Altered microbial biogeography in an innate model of colitis.
Altered microbial biogeography in an innate model of colitis.
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DOI：
10.1080/19490976.2022.2123677
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发表时间：
2022-01
期刊：
影响因子：
12.2
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中科院分区：
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在人类炎症性肠病（IBD）和IBD小鼠模型中观察到了结肠微生物的空间组织或肠道微生物学的变化。我们已经开发了一种IBD小鼠模型，该模型在缺乏适应性免疫的情况下自发且一致地发生。在肠上皮细胞中表达肿瘤坏死因子诱导蛋白3（TNFAIP 3）的小鼠（villin-TNFAIP 3）与RAG 1-/-缺陷型小鼠（RAG 1-/-）杂交后会发生结肠炎。villin-TNFAIP 3 × RAG 1 −/−（TRAG）小鼠的结肠炎可通过抗生素预防，表明微生物在这种先天性结肠炎中的作用。因此，我们探讨了TRAG结肠炎的微生物和抗生素的反应。激光捕获显微切割和16 S rRNA测序显示，随着TRAG而不是RAG 1 −/−小鼠的内粘液层被微生物浸润，结肠横轴上的微生物种群发生了变化，其中包括γ-变形菌和放线菌的丰度增加。沿着纵轴，抗生素预防结肠炎的疗效差异是明显的。新霉素对预防盲肠炎症最有效，而氨苄青霉素对近端和远端结肠最有效。RAG 1 −/−小鼠（而非TRAG）表现出细菌丰度的结构化模式，厚壁菌门和变形菌门减少，但拟杆菌门沿着肠道近端至远端轴增加。TRAG小鼠表现出增加的相对丰度的潜在的致病菌，包括动物双歧杆菌沿着肠道的纵轴，而其他人，如肝螺杆菌增加，仅在盲肠。包括罗斯拜瑞氏菌在内的潜在有益微生物在TRAG结肠近端区域减少，而假长双歧杆菌在TRAG远端结肠减少。因此，先天免疫系统沿着肠道的横轴和纵轴维持结构化的、空间上有组织的肠道微生物组，并且这种肠道造影的破坏是先天免疫性结肠炎的特征。
Changes in the spatial organization, or biogeography, of colonic microbes have been observed in human inflammatory bowel disease (IBD) and mouse models of IBD. We have developed a mouse model of IBD that occurs spontaneously and consistently in the absence of adaptive immunity. Mice expressing tumor necrosis factor-induced protein 3 (TNFAIP3) in intestinal epithelial cells (villin-TNFAIP3) develop colitis when interbred with Recombination Activating 1-deficient mice (RAG1−/−). The colitis in villin-TNFAIP3 × RAG1−/− (TRAG) mice is prevented by antibiotics, indicating a role for microbes in this innate colitis. We therefore explored the biogeography of microbes and responses to antibiotics in TRAG colitis. Laser capture microdissection and 16S rRNA sequencing revealed altered microbial populations across the transverse axis of the colon as the inner mucus layer of TRAG, but not RAG1−/−, mice was infiltrated by microbes, which included increased abundance of the classes Gammaproteobacteria and Actinobacteria. Along the longitudinal axis differences in the efficacy of antibiotics to prevent colitis were evident. Neomycin was most effective for prevention of inflammation in the cecum, while ampicillin was most effective in the proximal and distal colon. RAG1−/−, but not TRAG, mice exhibited a structured pattern of bacterial abundance with decreased Firmicutes and Proteobacteria but increased Bacteroidetes along the proximal to distal axis of the gut. TRAG mice exhibited increased relative abundance of potential pathobionts including Bifidobacterium animalis along the longitudinal axis of the gut whereas others, like Helicobacter hepaticus were increased only in the cecum. Potential beneficial organisms including Roseburia were decreased in the proximal regions of the TRAG colon, while Bifidobacterium pseudolongulum was decreased in the TRAG distal colon. Thus, the innate immune system maintains a structured, spatially organized, gut microbiome along the transverse and longitudinal axis of the gut, and disruption of this biogeography is a feature of innate immune colitis.
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DOI：
10.1038/nri.2016.88
发表时间：
2016-10
期刊：
Nature reviews. Immunology
影响因子：
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作者：
Johansson ME;Hansson GC
通讯作者：
Hansson GC
影响因子：
8
作者：
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通讯作者：
Chassaing B
DOI：
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发表时间：
2016-01
期刊：
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影响因子：
--
作者：
Donaldson GP;Lee SM;Mazmanian SK
通讯作者：
Mazmanian SK
影响因子：
48
作者：
Callahan BJ;McMurdie PJ;Rosen MJ;Han AW;Johnson AJ;Holmes SP
通讯作者：
Holmes SP
DOI：
10.1007/978-1-61779-513-8_13
发表时间：
2012-01-01
期刊：
MUCINS: METHODS AND PROTOCOLS
影响因子：
--
作者：
Johansson, Malin E. V.;Hansson, Gunnar C.
通讯作者：
Hansson, Gunnar C.