Background: Helminth-induced Th2 responses are essential to modify the structure and diversity of gut microbes. However, observations have come mainly from studies of helminth-infected humans or rodent models. Very little research has been conducted in veterinary animals. Methods: In this study, we searched for links between microbiota and Th2-biased responses during the time course of Fasciala gigantica infection in buffaloes.16S rRNA gene amplicon and metagenome sequencing were applied to analyze the structure and function of the gut microbiota. Results: Both alpha and beta diversities decreased during infection, and gut microbes differed considerably across different sections of the gut at different stages. Immune responses changed when the microbiota traverses the gut wall into the peritoneal cavity, in line with the changes in Th2 response induced by F. gigantica infection. We found that the order Coriobacteriales was greatly decreased at the early stages in which the Peptostreptococcaceae and Family_XIII families are closely linked to the upregulation of IgG1 and IL4, respectively. The F. gigantica infection significantly reduced short-chain fatty acid (SCFAs)-producing microbes, reduced the concentrations of gut SCFAs and downregulated the SCFAs-producing metabolic pathways. In addition, The microbes associated with TLR2 increased and showed similar trend to the TLR2 and Th2 cytokine production during infection, suggesting that bacteria ligands might recognize TLR2 and subsequently induce a Th2-biased response. Conclusions: Our data show that buffalo gut microbes may affect the host Th2 response during F. gigantica infection via the SCFAs metabolism and TLR signaling pathway. These findings provide new insights into the relationship between F. gigantica–microbiota-host, which may provide new potential therapeutic targets for prevention and control Fasciolosis.
