不同剂量生玉米淀粉对小鼠肠道黏膜屏障功能的损伤及机制研究OA

[Objective]To investigate the effects of different doses of uncooked corn starch(UCCS),type 2 resistant starch,on intestinal mucosal barrier function in mice and to explore the potentional underlying mechanisms.[Methods]Twenty C57BL/6 mice were randomly assigned to four groups and fed either a standard diet(control group)or diets supplemented with low(188.8 g/kg),medium(314.8 g/kg),or high(440.6 g/kg)doses of UCCS for 8 weeks.Body weight and disease activity index(DAI)were monitored.At the endpoint,colon length was measured;histopathological changes in were assessed via HE staining.The expression of tight junction proteins(ZO-1,E-cadherin,and Villin)in the colonic mucosa were detected using immunofluorescence.Serum inflammatory cytokines(IL-6,TNF-α,IL-1β,MIP-1α/CCL3)and fecal calprotectin levels were measured by ELISA.Gut microbiota alterations were analyzed via 16S rRNA gene sequencing and PICRUSt2 functional prediction.[Results]Compared with the control group,UCCS intervention across all doses significantly shortened colon length(P=0.000 5)and increased colonic inflammation scores(P=0.013 3).Immunofluorescence revealed a significantly reduction in the expression and co-localization of ZO-1 and Villin in the colonic mucosa(P＜0.05).Systemic inflammation was evidenced by significantly elevated serum levels of IL-6(P=0.006 4),TNF-α(P=0.000 1),IL-1β(P=0.001 4),and MIP-1α/CCL3(P＜0.000 1).Fecal calprotectin levels were also significantly increased during the early phase(weeks 1-2,P＜0.05).16S rRNA sequencing showed that UCCS significantly altered the β-diversity of the gut microbiota(P＜0.05),characterized by the enrichment of butyrate-producing Clostridia_UCG-014,and the opportunistic pathogen Desulfovibrio,alongside a decreased abundance of immunomodulatory genera Akkermansia and Dubosiella.PICRUSt2 analysis suggested that UCCS modulated metabolic pathways related to energy metabolism,glutathione metabolism,and sulfur cycling.[Conclusion]Long-term or high-dose intake of UCCS may disrupt gut microbiota homeostasis and trigger inflammation response,thereby damaging the intestinal mucosal barrier.These findings suggest that the clinical or dietary application of UCCS should be cautioned regarding dose-dependent risks of intestinal injury.