Preview

Experimental and Clinical Gastroenterology

Advanced search

Chemomicrobiome analysis of lithium ascorbate and other organic lithium salts

https://doi.org/10.31146/1682-8658-ecg-205-9-95-104

Abstract

Lithium salts are used in medicine as normotimics. An important aspect of the action of any medicine, incl. lithium salts is their effect on the human microbiota (microbiome). This work presents the results of a comparative chemomicrobiome analysis of organic lithium salts: ascorbate, comenate, nicotinate, oxybutyrate, aspartate and lithium orotate, carried out using modern technologies for the analysis of “big data”. For each of the studied lithium salts, estimates of the values of the area under the growth curve (AUC) were obtained for a representative sample of human microbiota, which included 38 commensal bacteria (including various species of bifidobacteria and lactobacilli) and the values of the minimum inhibitory concentrations (MIC) for 120 pathogenic bacteria. On average, over a representative sample of microbiota, lithium ascorbate supported the growth of all commensal bacteria to a somewhat greater extent (AUC = 0.57 ± 0.15) than comenat (AUC = 0.47 ± 0.17), nicotinate (AUC = 0.45 ± 0.22), lithium oxybutyrate (AUC = 0.22 ± 0.17), lithium aspartate (AUC = 0.31 ± 0.14) and lithium orotate (AUC = 0.50 ± 0.21). In the case of pathogens, MIC values were significantly lower for ascorbate (4.50 ± 3.69 μg/ml) than for comenat (6.31 ± 5.58 μg/ml), nicotinate (10.98 ± 9.37 μg/ml), oxybutyrate (7.45 ± 4.73 μg/ml), aspartate (6.37 ± 4.71 μg/ml) and lithium orotate (7.27 ± 5.81 μg/ml). Thus, lithium ascorbate is more effective in supporting commensal bacteria of a positive microbiota than the other three lithium salts and is characterized by certain antibacterial properties against pathogenic bacteria. At the same time, the ubiquitous lithium carbonate, which does not contain any fragments of organic molecules, will not have any positive effect on the state of the microbiota.

About the Authors

I. Yu. Torshin
Federal Research Center “Informatics and Management” RAS (FRC IU RAS)
Russian Federation


O. A. Gromova
Federal Research Center “Informatics and Management” RAS (FRC IU RAS)
Russian Federation


L. B. Lazebnik
Moscow State University of Medicine and Dentistry named after A. I. Evdokimov
Russian Federation


References

1. Ostrenko K. S., Gromova O. A., Pronin A. V., et al. Neuroprotective and adaptogenic effects of lithium ascorbate: studies in in vivo models and in vitro. Problems of the biology of productive animals. 2017(3):37-47. (In Russ.) @@Остренко К. С., Громова О. А., Пронин А. В., Торшин И. Ю., Хаспеков Л. Г., Стельмашук Е. В., Александрова О. П., Галочкина В. А., Галочкин В. А. Нейропротекторный и адаптогенный эффекты аскорбата лития: исследования на invivo моделях и invitro. Проблемы биологии продуктивных животных. 2017. № 3. С. 37-47.

2. Pronin A. V., Gromova O. A., Torshin I. Yu., Grishina T. R. Dynamics of distribution of lithium in different tissues after oral administration of lithium citrate in rats. Pharmacokinetics and Pharmacodynamics. 2017;(4):16-23. (In Russ.) @@Пронин А. В., Громова О. А., Торшин И. Ю., Гришина Т. Р. Динамика распределения лития в различных тканях после перорального приёма цитрата лития у крыс. Фармакокинетика и фармакодинамика № 4. 2017 C. 16-23

3. Torshin I. Yu., Gromova O. A., Mayorova L. A., Volkov A. Yu. Targeted proteins involved in the neuroprotective effects of lithium citrate. Neurology, Neuropsychiatry, Psychosomatics. 2017;9(1):78-83. (In Russ.) doi: 10.14412/2074-2711-2017-1-78-83 @@Торшин И. Ю., Громова О. А., Майорова Л. А., Волков А. Ю. О таргетных белках, участвующих в осуществлении нейропротекторных эффектов цитрата лития. Неврология, нейропсихиатрия, психосоматика. 2017. Т. 9. № 1. С. 78-83.

4. Pronin A. V., Gromova O. A., Torshin I. Yu., Stelmashuk E. V., Aleksandrova O. P., Genrikhs E. E., Khaspekov L. G. Neuroprotective properties of lithium salts during glutamate-induced stress. Neurology, Neuropsychiatry, Psychosomatics. 2017;9(3):111-119. (In Russ.) doi: 10.14412/2074-2711-2017-3-111-119 @@Пронин А. В., Громова О. А., Торшин И. Ю., Стельмашук Е. В., Александрова О. П., Генрихс Е. Е., Хаспеков Л. Г. О нейропротективных свойствах солей лития в условиях глутаматного стресса. Неврология, нейропсихиатрия, психосоматика. 2017. Т. 9. № 3. С. 111-119.

5. Pronin A. V., Gromova O. A., Sardaryan I. S., et al. Adaptogenic and neuroprotective effects of lithium ascorbate. Zhurnal Nevrologii i Psikhiatrii imeni S. S. Korsakova. 2016;116(12):86-91. doi: 10.17116/jnevro201611612186-91 @@Пронин А. В., Громова О. А., Сардарян И. С., и др. Адаптогенные и нейропротективные свойства аскорбата лития. Журнал неврологии и психиатрии им. C. C. Корсакова. 2016. Т. 116. № 12. С. 86-91.

6. Gromova O. A., Torshin I. Yu., Garasko E. V. Physiological and molecular mechanisms of the topical effect of ascorbic acid on the vaginal flora. Gynecology. 2010;12(5): 9-15. (In Russ.) @@Громова О. А., Торшин И. Ю., Гарасько Е. В. Физиологические и молекулярные механизмы топического воздействия аскорбиновой кислоты на вагинальную флору. Гинекология. 2010. Т. 12. № 5. С. 9-15.

7. Gromova O. A., Torshin I. Yu., Garasko E. A. Molecular mechanisms of destruction of bacterial films with topical application of ascorbic acid. Gynecology. 2010;12(6):12-17. (In Russ.) @@Громова О. А., Торшин И. Ю., Гарасько Е. А. Молекулярные механизмы разрушения бактериальных пленок при топическом применении аскорбиновой кислоты. Гинекология. 2010; 12(6):12-17.

8. Maier L., Pruteanu M., Kuhn M., et al. Extensive impact of non-antibiotic drugs on human gut bacteria. Nature. 2018 Mar 29;555(7698):623-628. doi: 10.1038/nature25979.

9. Gromova O. A., Torshin I. Yu., Maximov V. A., Gromov A. N., Rudakov K. V. Systematic analysis of lactitol studies. Experimental and Clinical Gastroenterology. 2019;(2):131-142. (In Russ.) doi: 10.31146/1682-8658-ecg-162-2-131-142. @@Громова О. А., Торшин И. Ю., Максимов В. А., Громов А. Н., Рудаков К. В. Систематический анализ исследований лактитола. Экспериментальная и клиническая гастроэнтерология. 2019;162(2): 131-142. doi: 10.31146/1682-8658-ecg-162-2-131-142.

10. Torshin I. Yu., Gromova O. A., Zakcharova I. N., Maximov V. A. Hemomikrobiomny lactitol analysis. Experimental and Clinical Gastroenterology. 2019;(4):111-121. (In Russ.) doi: 10.31146/1682-8658-ecg-164-4-111-121. @@Торшин И. Ю., Громова О. А., Захарова И. Н., Максимов В. А. Хемомикробиомный анализ Лактитола. Экспериментальная и клиническая гастроэнтерология. 2019;164(4): 111-121. doi: 10.31146/1682-8658-ecg-164-4-111-121.

11. Torshin I. Yu., Sardaryan I. S., Gromova O. A., Rastashansky V. A., Fedotova L. E. Chemoreactome modeling the effects of anions of lithium salts ascorbate, nicotinate, hydroxybutyrate komenata and lithium carbonate. Pharmacokinetics and Pharmacodynamics. 2016;(3):47-57. (In Russ.) @@Торшин И. Ю., Сардарян И. С., Громова О. А., Расташанский В. А., Федотова Л. Э. Хемореактомное моделирование эффектов аскорбата, никотината, оксибутирата, комената и карбоната лития. Фармакокинетика и фармакодинамика. 2016. № 3. С. 47-57.

12. Torshin I. Y., Rudakov K. V. On the application of the combinatorial theory of solvability to the analysis of chemographs. Part 1: Fundamentals of modern chemical bonding theory and the concept of the chemograph. Pattern Recognit. Image Anal. 2014;(24):11-23. doi: 10.1134/S1054661814010209.

13. Torshin I. Y., Rudakov K. V. On the Application of the Combinatorial Theory of Solvability to the Analysis of Chemographs: Part 2. Local Completeness of Invariants of Chemographs in View of the Combinatorial Theory of Solvability. Pattern Recognition and Image Analysis, 2014;24(2):196-208. doi: 10.1134/S1054661814020151.

14. Torshin I. Y., Rudakov K. V. On metric spaces arising during formalization of recognition and classification problems. Part 1: Properties of compactness. Pattern Recognition and Image Analysis, 2016;26(2):274-284. doi: 10.1134/S1054661816020255.

15. Torshin, I.Y., Rudakov, K. V. On metric spaces arising during formalization of problems of recognition and classification. Part 2: Density properties. Pattern Recognit. Image Anal. 2016;(26):483-496. doi: 10.1134/S1054661816030202

16. Torshin I. Y., Rudakov K. V.Combinatorial analysis of the solvability properties of the problems of recognition and completeness of algorithmic models. Part 1: factorization approach. Pattern Recognition and Image Analysis (Advances in Mathematical Theory and Applications). 2017;27(1):16-28.

17. Torshin I. Yu., Rudakov K. V.Combinatorial analysis of the solvability properties of the problems of recognition and completeness of algorithmic models. Part 2: metric approach within the framework of the theory of classification of feature values. Pattern Recognition and Image Analysis (Advances in Mathematical Theory and Applications). 2017;27(2):184-199.

18. Torshin I. Yu, Rudakov K. V. On the theoretical basis of metric analysis of poorly formalized problems of recognition and classification. Pattern Recognition and Image Analysis. 2015;25(4):577-587.

19. Torshin I. Yu, Rudakov K. V. On the procedures of generation of numerical features over the splits of a set of objects and the problem of prediction of numeric target variables. Pattern Recognition and Image Analysis. 2019;29(2):65-75.

20. Kim S., Chen J., Cheng T., et al. PubChem 2019 update: improved access to chemical data. Nucleic Acids Res. 2019 Jan 8;47(D1): D1102-D1109. doi: 10.1093/nar/gky1033. PMID: 30371825

21. A framework for human microbiome research. Nature. 2012 Jun 13;486(7402):215-21. doi: 10.1038/nature11209. PMID: 22699610

22. The Integrative Human Microbiome Project: dynamic analysis of microbiome-host omics profiles during periods of human health and disease. Cell Host Microbe. 2014 Sep 10;16(3):276-89. doi: 10.1016/j.chom.2014.08.014.

23. Torshin I. Y. On solvability, regularity, and locality of the problem of genome annotation. Pattern Recognition and Image Analysis (Advances in Mathematical Theory and Applications). 2010;20(3):386-395.

24. Torshin I. Y. The study of the solvability of the genome annotation problem on sets of elementary motifs. Pattern Recognition and Image Analysis (Advances in Mathematical Theory and Applications). 2011;21(4):652-662.

25. Torshin I. Y. Optimal dictionaries of the final information on the basis of the solvability criterion and their applications in bioinformatics. Pattern Recognition and Image Analysis (Advances in Mathematical Theory and Applications). 2013;23(2):319-327.

26. Mohandas R., Poduval R. D., Unnikrishnan D., Corpuz M. Clostridium ramosum bacteremia and osteomyelitis in a patient with infected pressure sores. Infectious Diseases in Clinical Practice. 2001 Jan 1;10(2):123-124. doi: 10.1097/00019048-200102000-00010

27. Shipman J. A., Cho K. H., Siegel H. A., Salyers A. A. Physiological characterization of SusG, an outer membrane protein essential for starch utilization by Bacteroides thetaiotaomicron. J Bacteriol. 1999 Dec;181(23):7206-11. PMID: 10572122

28. Caesar R., Tremaroli V., Kovatcheva-Datchary P., Cani P. D., Backhed F. Crosstalk between Gut Microbiota and Dietary Lipids Aggravates WAT Inflammation through TLR Signaling. Cell Metab. 2015 Oct 6;22(4):658-68. doi: 10.1016/j.cmet.2015.07.026.

29. Dao M. C., Everard A., Aron-Wisnewsky J., et al. Akkermansia muciniphila and improved metabolic health during a dietary intervention in obesity: relationship with gut microbiome richness and ecology. Gut. 2016 Mar;65(3):426-36. doi: 10.1136/gutjnl-2014-308778.

30. van Passel M. W., Kant R., Zoetendal E. G., et al. The genome of Akkermansia muciniphila, a dedicated intestinal mucin degrader, and its use in exploring intestinal metagenomes. PLoS One. 2011 Mar 3;6(3): e16876. doi: 10.1371/journal.pone.0016876.

31. Hsiao A., Ahmed A. M., Subramanian S., Griffin N. W., Drewry L. L., Petri W. A. Jr, Haque R., Ahmed T., Gordon J. I. Members of the human gut microbiota involved in recovery from Vibrio cholerae infection. Nature. 2014 Nov 20;515(7527):423-6. doi: 10.1038/nature13738.

32. Dabard J., Bridonneau C., Phillipe C., et al. A new lantibiotic produced by a Ruminococcus gnavus strain isolated from human feces. Appl Environ Microbiol. 2001 Sep;67(9):4111-8. doi: 10.1128/aem.67.9.4111-4118.2001.

33. Kolenbrander P. E., Palmer R. J. Jr, Rickard A. H., Jakubovics N. S., Chalmers N. I., Diaz P. I. Bacterial interactions and successions during plaque development. Periodontol. 2000. 2006;42:47-79. doi: 10.1111/j.1600-0757.2006.00187.x.

34. Corby P. M., Lyons-Weiler J., Bretz W. A., et al. Microbial risk indicators of early childhood caries. J Clin Microbiol. 2005 Nov;43(11):5753-9. doi: 10.1128/JCM.43.11.5753-5759.2005.

35. Oleskin A. V., El-Registan G.I., Shenderov B. A.Intermicrobial chemical interactions and microbiota-host dialogue: the role of neurotransmitters. Microbiology. 2016; 85(1):3-25. (In Russ.) doi: 10.7868/S0026365616010080. @@Олескин А. В., Эль-Регистан Г.И., Шендеров Б. А. Межмикробные химические взаимодействия и диалог микробиота-хозяин: роль нейромедиаторов. Микробиология, 2016, 85(1):3-25. doi: 10.7868/S0026365616010080.

36. Lyte M. Probiotics function mechanistically as delivery vehicles for neuroactive compounds: microbial endocrinology in the design and use of probiotics. Bioessays. 2011;(33):574-581.

37. Mosolov S. N., Kostyukova E. G., Ushkalova A. V., Shafarenko A. A., Alfimov P. V. Biological therapy algorithms for bipolar disorder. Modern therapy of mental disorders. 2013;4:31-39. (In Russ.) @@Мосолов С. Н., Костюкова Е. Г., Ушкалова А. В., Шафаренко А. А., Алфимов П. В. Алгоритмы биологической терапии биполярного аффективного расстройства. Современная терапия психических расстройств, 2013, 4:31-39

38. Ostrenko K. S., Sardaryan I. S., Gromova O. A., Koloskov E. M., Pronin A. V., Torshin I. Yu. Determination of acute toxicity and adverse effects of high doses of prolonged use of lithium ascorbate on Wistar rats. Pharmacokinetics and Pharmacodynamics. 2016;(4):43-54. (In Russ.) @@Остренко К. С., Сардарян И. С., Громова О. А., Колоскова Е. М., Пронин А. В., Торшин И. Ю. Определение острой токсичности и негативного воздействия высоких доз аскорбата лития при длительном применении на крысах линии вистар. Фармакокинетика и фармакодинамика, 2016, 4: 43-54.


Review

For citations:


Torshin I.Yu., Gromova O.A., Lazebnik L.B. Chemomicrobiome analysis of lithium ascorbate and other organic lithium salts. Experimental and Clinical Gastroenterology. 2022;(9):95-104. (In Russ.) https://doi.org/10.31146/1682-8658-ecg-205-9-95-104

Views: 984


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 1682-8658 (Print)