Prenatal supplementation with the gut-derived tryptophan metabolite indole-3-propionic acid alleviates colitis susceptibility in maternal immune-activated offspring mice

作者：Ying He, Chen Ding, Bo Zhang, B. Bao, Yantong Liu, Duo Yun, Xia Chen, Rui Guo, Yongbo She, Zhigang Liu · 发表于：Journal of Advanced Research · 年份：2025 · DOI：10.1016/j.jare.2025.05.051 · 被引用次数：10 · 研究领域：Gut microbiota and health、Tryptophan and brain disorders、Immune responses and vaccinations

INTRODUCTION: Maternal immune activation (MIA) impairs gut immune function in offspring, with maternal microbiota and their metabolites influencing intestinal development. Indole-3-propionic acid (IPA), a microbial metabolite derived from tryptophan, promotes gut health by enhancing epithelial proliferation. However, the impact of prenatal IPA supplementation on offspring gut outcomes remains unclear. OBJECTIVES: This study investigated whether prenatal IPA supplementation could mitigate the susceptibility of MIA offspring to colitis. METHODS: Pregnant mice received oral IPA (20 mg/kg body weight) from embryonic day 5.5 (E5.5) until delivery, with MIA induced at E12.5. Female offspring (7-8 weeks old) were exposed to 3.5 % dextran sulfate sodium (DSS)-induced colitis. IPA levels were measured in maternal serum and amniotic fluid at E14.5 to assess maternal-fetal transfer and potential effects on fetal gut development. RESULTS: Prenatal IPA supplementation attenuated colitis severity in MIA offspring, as evidenced by reduced body weight loss, milder diarrhea, lower disease activity index, and diminished colonic damage, along with alleviation of anxiety-like behavior. Moreover, prenatal IPA supplementation decreased serum and colonic proinflammatory factor levels and improved colonic barrier function following DSS-induced colitis. Additionally, prenatal IPA supplementation enhanced the proportion of beneficial gut microbiota, such as Bifidobacterium, Lactobacillus, Limosilactob...