3 Key Takeaways
Plain English Summary- 01Core Finding
Whether fiber promotes epithelial repair through microbiota-dependent mechanisms remains unclear.
- 02Study Evidence
Tested in a animal models + randomized controlled trial at the randomized clinical trial stage.
- 03Practical Meaning
Controlled trial findings show causal benefit under protocol rules; real-world effectiveness can vary across patients.
What This Means for You
Alginate engages a fiber-microbiota-taurine-epithelial signaling pathway that promotes recovery in preclinical models. The clinical trial did not meet its primary endpoint; however, the biological changes warrant further investigation of alginate as a microbiota-targeted intervention. Japan Registry of Clinical Trials, Number: jRCTs031200103 and UMIM Clinical Trials Registry, Number: UMIN000041968.
The Discovery
Dietary fibers modulate host-microbiota interactions. Whether fiber promotes epithelial repair through microbiota-dependent mechanisms remains unclear. How alginate influences colitis recovery and whether the pathway is relevant to ulcerative colitis was determined. Fibers in dextran sodium sulfate-induced murine colitis were screened and assessed for survival, inflammation, barrier function, and epithelial regeneration. Microbiota dependence was evaluated using antibiotics and bacterial supplementation. Metabolites were profiled using capillary electrophoresis-time-of-flight mass spectrometry, and epithelial programs were analyzed using RNA sequencing and colonic organoid injury assays. Slc6a6 -/- and Cyp2c55 -/- mice were used to determine mechanistic requirements. Translational relevance was examined in a randomized, placebo (inactive comparison treatment)-controlled trial of patients with ulcerative colitis receiving antibiotic-primed fecal microbiota transplantation followed by alginate or placebo. Clinical outcomes, histology, fecal taurine, and colonic CYP2C18 expression were assessed. Alginate improved dextran sodium sulfate colitis recovery, reducing inflammation, restoring barrier integrity, and enhancing crypt proliferation. Alginate enriched taurine-releasing bacteria, including Bacteroides acidifaciens and Ligilactobacillus murinus, and increased intestinal taurine; antibiotic disruption abrogated these effects. Taurine was required for benefit, as alginate failed in Slc6a6 -/- mice. Alginate and taurine induced epithelial Cyp2c55, and protection was lost in Cyp2c55 -/- mice and organoids. In the clinical trial, the primary endpoint was not met. However, alginate supplementation was associated with biological changes, including fecal taurine levels and colonic CYP2C18 expression, consistent with preclinical mechanisms.
How It Works, Simply
This gastroenterology research focuses on gut bacteria · Inflammation · Signalling pathway. Researchers evaluated it using an animal models + Randomized controlled trial at the randomized clinical trial stage of medical research.
3 Key Takeaways
Clinical Takeaways- 01Core Finding
Whether fiber promotes epithelial repair through microbiota-dependent mechanisms remains unclear.
- 02Study Evidence
Tested in a animal models + randomized controlled trial at the randomized clinical trial stage.
- 03Practical Meaning
Controlled trial findings show causal benefit under protocol rules; real-world effectiveness can vary across patients.
Biological Mechanism & Study Design
Study Design & Cohort
Animal models + Randomized controlled trial
Animal models + Randomized controlled trial · Randomized Clinical Trial
Biological Pathway & Modality
Gut bacteria · Inflammation · Signalling pathway
Intervention: Microbiota-Taurine Pathway Links Dietary Fiber to Mucosal Healing
Experimental Findings & Endpoints
Dietary fibers modulate host-microbiota interactions.
Whether fiber promotes epithelial repair through microbiota-dependent mechanisms remains unclear. How alginate influences colitis recovery and whether the pathway is relevant to ulcerative colitis was determined.
Fibers in dextran sodium sulfate-induced murine colitis were screened and assessed for survival, inflammation, barrier function, and epithelial regeneration. Microbiota dependence was evaluated using antibiotics and bacterial supplementation.
Metabolites were profiled using capillary electrophoresis-time-of-flight mass spectrometry, and epithelial programs were analyzed using RNA sequencing and colonic organoid injury assays. Slc6a6 -/- and Cyp2c55 -/- mice were used to determine mechanistic requirements.
Translational relevance was examined in a randomized, placebo-controlled trial of patients with ulcerative colitis receiving antibiotic-primed fecal microbiota transplantation followed by alginate or placebo. Clinical outcomes, histology, fecal taurine, and colonic CYP2C18 expression were assessed.
Alginate improved dextran sodium sulfate colitis recovery, reducing inflammation, restoring barrier integrity, and enhancing crypt proliferation. Alginate enriched taurine-releasing bacteria, including Bacteroides acidifaciens and Ligilactobacillus murinus, and increased intestinal taurine; antibiotic disruption abrogated these effects.
Taurine was required for benefit, as alginate failed in Slc6a6 -/- mice. Alginate and taurine induced epithelial Cyp2c55, and protection was lost in Cyp2c55 -/- mice and organoids.
In the clinical trial, the primary endpoint was not met. However, alginate supplementation was associated with biological changes, including fecal taurine levels and colonic CYP2C18 expression, consistent with preclinical mechanisms.
Clinical Translation & Practice Context
Alginate engages a fiber-microbiota-taurine-epithelial signaling pathway that promotes recovery in preclinical models.
The clinical trial did not meet its primary endpoint; however, the biological changes warrant further investigation of alginate as a microbiota-targeted intervention. Japan Registry of Clinical Trials, Number: jRCTs031200103 and UMIM Clinical Trials Registry, Number: UMIN000041968.
The Bottom Line · Clinical Pearl
“Alginate engages a fiber-microbiota-taurine-epithelial signaling pathway that promotes recovery in preclinical models.”
Published in Gastroenterology · Current Stage: Randomized Clinical Trial
