Gut microbiome as predictor of metabolic syndrome in young children born to mothers with gestational diabetes mellitus

Abstract

Relevance. The article presents the results of research of intestinal microbiocenosis in young children born from mothers with gestational diabetes. Indicators of functional activity of intestinal microbiome in the studied cohort of children are presented. The article forces the attention of specialists to the possibility of influence of the biochemically altered microbiome of the intestine on metabolism and health of the child in general.Research objective. To improve the early diagnosis of intestinal microecology disorders in children born to mothers with gestational diabetes by studying the species composition and state of functional activity of intestinal microbiome.Material and methods. Intestinal microbiome study (MK) conducted in 105 children aged 1–3, of whom 33 children from mothers with gestational diabetes mellitus insulin therapy (GDМ IT), 42 children from mothers with gestational diabetes mellitus on diet therapy (GDМ DT), 30 children from mothers without GDМ (control group — СG). To this end, methods were used: a standard stool study for dysbacteriosis, a functional state of intestinal microflora to determine the concentration of short-chain fatty acids (SHFA) by gas-liquid chromatography of acidified stool supernatant. Estimation of quantitative distribution of the main types of intestinal microorganisms in children of the studied groups using the method of sequencing 16s rRnk of bacteria. The measure of intestinal dysbiosis was the biodiversity of the microbial community, which in biology is quantified by the Shannon index, corresponds to the number of microbial species in the intestine microbial community and is calculated by the formula: = - ∑ 2= 1, where =∑ = 1The normalized Shannon index has a range of values from 0 to 1, which is suitable for interpreting the state of microbiome. The results were statistically processed using Statistica 8.0. and MS Office Excel 2010.Results and discussion. The NGS method of stool sequencing identified the distribution of types of microorganisms in the intestine: in the GDМ IT, GDМ DT and CG Actinobacteria and Firmicutes are the dominant types of bacteria, which is a regular distribution for the microbial community at this age. But in order for bacteria not to realize their pathogenic properties, it is important their intraspecific representation and relationship. It has been found that in children born to mothers with GDМ in general, there is a tendency to decrease the representation of Actinobacteria relative to Firmicutes, in contrast to CG. This may indicate an imbalance within the microbiome of the intestine in children from mothers with GDМ and lead to dysbiosis. So Actinobacteria, which are representatives of MK in the norm, in children from mothers with GDМ IT are represented in a reliably lower range of values than in children from CG (p=0,033). And in children from mothers with DSS DT Firmicutes are represented in greater quantities than in CG (p=0,039).The predominance of these bacteria in old age plays a crucial role in the development of metabolic disorders. According to this study, it has been found that children of GDМ mothers generally have a reasonably higher degree of MK biodiversity than children with GDS. Thus, in the group of GDМ IT 9 dominant types of micro- organisms were identified, in the group of GDМ DT — 7 species, in CG — 3 species. At the same time, children from mothers with GDМ IT have an increased representation of saprophyte flora (Clostridium hiranonis (р=0,023), Actinomyces spp. (р=0,023) and some representatives of resident fl ora (Coprococcus catus (р=0,045), Veillonellaceae (р=0,04) и Blautia producta (р=0,049)) compared to CG, which may indicate a competitive environment for pathogens, but also do not exclude the possibility of adverse changes in the body’s immune system. Children from mothers with GDМ DT found an increase in the level of Cl. hiranonis, compared to CG (p=0,041), as well as members of the genus Eggerthella (p=0,029) involved in mixed infections, which can lead to chronic inflammation of the intestine mucous and disorders of the body’s metabolic system. Revealed changes in MK in young children from mothers with GDМ are accompanied by peculiarities of metabolic activity. In children from mothers with GDМ IT and GDМ DT metabolic activity did not differ reliably. But the total level of SHFA characteristic for a well-functioning microbiota is more common in children in GDМ IT — 29 (88.0%) than in CG — 18 (60.0%), p=0.036. Also, children with GDМ mothers generally have metabolic pathways similar to those found in MK in children of CG, but have strong correlation and pathogenic types of bacteria. Probably, despite dysbiosis, there is the formation of compensatory metabolic pathways between the MK and the host organism. But these processes can not be called stable, because the MK children of these groups can manage their species and size without the participation of macroorganism.Conclusion. The composition of the MC for young children born to GDМ mothers in general diff ers reliably from the MC for CG children and is dysbiotic.In children born to GDМ mothers, MK is represented mainly by opportunistic and pathogenic bacteria. In the group of GDМ IT indigenic microflora is stronger.Metabolic activity of MK in this cohort of children is high, but is achieved due to the activity of both individual and saprophytic fl ora, which in the future may lead to the breakdown of compensatory mechanisms and the start of metabolic disorders in the child.