High-fat diet-induced obesity disrupts the gut microbiome and mucus secretion to aggravate experimental colitis.

Obesity and its associated comorbidities have emerged as a major public health crisis. Accumulating evidence indicates that a high fat diet (HFD) may promote intestinal injury. However, the roles of intestinal goblet cells and specific gut microbiota composition in colitis under obesity conditions remain unclear. In this study, we employed a HFD-induced obesity model combined with dextran sulfate sodium (DSS) to induce colitis in mice. Our results reveal that obesity exacerbates DSS-induced colitis in the colon, as evidenced by increased intestinal barrier injury. These changes are associated with impaired goblet cell maturation, reduced mucus production, and a disrupted microbiota composition, notably characterized by an enrichment of pro-inflammatory bacteria Escherichia-Shigella and Helicobacter. In vitro, combined HFD and DSS treatment suppresses mucus secretion and alters the metabolic profile of LS174T cells, particularly affecting amino acid metabolism. Collectively, our findings reveal that HFD-induced obesity aggravates colitis severity, involving disruption of goblet cell function and gut microbial homeostasis, highlighting the importance of dietary intervention in obese individuals to alleviate intestinal inflammation.