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, Limosilactobacillus, Allobaculum, and Faecalibaculum, which contributed to intestinal epithelial cell growth and helped preserve barrier integrity. Notably, IPA can be transferred from the mother to the fetus through blood and amniotic fluid, facilitating the mRNA expression of Mdr1b, Ctnnb1, and Lgr5, which are involved in gut cell proliferation and differentiation. CONCLUSION: Prenatal IPA is transferred to the fetus and promotes gut development, conferring long-term protection against colitis in MIA offspring. These findings underscore the enduring impact of maternal interventions on offspring intestinal health.