Microbiota dysbiosis in inflammatory bowel diseases: in silico investigation of the oxygen hypothesis.
Microbiota dysbiosis in inflammatory bowel diseases: in silico investigation of the oxygen hypothesis.
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DOI：
10.1186/s12918-017-0522-1
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发表时间：
2017-12-28
影响因子：
--
通讯作者：
Phalak P
中科院分区：
文献类型：
--
作者：
Henson MA;Phalak P
炎症性肠病 (IBD)，包括溃疡性结肠炎和克罗恩病，导致约 160 万美国人出现消化道慢性炎症。 IBD 的一个特征是肠道微生物群失调，其特点是专性厌氧菌显着减少和兼性厌氧菌急剧增加。大量实验研究表明，IBD与普拉梭菌的减少和大肠杆菌的增加密切相关。一种假设是，慢性炎症会导致肠道内氧含量增加，进而导致专性厌氧菌和兼性厌氧菌之间的不平衡。为了通过计算研究氧假说，我们基于普拉梭菌、大肠杆菌和常见肠道厌氧菌多形拟杆菌的基因组规模代谢重建开发了多物种生物膜模型。在生物膜边界应用低体积氧浓度再现了实验观察到的行为，其特征是普拉梭菌急剧减少和大肠杆菌大量增加，表明与 IBD 疾病进展一致的生态失调可以仅根据物种之间的代谢差异进行定性预测。碳水化合物和蛋白质含量均衡的饮食被预测为代谢“最佳点”，可增加氧气范围，在该范围内，普氏镰刀菌可以保持竞争力，IBD 可以升华。通过平均普氏梭菌浓度和总体氧浓度之间的简单线性反馈整合的宿主微生物群反馈并没有显着改变预测生态失调的氧浓度范围，但从正常物种丰度到严重生态失调的转变更加戏剧性，并且发生在更长的时间尺度上。通过持续的抗生素治疗代替持续的氧扰动也获得了类似的预测，这表明 IBD 可能会在几年内进展而几乎没有明显的影响，然后突然产生严重的疾病症状。多物种生物膜代谢模型预测，肠道内〜1微摩尔的氧气浓度可能会导致微生物群失调，这与炎症性肠病实验观察到的结果一致。我们的模型预测可以通过开发三个物种群落的适当体外系统并测试无菌小鼠中微生物群与宿主的相互作用来直接测试。本文的在线版本 (doi:10.1186/s12918-017-0522-1) 包含补充材料，可供授权用户使用。
Inflammatory bowel diseases (IBD), which include ulcerative colitis and Crohn’s disease, cause chronic inflammation of the digestive tract in approximately 1.6 million Americans. A signature of IBD is dysbiosis of the gut microbiota marked by a significant reduction of obligate anaerobes and a sharp increase in facultative anaerobes. Numerous experimental studies have shown that IBD is strongly correlated with a decrease of Faecalibacterium prausnitzii and an increase of Escherichia coli. One hypothesis is that chronic inflammation induces increased oxygen levels in the gut, which in turn causes an imbalance between obligate and facultative anaerobes. To computationally investigate the oxygen hypothesis, we developed a multispecies biofilm model based on genome-scale metabolic reconstructions of F. prausnitzii, E. coli and the common gut anaerobe Bacteroides thetaiotaomicron. Application of low bulk oxygen concentrations at the biofilm boundary reproduced experimentally observed behavior characterized by a sharp decrease of F. prausnitzii and a large increase of E. coli, demonstrating that dysbiosis consistent with IBD disease progression could be qualitatively predicted solely based on metabolic differences between the species. A diet with balanced carbohydrate and protein content was predicted to represent a metabolic “sweet spot” that increased the oxygen range over which F. prausnitzii could remain competitive and IBD could be sublimated. Host-microbiota feedback incorporated via a simple linear feedback between the average F. prausnitzii concentration and the bulk oxygen concentration did not substantially change the range of oxygen concentrations where dysbiosis was predicted, but the transition from normal species abundances to severe dysbiosis was much more dramatic and occurred over a much longer timescale. Similar predictions were obtained with sustained antibiotic treatment replacing a sustained oxygen perturbation, demonstrating how IBD might progress over several years with few noticeable effects and then suddenly produce severe disease symptoms. The multispecies biofilm metabolic model predicted that oxygen concentrations of ∼1 micromolar within the gut could cause microbiota dysbiosis consistent with those observed experimentally for inflammatory bowel diseases. Our model predictions could be tested directly through the development of an appropriate in vitro system of the three species community and testing of microbiota-host interactions in gnotobiotic mice. The online version of this article (doi:10.1186/s12918-017-0522-1) contains supplementary material, which is available to authorized users.
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DOI：
10.1126/science.aam9949
发表时间：
2017-08-11
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Byndloss MX;Olsan EE;Rivera-Chávez F;Tiffany CR;Cevallos SA;Lokken KL;Torres TP;Byndloss AJ;Faber F;Gao Y;Litvak Y;Lopez CA;Xu G;Napoli E;Giulivi C;Tsolis RM;Revzin A;Lebrilla CB;Bäumler AJ
通讯作者：
Bäumler AJ
影响因子：
64.8
作者：
Baughn, AD;Malamy, MH
通讯作者：
Malamy, MH
影响因子：
4.3
作者：
Hold, Georgina L.;Smith, Megan;Mukhopadhya, Indrani
通讯作者：
Mukhopadhya, Indrani
影响因子：
--
作者：
Baumler DJ;Peplinski RG;Reed JL;Glasner JD;Perna NT
通讯作者：
Perna NT
DOI：
10.1038/ijo.2015.84
发表时间：
2015-09
期刊：
International journal of obesity (2005)
影响因子：
--
作者：
Byrne CS;Chambers ES;Morrison DJ;Frost G
通讯作者：
Frost G