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Functional characterization of helminth-associated Clostridiales reveals covariates of Treg differentiation.

Shushan SargsianAlannah LejeuneDefne ErcelenWen-Bing JinAlan VargheseP'ng LokeYvonne Ai-Lian LimChun-Jun GuoKen H Cadwell
Published in: bioRxiv : the preprint server for biology (2023)
Parasitic helminths influence the composition of the gut microbiome. However, the microbiomes of individuals living in helminth-endemic regions are understudied. The Orang Asli, an indigenous population in Malaysia with high burdens of the helminth Trichuris trichiura , displayed microbiotas enriched in Clostridiales, an order of spore-forming obligate anaerobes previously shown to have immunogenic properties. We previously isolated novel Clostridiales that were enriched in these individuals and found that a subset promoted the Trichuris life cycle. Here, we further characterized the functional properties of these bacteria. Enzymatic and metabolomic profiling revealed a range of activities associated with metabolism and host response. Consistent with this finding, monocolonization of mice with individual isolates identified bacteria that were potent inducers of regulatory T cell (Treg) differentiation in the colon. Comparisons between variables revealed by these studies identified enzymatic properties correlated with Treg induction and Trichuris egg hatching. These results provide functional insights into the microbiotas of an understudied population.
Keyphrases
  • life cycle
  • hydrogen peroxide
  • transcription factor
  • single cell
  • adipose tissue
  • type diabetes
  • skeletal muscle
  • anti inflammatory
  • nitric oxide
  • genetic diversity
  • case control