Intermittent fasting exacerbates colon inflammation by promoting Th17 cell differentiation through inhibition of gut microbiota-derived indoleacrylic acid

BACKGROUND Intermittent fasting (IF), particularly time-restricted feeding (TRF), is increasingly popular has gained popularity for weight loss, yet management, but its effects impact on gut health remain unclear. Remains inadequately understood. This study explores how investigated the effects of TRF effects on intestinal health and explored the underlying mechanisms. AIM To assess the effects of IF on intestinal health, elucidate the mechanisms involved. METHODS Mice were divided into two groups: Normal control (NC) and IF. The IF group underwent TRF, while the NC group had unrestricted access to food. Body weight, fecal characteristics, and intestinal morphology were analyzed. Colon tissue, serum, and fecal samples were collected for histological analysis, enzyme-linked immunosorbent assay, flow cytometry, 16S rRNA sequencing, and metabolomic profiling. RESULTS IF significantly affected body weight and intestinal morphology, compromised the intestinal barrier, increased pro-inflammatory cytokines, and heightened gut immune activation (P < 0.05). It also disrupted the gut microbiota, promoting pro-inflammatory bacteria, reducing anti-inflammatory metabolites, and elevating pro-inflammatory metabolites (P < 0.05). Indoleacrylic acid (IAA) supplementation notably alleviated intestinal inflammation and reversed immune dysfunction induced by IF (P < 0.05). CONCLUSION Prolonged IF exacerbates intestinal inflammation by impairing gut barrier integrity and disrupting microbial homeostasis. However, IAA supplementation effectively mitigates fasting-induced intestinal inflammation and immune imbalance, suggesting its potential as a therapeutic agent.