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

TitleFunctional characterization of helminth-associated Clostridiales reveals covariates of Treg differentiation.
Publication TypeJournal Article
Year of Publication2023
AuthorsSargsian, S, Lejeune, A, Ercelen, D, Jin, W-B, Varghese, A, Loke, P'ng, Lim, YAL, Guo, C-J, Cadwell, K
JournalbioRxiv
Date Published2023 Jun 07
Abstract

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.

DOI10.1101/2023.06.05.543751
Alternate JournalbioRxiv
PubMed ID37333296
PubMed Central IDPMC10274677
Grant ListR01 DK135816 / DK / NIDDK NIH HHS / United States
R01 DK093668 / DK / NIDDK NIH HHS / United States
DP2 HD101401 / HD / NICHD NIH HHS / United States
R01 AI140754 / AI / NIAID NIH HHS / United States
R01 AI130945 / AI / NIAID NIH HHS / United States
R01 DK124336 / DK / NIDDK NIH HHS / United States
R01 AI133977 / AI / NIAID NIH HHS / United States
R01 HL123340 / HL / NHLBI NIH HHS / United States
T32 AI007180 / AI / NIAID NIH HHS / United States
R01 AI121244 / AI / NIAID NIH HHS / United States