Impact of prenatal stress on visceral sensitivity and intestinal homeostasis in adulthood
(2020) United European Gastroenterology Week — Location: Amsterdam, The Netherlands [Online]
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- Abstract
- Background: Environmental factors, and predominantly stress during pregnancy, could lead to gut microbiota dysbiosis in adult offspring and increase the risk of developing irritable bowel syndrome (IBS). However, a causal link between prenatal stress-induced compromised sensitivity and dysbiosis has yet to be established. We hypothesized that prenatal stress in mice would predispose adult offspring to visceral hypersensitivity and intestinal homeostasis disruption. Material and Methods: Prenatal stress (PS) was induced by using restriction stress with bright light for 30 minutes, three times a day, in dams, between day 13 and 18 of gestation. Eight-week-old offspring, both male and female, underwent colorectal distention to assess their visceral hypersensitivity. Cxcl2, Tgfb, Ccl5, Reg3g, Muc2, Occln, Ttf3, Mmp7, Penk and Ifng expressions in the colon were monitored by qRT-PCR and intestinal bioactive lipids by mass spectrometry. The gut microbiota was assessed by MiSeq-based microbial taxonomic analysis to determine the faecal microbiota composition and by 16S RNA FISH staining to visualise its organization as a biofilm. Results: WAS induced a significant increase of visceral sensitivity to colorectal distension in male and female PS mice. PS alone or WAS in control mice did not significantly modify visceral sensitivity. While there were no changes in gene expression in the colons of both sexes, PS-male colons were characterised by a decrease of the 5-lipoxygenase pathway metabolites. PS alone induced a disruption of the biofilm in 8-week-old male and female adult offspring, marked by a low number of bacterial infiltrations into the sterile mucus layer. WAS worsened the disruption of the biofilm in male and female PS mice characterized by numerous bacterial infiltrations in the sterile mucus layer and bacteria in contact with the epithelial cells. However, WAS did not induce any changes in the biofilm organisation in control mice. While Akkermansia muciniphila was increased in both male and female stressed mice, the strains Desulfovibrio sp and Lactobacillus animalis were decreased in male and in female stressed mice, respectively. Conclusion: Prenatal stress is sufficient to induce gut microbiota dysbiosis and biofilm disruption. WAS worsened the gut microbiota alteration and induced mechanical visceral hypersensitivity without modification of mucus, tight junction proteins, anti-microbial peptides, chemokines and cytokines genes expression. This study shows that prenatal stress could represent an important priming event for the development of IBS in response to harmless stress for adult controls.
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Petitfils, C., & et al. (2020). Impact of prenatal stress on visceral sensitivity and intestinal homeostasis in adulthood. European Medical Journal Gastroenterology, 9(1), 48-50. (Original work published 2020)