Chen Albert Sheng-Yin, Kim Hanseul, Nzabarushimana Etienne, Shen Jiaxian, Williams Katherine, Gurung Jenny, McGoldrick Jessica, Burke Kristin E, Yarze Joseph C, Nguyen Long H, Staller Kyle, Chung Daniel C, Xavier Ramnik J, Khalili Hamed
Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Nat Commun. 2025 May 23;16(1):4644. doi: 10.1038/s41467-025-59566-9.
Microscopic colitis (MC) is a chronic inflammatory disease of the large intestine that primarily affects older adults and presents with chronic diarrhea. The etiology is unknown and there are currently no FDA approved medications or biomarkers for treatment or monitoring of the disease. Emerging evidence have implicated the gut microbiome and metabolome disturbances in MC pathogenesis. We conduct a comprehensive analysis of gut microbial and metabolic changes in a cohort of 683 participants, including 131 patients with active MC, 159 with chronic diarrhea, and 393 age- and sex-matched controls without diarrhea. Stool microbiome and metabolome are profiled using whole-genome shotgun metagenomic sequencing and ultra-high performance liquid chromatography-mass spectrometry, respectively. Compared to controls, eight microbial species including pro-inflammatory oral-typical Veillonella dispar and Haemophilus parainfluenzae, and 11 species, including anti-inflammatory Blautia glucerasea and Bacteroides stercoris are enriched and depleted in MC, respectively. Pro-inflammatory metabolites, including lactosylceramides, ceramides, lysophospholipids, and lysoplasmalogens, are enriched in active MC. Multi-omics analyses reveal robust associations between microbial species, metabolic pathways, and metabolites, suggesting concordant disruptions in MC. Here, we show distinct shifts in gut microbiome and metabolome in MC that can inform the development of non-invasive biomarkers and novel therapeutics.
显微镜下结肠炎（MC）是一种主要影响老年人的大肠慢性炎症性疾病，表现为慢性腹泻。其病因不明，目前尚无美国食品药品监督管理局（FDA）批准的用于治疗或监测该疾病的药物或生物标志物。新出现的证据表明肠道微生物群和代谢组紊乱与MC的发病机制有关。我们对683名参与者进行了肠道微生物和代谢变化的综合分析，其中包括131名活动性MC患者、159名慢性腹泻患者以及393名年龄和性别匹配的无腹泻对照者。分别使用全基因组鸟枪法宏基因组测序和超高效液相色谱-质谱联用技术对粪便微生物群和代谢组进行分析。与对照组相比，包括促炎性口腔典型的差异韦荣球菌和副流感嗜血杆菌在内的8种微生物在MC中富集，而包括抗炎性的格氏布劳特氏菌和类杆菌在内的11种微生物在MC中减少。促炎性代谢产物，包括乳糖神经酰胺、神经酰胺、溶血磷脂和溶血缩醛磷脂，在活动性MC中富集。多组学分析揭示了微生物种类、代谢途径和代谢产物之间的紧密关联，表明MC中存在协同破坏。在此，我们展示了MC中肠道微生物群和代谢组的明显变化，这可为非侵入性生物标志物的开发和新型治疗方法提供依据。
