Bifidobacterium pseudocatenulatum alleviates neonatal calf diarrhea via acetate-associated attenuation of pathogen-induced Th17/IL-17A inflammatory responses

Abstract

Neonatal calf diarrhea is a major challenge in livestock production and is often driven by pathogen-induced intestinal inflammation and gut dysbiosis. While the therapeutic potential of Bifidobacterium ( B. ) pseudocatenulatum is recognized, its mechanistic interplay with diarrhea-associated inflammatory pathology in calves remains poorly defined. This study investigated how B. pseudocatenulatum alleviates calf diarrhea and intestinal inflammation, with a focus on acetate metabolism and the T helper 17 (Th17)/IL-17A immune axis. Diarrheic calves exhibited pronounced gut microbial dysbiosis, metabolic perturbation, and inflammatory activation. Fecal microbiota transplantation (FMT) from healthy calves alleviated diarrhea and was accompanied by enrichment of B. pseudocatenulatum and increased fecal acetate. In vitro, live B. pseudocatenulatum increased acetate production. In complementary murine inflammatory models, B. p seudocatenulatum and acetate alleviated intestinal injury and inflammatory phenotypes. The protective effect was attenuated in the heat-killed B. pseudocatenulatum -treated group. Mechanistically, these protective effects were accompanied by attenuation of pathogen-induced Th17/IL-17A-related responses rather than broad suppression of basal Th17 activation. Pharmacological blockade of free fatty acid receptor 2 (FFAR2) attenuated the protective effect of live B. pseudocatenulatum , supporting the involvement of acetate-associated receptor signaling. This study revealed B. pseudocatenulatum as a microbiota-associated candidate linked to calf diarrhea remission and supports acetate-associated attenuation of pathogen-induced Th17/IL-17A-related inflammatory responses as one component of its protective effect. These findings establish a microbiota–metabolite–immune regulatory framework, providing novel therapeutic strategies for alleviating intestinal inflammation and calf diarrhea.