Dietary betaine supplementation modulates feed intake via the microbiota–gut–brain axis in finishing pigs fed low-energy diets

Betaine (BET), a key metabolic intermediate, regulates energy metabolism and influences feed intake, yet its mechanism remains unclear. This study investigated whether BET modulates feed intake in finishing pigs via the microbiota–gut–brain axis under varying dietary net energy (NE) levels. Seventy-two pigs (82.63 ± 4.13 kg) were allotted to six treatments in a 2 × 3 factorial arrangement, including two BET levels (0 or 1,500 mg/kg) and three NE levels (2,555, 2,475, or 2,395 kcal/kg). Results showed that, in pigs fed low-NE diets, dietary BET significantly reduced average weekly feed intake (AWFI) during week 6 ( p < 0.05). Across the entire 42-day period, average daily feed intake (ADFI) was numerically reduced by 6.05%, although this difference was not significant ( p > 0.05), whereas no such effect occurred in pigs fed normal- or high-NE diets ( p > 0.05). The addition of BET to low-NE diets resulted in elevated serum levels of cholecystokinin (CCK) and peptide YY (PYY), as well as a decrease in orexigenic neuropeptides (AgRP) and an increase in anorexigenic neuropeptides (POMC) within the hypothalamus ( p < 0.05), indicating appetite suppression. Furthermore, BET was found to upregulate hypothalamic G protein-coupled receptor 41 (GPR41) and GPR43 mRNA expression in pigs on low-NE diets ( p < 0.01). This effect was accompanied by increased volatile fatty acid (VFA) levels in both serum and hindgut digesta ( p < 0.05), driven by BET-induced alterations in gut microbial composition. Notably, these compositional changes consisted of a reduction in the abundance of Prevotella and an increase in the populations of NK4A214_group and Methanobrevibacter ( p < 0.05). Collectively, these findings support the involvement of the microbiota–gut–brain axis in the feed-intake response to BET under low-NE conditions and provide a mechanistic basis for further evaluating BET as a nutritional strategy to improve feed-energy utilization.