Kudzu resistant starch effectively ameliorates non‐alcoholic fatty liver disease by protecting the gut microbiota intestinal barrier and suppressing inflammatory responses

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), including non-alcoholic steatohepatitis, may lead to a cocktail of disease consequences, for instance, type II diabetes, liver fibrosis, and even hepatocarcinogenesis. The complex pathogenesis of NAFLD results in a shortage of an effective drug for its treatment. Currently, a healthy diet and regular exercise are considered one of the most effective and safe ways to mitigate NAFLD as well as other types of metabolic disorders. Kudzu-resistant starch (KRS) has developed as a potential dietary supplement attributed to its prebiotic properties, particularly its ability to regulate gut microbiota and intestinal barrier function. This study discusses the alleviative effects of KRS on high-fat diet and dextran sulfate sodium induced intestinal barrier dysfunction, inflammation, gut microbial dysbiosis, and liver steatosis. RESULTS: The results identified KRS has ameliorated intestinal barrier dysfunction by increasing the expression of zonula occludens-1 (ZO-1) and mucin 2 (Muc2). Furthermore, it also down-regulated the gut-derived LPS/TLR4 signaling pathway, dramatically alleviating inflammatory responses, including serum, colon, and liver tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and monocyte chemotactic protein-1 (MCP-1) levels. KRS also had attenuating effects on gut microbiota dysbiosis, restored the gut microbiota abundance and diversity, and increased the butyric acid-producing bacteria, such as Coprococcus, Bifidobacterium, and Lactobacillus, and it exhibited positive effects in short-chain fatty acids (SCFAs). KRS attenuated fatty acid-induced lipid accumulation and regulates lipid metabolism via the sterol regulatory element-binding protein 1-c (SREBP-1c), G-protein coupled receptors 43 (GPR43), peroxisome proliferator-activated receptor-γ (PPAR-γ), and CCAAT/enhancer-binding proteins-α (C/EBP-α). CONCLUSION: The findings reveal that kudzu resistant starch could be a potential supplement for metabolic syndromes, and the efficacy and effectiveness might facilitate the multi-targeting strategy required to mitigate NAFLD. © 2025 Society of Chemical Industry.