Professor United Arab Emirates University Al-Ain, Abu Dhabi, United Arab Emirates
Disclosure(s):
Maria J. Fernandez-Cabezudo, PhD: No financial relationships to disclose
Introduction/Rationale: Gastrointestinal homeostasis relies on the integrity of the intestinal barrier and the composition of the gut microbiota. The microbiota contributes to epithelial renewal, tight junction integrity, and the production of short-chain fatty acids (SCFAs), all of which are essential for barrier function. Disruption of these processes can lead to microbial translocation and inflammatory immune responses. We previously demonstrated that cholinergic stimulation enhances resistance to oral infection with Salmonella typhimurium.
Methods: BALB/c mice were treated with pyridostigmine (a reversible acetylcholinesterase inhibitor), paraoxon (an irreversible inhibitor), or saline as a control. Fecal samples were collected before and after treatment and analyzed by 16S rRNA gene sequencing. Intestinal tissues were processed for immunocytochemistry, intestinal epithelial cells were isolated for protein expression analysis, and gut permeability was assessed using a FITC-dextran (4 kDa) assay.
Results: Cholinergic activation remodeled the gut microbiota toward SCFA-producing bacterial populations, significantly reduced intestinal permeability, and upregulated the expression of specific tight-junction proteins.
Conclusion: These results indicate that cholinergic activation strengthens intestinal barrier function and modulates gut microbiota composition, providing mechanistic insight into its protective role against orally acquired microbial infections. Moreover, they highlight the importance of the neuroimmune communication in regulating intestinal homeostasis.
