Letter to the Editor: Deciphering macrophage heterogeneity and optimizing probiotics via spatial multi-omics.

We read the paper published in World Journal of Gastroenterology by Yang et al on how Bifidobacterium species alleviate colitis by modulating deoxycholic acid (DCA) levels and macrophage polarization, which provides important insights into the microbiome-immune axis. However, the classic M1/M2 polarization model oversimplifies the plasticity of macrophages and fails to account for the spatial heterogeneity of the intestinal microenvironment. Therefore, we propose integrating spatial transcriptomics and spatial metabolomics to resolve the intricate correlations between DCA distribution and specific macrophage subsets. Building upon this, we further discuss the transition from broad-spectrum probiotic supplementation to mechanism-driven precision probiotic strategies, emphasizing the future need to develop engineered strains capable of spatial awareness and metabolic pathway remodeling. This spatial multiomics-guided precision intervention framework holds promise for advancing colitis treatment toward approaches with greater mechanistic depth.