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Abstract
The prevalence of inflammatory bowel disease (IBD) is increasing worldwide and correlates with dysregulated immune response because of gut microbiota dysbiosis. Some adverse early life events influence the establishment of the gut microbiota and act as risk factors for IBD. Prenatal maternal stress (PNMS) induces gut dysbiosis and perturbs the neuroimmune network of offspring. In this study, we aimed to investigate whether PNMS increases the susceptibility of offspring to colitis in adulthood. The related index was assessed during the weaning period and adulthood. We found that PNMS impaired the intestinal epithelial cell proliferation, goblet cell and Paneth cell differentiation, and mucosal barrier function in 3-week-old offspring. PNMS induced low-grade intestinal inflammation, but no signs of microscopic inflammatory changes were observed. Although there was no pronounced difference between the PNMS and control offspring in terms of their overall measures of alpha diversity for the gut microbiota, distinct microbial community changes characterized by increases in Desulfovibrio, Streptococcus, and Enterococcus and decreases in Bifidobacterium and Blautia were induced in the 3-week-old PNMS offspring. Notably, the overgrowth of Desulfovibrio persisted from the weaning period to adulthood, consistent with the results observed using fluorescence in situ hybridization in the colon mucosa. Mechanistically, the fecal microbiota transplantation experiment showed that the gut microbiota from the PNMS group impaired the intestinal barrier function and induced low-grade inflammation. The fecal bacterial solution from the PNMS group was more potent than that from the control group in inducing inflammation and gut barrier disruption in CaCo-2 cells. After treatment with a TNF-α inhibitor (adalimumab), no statistical difference in the indicators of inflammation and intestinal barrier function was observed between the two groups. Finally, exposure to PNMS remarkably increased the values of the histopathological parameters and the inflammatory cytokine production in a mouse model of experimental colitis in adulthood. These findings suggest that PNMS can inhibit intestinal development, impair the barrier function, and cause gut dysbiosis characterized by the persistent overgrowth of Desulfovibrio in the offspring, resulting in exacerbated experimental colitis in adulthood.
Highlights
Inflammatory bowel disease (IBD), comprising ulcerative colitis and Crohn’s disease, involves a group of chronic, recurrent, and destructive intestinal inflammatory conditions [1]
Our findings demonstrated that Prenatal maternal stress (PNMS), one of the common adverse early life events, has negative effects on the intestinal development and microbiota establishment of offspring, raising the risk of colitis
Through the fecal microbiota transplantation (FMT) experiment, we found that the gut microbiota from the PNMS group impaired the intestinal barrier function and induced low-grade inflammation
Summary
Inflammatory bowel disease (IBD), comprising ulcerative colitis and Crohn’s disease, involves a group of chronic, recurrent, and destructive intestinal inflammatory conditions [1]. IBD is becoming highly prevalent worldwide, showing pronounced growth in newly industrialized countries [2] and posing a challenge to health services. Potential factors that contribute to these transitions of incidence and prevalence include the urbanization, industrialization, and westernization of society [3]. Stress has become a sizeable component of modern lifestyle and greatly contributes to the increased prevalence of IBD. The importance of stress on IBD has long been recognized in the literature [4, 5]. Stress triggers the flares of patients with IBD [6,7,8,9,10,11], and the underlying mechanisms include the dysregulation of the gut–brain–microbiome axis and the neuroendocrine system [12, 13]
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