Implications of Bifidobacterium and deoxycholic acid in high-fat diet-associated colitis: Harnessing macrophage plasticity to modulate disease progression

Abstract

This editorial comments on the study by Yang et al published in the recent issue of the World Journal of Gastroenterology, which investigates the mechanistic link between a high-fat diet (HFD), the gut microbial metabolite deoxycholic acid (DCA), macrophage polarization, and colonic inflammation, while evaluating the protective role of Bifidobacterium. Using a mouse model, the authors demonstrate that HFD elevates fecal DCA levels, promotes infiltration and pro-inflammatory M1 polarization of colonic macrophages, and increases expression of inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1beta). Both the antibiotic vancomycin and Bifidobacterium supplementation attenuated these effects, reducing DCA levels, inflammation, and shifting macrophages toward an anti-inflammatory M2 phenotype. A key strength of the work is its multifaceted experimental design, which combines HFD with targeted interventions (vancomycin, DCA, and probiotic) to disentangle causal relationships within the gut-liver-immune axis. The findings suggest that Bifidobacterium may alleviate HFD-induced colitis partly by reducing the pool of DCA available to drive macrophage-mediated inflammation. However, a notable weakness is the incomplete restoration of gut microbial diversity by Bifidobacterium following vancomycin-induced dysbiosis, highlighting the context-dependent limitations of probiotic therapy. Furthermore, the precise and direct molecular mechanism by which Bifidobacterium lowers DCA remains unverified directly. Building on this foundation, we provide a detailed overview of macrophage polarization fundamentals and its critical, context-dependent role in metabolic disorders and colitis and inflammatory bowel diseases. We conclude that targeting macrophage plasticity represents a promising therapeutic strategy for these conditions, emphasizing the need for further mechanistic research to develop precise interventions.

Keywords: Bifidobacterium; Deoxycholic acid; High-fat diet; Macrophage plasticity; Disease progression

Core Tip: This editorial comments on the manuscript recently published by Yang et al. Their study demonstrates that high-fat diets elevate fecal deoxycholic acid (DCA) levels, which subsequently drive M1 macrophage polarization and exacerbate colonic inflammation. Crucially, they show that Bifidobacterium supplementation can mitigate these pathological effects by reducing DCA concentrations and shifting macrophage polarization toward the anti-inflammatory M2 phenotype. Building upon these findings, we further reviewed the sophisticated mechanisms governing macrophage polarization and its dual role in metabolic disorders and inflammatory bowel diseases. We offer a deeper exploration of the mechanistic intricacies and contextual limitations inherent in this interaction. While expounding on the experimental merits of the article, we also identify existing knowledge gaps that warrant further investigation. Ultimately, we emphasize that harnessing the gut microbiome and its metabolites represents a critical next step in developing therapeutic strategies for intestinal inflammatory diseases.