Dietary supplementation with raw potato starch reversed enteritis-induced bone loss via Malt1 paracaspase inhibition in meat ducks.

Intestinal inflammation is a key driver of progressive bone deterioration, elevating the risk of fractures and chronic pain in meat ducks. As a fermentable type II resistant starch, raw potato starch (RPS) probably supports gut health and potentially mitigate this inflammatory bone loss. In this study, an enteritis model was established in meat ducks using dextran sodium sulphate (DSS) and to assess its effect on bone metabolism, as well as to determine the role of RPS in enteritis-mediated bone loss. In enteritis-induced meat duck models, dietary supplementation with 12% RPS reversed intestinal inflammation‑induced bone loss, an effect accompanied by improved intestinal homeostasis and reduced bone resorption (P < 0.05). These changes were associated with alterations in inflammatory cytokine secretion, osteoclastic differentiation, and the mucosa-associated lymphoid tissue 1 (Malt1) mediated nuclear factor kappa-B (NF-κB) pathway, as supported by transcriptional analysis of the bone marrow and AlphaFold predictions. To elucidate the mechanism by which RPS restores bone mass in the DSS-treated ducks, a specific Malt1 inhibitor (mepazine) was employed. Ducks were fed either a basal diet or a 12% RPS diet, with or without supplemental mepazine at 20 mg/kg body weight, and all were challenged with DSS from d 7 to 21. Herein, with unchanged expressions of regulatory T cell cytokines (P > 0.05), Malt1 protease inactivation or dietary RPS supplementation enhanced tibia ash and bone volume in metaphysis (Both P < 0.05). Along with increased Firmicutes levels and the production of short chain fatty acids (P < 0.05), mepazine or dietary RPS inclusion downregulated NF-κB inflammatory pathway, resulting in decreased the osteoclastic activity. Co-treatment with mepazine and RPS further amplified this effect, implicating Malt1 protease inhibition as the mechanism by which RPS protects against enteritis-induced osteopenia. These findings revealed that diet contained 12% RPS reverses enteritis-induced bone loss in meat ducks, likely by inhibiting Malt1 paracaspase and subsequently suppressing NF-κB pathway-mediated bone resorption.