Dataset Information

Gut microbiota-mediated Gene-Environment interaction in the TashT mouse model of Hirschsprung disease.

ABSTRACT: Based on the bilateral relationship between the gut microbiota and formation/function of the enteric nervous system (ENS), we sought to determine whether antibiotics-induced dysbiosis might impact the expressivity of genetically-induced ENS abnormalities. To address this, we took advantage of the TashT mouse model of Hirschsprung disease, in which colonic aganglionosis and hypoganglionosis are both much more severe in males. These defects result into two male-biased colon motility phenotypes: either megacolon that is lethal around weaning age or chronic constipation in adults, the latter being also associated with an increased proportion of nitrergic neurons in the distal ENS. Induction of dysbiosis using a cocktail of broad-spectrum antibiotics specifically impacted the colonic ENS of TashTTg/Tg mice in a stage-dependent manner. It further decreased the neuronal density at post-weaning age and differentially modulated the otherwise increased proportion of nitrergic neurons, which appeared normalized around weaning age and further increased at post-weaning age. These changes delayed the development of megacolon around weaning age but led to premature onset of severe constipation later on. Finally, local inhibition of nitric oxide signaling improved motility and prevented death by megacolon. We thus conclude that exposure to antibiotics can negatively influence the expressivity of a genetically-induced enteric neuropathy.

SUBMITTER: Toure AM

PROVIDER: S-EPMC6345786 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Migraine is a prevalent clinical disorder characterized by recurrent unilateral throbbing headache episodes accompanied by symptoms such as nausea, vomiting, photophobia, and phonophobia. Despite its common occurrence, the diagnosis, pathophysiology, and treatment of migraine remain controversial. Extensive research has implicated the gut microbiota in various central nervous system disorders, including anxiety disorders, depression, and Parkinson's disease. Some studies have also suggested that migraine may stem from disruptions to neurohormones and metabolism. This study aimed to investigate the disparities in gut microbiota and metabolites between migraine mice model and normal mice to shed light on the underlying mechanisms and potential therapeutic approaches. Distinct differences in gut microbial composition were observed between the migraine mouse model and normal mouse, indicating a potential correlation between these variations and the pathogenesis of migraine. This study provides evidence of differences in gut microbiota composition and metabolites between a migraine mouse model and normal mice, which showed that Akkermansiaceae constituted the most abundant taxon in the sham injection mouse group, while Lachnospiraceae constituted the most prevalent group in the migraine mouse model group. The associations between the abundances of Akkermansia muciniphila and Lachnospiraceae bacteria and metabolites suggested their potential roles in the pathogenesis of migraine. The altered abundance of Lachnospiraceae observed in migraine-afflicted mice and its correlations with changes in metabolites suggest that it may affect the host's health. Thus, probiotic therapy emerges as a possible treatment for migraine. Moreover, significant disparities in gut metabolites were observed between the migraine mouse model and normal mice. These alterations encompass multiple metabolic pathways, suggesting that metabolic disturbances may also contribute to the development of migraines.

Dataset Information

Gut microbiota-mediated Gene-Environment interaction in the TashT mouse model of Hirschsprung disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets