The enteric nervous system promotes intestinal health by constraining microbiota composition.
The enteric nervous system promotes intestinal health by constraining microbiota composition.
复制标题
肠神经系统通过限制微生物群组成来促进肠道健康。
DOI：
10.1371/journal.pbio.2000689
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发表时间：
2017-02
期刊：
影响因子：
9.8
通讯作者：
Guillemin K
中科院分区：
文献类型：
--
作者：
Rolig AS;Mittge EK;Ganz J;Troll JV;Melancon E;Wiles TJ;Alligood K;Stephens WZ;Eisen JS;Guillemin K
维持平衡的肠道微生物群落对于维持肠道健康和预防慢性炎症至关重要。肠道是一个高度动态的环境，受到周期性蠕动活动的影响。我们假设这种动态环境是平衡微生物群落的先决条件，而肠神经系统（ENS）是肠道内生理过程的主要调节者，深刻影响肠道微生物群的组成。我们发现，由于先天性巨结肠病基因 sox10 突变而缺乏 ENS，斑马鱼会产生可在宿主之间传播的微生物群依赖性炎症。对一系列炎症表型的微生物群落进行分析表明，炎症水平的升高与促炎细菌谱系过多和抗炎细菌谱系缺乏有关。此外，施用代表性抗炎菌株或恢复 ENS 功能可以纠正病理学。因此，我们证明 ENS 调节肠道微生物群成员以维持肠道健康。肠道健康取决于在高度动态的肠道环境中维持平衡的微生物群落。每隔几分钟，这个环境就会受到肠神经系统 (ENS) 调节过程中肌肉收缩和放松的蠕动波的震动。我们假设正常、健康的肠道微生物群落适应了这种动态环境，并且如果没有功能性的 ENS，它们的组成就会受到干扰。为了验证这个想法，我们使用了一种模型生物——斑马鱼，它的基因突变阻止了 ENS 的形成。我们发现一些没有 ENS 的突变个体会出现高水平的炎症，而其他突变个体则具有正常的肠道。我们对发炎和健康突变体的肠道细菌进行了分析，发现发炎个体的肠道具有过多的促炎细菌谱系，缺乏抗炎细菌谱系，并且能够将炎症传递给具有正常功能的ENS的个体。相反，我们能够通过施用代表性抗炎菌株或恢复 ENS 功能来预防 ENS 突变体的炎症。从这些实验中，我们得出结论，ENS 调节肠道微生物群落成员以维持肠道健康。
Sustaining a balanced intestinal microbial community is critical for maintaining intestinal health and preventing chronic inflammation. The gut is a highly dynamic environment, subject to periodic waves of peristaltic activity. We hypothesized that this dynamic environment is a prerequisite for a balanced microbial community and that the enteric nervous system (ENS), a chief regulator of physiological processes within the gut, profoundly influences gut microbiota composition. We found that zebrafish lacking an ENS due to a mutation in the Hirschsprung disease gene, sox10, develop microbiota-dependent inflammation that is transmissible between hosts. Profiling microbial communities across a spectrum of inflammatory phenotypes revealed that increased levels of inflammation were linked to an overabundance of pro-inflammatory bacterial lineages and a lack of anti-inflammatory bacterial lineages. Moreover, either administering a representative anti-inflammatory strain or restoring ENS function corrected the pathology. Thus, we demonstrate that the ENS modulates gut microbiota community membership to maintain intestinal health. Intestinal health depends on maintaining a balanced microbial community within the highly dynamic environment of the intestine. Every few minutes, this environment is rocked by peristaltic waves of muscular contraction and relaxation through a process regulated by the enteric nervous system (ENS). We hypothesized that normal, healthy intestinal microbial communities are adapted to this dynamic environment, and that their composition would become perturbed without a functional ENS. To test this idea, we used a model organism, the zebrafish, with a genetic mutation that prevents formation of the ENS. We found that some mutant individuals without an ENS develop high levels of inflammation, whereas other mutants have normal intestines. We profiled the intestinal bacteria of inflamed and healthy mutants and found that the intestines of inflamed individuals have an overabundance of pro-inflammatory bacterial lineages, lack anti-inflammatory bacterial lineages, and are able to transmit inflammation to individuals with a normally functioning ENS. Conversely, we were able to prevent inflammation in the ENS mutants by either administering a representative anti-inflammatory bacterial strain or restoring ENS function. From these experiments, we conclude that the ENS modulates intestinal microbiota community membership to maintain intestinal health.