Meng D, Zhang BB, Zhao JN. Letter to the Editor: Deciphering macrophage heterogeneity and optimizing probiotics via spatial multi-omics. World J Gastrointest Pharmacol Ther 2026; 17(2): 118195 [DOI: 10.4292/wjgpt.v17.i2.118195]
Corresponding Author of This Article
Jia-Nan Zhao, PhD, Department of Cardiovascular Sciences, Temple University, No. 3440 North Carlisle Street, Philadelphia, PA 19140, United States. tuv36393@temple.edu
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Biology
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Correspondence
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World Journal of Gastrointestinal Pharmacology and Therapeutics
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2150-5349
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Meng D, Zhang BB, Zhao JN. Letter to the Editor: Deciphering macrophage heterogeneity and optimizing probiotics via spatial multi-omics. World J Gastrointest Pharmacol Ther 2026; 17(2): 118195 [DOI: 10.4292/wjgpt.v17.i2.118195]
World J Gastrointest Pharmacol Ther. Jun 5, 2026; 17(2): 118195 Published online Jun 5, 2026. doi: 10.4292/wjgpt.v17.i2.118195
Letter to the Editor: Deciphering macrophage heterogeneity and optimizing probiotics via spatial multi-omics
Di Meng, Bin-Bin Zhang, Jia-Nan Zhao
Di Meng, School of Public Health and Nursing, Hangzhou Normal University, Hangzhou 311121, Zhejiang Province, China
Bin-Bin Zhang, School of Clinical Medicine, Hangzhou Normal University, Hangzhou 311121, Zhejiang Province, China
Jia-Nan Zhao, Department of Cardiovascular Sciences, Temple University, Philadelphia, PA 19140, United States
Co-corresponding authors: Bin-Bin Zhang and Jia-Nan Zhao.
Author contributions: Meng D performed the literature investigation and synthesis, developed the central scientific arguments (macrophage spatial heterogeneity and spatial multi-omics–guided precision probiotics), and drafted the original manuscript. Zhang BB and Zhao JN jointly conceptualized the overall framework of the Letter to the Editor, defined the key scientific positioning and scope, and provided methodological and mechanistic guidance to ensure the proposed hypotheses were coherent, testable, and aligned with current spatial multi-omics and microbiome–immune research. Zhang BB and Zhao JN carried out substantive critical revision throughout, strengthening the logical structure and academic rigor, refining the key messages, and improving clarity, accuracy, and coherence across all sections. Zhang BB and Zhao JN served as co-corresponding authors because they shared primary senior responsibility for the work from conception to submission, jointly supervised and directed the manuscript’s scientific trajectory, and took final decision-making authority on content and framing. They also provided complementary expertise and cross-disciplinary oversight that was essential to integrate the microbiome–bile acid–macrophage axis with spatially resolved multi-omics reasoning and translational interpretation, and they jointly assumed accountability for the integrity of the work, including verification of key statements, consistency of interpretation, and approval of the final version. In addition, they coordinated submission-related tasks and communication with the journal, responded to editorial/reviewer queries, and ensured that all revisions were implemented accurately and on time. All authors read and approved the final manuscript.
Supported by National Natural Science Foundation of China, No. 82204827.
Conflict-of-interest statement: All authors declare that they have no conflict of interest to disclose.
Corresponding author: Jia-Nan Zhao, PhD, Department of Cardiovascular Sciences, Temple University, No. 3440 North Carlisle Street, Philadelphia, PA 19140, United States. tuv36393@temple.edu
Received: December 28, 2025 Revised: February 1, 2026 Accepted: February 26, 2026 Published online: June 5, 2026 Processing time: 152 Days and 6.6 Hours
Abstract
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.
Core Tip: In colitis, macrophage phenotypes extend beyond the simple M1/M2 dichotomy, and their functions are shaped by the spatial microenvironment wherein they reside. Although existing spatial omics studies have delineated the cellular distributions within inflammatory regions, whether the spatial enrichment of key metabolites (such as deoxycholic acid) across distinct mucosal layers drives divergent macrophage transcriptional programs remains unclear. Spatial multiomics offers the potential to resolve the issue of metabolite-immune spatial specificity, thereby providing a reference for developing precise probiotic therapies with well-defined targets of action.
