Cooperation between host immunity and the gut bacteria is essential for helminth-evoked suppression of colitis

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dc.contributor.authorShute, Adam
dc.contributor.authorCallejas, Blanca E.
dc.contributor.authorLi, ShuHua
dc.contributor.authorWang, Arthur
dc.contributor.authorJayme, Timothy S.
dc.contributor.authorOhland, Christina
dc.contributor.authorLewis, Ian A.
dc.contributor.authorLayden, Brian T.
dc.contributor.authorBuret, André G.
dc.contributor.authorMcKay, Derek M.
dc.date.accessioned2021-09-19T00:02:26Z
dc.date.available2021-09-19T00:02:26Z
dc.date.issued2021-09-13
dc.date.updated2021-09-19T00:02:25Z
dc.description.abstractAbstract Background Studies on the inhibition of inflammation by infection with helminth parasites have, until recently, overlooked a key determinant of health: the gut microbiota. Infection with helminths evokes changes in the composition of their host’s microbiota: one outcome of which is an altered metabolome (e.g., levels of short-chain fatty acids (SCFAs)) in the gut lumen. The functional implications of helminth-evoked changes in the enteric microbiome (composition and metabolites) are poorly understood and are explored with respect to controlling enteric inflammation. Methods Antibiotic-treated wild-type, germ-free (GF) and free fatty-acid receptor-2 (ffar2) deficient mice were infected with the tapeworm Hymenolepis diminuta, then challenged with DNBS-colitis and disease severity and gut expression of the il-10 receptor-α and SCFA receptors/transporters assessed 3 days later. Gut bacteria composition was assessed by 16 s rRNA sequencing and SCFAs were measured. Other studies assessed the ability of feces or a bacteria-free fecal filtrate from H. diminuta-infected mice to inhibit colitis. Results Protection against disease by infection with H. diminuta was abrogated by antibiotic treatment and was not observed in GF-mice. Bacterial community profiling revealed an increase in variants belonging to the families Lachnospiraceae and Clostridium cluster XIVa in mice 8 days post-infection with H. diminuta, and the transfer of feces from these mice suppressed DNBS-colitis in GF-mice. Mice treated with a bacteria-free filtrate of feces from H. diminuta-infected mice were protected from DNBS-colitis. Metabolomic analysis revealed increased acetate and butyrate (both or which can reduce colitis) in feces from H. diminuta-infected mice, but not from antibiotic-treated H. diminuta-infected mice. H. diminuta-induced protection against DNBS-colitis was not observed in ffar2−/− mice. Immunologically, anti-il-10 antibodies inhibited the anti-colitic effect of H. diminuta-infection. Analyses of epithelial cell lines, colonoids, and colon segments uncovered reciprocity between butyrate and il-10 in the induction of the il-10-receptor and butyrate transporters. Conclusion Having defined a feed-forward signaling loop between il-10 and butyrate following infection with H. diminuta, this study identifies the gut microbiome as a critical component of the anti-colitic effect of this helminth therapy. We suggest that any intention-to-treat with helminth therapy should be based on the characterization of the patient’s immunological and microbiological response to the helminth.
dc.identifier.citationMicrobiome. 2021 Sep 13;9(1):186
dc.identifier.doihttps://doi.org/10.1186/s40168-021-01146-2
dc.identifier.urihttp://hdl.handle.net/1880/113899
dc.identifier.urihttps://doi.org/10.11575/PRISM/44219
dc.language.rfc3066en
dc.rights.holderThe Author(s)
dc.titleCooperation between host immunity and the gut bacteria is essential for helminth-evoked suppression of colitis
dc.typeJournal Article
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