectal cancer. World J Gastroenterol. 2015 Feb 28;21(8):2405-12. doi: 10.3748/wjg.v21.i8.2405.

193. Segal LN, Clemente JC, Wu BG, Wikoff WR, Gao Z, Li Y, Ko JP, Rom WN, Blaser MJ, Weiden MD. Randomised, double-blind, placebo-controlled trial with azithromycin selects for anti-inflammatory microbial metabolites in the emphysematous lung. Thorax. 2017 Jan;72(1):13-22. doi: 10.1136/thoraxjnl-2016-208599.

194. Li M, Wang B, Zhang M, Rantalainen M, Wang S, Zhou H, Zhang Y, Shen J, Pang X, Zhang M, Wei H, Chen Y, Lu H, Zuo J, Su M, Qiu Y, Jia W, Xiao C, Smith LM, Yang S, Holmes E, Tang H, Zhao G, Nicholson JK, Li L, Zhao L. Symbiotic gut microbes modulate human metabolic phenotypes. Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):2117-22. doi: 10.1073/pnas.0712038105.

195. Hsiao EY, McBride SW, Hsien S, Sharon G, Hyde ER, McCue T, Codelli JA, Chow J, Reisman SE, Petrosino JF, Patterson PH, Mazmanian SK. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell. 2013 Dec 19;155(7):1451-63. doi: 10.1016/j.cell.2013.11.024.

196. Chen HH, Tseng YJ, Wang SY, Tsai YS, Chang CS, Kuo TC, Yao WJ, Shieh CC, Wu CH, Kuo PH. The metabolome profiling and pathway analysis in metabolic healthy and abnormal obesity. Int J Obes (Lond). 2015 Aug;39(8):1241-8. doi: 10.1038/ijo.2015.65.

197. Belenguer A, Duncan SH, Holtrop G, Anderson SE, Lobley GE, Flint HJ. Impact of pH on lactate formation and utilization by human fecal microbial communities. Appl Environ Microbiol. 2007 Oct;73(20):6526-33.

198. Pessione E. Lactic acid bacteria contribution to gut microbiota complexity: lights and shadows. Front Cell Infect Microbiol. 2012 Jun 22;2:86. doi: 10.3389/fcimb.2012.00086.

199. Hove H, Holtug K, Jeppesen PB, Mortensen PB. Butyrate absorption and lactate secretion in ulcerative colitis. Dis Colon Rectum. 1995 May;38(5):519-25.

200. Song WB, Lv YH, Zhang ZS, Li YN, Xiao LP, Yu XP, Wang YY, Ji HL, Ma L. Soluble intercellular adhesion molecule-1, D-lactate and diamine oxidase in patients with inflammatory bowel disease. World J Gastroenterol. 2009 Aug 21;15(31):3916-9.

201. Xie Q, Gan HT. Controversies about the use of serological markers in diagnosis of inflammatory bowel disease. World J Gastroenterol. 2010 Jan 14;16(2):279-80.

202. Williams HR, Willsmore JD, Cox IJ, Walker DG, Cobbold JF, Taylor-Robinson SD, Orchard TR. Serum metabolic profiling in inflammatory bowel disease. Dig Dis Sci. 2012 Aug;57(8):2157-65. doi: 10.1007/s10620-012-2127-2.

203. Dawiskiba T, Deja S, Mulak A, Ząbek A, Jawień E, Pawełka D, Banasik M, Mastalerz-Migas A, Balcerzak W, Kaliszewski K, Skóra J, Barć P, Korta K, Pormańczuk K, Szyber P, Litarski A, Młynarz P. Serum and urine metabolomic fingerprinting in diagnostics of inflammatory bowel diseases. World J Gastroenterol. 2014 Jan 7;20(1):163-74. doi: 10.3748/wjg.v20.i1.163.

204. Spratlin JL, Serkova NJ, Eckhardt SG. Clinical applications of metabolomics in oncology: a review. Clin Cancer Res. 2009 Jan 15;15(2):431-40. doi: 10.1158/1078-0432.CCR-08-1059.

205. Kouremenos KA, Johansson M, Marriott PJ. Advances in gas chromatographic methods for the identification of biomarkers in cancer. J Cancer. 2012;3:404-20. doi: 10.7150/jca.4956.

206. Dutta M, Joshi M, Srivastava S, Lodh I, Chakravarty B, Chaudhury K. A metabonomics approach as a means for identification of potential biomarkers for early diagnosis of endometriosis. Mol Biosyst. 2012 Oct 30;8(12):3281-7. doi: 10.1039/c2mb25353d.

207. Komaromy-Hiller G, Sundquist PD, Jacobsen LJ, Nuttall KL. Serum succinate by capillary zone electrophoresis: marker candidate for hypoxia. Ann Clin Lab Sci. 1997 Mar-Apr;27(2):163-8.

208. Bertini I, Calabrò A, De Carli V, Luchinat C, Nepi S, Porfirio B, Renzi D, Saccenti E, Tenori L. The metabonomic signature of celiac disease. J Proteome Res. 2009 Jan;8(1):170-7. doi: 10.1021/pr800548z.

209. Fathi F, Ektefa F, Arefi Oskouie A, Rostami K, Rezaei-Tavirani M, Mohammad Alizadeh AH, Tafazzoli M, Rostami Nejad M. NMR based metabonomics study on celiac disease in the blood serum. Gastroenterol Hepatol Bed Bench. 2013 Fall;6(4):190-4.

210. Chassard C, Dapoigny M, Scott KP, Crouzet L, Del'homme C, Marquet P, Martin JC, Pickering G, Ardid D, Eschalier A, Dubray C, Flint HJ, Bernalier-Donadille A. Functional dysbiosis within the gut microbiota of patients with constipated-irritable bowel syndrome. Aliment Pharmacol Ther. 2012 Apr;35(7):828-38. doi: 10.1111/j.1365-2036.2012.05007.x.

211. Duncan SH, Louis P, Thomson JM, Flint HJ. The role of pH in determining the species composition of the human colonic microbiota. Environ Microbiol. 2009 Aug;11(8):2112-22. doi: 10.1111/j.1462-2920.2009.01931.x.

212. Marquet P, Duncan SH, Chassard C, Bernalier-Donadille A, Flint HJ. Lactate has the potential to promote hydrogen sulphide formation in the human colon. FEMS Microbiol Lett. 2009 Oct;299(2):128-34. doi: 10.1111/j.1574-6968.2009.01750.x.

213. Belenguer A, Holtrop G, Duncan SH, Anderson SE, Calder AG, Flint HJ, Lobley GE. Rates of production and utilization of lactate by microbial communities from the human colon. FEMS Microbiol Ecol. 2011 Jul;77(1):107-19. doi: 10.1111/j.1574-6941.2011.01086.x.

214. Hulin SJ, Singh S, Chapman MA, Allan A, Langman MJ, Eggo MC. Sulphide-induced energy deficiency in colonic cells is prevented by glucose but not by butyrate. Aliment Pharmacol Ther. 2002 Feb;16(2):325-31.

215. Pitcher MC, Cummings JH. Hydrogen sulphide: a bacterial toxin in ulcerative colitis? Gut. 1996 Jul;39(1):1-4.

216. Attene-Ramos MS, Wagner ED, Plewa MJ, Gaskins HR. Evidence that hydrogen sulfide is a genotoxic agent. Mol Cancer Res. 2006 Jan;4(1):9-14. doi: 10.1158/1541-7786.MCR-05-0126.

217. Rowan FE, Docherty NG, Coffey JC, O'Connell PR. Sulphate-reducing bacteria and hydrogen sulphide in the aetiology of ulcerative colitis. Br J Surg. 2009 Feb;96(2):151-8. doi: 10.1002/bjs.6454.

218. Rowan F, Docherty NG, Murphy M, Murphy B, Calvin Coffey J, O'Connell PR. Desulfovibrio bacterial species are increased in ulcerative colitis. Dis Colon Rectum. 2010 Nov;53(11):1530-6. doi: 10.1007/DCR.0b013e3181f1e620.

219. Cai WJ, Wang MJ, Ju LH, Wang C, Zhu YC. Hydrogen sulfide induces human colon cancer cell proliferation: role of Akt, ERK and p21. Cell Biol Int. 2010 Apr 14;34(6):565-72. doi: 10.1042/CBI20090368.

220. Khalil NA, Walton GE, Gibson GR, Tuohy KM, Andrews SC. In vitro batch cultures of gut microbiota from healthy and ulcerative colitis (UC) subjects suggest that sulphate-reducing bacteria levels are raised in UC and by a protein-rich diet. Int J Food Sci Nutr. 2014 Feb;65(1):79-88. doi: 10.3109/09637486.2013.825700.

221. Ando T, Rasmussen K, Nyhan WL, Hull D. 3-hydroxypropionate: significance of -oxidation of propionate in patients with propionic acidemia and methylmalonic acidemia. Proc Natl Acad Sci U S A. 1972 Oct;69(10):2807-11.

222. Shchelochkov OA, Carrillo N, Venditti C. Propionic Acidemia. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH, Stephens K, editors. SourceGeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017.

223. Haan E, Brown G, Bankier A, Mitchell D, Hunt S, Blakey J, Barnes G. Severe illness caused by the products of bacterial metabolism in a child with a short gut. Eur J Pediatr. 1985 May;144(1):63-5.

224. Pollitt RJ, Fowler B, Sardharwalla IB, Edwards MA, Gray RG. Increased excretion of propan-1,3-diol and 3-hydroxypropionic acid apparently caused by abnormal bacterial metabolism in the gut. Clin Chim Acta. 1987 Nov 16;169(2-3):151-7.

225. Ikeda A, Nishiumi S, Shinohara M, Yoshie T, Hatano N, Okuno T, Bamba T, Fukusaki E, Takenawa T, Azuma T, Yoshida M. Serum metabolomics as a novel diagnostic approach for gastrointestinal cancer. Biomed Chromatogr. 2012 May;26(5):548-58. doi: 10.1002/bmc.1671.

226. Landaas S. The formation of 2-hydroxybutyric acid in experimental animals. Clin Chim Acta. 1975 Jan 6;58(1):23-32.

227. Zheng Y, Yu B, Alexander D, Steffen LM, Boerwinkle E. Human metabolome associates with dietary intake habits among African Americans in the atherosclerosis risk in communities study. Am J Epidemiol. 2014 Jun 15;179(12):1424-33. doi: 10.1093/aje/kwu073.

228. Miyazaki T, Honda A, Ikegami T, Iwamoto J, Monma T, Hirayama T, Saito Y, Yamashita K, Matsuzaki Y. Simultaneous quantification of salivary 3-hydroxybutyrate, 3-hydroxyisobutyrate, 3-hydroxy-3-methylbutyrate, and 2-hydroxybutyrate as possible markers of amino acid and fatty acid catabolic pathways by LC-ESI-MS/MS. Springerplus. 2015 Sep 15;4:494. doi: 10.1186/s40064-015-1304-0.

229. Lord RS, Bralley JA. Clinical applications of urinary organic acids. Part I: Detoxification markers. Altern Med Rev. 2008 Sep;13(3):205-15.

230. Kageyama Y, Kasahara T, Morishita H, Mataga N, Deguchi Y, Tani M, Kuroda K, Hattori K, Yoshida S, Inoue K, Kato T. Search for plasma biomarkers in drug-free patients with bipolar disorder and schizophrenia using metabolome analysis. Psychiatry Clin Neurosci. 2017 Feb;71(2):115-123. doi: 10.1111/pcn.12461.

231. Gall WE, Beebe K, Lawton KA, Adam KP, Mitchell MW, Nakhle PJ, Ryals JA, Milburn MV, Nannipieri M, Camastra S, Natali A, Ferrannini E; RISC Study Group. α-Hydroxybutyrate Is an Early Biomarker of Insulin Resistance and Glucose Intolerance in a Nondiabetic Population. PLoS One. 2010 May 28;5(5): e10883. doi: 10.1371/journal.pone.0010883.

232. Ferrannini E, Natali A, Camastra S, Nannipieri M, Mari A, Adam KP, Milburn MV, Kastenmüller G, Adamski J, Tuomi T, Lyssenko V, Groop L, Gall WE. Early metabolic markers of the development of dysglycemia and type 2 diabetes and their physiological significance. Diabetes. 2013 May;62(5):1730-7. doi: 10.2337/db12-0707.

233. Varvel SA, Pottala JV, Thiselton DL, Caffrey R, Dall T, Sasinowski M, McConnell JP, Warnick GR, Voros S, Graham TE. Serum α-hydroxybutyrate (α-HB) predicts elevated 1 h glucose levels and early-phase β-cell dysfunction during OGTT. BMJ Open Diabetes Res Care. 2014 Sep 24;2(1): e000038. doi: 10.1136/bmjdrc-2014-000038.

234. Delanghe JR, Speeckaert MM. Translational research and biomarkers in neonatal sepsis. Clin Chim Acta. 2015 Dec 7;451(Pt A):46-64. doi: 10.1016/j.cca.2015.01.031.

235. Kano K, Ichimura T. Increased alpha-hydroxybutyrate dehydrogenase in serum from children with measles. Clin Chem. 1992 May;38(5):624-7.

236. Hoerr V, Zbytnuik L, Leger C, Tam PP, Kubes P, Vogel HJ. Gram-negative and Gram-positive bacterial infections give rise to a different metabolic response in a mouse model. J Proteome Res. 2012 Jun 1;11(6):3231-45. doi: 10.1021/pr201274r.

237. Qiu Y, Cai G, Su M, Chen T, Zheng X, Xu Y, Ni Y, Zhao A, Xu LX, Cai S, Jia W. Serum metabolite profiling of human colorectal cancer using GC-TOFMS and UPLC-QTOFMS. J Proteome Res. 2009 Oct;8(10):4844-50. doi: 10.1021/pr9004162.

238. Nishiumi S, Kobayashi T, Ikeda A, Yoshie T, Kibi M, Izumi Y, Okuno T, Hayashi N, Kawano S, Takenawa T, Azuma T, Yoshida M. A novel serum metabolomics-based diagnostic approach for colorectal cancer. PLoS One. 2012;7(7): e40459. doi: 10.1371/journal.pone.0040459.

239. Zeng J, Yin P, Tan Y, Dong L, Hu C, Huang Q, Lu X, Wang H, Xu G. Metabolomics study of hepatocellular carcinoma: discovery and validation of serum potential biomarkers by using capillary electrophoresis-mass spectrometry. J Proteome Res. 2014 Jul 3;13(7):3420-31. doi: 10.1021/pr500390y.

240. Vicente-Muñoz S, Morcillo I, Puchades-Carrasco L, Payá V, Pellicer A, Pineda-Lucena A. Nuclear magnetic resonance metabolomic profiling of urine provides a noninvasive alternative to the identification of biomarkers associated with endometriosis. Fertil Steril. 2015 Nov;104(5):1202-9. doi: 10.1016/j.fertnstert.2015.07.1149.

241. Schicho R, Shaykhutdinov R, Ngo J, Nazyrova A, Schneider C, Panaccione R, Kaplan GG, Vogel HJ, Storr M. Quantitative metabolomic profiling of serum, plasma, and urine by 1H NMR spectroscopy discriminates between patients with inflammatory bowel disease and healthy individuals. J Proteome Res. 2012 Jun 1;11(6):3344-57. doi: 10.1021/pr300139q.

242. Letto J, Brosnan ME, Brosnan JT. Valine metabolism. Gluconeogenesis from 3-hydroxyisobutyrate. Biochem J. 1986 Dec 15;240(3):909-12.

243. Hu H, Jaskiewicz JA, Harris RA. Ethanol and oleate inhibition of alpha-ketoisovalerate and 3-hydroxyisobutyrate metabolism by isolated hepatocytes. Arch Biochem Biophys. 1992 Nov 15;299(1):57-62.

244. Landaas S. Accumulation of 3-hydroxyisobutyric acid, 2-methyl-3-hydroxybutyric acid and 3-hydroxyisovaleric acid in ketoacidosis. Clin Chim Acta. 1975 Oct 15;64(2):143-54.

245. Zabek A, Swierkot J, Malak A, Zawadzka I, Deja S, Bogunia-Kubik K, Mlynarz P. Application of (1) H NMR-based serum metabolomic studies for monitoring female patients with rheumatoid arthritis. J Pharm Biomed Anal. 2016 Jan 5;117:544-50. doi: 10.1016/j.jpba.2015.10.007.

246. Podebrad F, Heil M, Beck T, Mosandl A, Sewell AC, Böhles H. Stereodifferentiation of 3-hydroxyisobutyric- and 3-aminoisobutyric acid in human urine by enantioselective multidimensional capillary gas chromatography-mass spectrometry. Clin Chim Acta. 2000 Feb 25;292(1-2):93-105.

247. Loupatty FJ, van der Steen A, Ijlst L, Ruiter JP, Ofman R, Baumgartner MR, Ballhausen D, Yamaguchi S, Duran M, Wanders RJ. Clinical, biochemical, and molecular findings in three patients with 3-hydroxyisobutyric aciduria. Mol Genet Metab. 2006 Mar;87(3):243-8. doi: 10.1016/j.ymgme.2005.09.019.

248. Viegas CM, da Costa Ferreira G, Schuck PF, Tonin AM, Zanatta A, de Souza Wyse AT, Dutra-Filho CS, Wannmacher CM, Wajner M. Evidence that 3-hydroxyisobutyric acid inhibits key enzymes of energy metabolism in cerebral cortex of young rats. Int J Dev Neurosci. 2008 May-Jun;26(3-4):293-9. doi: 10.1016/j.ijdevneu.2008.01.007.

249. Lutz NW, Viola A, Malikova I, Confort-Gouny S, Audoin B, Ranjeva JP, Pelletier J, Cozzone PJ. Inflammatory multiple-sclerosis plaques generate characteristic metabolic profiles in cerebrospinal fluid. PLoS One. 2007 Jul 4;2(7): e595. doi: 10.1371/journal.pone.0000595.

250. Jaskiewicz J, Zhao Y, Hawes JW, Shimomura Y, Crabb DW, Harris RA. Catabolism of isobutyrate by colonocytes. Arch Biochem Biophys. 1996 Mar 15;327(2):265-70. doi: 10.1006/abbi.1996.0120.

251. Liebich HM, Först C. Hydroxycarboxylic and oxocarboxylic acids in urine: products from branched-chain amino acid degradation and from ketogenesis. J Chromatogr. 1984 Aug 10;309(2):225-42.

252. Landaas S, Jakobs C. The occurrence of 2-hydroxyisovaleric acid in patients with lactic acidosis and ketoacidosis. Clin Chim Acta. 1977 Aug 1;78(3):489-93.

253. Reinke SN, Broadhurst DL, Sykes BD, Baker GB, Catz I, Warren KG, Power C. Metabolomic profiling in multiple sclerosis: insights into biomarkers and pathogenesis. Mult Scler. 2014 Sep;20(10):1396-400. doi: 10.1177/1352458513516528.

254. Kortman GA, Dutilh BE, Maathuis AJ, Engelke UF, Boekhorst J, Keegan KP, Nielsen FG, Betley J, Weir JC, Kingsbury Z, Kluijtmans LA, Swinkels DW, Venema K, Tjalsma H. Microbial Metabolism Shifts Towards an Adverse Profile with Supplementary Iron in the TIM-2 In vitro Model of the Human Colon. Front Microbiol. 2016 Jan 6;6:1481. doi: 10.3389/fmicb.2015.01481.

255. Pine L, Malcolm GB, Brooks JB, Daneshvar MI. Physiological studies on the growth and utilization of sugars by Listeria species. Can J Microbiol. 1989 Feb;35(2):245-54.

256. Thota VR, Dacha S, Natarajan A, Nerad J. Eggerthella lenta bacteremia in a Crohn's disease patient after ileocecal resection. Future Microbiol. 2011 May;6(5):595-7. doi: 10.2217/fmb.11.31.

257. Venugopal AA, Szpunar S, Johnson LB. Risk and prognostic factors among patients with bacteremia due to Eggerthella lenta. Anaerobe. 2012 Aug;18(4):475-8. doi: 10.1016/j.anaerobe.2012.05.005.

258. Miranda-Bautista J, Padilla-Suárez C, Bouza E, Muñoz P, Menchén L, Marín-Jiménez I. Listeria monocytogenes infection in inflammatory bowel disease patients: case series and review of the literature. Eur J Gastroenterol Hepatol. 2014 Nov;26(11):1247-52. doi: 10.1097/MEG.0000000000000188.

259. Gardiner BJ, Tai AY, Kotsanas D, Francis MJ, Roberts SA, Ballard SA, Junckerstorff RK, Korman TM. Clinical and microbiological characteristics of Eggerthella lenta bacteremia. J Clin Microbiol. 2015 Feb;53(2):626-35. doi: 10.1128/JCM.02926-14.

260. Woerther PL, Antoun S, Chachaty E, Merad M. Eggerthella lenta bacteremia in solid tumor cancer patients: Pathogen or witness of frailty? Anaerobe. 2017 Apr 22;47:70-72. doi: 10.1016/j.anaerobe.2017.04.010.

261. McMillan A, Rulisa S, Sumarah M, Macklaim JM, Renaud J, Bisanz JE, Gloor GB, Reid G. A multi-platform metabolomics approach identifies highly specific biomarkers of bacterial diversity in the vagina of pregnant and non-pregnant women. Sci Rep. 2015 Sep 21;5:14174. doi: 10.1038/srep14174.

262. Zhu H, Li YR. Oxidative stress and redox signaling mechanisms of inflammatory bowel disease: updated experimental and clinical evidence. Exp Biol Med (Maywood). 2012 May;237(5):474-80. doi: 10.1258/ebm.2011.011358.

263. Piechota-Polanczyk A, Fichna J. Review article: the role of oxidative stress in pathogenesis and treatment of inflammatory bowel diseases. Naunyn Schmiedebergs Arch Pharmacol. 2014 Jul;387(7):605-20. doi: 10.1007/s00210-014-0985-1.

264. Zhang Y, Lin L, Xu Y, Lin Y, Jin Y, Zheng C. 1H NMR-based spectroscopy detects metabolic alterations in serum of patients with early-stage ulcerative colitis. Biochem Biophys Res Commun. 2013 Apr 19;433(4):547-51. doi: 10.1016/j.bbrc.2013.03.012.

265. De Palma G, Nadal I, Medina M, Donat E, Ribes-Koninckx C, Calabuig M, Sanz Y. Intestinal dysbiosis and reduced immunoglobulin-coated bacteria associated with coeliac disease in children. BMC Microbiol. 2010 Feb 24;10:63. doi: 10.1186/1471-2180-10-63.

266. Hedberg ME, Israelsson A, Moore ER, Svensson-Stadler L, Wai SN, Pietz G, Sandström O, Hernell O, Hammarström ML, Hammarström S. Prevotella jejuni sp. nov., isolated from the small intestine of a child with coeliac disease. Int J Syst Evol Microbiol. 2013 Nov;63(Pt 11):4218-23. doi: 10.1099/ijs.0.052647-0.

267. Sjöberg V, Sandström O, Hedberg M, Hammarström S, Hernell O, Hammarström ML. Intestinal T-cell responses in celiac disease - impact of celiac disease associated bacteria. PLoS One. 2013;8(1): e53414. doi: 10.1371/journal.pone.0053414.

268. Krebs HA. The history of the tricarboxylic acid cycle. Perspect Biol Med. 1970 Autumn;14(1):154-70.

269. Brière JJ, Favier J, Gimenez-Roqueplo AP, Rustin P. Tricarboxylic acid cycle dysfunction as a cause of human diseases and tumor formation. Am J Physiol Cell Physiol. 2006 Dec;291(6): C1114-20. doi: 10.1152/ajpcell.00216.2006.

270. Watford M. The urea cycle: Teaching intermediary metabolism in a physiological setting. Biochem Mol Biol Educ. 2003;31:289-97. doi:10.1002/bmb.2003.494031050249.

271. Robert C, Chassard C, Lawson PA, Bernalier-Donadille A. Bacteroides cellulosilyticus sp. nov., a cellulolytic bacterium from the human gut microbial community. Int J Syst Evol Microbiol. 2007 Jul;57(Pt 7):1516-20. doi: 10.1099/ijs.0.64998-0.

272. Shah HN, Olsen I, Bernard K, Finegold SM, Gharbia S, Gupta RS. Approaches to the study of the systematics of anaerobic, gram-negative, non-sporeforming rods: current status and perspectives. Anaerobe. 2009 Oct;15(5):179-94. doi: 10.1016/j.anaerobe.2009.08.003.

273. Morotomi M, Nagai F, Sakon H, Tanaka R. Paraprevotella clara gen. nov., sp. nov. and Paraprevotella xylaniphila sp. nov., members of the family 'Prevotellaceae' isolated from human faeces. Int J Syst Evol Microbiol. 2009 Aug;59(Pt 8):1895-900. doi: 10.1099/ijs.0.008169-0.

274. Rey FE, Faith JJ, Bain J, Muehlbauer MJ, Stevens RD, Newgard CB, Gordon JI. Dissecting the in vivo metabolic potential of two human gut acetogens. J Biol Chem. 2010 Jul 16;285(29):22082-90. doi: 10.1074/jbc.M110.117713.

275. Chassard C, Delmas E, Robert C, Lawson PA, Bernalier-Donadille A. Ruminococcus champanellensis sp. nov., a cellulose-degrading bacterium from human gut microbiota. Int J Syst Evol Microbiol. 2012 Jan;62(Pt 1):138-43. doi: 10.1099/ijs.0.027375-0.

276. Milstien S, Goldman P. Role of intestinal microflora in the metabolism of guanidinosuccinic acid. J Bacteriol. 1973 May;114(2):641-4.

277. Ryu HW, Kang KH, Pan JG, Chang HN. Characteristics and glycerol metabolism of fumarate-reducing Enterococcus faecalis RKY 1. Biotechnol Bioeng. 2001 Jan 5;72(1):119-24.

278. Watanabe Y, Nagai F, Morotomi M. Characterization of Phascolarctobacterium succinatutens sp. nov., an asaccharolytic, succinate-utilizing bacterium isolated from human feces. Appl Environ Microbiol. 2012 Jan;78(2):511-8. doi: 10.1128/AEM.06035-11.

279. Morgan XC, Tickle TL, Sokol H, Gevers D, Devaney KL, Ward DV, Reyes JA, Shah SA, LeLeiko N, Snapper SB, Bousvaros A, Korzenik J, Sands BE, Xavier RJ, Huttenhower C. Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment. Genome Biol. 2012 Apr 16;13(9): R 79. doi: 10.1186/gb-2012-13-9-r79.

280. Hopkins MJ, Macfarlane GT. Nondigestible oligosaccharides enhance bacterial colonization resistance against Clostridium difficile in vitro. Appl Environ Microbiol. 2003 Apr;69(4):1920-7.

281. Flint HJ, Scott KP, Duncan SH, Louis P, Forano E. Microbial degradation of complex carbohydrates in the gut. Gut Microbes. 2012 Jul-Aug;3(4):289-306. doi: 10.4161/gmic.19897.

282. Reichardt N, Duncan SH, Young P, Belenguer A, McWilliam Leitch C, Scott KP, Flint HJ, Louis P. Phylogenetic distribution of three pathways for propionate production within the human gut microbiota. ISME J. 2014 Jun;8(6):1323-35. doi: 10.1038/ismej.2014.14.

283. Ladirat SE, Schoterman MH, Rahaoui H, Mars M, Schuren FH, Gruppen H, Nauta A, Schols HA. Exploring the effects of galacto-oligosaccharides on the gut microbiota of healthy adults receiving amoxicillin treatment. Br J Nutr. 2014 Aug 28;112(4):536-46. doi: 10.1017/S 0007114514001135.

284. Ferreyra JA, Wu KJ, Hryckowian AJ, Bouley DM, Weimer BC, Sonnenburg JL. Gut microbiota-produced succinate promotes C. difficile infection after antibiotic treatment or motility disturbance. Cell Host Microbe. 2014 Dec 10;16(6):770-7. doi: 10.1016/j.chom.2014.11.003.

285. Vogt SL, Peña-Díaz J, Finlay BB. Chemical communication in the gut: Effects of microbiota-generated metabolites on gastrointestinal bacterial pathogens. Anaerobe. 2015 Aug;34:106-15. doi: 10.1016/j.anaerobe.2015.05.002.

286. Rotstein OD, Nasmith PE, Grinstein S. The Bacteroides by-product succinic acid inhibits neutrophil respiratory burst by reducing intracellular pH. Infect Immun. 1987 Apr;55(4):864-70.

287. Abdul-Majid KB, Kenny PA, Finlay-Jones JJ. The effect of the bacterial product, succinic acid, on neutrophil bactericidal activity. FEMS Immunol Med Microbiol. 1997 Feb;17(2):79-86.

288. Fukui S, Shimoyama T, Tamura K, Yamamura M, Satomi M. Mucosal blood flow and generation of superoxide in rat experimental colitis induced by succinic acid. J Gastroenterol. 1997 Aug;32(4):464-71.

289. Ariake K, Ohkusa T, Sakurazawa T, Kumagai J, Eishi Y, Hoshi S, Yajima T. Roles of mucosal bacteria and succinic acid in colitis caused by dextran sulfate sodium in mice. J Med Dent Sci. 2000 Dec;47(4):233-41.

290. Shiomi Y, Nishiumi S, Ooi M, Hatano N, Shinohara M, Yoshie T, Kondo Y, Furumatsu K, Shiomi H, Kutsumi H, Azuma T, Yoshida M. GCMS-based metabolomic study in mice with colitis induced by dextran sulfate sodium. Inflamm Bowel Dis. 2011 Nov;17(11):2261-74. doi: 10.1002/ibd.21616.

291. Nagao-Kitamoto H, Kamada N. Host-microbial Cross-talk in Inflammatory Bowel Disease. Immune Netw. 2017 Feb;17(1):1-12. doi: 10.4110/in.2017.17.1.1.

292. Tannahill GM, Curtis AM, Adamik J, Palsson-McDermott EM, McGettrick AF, Goel G, Frezza C, Bernard NJ, Kelly B, Foley NH, Zheng L, Gardet A, Tong Z, Jany SS, Corr SC, Haneklaus M, Caffrey BE, Pierce K, Walmsley S, Beasley FC, Cummins E, Nizet V, Whyte M, Taylor CT, Lin H, Masters SL, Gottlieb E, Kelly VP, Clish C, Auron PE, Xavier RJ, O'Neill LA. Succinate is an inflammatory signal that induces IL-1β through HIF-1α. Nature. 2013 Apr 11;496(7444):238-42. doi: 10.1038/nature11986.

293. Mills E, O'Neill LA. Succinate: a metabolic signal in inflammation. Trends Cell Biol. 2014 May;24(5):313-20. doi: 10.1016/j.tcb.2013.11.008.

294. Curtis MM, Hu Z, Klimko C, Narayanan S, Deberardinis R, Sperandio V. The Gut Commensal Bacteroides thetaiotaomicron Exacerbates Enteric Infection through Modification of the Metabolic Landscape. Cell Host Microbe. 2014 Dec 10;16(6):759-69. doi: 10.1016/j.chom.2014.11.005.

295. Deen PM, Robben JH. Succinate receptors in the kidney. J Am Soc Nephrol. 2011 Aug;22(8):1416-22. doi: 10.1681/ASN.2010050481.

296. Ariza AC, Deen PM, Robben JH. The succinate receptor as a novel therapeutic target for oxidative and metabolic stress-related conditions. Front Endocrinol (Lausanne). 2012 Feb 16;3:22. doi: 10.3389/fendo.2012.00022.

297. Inagaki A, Ichikawa H, Sakata T. Inhibitory effect of succinic acid on epithelial cell proliferation of colonic mucosa in rats. J Nutr Sci Vitaminol (Tokyo). 2007 Aug;53(4):377-9. doi: 10.3177/jnsv.53.377.

298. Tamura K, Yamamura M, Satomi M. Effect of butyrate on colonic mucosa. JJPEN Jpn J Parenter Enteral Nutr. 1995;17:481-4.

299. Kanauchi O, Mitsuyama K, Andoh A, Iwanaga T. Modulation of intestinal environment by prebiotic germinated barley foodstuff prevents chemo-induced colonic carcinogenesis in rats. Oncol Rep. 2008 Oct;20(4):793-801. doi: 10.3892/or_00000076.

300. Komiyama Y, Mitsuyama K, Masuda J, Yamasaki H, Takedatsu H, Andoh A, Tsuruta O, Fukuda M, Kanauchi O. Prebiotic treatment in experimental colitis reduces the risk of colitic cancer. J Gastroenterol Hepatol. 2011 Aug;26(8):1298-308. doi: 10.1111/j.1440-1746.2011.06690.x.

301. Kanauchi O, Mitsuyama K, Homma T, Takahama K, Fujiyama Y, Andoh A, Araki Y, Suga T, Hibi T, Naganuma M, Asakura H, Nakano H, Shimoyama T, Hida N, Haruma K, Koga H, Sata M, Tomiyasu N, Toyonaga A, Fukuda M, Kojima A, Bamba T. Treatment of ulcerative colitis patients by long-term administration of germinated barley foodstuff: multi-center open trial. Int J Mol Med. 2003 Nov;12(5):701-4. doi: 10.3892/ijmm.12.5.701.

302. Hanai H, Kanauchi O, Mitsuyama K, Andoh A, Takeuchi K, Takayuki I, Araki Y, Fujiyama Y, Toyonaga A, Sata M, Kojima A, Fukuda M, Bamba T. Germinated barley foodstuff prolongs remission in patients with ulcerative colitis. Int J Mol Med. 2004 May;13(5):643-7. doi: 10.3892/ijmm.13.5.643.

303. Jakobsdottir G., Xu J, Molin G, Ahrné S, Nyman M. High-fat diet reduces the formation of butyrate, but increases succinate, inflammation, liver fat and cholesterol in rats, while dietary fibre counteracts these effects. PLoS One. 2013 Nov 13;8(11): e80476. doi: 10.1371/journal.pone.0080476.

304. Zhu J, Djukovic D, Deng L, Gu H, Himmati F, Abu Zaid M, Chiorean EG, Raftery D. Targeted serum metabolite profiling and sequential metabolite ratio analysis for colorectal cancer progression monitoring. Anal Bioanal Chem. 2015 Oct;407(26):7857-63. doi: 10.1007/s00216-015-8984-8.

305. Hirayama A, Kami K, Sugimoto M, Sugawara M, Toki N, Onozuka H, Kinoshita T, Saito N, Ochiai A, Tomita M, Esumi H, Soga T. Quantitative metabolome profiling of colon and stomach cancer microenvironment by capillary electrophoresis time-of-flight mass spectrometry. Cancer Res. 2009 Jun 1;69(11):4918-25. doi: 10.1158/0008-5472.CAN-08-4806.

306. Qiu Y, Cai G, Su M, Chen T, Liu Y, Xu Y, Ni Y, Zhao A, Cai S, Xu LX, Jia W. Urinary metabonomic study on colorectal cancer. J Proteome Res. 2010 Mar 5;9(3):1627-34. doi: 10.1021/pr901081y.

307. Chouchani ET, Pell VR, Gaude E, Aksentijević D, Sundier SY, Robb EL, Logan A, Nadtochiy SM, Ord EN, Smith AC, Eyassu F, Shirley R, Hu CH, Dare AJ, James AM, Rogatti S, Hartley RC, Eaton S, Costa AS, Brookes PS, Davidson SM, Duchen MR, Saeb-Parsy K, Shattock MJ, Robinson AJ, Work LM, Frezza C, Krieg T, Murphy MP. Ischaemic accumulation of succinate controls reperfusion injury through mitochondrial ROS. Nature. 2014 Nov 20;515(7527):431-5. doi: 10.1038/nature13909.

308. O'Neill LA. Biochemistry: succinate strikes. Nature. 2014 Nov 20;515(7527):350-1. doi: 10.1038/nature13941.

309. Bar-Or D, Carrick MM, Mains CW, Rael LT, Slone D, Brody EN. Sepsis, oxidative stress, and hypoxia: Are there clues to better treatment? Redox Rep. 2015 Sep;20(5):193-7. doi: 10.1179/1351000215Y.0000000005.

310. Fischbach MA, Sonnenburg JL. Eating for two: how metabolism establishes interspecies interactions in the gut. Cell Host Microbe. 2011 Oct 20;10(4):336-47. doi: 10.1016/j.chom.2011.10.002.

311. Steinsiek S, Frixel S, Stagge S; SUMO, Bettenbrock K. Characterization of E. coli MG1655 and frdA and sdhC mutants at various aerobiosis levels. J Biotechnol. 2011 Jun 10;154(1):35-45. doi: 10.1016/j.jbiotec.2011.03.015.

312. Chan EC, Koh PK, Mal M, Cheah PY, Eu KW, Backshall A, Cavill R, Nicholson JK, Keun HC. Metabolic profiling of human colorectal cancer using high-resolution magic angle spinning nuclear magnetic resonance (HR-MAS NMR) spectroscopy and gas chromatography mass spectrometry (GC/MS). J Proteome Res. 2009 Jan;8(1):352-61. doi: 10.1021/pr8006232.

313. Lampropoulou V, Sergushichev A, Bambouskova M, Nair S, Vincent EE, Loginicheva E, Cervantes-Barragan L, Ma X, Huang SC, Griss T, Weinheimer CJ, Khader S, Randolph GJ, Pearce EJ, Jones RG, Diwan A, Diamond MS, Artyomov MN. Itaconate Links Inhibition of Succinate Dehydrogenase with Macrophage Metabolic Remodeling and Regulation of Inflammation. Cell Metab. 2016 Jul 12;24(1):158-66. doi: 10.1016/j.cmet.2016.06.004.

314. Mills EL, Kelly B, Logan A, Costa AS, Varma M, Bryant CE, Tourlomousis P, Däbritz JH, Gottlieb E, Latorre I, Corr SC, McManus G, Ryan D, Jacobs HT, Szibor M, Xavier RJ, Braun T, Frezza C, Murphy MP, O'Neill LA. Succinate Dehydrogenase Supports Metabolic Repurposing of Mitochondria to Drive Inflammatory Macrophages. Cell. 2016 Oct 6;167(2):457-470.e13. doi: 10.1016/j.cell.2016.08.064.

315. Dong F, Zhang L, Hao F, Tang H, Wang Y. Systemic responses of mice to dextran sulfate sodium-induced acute ulcerative colitis using 1H NMR spectroscopy. J Proteome Res. 2013 Jun 7;12(6):2958-66. doi: 10.1021/pr4002383.

316. Sharma U, Upadhyay D, Mewar S, Mishra A, Das P, Gupta SD, Dwivedi SN, Makharia GK, Jagannathan NR. Metabolic abnormalities of gastrointestinal mucosa in celiac disease: An in vitro proton nuclear magnetic resonance spectroscopy study. J Gastroenterol Hepatol. 2015 Oct;30(10):1492-8. doi: 10.1111/jgh.12979.

317. Raimundo N, Baysal BE, Shadel GS. Revisiting the TCA cycle: signaling to tumor formation. Trends Mol Med. 2011 Nov;17(11):641-9. doi: 10.1016/j.molmed.2011.06.001.

318. Cardaci S, Ciriolo MR. TCA Cycle Defects and Cancer: When Metabolism Tunes Redox State. Int J Cell Biol. 2012;2012:161837. doi: 10.1155/2012/161837.

319. Wu W, Zhao S. Metabolic changes in cancer: beyond the Warburg effect. Acta Biochim Biophys Sin (Shanghai). 2013 Jan;45(1):18-26. doi: 10.1093/abbs/gms104.

320. Yang M, Soga T, Pollard PJ. Oncometabolites: linking altered metabolism with cancer. J Clin Invest. 2013 Sep 3;123(9):3652-8. doi: 10.1172/JCI67228.

321. Laurenti G, Tennant DA. Isocitrate dehydrogenase (IDH), succinate dehydrogenase (SDH), fumarate hydratase (FH): three players for one phenotype in cancer? Biochem Soc Trans. 2016 Aug 15;44(4):1111-6. doi: 10.1042/BST20160099.

322. Smith EA, Macfarlane GT. Enumeration of human colonic bacteria producing phenolic and indolic compounds: effects of pH, carbohydrate availability and retention time on dissimilatory aromatic amino acid metabolism. J Appl Bacteriol. 1996 Sep;81(3):288-302.

323. Smith EA, Macfarlane GT. Formation of phenolic and indolic compounds by anaerobic bacteria in the human large intestine. Microb Ecol. 1997 Apr;33(3):180-8.

324. Elsden SR, Hilton MG. Amino acid utilization patterns in clostridial taxonomy. Arch Microbiol. 1979 Nov;123(2):137-41.

325. Mayrand D, Bourgeau G. Production of phenylacetic acid by anaerobes. J Clin Microbiol. 1982 Oct;16(4):747-50.

326. Russell WR, Duncan SH, Scobbie L, Duncan G, Cantlay L, Calder AG, Anderson SE, Flint HJ. Major phenylpropanoid-derived metabolites in the human gut can arise from microbial fermentation of protein. Mol Nutr Food Res. 2013 Mar;57(3):523-35. doi: 10.1002/mnfr.201200594.

327. Mao LF, Chu C, Schulz H. Hepatic beta-oxidation of 3-phenylpropionic acid and the stereospecific dehydration of (R)- and (S)-3-hydroxy-3-phenylpropionyl-CoA by different enoyl-CoA hydratases. Biochemistry. 1994 Mar 22;33(11):3320-6.

328. Gonthier MP, Remesy C, Scalbert A, Cheynier V, Souquet JM, Poutanen K, Aura AM. Microbial metabolism of caffeic acid and its esters chlorogenic and caftaric acids by human faecal microbiota in vitro. Biomed Pharmacother. 2006 Nov;60(9):536-40. doi: 10.1016/j.biopha.2006.07.084.

329. Lennerz BS, Vafai SB, Delaney NF, Clish CB, Deik AA, Pierce KA, Ludwig DS, Mootha VK. Effects of sodium benzoate, a widely used food preservative, on glucose homeostasis and metabolic profiles in humans. Mol Genet Metab. 2015 Jan;114(1):73-9. doi: 10.1016/j.ymgme.2014.11.010.

330. van Assche PF. Differentiation of Bacteroides fragilis species by gas chromatographic detection of phenylacetic acid. J Clin Microbiol. 1978 Nov;8(5):614-5.

331. Lambert MA, Moss CW. Production of p-hydroxyhydrocinnamic acid from tyrosine by Peptostreptococcus anaerobius. J Clin Microbiol. 1980 Aug;12(2):291-3.

332. Burlingame R, Chapman PJ. Catabolism of phenylpropionic acid and its 3-hydroxy derivative by Escherichia coli. J Bacteriol. 1983 Jul;155(1):113-21.

333. Hill GB, Ayers OM, Kohan AP. Characteristics and sites of infection of Eubacterium nodatum, Eubacterium timidum, Eubacterium brachy, and other asaccharolytic eubacteria. J Clin Microbiol. 1987 Aug;25(8):1540-5.

334. Nakazawa F, Poco SE Jr, Sato M, Ikeda T, Kalfas S, Sundqvist G, Hoshino E. Taxonomic characterization of Mogibacterium diversum sp. nov. and Mogibacterium neglectum sp. nov., isolated from human oral cavities. Int J Syst Evol Microbiol. 2002 Jan;52(Pt 1):115-22. doi: 10.1099/00207713-52-1-115.

335. Nakazawa F, Sato M, Poco SE, Hashimura T, Ikeda T, Kalfas S, Sundqvist G, Hoshino E. Description of Mogibacterium pumilum gen. nov., sp. nov. and Mogibacterium vescum gen. nov., sp. nov., and reclassification of Eubacterium timidum (Holdeman et al. 1980) as Mogibacterium timidum gen. nov., comb. nov. Int J Syst Evol Microbiol. 2000 Mar;50 Pt 2:679-88. doi: 10.1099/00207713-50-2-679.

336. Chen W, Liu F, Ling Z, Tong X, Xiang C. Human intestinal lumen and mucosa-associated microbiota in patients with colorectal cancer. PLoS One. 2012;7(6): e39743. doi: 10.1371/journal.pone.0039743.

337. Candela M, Turroni S, Biagi E, Carbonero F, Rampelli S, Fiorentini C, Brigidi P. Inflammation and colorectal cancer, when microbiota-host mutualism breaks. World J Gastroenterol. 2014 Jan 28;20(4):908-22. doi: 10.3748/wjg.v20.i4.908.

338. Jackson HT, Mongodin EF, Davenport KP, Fraser CM, Sandler AD, Zeichner SL. Culture-independent evaluation of the appendix and rectum microbiomes in children with and without appendicitis. PLoS One. 2014 Apr 23;9(4): e95414. doi: 10.1371/journal.pone.0095414.

339. Song YL, Liu CX, McTeague M, Summanen P, Finegold SM. Clostridium bartlettii sp. nov., isolated from human faeces. Anaerobe. 2004 Jun;10(3):179-84. doi: 10.1016/j.anaerobe.2004.04.004.

340. Nordlund E, Aura AM, Mattila I, Kössö T, Rouau X, Poutanen K. Formation of phenolic microbial metabolites and short-chain Fatty acids from rye, wheat, and oat bran and their fractions in the metabolical in vitro colon model. J Agric Food Chem. 2012 Aug 22;60(33):8134-45. doi: 10.1021/jf3008037.

341. Duncan SH, Russell WR, Quartieri A, Rossi M, Parkhill J, Walker AW, Flint HJ. Wheat bran promotes enrichment within the human colonic microbiota of butyrate-producing bacteria that release ferulic acid. Environ Microbiol. 2016 Jul;18(7):2214-25. doi: 10.1111/1462-2920.13158.

342. Белобородова Н. В., Архипова А. С., Белобородов Д. М., Бойко Н. Б., Мелько А. И., Оленин А. Ю. Хромато-масс-спектрометрическое определение низкомолекулярных ароматических соединений микробного происхождения в сыворотке крови больных сепсисом // Клиническая лабораторная диагностика. - 2006. - № 2. - С. 3-6.

343. Белобородова Н. В., Мороз В. В., Осипов А. А., Бедова А. Ю., Оленин А. Ю., Гецина М. Л., Карпова О. В., Оленина Е. Г. Нормальный уровень сепсис-ассоциированных фенилкарбоновых кислот в сыворотке крови человека // Биохимия. - 2015. - Том 80, вып. 3. - С. 449-455.

344. Karoum F, Potkin S, Chuang LW, Murphy DL, Liebowitz MR, Wyatt RJ. Phenylacetic acid excretion in schizophrenia and depression: the origins of PAA in man. Biol Psychiatry. 1984 Feb;19(2):165-78.

345. Белобородова Н. В., Мороз В. В., Бедова А. Ю., Осипов А. А., Саршор Ю. Н., Черневская Е. А. Участие ароматических микробных метаболитов в развитии тяжелой инфекции и сепсиса // Анестезиология и реаниматология. - 2016. - Том 61, № 3. - С. 202-208.

346. Jankowski J, van der Giet M, Jankowski V, Schmidt S, Hemeier M, Mahn B, Giebing G, Tolle M, Luftmann H, Schluter H, Zidek W, Tepel M. Increased plasma phenylacetic acid in patients with end-stage renal failure inhibits iNOS expression. J Clin Invest. 2003 Jul;112(2):256-64. doi: 10.1172/JCI15524.

347. Kopple JD. Phenylalanine and tyrosine metabolism in chronic kidney failure. J Nutr. 2007 Jun;137(6 Suppl 1):1586S-1590S; discussion 1597S-1598S.

348. Mutsaers HA, van den Heuvel LP, Ringens LH, Dankers AC, Russel FG, Wetzels JF, Hoenderop JG, Masereeuw R. Uremic toxins inhibit transport by breast cancer resistance protein and multidrug resistance protein 4 at clinically relevant concentrations. PLoS One. 2011 Apr 4;6(4): e18438. doi: 10.1371/journal.pone.0018438.

349. Schmidt S, Westhoff TH, Krauser P, Ignatius R, Jankowski J, Jankowski V, Zidek W, van der Giet M. The uraemic toxin phenylacetic acid impairs macrophage function. Nephrol Dial Transplant. 2008 Nov;23(11):3485-93. doi: 10.1093/ndt/gfn266.

350. Qi Y, Li P, Zhang Y, Cui L, Guo Z, Xie G, Su M, Li X, Zheng X, Qiu Y, Liu Y, Zhao A, Jia W, Jia W. Urinary metabolite markers of precocious puberty. Mol Cell Proteomics. 2012 Jan;11(1): M111.011072. doi: 10.1074/mcp.M111.011072.

351. Koike S, Bundo M, Iwamoto K, Suga M, Kuwabara H, Ohashi Y, Shinoda K, Takano Y, Iwashiro N, Satomura Y, Nagai T, Natsubori T, Tada M, Yamasue H, Kasai K. A snapshot of plasma metabolites in first-episode schizophrenia: a capillary electrophoresis time-of-flight mass spectrometry study. Transl Psychiatry. 2014 Apr 8;4: e379. doi: 10.1038/tp.2014.19.

352. Jansson J, Willing B, Lucio M, Fekete A, Dicksved J, Halfvarson J, Tysk C, Schmitt-Kopplin P. Metabolomics reveals metabolic biomarkers of Crohn's disease. PLoS One. 2009 Jul 28;4(7): e6386. doi: 10.1371/journal.pone.0006386.

353. Uchiyama K, Yagi N, Mizushima K, Higashimura Y, Hirai Y, Okayama T, Yoshida N, Katada K, Kamada K, Handa O, Ishikawa T, Takagi T, Konishi H, Kuriu Y, Nakanishi M, Otsuji E, Itoh Y, Naito Y. Serum metabolomics analysis for early detection of colorectal cancer. J Gastroenterol. 2017 Jun;52(6):677-694. doi: 10.1007/s00535-016-1261-6.

354. van der Heiden C, Wauters EA, Duran M, Wadman SK, Ketting D. Gas chromatographic analysis of urinary tyrosine and phenylalanine metabolites in patients with gastrointestinal disorders. Clin Chim Acta. 1971 Sep;34(2):289-96.

355. Fava F, Danese S. Intestinal microbiota in inflammatory bowel disease: Friend of foe? World J Gastroenterol. 2011 Feb 7;17(5):557-66. doi: 10.3748/wjg.v17.i5.557.

356. De Cruz P, Prideaux L, Wagner J, Ng SC, McSweeney C, Kirkwood C, Morrison M, Kamm MA. Characterization of the gastrointestinal microbiota in health and inflammatory bowel disease. Inflamm Bowel Dis. 2012 Feb;18(2):372-90. doi: 10.1002/ibd.21751.

357. Rubio-Tapia A, Barton SH, Rosenblatt JE, Murray JA. Prevalence of small intestine bacterial overgrowth diagnosed by quantitative culture of intestinal aspirate in celiac disease. J Clin Gastroenterol. 2009 Feb;43(2):157-61. doi: 10.1097/MCG.0b013e3181557e67.

358. Nistal E, Caminero A, Vivas S, Ruiz de Morales JM, Sáenz de Miera LE, Rodríguez-Aparicio LB, Casqueiro J. Differences in faecal bacteria populations and faecal bacteria metabolism in healthy adults and celiac disease patients. Biochimie. 2012 Aug;94(8):1724-9. doi: 10.1016/j.biochi.2012.03.025.

359. Selmer T, Andrei PI. p-Hydroxyphenylacetate decarboxylase from Clostridium difficile. A novel glycyl radical enzyme catalysing the formation of p-cresol. Eur J Biochem. 2001 Mar;268(5):1363-72.

360. Walk ST, Young VB. Emerging Insights into Antibiotic-Associated Diarrhea and Clostridium difficile Infection through the Lens of Microbial Ecology. Interdiscip Perspect Infect Dis. 2008;2008:125081. doi: 10.1155/2008/125081.

361. Navaneethan U, Venkatesh PG, Shen B. Clostridium difficile infection and inflammatory bowel disease: understanding the evolving relationship. World J Gastroenterol. 2010 Oct 21;16(39):4892-904. doi: 10.3748/wjg.v16.i39.4892.

362. Surawicz CM. The microbiota and infectious diarrhea. Le microbiote dans les diarrhées infectieuses. Gastroenterol Clin Biol. 2010 Sep;34 Suppl 1: S 29-36. doi: 10.1016/S 0399-8320(10)70018-X.

363. Berg AM, Kelly CP, Farraye FA. Clostridium difficile infection in the inflammatory bowel disease patient. Inflamm Bowel Dis. 2013 Jan;19(1):194-204. doi: 10.1002/ibd.22964.

364. Bien J, Palagani V, Bozko P. The intestinal microbiota dysbiosis and Clostridium difficile infection: is there a relationship with inflammatory bowel disease? Therap Adv Gastroenterol. 2013 Jan;6(1):53-68. doi: 10.1177/1756283X12454590.

365. Negrón ME, Barkema HW, Rioux K, De Buck J, Checkley S, Proulx MC, Frolkis A, Beck PL, Dieleman LA, Panaccione R, Ghosh S, Kaplan GG. Clostridium difficile infection worsens the prognosis of ulcerative colitis. Can J Gastroenterol Hepatol. 2014 Jul-Aug;28(7):373-80.

366. Симонян А. В. Активность производных коричных кислот и новые методы их синтеза // Химико-фармацевтический журнал. - 1993. - Том 27, № 2. - С. 21-23.

367. Konishi Y, Kobayashi S. Microbial metabolites of ingested caffeic acid are absorbed by the monocarboxylic acid transporter (MCT) in intestinal Caco-2 cell monolayers. J Agric Food Chem. 2004 Oct 20;52(21):6418-24. doi: 10.1021/jf049560y.

368. Gómez-Ruiz JA, Leake DS, Ames JM. In vitro antioxidant activity of coffee compounds and their metabolites. J Agric Food Chem. 2007 Aug 22;55(17):6962-9. doi: 10.1021/jf0710985.

369. Tomas-Barberan F, García-Villalba R, Quartieri A, Raimondi S, Amaretti A, Leonardi A, Rossi M. In vitro transformation of chlorogenic acid by human gut microbiota. Mol Nutr Food Res. 2014 May;58(5):1122-31. doi: 10.1002/mnfr.201300441.

370. Raimondi S, Anighoro A, Quartieri A, Amaretti A, Tomás-Barberán FA, Rastelli G, Rossi M. Role of bifidobacteria in the hydrolysis of chlorogenic acid. Microbiologyopen. 2015 Feb;4(1):41-52. doi: 10.1002/mbo3.219.

371. Li L, Huang L, Lemos HP, Mautino M, Mellor AL. Altered tryptophan metabolism as a paradigm for good and bad aspects of immune privilege in chronic inflammatory diseases. Front Immunol. 2012 May 11;3:109. doi: 10.3389/fimmu.2012.00109.

372. Kline EL, Brown CS, Bankaitis V, Montefiori DC, Craig K. Metabolite gene regulation of the L-arabinose operon in Escherichia coli with indoleacetic acid and other indole derivatives. Proc Natl Acad Sci U S A. 1980 Apr;77(4):1768-72.

373. Marklová E, Hak J, Parízek J, Morávek P. Urinary excretion of some metabolites of tryptophan in malignant diseases. Sb Ved Pr Lek Fak Karlovy Univerzity Hradci Kralove. 1992;35(3):275-9.

374. Vanholder R, Schepers E, Pletinck A, Neirynck N, Glorieux G. An update on protein-bound uremic retention solutes. J Ren Nutr. 2012 Jan;22(1):90-4. doi: 10.1053/j.jrn.2011.10.026.

375. Rossiter S, Folkes LK, Wardman P. Halogenated indole-3-acetic acids as oxidatively activated prodrugs with potential for targeted cancer therapy. Bioorg Med Chem Lett. 2002 Sep 16;12(18):2523-6.

376. De Melo MP, Pithon-Curi TC, Curi R. Indole-3-acetic acid increases glutamine utilization by high peroxidase activity-presenting leukocytes. Life Sci. 2004 Aug 20;75(14):1713-25. doi: 10.1016/j.lfs.2004.03.021.

377. Jeong YM, Oh MH, Kim SY, Li H, Yun HY, Baek KJ, Kwon NS, Kim WY, Kim DS. Indole-3-acetic acid/horseradish peroxidase induces apoptosis in TCCSUP human urinary bladder carcinoma cells. Pharmazie. 2010 Feb;65(2):122-6.

378. Hubbard TD, Murray IA, Bisson WH, Lahoti TS, Gowda K, Amin SG, Patterson AD, Perdew GH. Adaptation of the human aryl hydrocarbon receptor to sense microbiota-derived indoles. Sci Rep. 2015 Aug 3;5:12689. doi: 10.1038/srep12689.

379. Dou L, Sallée M, Cerini C, Poitevin S, Gondouin B, Jourde-Chiche N, Fallague K, Brunet P, Calaf R, Dussol B, Mallet B, Dignat-George F, Burtey S. The cardiovascular effect of the uremic solute indole-3 acetic acid. J Am Soc Nephrol. 2015 Apr;26(4):876-87. doi: 10.1681/ASN.2013121283.

380. Yokoyama MT, Carlson JR. Microbial metabolites of tryptophan in the intestinal tract with special reference to skatole. Am J Clin Nutr. 1979 Jan;32(1):173-8.

381. Chung KT, Anderson GM, Fulk GE. Formation of indoleacetic acid by intestinal anaerobes. J Bacteriol. 1975 Oct;124(1):573-5.

382. Chyan YJ, Poeggeler B, Omar RA, Chain DG, Frangione B, Ghiso J, Pappolla MA. Potent neuroprotective properties against the Alzheimer beta-amyloid by an endogenous melatonin-related indole structure, indole-3-propionic acid. J Biol Chem. 1999 Jul 30;274(31):21937-42.

383. Bendheim PE, Poeggeler B, Neria E, Ziv V, Pappolla MA, Chain DG. Development of indole-3-propionic acid (OXIGON) for Alzheimer's disease. J Mol Neurosci. 2002 Aug-Oct;19(1-2):213-7.

384. Cheng X, van Breemen RB. Mass spectrometry-based screening for inhibitors of beta-amyloid protein aggregation. Anal Chem. 2005 Nov 1;77(21):7012-5. doi: 10.1021/ac050556a.

385. Karbownik M, Stasiak M, Zasada K, Zygmunt A, Lewinski A. Comparison of potential protective effects of melatonin, indole-3-propionic acid, and propylthiouracil against lipid peroxidation caused by potassium bromate in the thyroid gland. J Cell Biochem. 2005 May 1;95(1):131-8. doi: 10.1002/jcb.20404.

386. Karbownik M, Stasiak M, Zygmunt A, Zasada K, Lewiński A. Protective effects of melatonin and indole-3-propionic acid against lipid peroxidation, caused by potassium bromate in the rat kidney. Cell Biochem Funct. 2006 Nov-Dec;24(6):483-9. doi: 10.1002/cbf.1321.

387. Hwang IK, Yoo KY, Li H, Park OK, Lee CH, Choi JH, Jeong YG, Lee YL, Kim YM, Kwon YG, Won MH. Indole-3-propionic acid attenuates neuronal damage and oxidative stress in the ischemic hippocampus. J Neurosci Res. 2009 Jul;87(9):2126-37. doi: 10.1002/jnr.22030.

388. Mandelbaum-Shavit F, Barak V, Saheb-Tamimi K, Grossowicz N. Susceptibility of Legionella pneumophila grown extracellularly and in human monocytes to indole-3-propionic acid. Antimicrob Agents Chemother. 1991 Dec;35(12):2526-30.

389. Rothhammer V, Mascanfroni ID, Bunse L, Takenaka MC, Kenison JE, Mayo L, Chao CC, Patel B, Yan R, Blain M, Alvarez JI, Kébir H, Anandasabapathy N, Izquierdo G, Jung S, Obholzer N, Pochet N, Clish CB, Prinz M, Prat A, Antel J, Quintana FJ. Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor. Nat Med. 2016 Jun;22(6):586-97. doi: 10.1038/nm.4106.

390. Venkatesh M., Mukherjee S, Wang H, Li H, Sun K, Benechet AP, Qiu Z, Maher L, Redinbo MR, Phillips RS, Fleet JC, Kortagere S, Mukherjee P, Fasano A, Le Ven J, Nicholson JK, Dumas ME, Khanna KM, Mani S. Symbiotic Bacterial Metabolites Regulate Gastrointestinal Barrier Function via the Xenobiotic Sensor PXR and Toll-like Receptor 4. Immunity. 2014 Aug 21;41(2):296-310. doi: 10.1016/j.immuni.2014.06.014.

391. Ranhotra HS, Flannigan KL, Brave M, Mukherjee S, Lukin DJ, Hirota SA, Mani S. Xenobiotic Receptor-Mediated Regulation of Intestinal Barrier Function and Innate Immunity. Nucl Receptor Res. 2016;3. pii: 101199. doi: 10.11131/2016/101199.

392. Elsden SR, Hilton MG, Waller JM. The end products of the metabolism of aromatic amino acids by Clostridia. Arch Microbiol. 1976 Apr 1;107(3):283-8.

393. Jellet JJ, Forrest TP, Macdonald IA, Marrie TJ, Holdeman LV. Production of indole-3-propanoic acid and 3-(p-hydroxyphenyl)propanoic acid by Clostridium sporogenes: a convenient thin-layer chromatography detection system. Can J Microbiol. 1980 Apr;26(4):448-53.

394. Wikoff WR, Anfora AT, Liu J, Schultz PG, Lesley SA, Peters EC, Siuzdak G. Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proc Natl Acad Sci U S A. 2009 Mar 10;106(10):3698-703. doi: 10.1073/pnas.0812874106.

395. Young SN, Anderson GM, Gauthier S, Purdy WC. The origin of indoleacetic acid and indolepropionic acid in rat and human cerebrospinal fluid. J Neurochem. 1980 May;34(5):1087-92.

396. Danaceau JP, Anderson GM, McMahon WM, Crouch DJ. A liquid chromatographic-tandem mass spectrometric method for the analysis of serotonin and related indoles in human whole blood. J Anal Toxicol. 2003 Oct;27(7):440-4.

397. Wolf AM, Wolf D, Rumpold H, Moschen AR, Kaser A, Obrist P, Fuchs D, Brandacher G, Winkler C, Geboes K, Rutgeerts P, Tilg H. Overexpression of indoleamine 2,3-dioxygenase in human inflammatory bowel disease. Clin Immunol. 2004 Oct;113(1):47-55. doi: 10.1016/j.clim.2004.05.004.

398. Torres MI, López-Casado MA, Lorite P, Ríos A. Tryptophan metabolism and indoleamine 2,3-dioxygenase expression in coeliac disease. Clin Exp Immunol. 2007 Jun;148(3):419-24. doi: 10.1111/j.1365-2249.2007.03365.x.

399. Etienne-Mesmin L, Chassaing B, Gewirtz AT. Tryptophan: A gut microbiota-derived metabolites regulating inflammation. World J Gastrointest Pharmacol Ther. 2017 Feb 6;8(1):7-9. doi: 10.4292/wjgpt.v8.i1.7.

400. Lustgarten MS, Fielding RA. Metabolites Associated With Circulating Interleukin-6 in Older Adults. J Gerontol A Biol Sci Med Sci. 2017 Sep 1;72(9):1277-83. doi: 10.1093/gerona/glw039.

401. Lamas B, Richard ML, Leducq V, Pham HP, Michel ML, Da Costa G, Bridonneau C, Jegou S, Hoffmann TW, Natividad JM, Brot L, Taleb S, Couturier-Maillard A, Nion-Larmurier I, Merabtene F, Seksik P, Bourrier A, Cosnes J, Ryffel B, Beaugerie L, Launay JM, Langella P, Xavier RJ, Sokol H. CARD 9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands. Nat Med. 2016 Jun;22(6):598-605. doi: 10.1038/nm.4102.

402. Martin FP, Su MM, Xie GX, Guiraud SP, Kussmann M, Godin JP, Jia W, Nydegger A. Urinary metabolic insights into host-gut microbial interactions in healthy and IBD children. World J Gastroenterol. 2017 May 28;23(20):3643-3654. doi: 10.3748/wjg.v23.i20.3643.

403. Qu D, Shen L, Liu S, Li H, Ma Y, Zhang R, Wu K, Yao L, Li J, Zhang J. Chronic inflammation confers to the metabolic reprogramming associated with tumorigenesis of colorectal cancer. Cancer Biol Ther. 2017 Apr 3;18(4):237-244. doi: 10.1080/15384047.2017.1294292.

404. Maccaferri S., Vitali B, Klinder A, Kolida S, Ndagijimana M, Laghi L, Calanni F, Brigidi P, Gibson GR, Costabile A. Rifaximin modulates the colonic microbiota of patients with Crohn's disease: an in vitro approach using a continuous culture colonic model system. J Antimicrob Chemother. 2010 Dec;65(12):2556-65. doi: 10.1093/jac/dkq345.

405. Ардатская М. Д. Пробиотики, пребиотики и метабиотики в коррекции микроэкологических нарушений кишечника // Медицинский совет. - 2015. - № 13. - С. 94-99.

406. Ip WKE, Hoshi N, Shouval DS, Snapper S, Medzhitov R. Anti-inflammatory effect of IL-10 mediated by metabolic reprogramming of macrophages. Science. 2017 May 5;356(6337):513-519. doi: 10.1126/science.aal3535.

407. Shenderov BA. Metabiotics: novel idea or natural development of probiotic conception. Microb Ecol Health Dis. 2013 Apr 12;24. doi: 10.3402/mehd.v24i0.20399.

408. de Sousa Moraes LF, Grzeskowiak LM, de Sales Teixeira TF, Gouveia Peluzio Mdo C. Intestinal microbiota and probiotics in celiac disease. Clin Microbiol Rev. 2014 Jul;27(3):482-9. doi: 10.1128/CMR.00106-13.


Для цитирования:


Ситкин С.И., Вахитов Т.Я., Ткаченко Е.И., Лазебник Л.Б., Орешко Л.С., Жигалова Т.Н., Радченко В.Г., Авалуева Е.Б., Селиверстов П.В., Утсаль В.А., Комличенко Э.В. НАРУШЕНИЯ МИКРОБНОГО И ЭНДОГЕННОГО МЕТАБОЛИЗМА ПРИ ЯЗВЕННОМ КОЛИТЕ И ЦЕЛИАКИИ: МЕТАБОЛОМНЫЙ ПОДХОД К ВЫЯВЛЕНИЮ ПОТЕНЦИАЛЬНЫХ БИОМАРКЕРОВ ХРОНИЧЕСКОГО ВОСПАЛЕНИЯ В КИШЕЧНИКЕ, СВЯЗАННОГО С ДИСБИОЗОМ. Экспериментальная и клиническая гастроэнтерология. 2017;(7):4-50.

For citation:


Sitkin S.I., Vakhitov T.Y., Tkachenko E.I., Lazebnik L.B., Oreshko L.S., Zhigalova T.N., Radchenko V.G., Avalueva E.B., Seliverstov P.V., Utsal V.A., Komlichenko E.V. GUT MICROBIAL AND ENDOGENOUS METABOLISM ALTERATIONS IN ULCERATIVE COLITIS AND CELIAC DISEASE: A METABOLOMICS APPROACH TO IDENTIFY CANDIDATE BIOMARKERS OF CHRONIC INTESTINAL INFLAMMATION ASSOCIATED WITH DYSBIOSIS. Experimental and Clinical Gastroenterology. 2017;(7):4-50. (In Russ.)

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