Yang Julianne C, Lagishetty Venu, Aja Ezinne, Arias-Jayo Nerea, Chang Candace, Hauer Megan, Katzka William, Zhou Yi, Sedighian Farzaneh, Koletic Carolina, Liang Fengting, Dong Tien S, Situ Jamilla, Troutman Ryan, Buri Heidi, Bhute Shrikant, Simpson Carra A, Braun Jonathan, Jacob Noam, Jacobs Jonathan P
UCLA Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, 200 Medical Plaza, Los Angeles, CA 90024-2484, United States.
Goodman-Luskin Microbiome Center at UCLA, Center for Health Sciences 42-210, 650 Charles E. Young Dr. S., Los Angeles, CA 90095-7378, United States.
ISME J. 2025 Jan 2;19(1). doi: 10.1093/ismejo/wrae250.
Fecal microbiota transplantation has been vital for establishing whether host phenotypes can be conferred through the microbiome. However, whether the existing microbial ecology along the mouse gastrointestinal tract can be recapitulated in germ-free mice colonized with stool remains unknown. We first identified microbes and their predicted functions specific to each of six intestinal regions in three cohorts of specific pathogen-free mice spanning two facilities. Of these region-specific microbes, the health-linked genus Akkermansia was consistently enriched in the lumen of the small intestine compared to the colon. Predictive functional modeling on 16S rRNA gene amplicon sequencing data recapitulated in shotgun sequencing data revealed increased microbial central metabolism, lipolytic fermentation, and cross-feeding in the small intestine, whereas butyrate synthesis was colon-enriched. Neuroactive compound metabolism also demonstrated regional specificity, including small intestine-enriched gamma-aminobutyric acid degradation and colon-enriched tryptophan degradation. Specifically, the jejunum and ileum stood out as sites with high predicted metabolic and neuromodulation activity. Differences between luminal and mucosal microbiomes within each site of the gastrointestinal tract were largely facility-specific, though there were a few consistent patterns in microbial metabolism in specific pathogen-free mice. These included luminal enrichment of central metabolism and cross-feeding within both the small intestine and the colon, and mucosal enrichment of butyrate synthesis within the colon. Across three cohorts of germ-free mice colonized with mice or human stool, compositional and functional region specificity were inconsistently reproduced. These results underscore the importance of investigating the spatial variation of the gut microbiome to better understand its impact on host physiology.
粪便微生物群移植对于确定宿主表型是否可通过微生物组赋予至关重要。然而，在无菌小鼠中植入粪便后，是否能重现沿小鼠胃肠道存在的现有微生物生态仍不清楚。我们首先在跨越两个设施的三个无特定病原体小鼠队列中，鉴定了六个肠道区域各自特有的微生物及其预测功能。在这些区域特异性微生物中，与结肠相比，与健康相关的阿克曼氏菌属在小肠肠腔中始终富集。对16S rRNA基因扩增子测序数据进行的预测功能建模在鸟枪法测序数据中得到重现，结果显示小肠中微生物的中心代谢、脂肪分解发酵和交叉喂养增加，而丁酸盐合成在结肠中富集。神经活性化合物代谢也表现出区域特异性，包括小肠中富集的γ-氨基丁酸降解和结肠中富集的色氨酸降解。具体而言，空肠和回肠作为预测代谢和神经调节活性较高的部位脱颖而出。胃肠道每个部位的肠腔和黏膜微生物群之间的差异在很大程度上是设施特异性的，尽管在无特定病原体小鼠的微生物代谢中存在一些一致的模式。这些模式包括小肠和结肠中中心代谢和交叉喂养在肠腔中的富集，以及结肠中丁酸盐合成在黏膜中的富集。在用小鼠或人类粪便定植的三个无菌小鼠队列中，组成和功能区域特异性的重现并不一致。这些结果强调了研究肠道微生物群空间变异以更好理解其对宿主生理学影响的重要性。
