2025-02-14
MicroRNAs & Microbiota: An Inflammatory Duo?
Gastroenterology and Hepatology
#MicroRNA #Microbiota #IBD #Immunotherapy #Innovation
Chronic inflammatory bowel diseases (IBD), such as Crohn's disease and ulcerative colitis, are characterized by persistent inflammation of the digestive tract, associated with an imbalance in the gut microbiota. This dysbiosis, combined with an exacerbated immune response, contributes to the chronicity of symptoms and complicates patient management.
Recent research suggests that fecal microRNAs (miRNAs), particularly let-7b and miR-21, may play a central role in regulating interactions between the host and its gut microbiota. These small regulatory molecules, known for their involvement in inflammatory and immune processes, are thought to directly influence the composition and activity of the gut microbiota. However, the precise mechanisms by which let-7b and miR-21 modulate microbial balance and intestinal inflammation remain largely unknown.
This study explores how fecal microRNAs let-7b and miR-21 modulate host-microbiota interactions, thereby influencing inflammation in IBD.
The analyses revealed a significant increase in let-7b and miR-21 levels in the stools of IBD patients. In vitro, these microRNAs altered microbiota composition by promoting the proliferation of pro-inflammatory bacteria while reducing beneficial populations. In vivo, let-7b administration induced long-term alterations in gut microbiota and low-grade chronic inflammation, whereas miR-21 compromised intestinal permeability, leading to acute inflammation. Finally, the inhibition of these microRNAs reduced intestinal inflammation and improved barrier function, suggesting a potential therapeutic approach for IBD by directly targeting these molecular regulators.
This study aimed to explore the role of fecal microRNAs let-7b and miR-21 in modulating intestinal inflammation and microbiota composition. By combining in vitro and in vivo analyses, researchers examined how these microRNAs influence host-microbiota interactions and assessed the impact of their inhibition on inflammatory responses.
The results show that let-7b and miR-21 exert distinct yet complementary effects on intestinal inflammation. Let-7b modifies microbiota composition and enhances its pro-inflammatory potential, while miR-21 disrupts the intestinal barrier, promoting more acute inflammation. Inhibiting these microRNAs significantly reduces inflammation and improves intestinal integrity, suggesting a new therapeutic approach for IBD.
This study has certain limitations, including a small patient cohort and experimental models, requiring validation in larger populations. Moreover, interactions between microRNAs, the microbiota, and intestinal immunity remain unclear, necessitating further research before clinical applications. Future studies should refine microRNA inhibition strategies and test their effectiveness in clinical trials. Combined with microbiota-modulating therapies, these approaches could lead to more targeted and personalized treatments for IBD patients.
Chronic inflammatory bowel diseases (IBD), such as Crohn's disease and ulcerative colitis, are characterized by persistent inflammation of the digestive tract, associated with an imbalance in the gut microbiota. This dysbiosis, combined with an exacerbated immune response, contributes to the chronicity of symptoms and complicates patient management.
Recent research suggests that fecal microRNAs (miRNAs), particularly let-7b and miR-21, may play a central role in regulating interactions between the host and its gut microbiota. These small regulatory molecules, known for their involvement in inflammatory and immune processes, are thought to directly influence the composition and activity of the gut microbiota. However, the precise mechanisms by which let-7b and miR-21 modulate microbial balance and intestinal inflammation remain largely unknown.
This study explores how fecal microRNAs let-7b and miR-21 modulate host-microbiota interactions, thereby influencing inflammation in IBD.
Read next: Post-Traumatic Stress Disorder, Gut Microbiota, and Inflammation: A Complex Interconnection
MicroRNAs: The Master Regulators of Intestinal Inflammation?
To investigate the influence of microRNAs on gut microbiota and inflammation in IBD, this study combined in vitro and in vivo analyses. Fecal samples from patients with IBD were analyzed to identify microRNAs involved in intestinal inflammation. In parallel, murine models of chronic colitis (IL-10⁻/⁻ mice) were studied. The direct influence of let-7b and miR-21 on the composition and activity of human microbiota was explored using a bacterial culture model (MiniBioReactor Array). In vivo experiments were conducted on mice, administering these microRNAs to assess their effects on intestinal barrier integrity and immune response. Finally, the inhibition of let-7b and miR-21 using anti-miRNAs was tested to evaluate its therapeutic potential in modulating intestinal inflammation.The analyses revealed a significant increase in let-7b and miR-21 levels in the stools of IBD patients. In vitro, these microRNAs altered microbiota composition by promoting the proliferation of pro-inflammatory bacteria while reducing beneficial populations. In vivo, let-7b administration induced long-term alterations in gut microbiota and low-grade chronic inflammation, whereas miR-21 compromised intestinal permeability, leading to acute inflammation. Finally, the inhibition of these microRNAs reduced intestinal inflammation and improved barrier function, suggesting a potential therapeutic approach for IBD by directly targeting these molecular regulators.
Towards a New Therapeutic Target for IBD?
IBD, including Crohn’s disease and ulcerative colitis, is characterized by persistent inflammation and gut microbiota imbalance. Despite therapeutic advances, managing these diseases remains complex due to variability in treatment responses and the lack of curative therapies. Identifying new mechanisms involved in intestinal inflammation is essential for developing targeted and sustainable therapeutic approaches.This study aimed to explore the role of fecal microRNAs let-7b and miR-21 in modulating intestinal inflammation and microbiota composition. By combining in vitro and in vivo analyses, researchers examined how these microRNAs influence host-microbiota interactions and assessed the impact of their inhibition on inflammatory responses.
The results show that let-7b and miR-21 exert distinct yet complementary effects on intestinal inflammation. Let-7b modifies microbiota composition and enhances its pro-inflammatory potential, while miR-21 disrupts the intestinal barrier, promoting more acute inflammation. Inhibiting these microRNAs significantly reduces inflammation and improves intestinal integrity, suggesting a new therapeutic approach for IBD.
This study has certain limitations, including a small patient cohort and experimental models, requiring validation in larger populations. Moreover, interactions between microRNAs, the microbiota, and intestinal immunity remain unclear, necessitating further research before clinical applications. Future studies should refine microRNA inhibition strategies and test their effectiveness in clinical trials. Combined with microbiota-modulating therapies, these approaches could lead to more targeted and personalized treatments for IBD patients.
Read next: Efficacy and safety of etrolizumab in the treatment of inflammatory bowel disease: a meta-analysis
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