Formation of intestinal microbiocenosis in children born to mothers with gestational diabetes mellitus

Rationale. The global medical community currently studies the influence of microbiocenosis on macroorganism. The metabolome of the human gut microbiome may be a factor in the development of pathology in tissues and organs.

Objective. To improve the early diagnosis of intestinal microecology disorders in infants by determining the species composition and functional activity of the intestinal microflora to predict the health status of children born to mothers with diabetes.

Materials and methods. We studied the intestinal microbiocenosis in 60 infants aged 1–28 days, including 22 infants by healthy mothers (control group) and 38 infants by mothers with diabetes (study group). The following was evaluated: the species composition of the intestinal microbiocenosis; its functional state by concentrations of short-chain fatty acids (SCFA); the content of elastase and simple carbohydrates in feces. The species composition was studied by fecal next generation sequencing (NGS), SCFA concentration was studied by gas-liquid chromatography of acidified fecal supernatant, pancreatic elastase in fecal samples was quantified by ELISA, and fecal carbohydrate content was determined by Benedict’s test. The gut dysbiosis was measured by the biodiversity of the microbial community quantified in biology by Shannon index according to the formula:

where

and corresponds to the number of microbial species in the intestinal microbial community. Normalized Shannon index has a range of values from 0 to 1, convenient for the interpretation of the microbiocenosis condition. An increase in the biodiversity of the microbial community was associated with an increase in dysbiotic changes of the gut microbiocenosis. Statistical analysis was performed with Statistica 8.0 and MS Office Excel 2010.

Results. In children born by mothers with diabetes, the formation of microbial community at the stage of intestinal tract settlement occurs because of the increase of species biodiversity and formation of strong correlation between different classes of microorganisms, indicating a decrease of symbiont relationships of microbiocenosis with macroorganism normally mediated by intestinal epithelial cells condition and cooperation of the cells with intestinal mucosal barrier components. Due to the pronounced biodiversity and interspecies symbiosis of bacteria, compensatory mechanisms are formed in the colon for coexistence of macroorganism and microbiota. Thus, not only the butyric acid is produced in sufficient quantities but also the microbiota consumes SCFA releasing an increased amounts of iso-acids and promoting the growth of putrefactive microbial flora.

1. Vorobiev A. A. Bacteria of normal microflora: biological properties and protective functions. ZhMEI. 1999, no. 6, pp. 102–105. (In Russ).

2. Kuchumova S. Yu., Poluektova E. A., Sheptulin A. A., et al. Physiological significance of intestinal microflora. RZhGGK. 2011, Vol. 21, No. 5, pp. 17–27. (In Russ).

3. Douglas A. Symbiotic interaction. Oxford Univer Press. Oxford: Y-N, Toronto, 1994, 148 p.

4. Zatevalov A. M., Kiseleva I. A., Kopanev Yu. A., Aleshkin A. V., Afanasyev S. S., Selkova E. P. The influence of bacteriophages on the microflora of the large intestine. Materials of the 1st international scientific-practical conference “Bacteriophages: theoretical and practical aspects of application in medicine, veterinary medicine and food industry.” Ulyanovsk. UGSKhA them. P. A. Stolypin. 2013, no.2, pp.9–14.

5. Zatevalov A.M., Alyoshkin V. A., Selkova E. P., Grenkova T. A. Determination of the concentration of butyric acid in feces, critical for the functional activity of normal intestinal and oropharyngeal microflora, of butyric acid concentration in the feces of patients of the intensive care unit who are on tube feeding. Fundamental and clinical medicine. 2017, Vol. 2, no. 1, pp. 14–22. (In Russ).

6. Onishchenko G.G., Aleshkin V. A., Afanasyev S. S., et al. Immunobiological preparations and prospects for their use in infectious diseases. GOUVUMNTSMZRF Publ., Moscow, 2002. (In Russ).

7. Aagaard K. et al., 2014.

8. Donlan R. M., Costerton J. W. Biofilms: survival mechanisms of clinically relevant microorganisms. Clin. Microbiol. Rev. 2002, Vol. 15, pp. 167–193.

9. Macfarlane S. Microbial biofilm communities in the gastrointestinal tract. J. Clin. Gastroenterol. 2008, Vol. 242(Suppl. 3), pp. S142–S143.