Impact of prenatal stress on visceral hypersensitivity and gut microbiota in adulthood
(2021) European Society of NeuroMotility — Location: Online
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- Abstract
- Irritable bowel syndrome (IBS) is the most common intestinal disorder and is characterized by visceral pain and altered gut transit. The pathophysiology of IBS, which differs between patients, is mainly defined by an increased visceral sensitivity and gut microbiota dysbiosis. This syndrome leads to a reduced quality of life and is linked to anxiety and depression, making it a pathology of the microbiota-gut-brain axis. Prenatal stress (PS) has been identified as major risk factor for the onset of IBS symptoms and their severity. However, the causal link between prenatal stress and IBS has to be established. We hypothesized that PS induces a gut microbiota dysbiosis, and a change in bacterial metabolites, predisposing the adult offspring to visceral hypersensitivity and intestinal homeostasis disruption. In mice, PS was induced by restriction stress with bright light for 30 minutes, three times a day between day 13 and 18 of gestation. In the adult offspring of both sexes, we evaluated visceral sensitivity to colorectal distention, paracellular permeability by 4kDa FITC-dextran gavages followed by fluorescence measurements in the plasma 4h later, mRNA expression of inflammatory genes in the colon by qRT-PCR and intestinal bioactive lipid concentration by mass spectrometry. The gut microbiota was assessed by MiSeq-based microbial for taxonomic analyses and by 16S RNA FISH staining to visualise its organization. Bacterial lipopeptides production was identified and quantified by mass spectrometry. PS significantly increased visceral sensitivity to colorectal distensions. Paracellular permeability, gene expression and bioactive lipids concentration in the colon remained unaltered in PS offspring. The gut microbiota organization was modified with a bacterial infiltration in the sterile mucus layer and its composition altered in PS mice. The abundance of Lactobacillus animalis was decreased in PS mice and inversely correlated with visceral hypersensitivity. This bacterium produces two lipopeptides, C14asnGABAOH and C16PheGABAOH. Intracolonic administration of C14AsnGABAOH decreased PS-induced visceral hypersensitivity in mice. Prenatal stress is sufficient to induce microbiota dysbiosis and visceral hypersensitivity in adulthood. This could represent a priming event for the development of functional disorders such as IBS. Bacterial lipopeptides containing GABA could represent a new therapeutic strategy to alleviate visceral hypersensitivity in IBS patients.
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Petitfils, C., & et al. (2021). Impact of prenatal stress on visceral hypersensitivity and gut microbiota in adulthood. European Society of NeuroMotility, Online.