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

Sargsian S 1 , Mondragón-Palomino O 2 , Lejeune A 1 , Ercelen D 3 , Jin WB 4 , Varghese A 5 Show all authors , Lim YAL 6 , Guo CJ 4 , Loke P 7 , Cadwell K 8

Affiliations 

  • 1 Department of Microbiology, New York University Grossman School of Medicine, New York, NY, 10016, USA
  • 2 Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA
  • 3 Department of Medicine, Division of Gastroenterology and Hepatology, New York University Langone Health, New York, NY, 10016, USA
  • 4 Weill Cornell Medicine, Jill Roberts Institute for Research in Inflammatory Bowel Disease, Cornell University, New York, NY, 10021, USA
  • 5 Department of Cell Biology, New York University Grossman School of Medicine, New York, NY, 10016, USA
  • 6 Department of Parasitology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, 50603, Malaysia
  • 7 Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 20892, USA. png.loke@nih.gov
  • 8 Department of Medicine, Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA. ken.cadwell@pennmedicine.upenn.edu
Microbiome, 2024 May 10;12(1):86.
PMID: 38730492 DOI: 10.1186/s40168-024-01793-1

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. Video Abstract.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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