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

Sargsian, Shushan and Mondragon-Palomino, Octavio and Lejeune, Alannah and Ercelen, Defne and Jin, Wen-Bing and Varghese, Alan and Lim, Yvonne Ai Lian and Guo, Chun-Jun and Loke, P'ng and Cadwell, Ken (2024) Functional characterization of helminth-associated Clostridiales reveals covariates of Treg differentiation. Microbiome, 12 (1). ISSN 2049-2618, DOI https://doi.org/10.1186/s40168-024-01793-1.

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Abstract

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. Conclusion We identified Clostridiales species that are sufficient to induce high levels of Tregs. We also identified a set of metabolic activities linked with Treg differentiation and Trichuris egg hatching mediated by these newly isolated bacteria. Altogether, this study provides functional insights into the microbiotas of individuals residing in a helminth-endemic region. -EyM7p7tfAvrAjtAePB85J Video Abstract Conclusion We identified Clostridiales species that are sufficient to induce high levels of Tregs. We also identified a set of metabolic activities linked with Treg differentiation and Trichuris egg hatching mediated by these newly isolated bacteria. Altogether, this study provides functional insights into the microbiotas of individuals residing in a helminth-endemic region. -EyM7p7tfAvrAjtAePB85J Video Abstract

Item Type: Article
Funders: W. M. Keck Foundation
Uncontrolled Keywords: Clostridia; Helminth; Trichuris; Microbiome; Immune modulation; Regulatory T cells; Metabolites; Bacterial enzymes
Subjects: R Medicine
R Medicine > RB Pathology
R Medicine > RM Therapeutics. Pharmacology
Divisions: Faculty of Medicine > Parasitology Deparment
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 13 Aug 2024 02:33
Last Modified: 13 Aug 2024 02:33
URI: http://eprints.um.edu.my/id/eprint/45240

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