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

Background: 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, display microbiotas enriched in Clostridiales, an order of spore-forming obligate anaerobes with immunogenic properties. We previously isolated novel Clostridiales that were enriched in these individuals and found that a subset promoted the Trichuris life cycle. In this study, we aimed to further characterize the functional properties of these bacteria.Results: Clostridiales isolates were profiled for their ability to perform 57 enzymatic reactions and produce short chain fatty acids (SCFAs) and hydrogen sulfide, revealing that these bacteria were capable of 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. R. hominis-OA6 is unable to induce Tregs despite its taxonomic relationship to the other two Peptostreptococcaceae isolates, the Treg-inducing R. hominis-OA2 and P. sordellii-OA8. To better characterize the host response to the three Peptostreptococcaceae isolates, we performed RNAseq on colonic tissue from mice monocolonized with these three bacteria, as well as GF mice (Figure S3). Principal coordinate analysis (PCA) showed that the four conditioned mainly separated on the PC1 axis, with R. hominis-OA2 the farthest from GF controls, and R. hominis-OA6 and P. sordellii-OA8 in-between (Figure S3a).