Self-reinoculation with fecal flora changes microbiota density and composition leading to an altered bile-acid profile in the mouse small intestine
Self-reinoculation with fecal flora changes microbiota density and composition leading to an altered bile-acid profile in the mouse small intestine
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DOI：
10.1186/s40168-020-0785-4
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发表时间：
2020-02-12
期刊：
影响因子：
15.5
通讯作者：
Ismagilov, Rustem F.
中科院分区：
文献类型：
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作者：
Bogatyrev, Said R.;Rolando, Justin C.;Ismagilov, Rustem F.
背景上胃肠道在人体生理中起着重要的作用，是酶消化和营养吸收、免疫采样和药物摄取的主要场所。小肠微生物群的改变与各种人类疾病有关，如非酒精性脂肪性肝炎和炎症性肠病。然而，由于与其采样相关的复杂性，人类小肠微生物区系的生理和功能角色仍然缺乏特征。啮齿动物模型被广泛应用于微生物组研究中，能够对胃肠道微生物区系及其对宿主生理和疾病表型的影响进行空间、时间、组成和功能的研究。经典的、以培养为基础的研究已经证明，粪便微生物的自我定位(通过共吞噬)影响小鼠近端胃肠道中微生物的组成和丰度。当研究小肠微生物区系时，这种普遍的自我重新定位行为可能是一个特别相关的研究因素。现代微生物组研究要么不考虑自身重新定位，要么假设采用诸如单独安置老鼠或在金属丝网地板上安置的方法来消除这种情况。这些假设还没有用现代工具进行严格的检验。在这里，我们使用定量16S rRNA基因扩增序列、定量微生物功能基因含量推断和胆汁酸代谢组学分析来评估自我重新定位对小鼠上胃肠道微生物负荷、组成和功能的影响。结果在共食小鼠中，持续自身暴露于粪便菌群对上胃肠道菌群有显著的定量和定性影响。微生物丰度和群落组成的这些差异与小肠胆汁酸池的变化有关，重要的是，无法从大肠或大便样本中推断出这些差异。总体而言，在非共食小鼠的小肠中观察到的模式(总微生物负荷减少，厌氧微生物区系低丰度，胆汁酸主要以结合形式存在)类似于通常在人类小肠中看到的模式。结论未来的研究需要在使用小鼠模型来评估胃肠道微生物定植和功能与异体转化和药代动力学的关系，或者在与小肠微生物群和小肠生物失调相关的生理状态和疾病的背景下，考虑自身重新定位。
Background The upper gastrointestinal tract plays a prominent role in human physiology as the primary site for enzymatic digestion and nutrient absorption, immune sampling, and drug uptake. Alterations to the small intestine microbiome have been implicated in various human diseases, such as non-alcoholic steatohepatitis and inflammatory bowel conditions. Yet, the physiological and functional roles of the small intestine microbiota in humans remain poorly characterized because of the complexities associated with its sampling. Rodent models are used extensively in microbiome research and enable the spatial, temporal, compositional, and functional interrogation of the gastrointestinal microbiota and its effects on the host physiology and disease phenotype. Classical, culture-based studies have documented that fecal microbial self-reinoculation (via coprophagy) affects the composition and abundance of microbes in the murine proximal gastrointestinal tract. This pervasive self-reinoculation behavior could be a particularly relevant study factor when investigating small intestine microbiota. Modern microbiome studies either do not take self-reinoculation into account, or assume that approaches such as single housing mice or housing on wire mesh floors eliminate it. These assumptions have not been rigorously tested with modern tools. Here, we used quantitative 16S rRNA gene amplicon sequencing, quantitative microbial functional gene content inference, and metabolomic analyses of bile acids to evaluate the effects of self-reinoculation on microbial loads, composition, and function in the murine upper gastrointestinal tract. Results In coprophagic mice, continuous self-exposure to the fecal flora had substantial quantitative and qualitative effects on the upper gastrointestinal microbiome. These differences in microbial abundance and community composition were associated with an altered profile of the small intestine bile acid pool, and, importantly, could not be inferred from analyzing large intestine or stool samples. Overall, the patterns observed in the small intestine of non-coprophagic mice (reduced total microbial load, low abundance of anaerobic microbiota, and bile acids predominantly in the conjugated form) resemble those typically seen in the human small intestine. Conclusions Future studies need to take self-reinoculation into account when using mouse models to evaluate gastrointestinal microbial colonization and function in relation to xenobiotic transformation and pharmacokinetics or in the context of physiological states and diseases linked to small intestine microbiome and to small intestine dysbiosis.