Related Experiment Video
Updated: Oct 12, 2025
Using a Murine Model of Psychosocial Stress in Pregnancy as a Translationally Relevant Paradigm for Psychiatric Disorders in Mothers and Infants
Published on: June 13, 2021
Prenatal Maternal Stress Exacerbates Experimental Colitis of Offspring in Adulthood
Yue Sun1,2, Runxiang Xie1,2, Lu Li1,2
1Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin, China.
Insights
Prenatal maternal stress (PNMS) impairs offspring gut development and barrier function, leading to dysbiosis and increased susceptibility to colitis in adulthood. This highlights early life stress as a risk factor for inflammatory bowel disease (IBD).
Area of Science:
- Immunology
- Microbiology
- Gastroenterology
- Developmental Biology
Background:
- Inflammatory bowel disease (IBD) prevalence is rising globally, linked to immune dysregulation and gut microbiota imbalances.
- Early life events, including prenatal maternal stress (PNMS), can disrupt gut microbiota establishment and increase IBD risk.
- PNMS affects offspring neuroimmune networks and gut development, potentially influencing long-term health outcomes.
Purpose of the Study:
- To investigate if prenatal maternal stress (PNMS) heightens offspring susceptibility to colitis in adulthood.
- To analyze the impact of PNMS on intestinal development, barrier function, and gut microbiota composition during early life and adulthood.
- To explore the mechanisms by which PNMS-induced gut dysbiosis contributes to colitis development.
Main Methods:
- Assessment of intestinal development, barrier function, and low-grade inflammation in offspring exposed to PNMS.
- Gut microbiota profiling (16S rRNA sequencing) and fecal microbiota transplantation (FMT) experiments.
- In vitro studies using CaCo-2 cells and in vivo experimental colitis model in adult mice treated with TNF-α inhibitor.
Main Results:
- PNMS impaired intestinal epithelial cell proliferation, goblet/Paneth cell differentiation, and mucosal barrier function in young offspring.
- PNMS induced gut dysbiosis, notably a persistent increase in Desulfovibrio, and impaired intestinal barrier function.
- PNMS significantly exacerbated experimental colitis in adult mice, increasing inflammation and cytokine production.
Conclusions:
- Prenatal maternal stress inhibits intestinal development, compromises barrier function, and causes persistent gut dysbiosis (Desulfovibrio overgrowth) in offspring.
- PNMS-induced gut dysbiosis is mechanistically linked to impaired intestinal barrier function and low-grade inflammation.
- These findings establish PNMS as a critical risk factor that increases offspring susceptibility to colitis in adulthood.
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.
