Abstract

High-fertility sheep experience undernutrition during late gestation, which induces body metabolic disruption and intestinal inflammation. Crucially, the gut microbiota-bile acid axis is a promising intestinal inflammation target, but how choline modulates this axis in livestock enteritis is unknown. This study investigated choline’s protective mechanisms against undernutrition-induced intestinal inflammation in sheep, focusing on gut microbiota and bile acid regulation. Choline consistently alleviates colitis severity, restores epithelial barrier integrity, and suppresses intestinal inflammation. These protective effects are accompanied by pronounced remodeling of the colonic microbial ecosystem, characterized by the enrichment of Clostridiales bacterium to elevate bile salt hydrolase activity and regulate bile acid homeostasis. Concomitantly, choline reshapes colonic bile acid profiles, normalizing total bile acid levels and selectively restoring DCA abundances. Mechanistically, the anti-inflammatory effects of DCA depend on Nur77 activation and subsequent suppression of NF-κB signaling across in vivo and in vitro systems. These findings provide preliminary evidence for a putative choline-microbiota-bile acid-immune signaling axis that confers protection against undernutrition-associated colitis and support choline intervention as a pregnancy-compatible nutritional strategy for intestinal inflammatory disorders in animal. The alternative text for this image may have been generated using AI.