Anaerostipes hadrus ability to degrade inositol relates to human health: implications for possible PCOS treatment


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Liu L., Tsompanidou E., Güçlü Durgun S., Fu J., Harmsen H. J.

The 9th International Human Microbiome Consortium Congres 2022, Kobe, Japonya, 9 - 10 Kasım 2022, ss.1-2

  • Yayın Türü: Bildiri / Özet Bildiri
  • Basıldığı Şehir: Kobe
  • Basıldığı Ülke: Japonya
  • Sayfa Sayıları: ss.1-2
  • Lokman Hekim Üniversitesi Adresli: Evet

Özet

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.