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

Abstract 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.