Gut Colonization with Methanogenic Archaea Lowers Plasma Trimethylamine N-oxide Concentrations in Apolipoprotein e-/- Mice.
Gut Colonization with Methanogenic Archaea Lowers Plasma Trimethylamine N-oxide Concentrations in Apolipoprotein e-/- Mice.
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DOI：
10.1038/s41598-018-33018-5
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发表时间：
2018-10-03
影响因子：
4.6
通讯作者：
Raj DS
中科院分区：
文献类型：
--
作者：
Ramezani A;Nolin TD;Barrows IR;Serrano MG;Buck GA;Regunathan-Shenk R;West RE 3rd;Latham PS;Amdur R;Raj DS
已经报道了三甲胺N-氧化物（TMAO）和动脉粥样硬化形成之间的机制联系。氧化三甲胺（TMA）是由肠道细菌从膳食胆碱、肉毒碱和甜菜碱中产生的，在肝脏中通过氧化三甲胺（TMA）酶促产生。已知产甲烷古菌（MA）的某些成员可以使用甲基化胺（如三甲胺）作为培养基中的生长底物。因此，我们研究了MA肠道定植对降低血浆TMAO浓度的功效。最初，我们在喂食高胆碱/TMA补充饮食的C57 BL/6小鼠中筛选了五种MA的定殖潜力和TMAO降低功效，并发现所有五种MA都可以定殖并降低血浆TMAO水平，尽管功效不同。将表现最好的MA、史氏甲烷短杆菌、马氏甲烷八叠球菌和甲烷微球菌移植到用高胆碱/TMA补充饮食喂养的Apoe−/−小鼠中。与C57 BL/6小鼠相似，在最初提供MA后，在研究的最初3周期间，移植后粪便微生物群落中的MA逐渐减少。在一般情况下，血浆TMAO浓度显着降低比例的MA殖民化的水平。在随后的实验中，使用抗生素和重复移植Apoe−/−小鼠与M。smithii的小鼠在9周的研究期间导致高植入水平，导致与模拟移植对照小鼠（120.8 ± 13.0 μM，p < 0.001）相比，持续且显著较低的平均血浆TMAO浓度（18.2 ± 19.6 μM）。与对照Apoe−/−小鼠相比，M. Smithii定殖小鼠的主动脉斑块面积也减少了44（8，570 μm [95% CI 19587-151821] vs. 15，369 μm [95% CI [70058-237321]，p = 0.34），动脉粥样硬化斑块中的脂肪含量减少52%（14，283 μm [95% CI 4，957 - 23，608] vs. 29，870 μm [95% CI 18，074 - 41，666]，p = 0.10），尽管这些差异未达到显著性。肠道定植M. Smithii导致血浆TMAO水平显著降低，具有减轻Apoe−/−小鼠动脉粥样硬化负担的趋势。MA的抗动脉粥样硬化潜力应在充分的实验中进一步测试。
A mechanistic link between trimethylamine N-oxide (TMAO) and atherogenesis has been reported. TMAO is generated enzymatically in the liver by the oxidation of trimethylamine (TMA), which is produced from dietary choline, carnitine and betaine by gut bacteria. It is known that certain members of methanogenic archaea (MA) could use methylated amines such as trimethylamine as growth substrates in culture. Therefore, we investigated the efficacy of gut colonization with MA on lowering plasma TMAO concentrations. Initially, we screened for the colonization potential and TMAO lowering efficacy of five MA species in C57BL/6 mice fed with high choline/TMA supplemented diet, and found out that all five species could colonize and lover plasma TMAO levels, although with different efficacies. The top performing MA, Methanobrevibacter smithii, Methanosarcina mazei, and Methanomicrococcus blatticola, were transplanted into Apoe−/− mice fed with high choline/TMA supplemented diet. Similar to C57BL/6 mice, following initial provision of the MA, there was progressive attrition of MA within fecal microbial communities post-transplantation during the initial 3 weeks of the study. In general, plasma TMAO concentrations decreased significantly in proportion to the level of MA colonization. In a subsequent experiment, use of antibiotics and repeated transplantation of Apoe−/− mice with M. smithii, led to high engraftment levels during the 9 weeks of the study, resulting in a sustained and significantly lower average plasma TMAO concentrations (18.2 ± 19.6 μM) compared to that in mock-transplanted control mice (120.8 ± 13.0 μM, p < 0.001). Compared to control Apoe−/− mice, M. smithii-colonized mice also had a 44% decrease in aortic plaque area (8,570 μm [95% CI 19587–151821] vs. 15,369 μm [95% CI [70058–237321], p = 0.34), and 52% reduction in the fat content in the atherosclerotic plaques (14,283 μm [95% CI 4,957–23,608] vs. 29,870 μm [95% CI 18,074–41,666], p = 0.10), although these differences did not reach significance. Gut colonization with M. smithii leads to a significant reduction in plasma TMAO levels, with a tendency for attenuation of atherosclerosis burden in Apoe−/− mice. The anti-atherogenic potential of MA should be further tested in adequately powered experiments.
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影响因子：
5.1
作者：
Casamayor, EO;Massana, R;Pedrós-Alió, C
通讯作者：
Pedrós-Alió, C
影响因子：
4.4
作者：
Fettweis JM;Serrano MG;Sheth NU;Mayer CM;Glascock AL;Brooks JP;Jefferson KK;Vaginal Microbiome Consortium (additional members);Buck GA
通讯作者：
Buck GA
影响因子：
3
作者：
Kwon S;Lee B;Yoon S
通讯作者：
Yoon S
影响因子：
12.2
作者：
Brugère JF;Borrel G;Gaci N;Tottey W;O'Toole PW;Malpuech-Brugère C
通讯作者：
Malpuech-Brugère C
DOI：
10.1016/j.jpba.2015.02.040
发表时间：
2015-05-10
影响因子：
3.4
作者：
Ocque, Andrew J.;Stubbs, Jason R.;Nolin, Thomas D.
通讯作者：
Nolin, Thomas D.