Dietary fermentable polyols fuel gut inflammation through M1 macrophage polarization and gut microbiota

Area of Science:

• Gastroenterology
• Immunology
• Microbiome Research

Background:

• Fermentable oligo-, di-, mono-saccharides, and polyols (FODMAPs) are linked to inflammatory bowel disease (IBD) symptom exacerbation.
• The precise mechanisms by which FODMAPs influence gut microbiota and inflammation remain unclear.

Purpose of the Study:

• To investigate the impact of sorbitol, a common polyol, on dextran sodium sulfate (DSS)-induced colitis in mice.
• To elucidate the role of sorbitol in modulating gut microbiota, macrophage polarization, and intestinal inflammation.

Main Methods:

• Induction of colitis in mice using DSS and administration of sorbitol.
• Analysis of inflammatory gene expression (e.g., Il1b) and macrophage polarization (M1) in the colon.
• Assessment of gut microbiota composition and metabolite profiling.
• Experiments using IL-1β-deficient mice and antibiotic treatment to evaluate protective effects.

Main Results:

• Sorbitol exacerbated DSS-induced colitis, increasing colonic expression of inflammatory genes like Il1b.
• Sorbitol treatment led to a higher proportion of M1 macrophages in the colon, worsening colitis.
• These effects were reversed in IL-1β-deficient mice and mitigated by antibiotic treatment.
• Sorbitol altered gut microbiota composition and metabolites, with Prevotellaceae and tryptamine positively correlated with M1 macrophages.
• Tryptamine stimulation was found to enhance M1 macrophage polarization.

Conclusions:

• Polyol consumption, specifically sorbitol, activates intestinal macrophages via gut microbiome alterations.
• This activation promotes intestinal inflammation and exacerbates colitis, highlighting a potential dietary trigger in IBD.
• Targeting the microbiome and its metabolites may offer therapeutic strategies for managing polyol-induced gut inflammation.