oral-gavage-neonatal-mouse-pups-functional-assessment-gut-barrier

Oral Gavage in Neonatal Mouse Pups and Functional Assessment of Gut Barrier Integrity Using Ussing Chambers

Growing evidence underscores the importance of the first 1,000 days of life in shaping the gut-microbiome axis. This early-life window is critical in the ...

Université Paris Cité

Inflammatory bowel diseases (IBD) etiology is multifactorial. Luminal microRNAs (miRNAs) have been suspected to play a role in the promotion of chronic inflammation, but the extent to which fecal miRNAs are interacting with the intestinal ecosystem in a way that contribute to diseases, including IBD, remains unknown. Here, fecal let-7b and miR-21 were found elevated, associated with inflammation, and correlating with multiple bacteria in IBD patients and IL-10 mice, model of spontaneous colitis. Using an  microbiota modeling system, we revealed that these two miRNAs can directly modify the composition and function of complex human microbiota, increasing their proinflammatory potential.  investigations revealed that luminal increase of let-7b drastically alters the intestinal microbiota and enhances macrophages' associated proinflammatory cytokines (TNF, IL-6, and IL-1β). Such proinflammatory effects are resilient and dependent on the bacterial presence. Moreover, we identified that besides impairing the intestinal barrier function, miR-21 increases myeloperoxidase and antimicrobial peptides secretion, causing intestinal dysbiosis. More importantly,  inhibition of let-7b and miR-21 with anti-miRNAs significantly improved the intestinal mucosal barrier function and promoted a healthier host-microbiota interaction in the intestinal lining, which altogether conferred protection against colitis. In summary, we provide evidence of the functional significance of fecal miRNAs in host-microbiota communication, highlighting their therapeutic potential in intestinal inflammation and dysbiosis-related conditions, such as IBD.

Fecal let-7b and miR-21 directly modulate the intestinal microbiota, driving chronic inflammation.

There is growing evidence that micro-RNAs (miRNAs) are key players in the regulation of gut health. In this issue of Cell Metabolism, Li et al. uncovered that the dietary fiber stachyose can modulate the luminal miRNA load of the intestinal tracts by binding to HSP90β, thereby altering the gut's microbial composition.

Article	Year
Fecal let-7b and miR-21 directly modulate the intestinal microbiota, driving chronic inflammation. Gut microbes\| PubMed ID: 39224018	2024
Challenges and hopes of gastrointestinal miRNA regulation: The example of stachyose. Cell metabolism\| PubMed ID: 39908984	2025

Louis Berthet

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