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

ABSTRACT:

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.

SUBMITTER: Shute A

PROVIDER: S-EPMC8438845 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundPrevious reports show altered gut bacterial profiles are associated with helminth infected individuals. Our recently published molecular survey of clinical helminthiases in Thailand border regions demonstrated a more comprehensive picture of infection prevalence when Kato Katz microscopy and copro-qPCR diagnostics were combined. We revealed that Opisthorchis viverrini, hookworm, Ascaris lumbricoides and Trichuris trichiura were the most predominant helminth infections in these regions. In the current study, we have profiled the faecal and saliva microbiota of a subset of these helminth infected participants, in order to determine if microbial changes are associated with parasite infection.MethodsA subset of 66 faecal samples from Adisakwattana et al., (2020) were characterised for bacterial diversity using 16S rRNA gene profiling. Of these samples a subset of 24 participant matched saliva samples were also profiled for microbiota diversity. Sequence data were compiled, OTUs assigned, and diversity and abundance analysed using the statistical software Calypso.ResultsThe data reported here indicate that helminth infections impact on both the host gut and oral microbiota. The profiles of faecal and saliva samples, irrespective of the infection status, were considerably different from each other, with more alpha diversity associated with saliva (p-value≤ 0.0015). Helminth infection influenced the faecal microbiota with respect to specific taxa, but not overall microbial alpha diversity. Conversely, helminth infection was associated with increased saliva microbiota alpha diversity (Chao 1 diversity indices) at both the genus (p-value = 0.042) and phylum (p-value = 0.026) taxa levels, compared to uninfected individuals. Elevated individual taxa in infected individuals saliva were noted at the genus and family levels. Since Opisthorchis viverrini infections as a prominent health concern to Thailand, this pathogen was examined separately to other helminths infections present. Individuals with an O. viverrini mono-infection displayed both increases and decreases in genera present in their faecal microbiota, while increases in three families and one order were also observed in these samples.DiscussionIn this study, helminth infections appear to alter the abundance of specific faecal bacterial taxa, but do not impact on overall bacterial alpha or beta diversity. In addition, the faecal microbiota of O. viverrini only infected individuals differed from that of other helminth single and dual infections. Saliva microbiota analyses of individuals harbouring active helminth infections presented increased levels of both bacterial alpha diversity and abundance of individual taxa. Our data demonstrate that microbial change is associated with helminthiases in endemic regions of Thailand, and that this is reflected in both faecal and saliva microbiota. To our knowledge, this is the first report of an altered saliva microbiota in helminth infected individuals. This work may provide new avenues for improved diagnostics; and an enhanced understanding of both helminth infection pathology and the interplay between helminths, bacteria and their host.

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