The 9th International Human Microbiome Consortium Congres 2022, Kobe, Japonya, 9 - 10 Kasım 2022, ss.1-2
The gut microbiota play a vital role in human health and disease. The composition of the gut microbiota
is characterized by genetic and environmental factors, especially dietary habits. The level of short-chain
fatty acid (SCFA) production dependents on the hosts diet and is related to health. Especially a low
production of butyrate and propionate is associated with a leaky gut and may lead to disease conditions
like metabolic syndrome and autoimmunity. One of the bacteria known to produce butyrate is
Anaerostipes hadrus, a dominate species within the human colonic microbiota. A genomic region of
some A. hadrus strains encodes a specific inositol degradation pathway that leads to SCFA production,
and the deletion of this region was recently found to be associated with a high level of body mass index
(BMI). Intriguingly, inositol is a vitamin B-like carbocyclic sugar, and it has been used clinically to treat
patients who have Polycystic Ovary Syndrome (PCOS) accompanied with a metabolic syndrome, such
as obesity and high insulin resistance. However, the treatment outcome is variable and the mechanism
behind it is poorly understood. We hypothesize that inositol-degrading A. hadrus may contribute to the
efficacy of inositol treatment by enhancing SCFA production. The aim of this study is to investigate the
role of A. hadrus in inositol metabolism and to seek for a microbiome-based approach to improve drug
efficacy. In this study, 21 strains of A. hadrus were isolated from healthy volunteers, and their whole
genomes were sequenced. Different carbohydrates were tested in vitro on the growth of eight A. hadrus
strains which were selected by the variations on inositol degradation genes, and the SCFA production
was determined. With the comparison of A. hadrus genomes, the deletion was found in two of strains
and they could not utilize inositol for growth. Additionally, a key gene for folic acid production was
missing in five strains including the above two strains. However, growth on inositol was observed in the
remaining six strains without deletion and this led to, not only butyrate production, but also acetate and
propionate. The presence of inositol and folate pathway resulted in a higher production of SCFA and
will influence the folate production, a finding that provides us with new insight to the inositol treatment
for PCOS. Further studies will focus on the use of inositol to culture bacteria from fecal samples of
PCOS patients in host-microbe interaction models with the human epithelial cells. The evidence found
by this study suggests that co-supplementation with both of inositol and A. hadrus is a potential
therapeutic approach to improve metabolic dysfunction.