Corncob-Derived Xylo-Oligosaccharides Attenuate Acrylamide-Induced Gut–Liver Toxicity in Mice, Associated with Modulation of Gut Microbiota and SCFA Metabolism

Simple SummaryAcrylamide (AA), a prevalent foodborne contaminant formed during high-temperature food processing, poses significant health risks; however, effective and practical dietary countermeasures remain scarce. Our study provides compelling evidence that a prebiotic, xylo-oligosaccharides (XOS) derived from corncobs, effectively mitigates AA-induced gut–liver toxicity in mice, characterized by alleviation of colonic and hepatic inflammation, amelioration of intestinal barrier dysfunction, and reduction in hepatic oxidative stress. These protective effects were closely associated with the remodeling of gut microbiota, characterized by a marked enrichment of short-chain fatty acid (SCFA)-producing genera and a concomitant reduction in pro-inflammatory taxa, resulting in significantly elevated SCFA levels. These findings indicate that corncob-derived XOS represents a potential prebiotic candidate for counteracting AA-induced toxicity and support further investigation into its value for future applications in the food safety field.Acrylamide (AA) is a common foodborne toxicant formed during the thermal processing of starch-rich foods and poses significant risks to the gut–liver axis. Although corncob-derived xylo-oligosaccharides (XOS) have emerged as promising prebiotics with multiple bioactivities, their protective effects against foodborne toxicants have not been explored. This study investigated the ameliorative effects of dietary corncob-derived XOS on AA-induced gut–liver toxicity and the underlying mechanisms in mice. Female C57BL/6J mice were gavaged with AA and concurrently fed diets with or without 7.0% XOS for 7 weeks. The results showed that XOS effectively alleviated AA-induced gut–liver toxicity, as evidenced by attenuated intestinal and hepatic inflammation (decreased pro-inflammatory cytokines IL-6 in colon, TNF-α, and IL1-β in liver; increased anti-inflammatory IL-10 in colon and liver), restored intestinal barrier integrity (upregulatedZo-1,Occludin, andClaudin-1mRNA, along with increased goblet cell numbers and mucus secretion), and ameliorated hepatic oxidative stress (upregulatedNrf2/Nqo1/Ho1mRNA expression, restored CAT activity, and reduced H2O2accumulation). 16S sequencing revealed that XOS supplementation significantly increased the Shannon index in AA-exposed mice compared with the AA group, suggesting enhanced cecal microbial diversity, although AA exposure did not significantly reduce α-diversity. Further analysis showed that XOS reshaped the community composition, particularly by reducing pro-inflammatory genera (Dubosiella,Desulfovibrio,Faecalibaculum, andFaecalimonas) and enriching short chain fatty acid (SCFA)-producing bacteria (Bifidobacterium,norank_f__Muribaculaceae, andAkkermansia). Furthermore, XOS significantly elevated SCFA levels in AA-treated mice, including acetic, propionic, butyric, valeric, and isovaleric acids. Collectively, these findings demonstrate that dietary XOS ameliorates AA-induced gut–liver toxicity in mice when co-administered with AA. This protective effect was associated with modulation of the gut microbiota and SCFA metabolism, providing a basis for future studies exploring the potential of XOS against foodborne contaminant toxicity.