The gut microbiota is essential forTrichinella spiralis- evoked suppression of colitis

Abstract

AbstractInflammatory bowel disease (IBD) increases the risk of colorectal cancer, and it has the potential to diminish the quality of life. Clinical and experimental evidence demonstrate protective aspects of parasitic helminth infection against IBD. However, studies on the inhibition of inflammation by helminth infection have overlooked a key determinant of health: the gut microbiota. Infection with helminths induces alterations in the host microbiota composition. However, the potential influence and mechanism of helminth infections induced changes in the gut microbiota on the development of IBD has not yet been elucidated. In this study, we analyzed the intersection of helminthTrichinella spiralisand gut bacteria in the regulation of colitis and related mechanisms.T. spiralisinfected mice were treated with antibiotics or cohused with wild type mice, then challenged with DSS-colitis and disease severity, immune responses and goblet cells assessed. Gut bacteria composition was assessed by 16 s rRNA sequencing and SCFAs were measured. Results showed that protection against disease by infection withT. spiraliswas abrogated by antibiotic treatment, and cohousing withT. spiralis- infected mice suppressed DSS-colitis in wild type mice. Bacterial community profiling revealed an increase in the abundance of the bacterial genusMuribaculumandunclassified_Muribaculaceaein mice withT. spiralisinfection or mice cohoused withT. spiralis- infected mice. Metabolomic analysis demonstrated increased propionic acid in feces fromT. spiralis- infected mice. Data also showed that the gut microbiome modulated byT. spiralisexhibited enhanced goblet cell differentiation and elevated IL-10 levels in mice. Taken together, these findings identify the gut microbiome as a critical component of the anti-colitic effect ofT. spiralisand gives beneficial insights into the processes by which helminth alleviates colitis.Author SummaryInflammatory bowel disease (IBD) encompasses Crohn’s Disease and Ulcerative Colitis. It affects both children and adults. Reports have highlighted the potential use of helminths or their byproducts as a possible treatment for IBD. Accumulating evidence also suggests that the gut microbiota is a key factor in modulating IBD. In this study, we revealed the protective effect of a prior infection withT. spiralison DSS-induced colitis in mice. Specifically,T. spiralisinfection reshaped the gut microbiome of mice, resulting in an increased abundance of SCFA-producing bacteriaMuribaculumandunclassified_Muribaculaceaeand thereby producing a larger amount of propionic acid. Furthermore, the gut microbiome modulated byT. spiralisexhibited enhanced goblet cell differentiation and elevated IL-10 levels, ultimately ameliorating experimental colitis. These findings suggest that the modulation of host microbiota duringT. spiralisinfection plays a crucial role in the suppression of colitis, and any intention-to-treat with helminth therapy should be based on the patient’s immunological and microbiological response to the helminth.