Chemical and pathogen-induced inflammation disrupt the murine intestinal microbiome.
Chemical and pathogen-induced inflammation disrupt the murine intestinal microbiome.
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DOI：
10.1186/s40168-017-0264-8
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发表时间：
2017-04-27
期刊：
影响因子：
15.5
通讯作者：
Wrighton KC
中科院分区：
文献类型：
--
作者：
Borton MA;Sabag-Daigle A;Wu J;Solden LM;O'Banion BS;Daly RA;Wolfe RA;Gonzalez JF;Wysocki VH;Ahmer BMM;Wrighton KC
沙门氏菌是影响人类和农业的最重要的食源性病原体之一。虽然有充分的证据表明沙门氏菌感染会引发宿主炎症，但对肠道环境的影响在很大程度上是未知的。采用CBA/J小鼠模型评价肠道对沙门氏菌诱导炎症的反应。同时，我们评估了右旋糖酐硫酸钠（DSS）和非炎症对照组的化学诱导炎症。我们通过对粪便和盲肠样本的16S核糖体核糖核酸（rRNA）基因进行测序，分析了肠道微生物的多样性。这些数据与炎症标志物脂钙素-2和短链脂肪酸浓度相关。我们证明了炎症，化学或生物诱导，在16天的时间内重建了肠道的化学和微生物环境。我们观察到，沙门菌治疗组的10只小鼠具有可变的沙门菌相对丰度，其中3只高应答小鼠在后期时间点以b> 46%的沙门菌为主，其余7只小鼠为低应答小鼠。这些低反应和高反应的沙门氏菌组，以及化学DSS治疗，建立了炎症梯度，化学和低水平的沙门氏菌的脂钙素-2浓度比高反应的沙门氏菌小鼠低至少3倍。总短链脂肪酸和个体丁酸盐浓度均与炎症水平负相关。微生物群落也沿着这种炎症梯度结构。低水平的炎症，无论化学或生物诱导，在Verrucomicrobiaceae中的Akkermansia spp和Bacteroidetes家族S24-7成员中都很丰富。与对照组或低炎症组相比，高水平的沙门氏菌显著降低了整体微生物多样性，特别是由拟杆菌门和厚壁菌门中Alistipes和Lachnospiraceae的减少所驱动。相反，肠杆菌科和乳酸杆菌的成员与沙门氏菌引起的高水平炎症呈正相关。我们的研究结果表明，肠道病原菌感染和肠道炎症是调节肠道内稳态的相关因素。这些发现可能为预防或治疗策略提供信息，以防止微生物群落的破坏，或促进其恢复。本文的在线版本（doi:10.1186/s40168-017-0264-8）包含补充材料，可供授权用户使用。
Salmonella is one of the most significant food-borne pathogens to affect humans and agriculture. While it is well documented that Salmonella infection triggers host inflammation, the impacts on the gut environment are largely unknown. A CBA/J mouse model was used to evaluate intestinal responses to Salmonella-induced inflammation. In parallel, we evaluated chemically induced inflammation by dextran sodium sulfate (DSS) and a non-inflammation control. We profiled gut microbial diversity by sequencing 16S ribosomal ribonucleic acid (rRNA) genes from fecal and cecal samples. These data were correlated to the inflammation marker lipocalin-2 and short-chain fatty acid concentrations. We demonstrated that inflammation, chemically or biologically induced, restructures the chemical and microbial environment of the gut over a 16-day period. We observed that the ten mice within the Salmonella treatment group had a variable Salmonella relative abundance, with three high responding mice dominated by >46% Salmonella at later time points and the remaining seven mice denoted as low responders. These low- and high-responding Salmonella groups, along with the chemical DSS treatment, established an inflammation gradient with chemical and low levels of Salmonella having at least 3 log-fold lower lipocalin-2 concentration than the high-responding Salmonella mice. Total short-chain fatty acid and individual butyrate concentrations each negatively correlated with inflammation levels. Microbial communities were also structured along this inflammation gradient. Low levels of inflammation, regardless of chemical or biological induction, enriched for Akkermansia spp. in the Verrucomicrobiaceae and members of the Bacteroidetes family S24-7. Relative to the control or low inflammation groups, high levels of Salmonella drastically decreased the overall microbial diversity, specifically driven by the reduction of Alistipes and Lachnospiraceae in the Bacteroidetes and Firmicutes phyla, respectively. Conversely, members of the Enterobacteriaceae and Lactobacillus were positively correlated to high levels of Salmonella-induced inflammation. Our results show that enteropathogenic infection and intestinal inflammation are interrelated factors modulating gut homeostasis. These findings may prove informative with regard to prophylactic or therapeutic strategies to prevent disruption of microbial communities, or promote their restoration. The online version of this article (doi:10.1186/s40168-017-0264-8) contains supplementary material, which is available to authorized users.