Gut commensals expand vitamin A metabolic capacity of the mammalian host.
Gut commensals expand vitamin A metabolic capacity of the mammalian host.
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DOI：
10.1016/j.chom.2022.06.011
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发表时间：
2022-08-10
影响因子：
30.3
通讯作者：
Vaishnava, Shipra
中科院分区：
文献类型：
--
作者：
Bonakdar, Maryam;Czuba, Lindsay C.;Han, Geongoo;Zhong, Guo;Luong, Hien;Isoherrannen, Nina;Vaishnava, Shipra
膳食维生素A （VA）转化为维甲酸（RA）对许多生物过程至关重要，迄今为止在哺乳动物细胞中进行了大量研究。利用靶向代谢组学，我们发现小鼠肠道腔内的共生细菌产生高浓度的活性类维甲酸，全反式维甲酸（atRA）和13顺式维甲酸（13cisRA），以及主要的循环类维甲酸视黄醇。消融性厌氧菌显著降低视黄醇、atRA和13cisRA，而将这些细菌引入无菌小鼠显著增强类视黄醇。值得注意的是，补充了VA的盲肠细菌在体外产生了活性类维生素a，这表明肠道细菌编码了将膳食VA多步骤转化为活性形式所必需的代谢机制。最后，肠道细菌肠乳杆菌代谢VA并特异性恢复万古霉素处理小鼠肠道中的RA水平。我们的工作建立了维生素A代谢作为肠道微生物组的一种新兴特性，并为开发基于益生菌的类视黄醇治疗奠定了基础。Bonakdar、Czuba等研究表明，共生菌将膳食中的维生素A多步骤转化为维甲酸，显著提高了肠道内维生素A代谢物的浓度。维生素A代谢是肠道微生物群的一种新兴特性，指出肠道微生物调节宿主生理的一种机制。
Conversion of dietary Vitamin A (VA) into retinoic acid (RA) is essential for many biological processes and thus far studied largely in mammalian cells. Using targeted metabolomics, we found that commensal bacteria in the mouse gut lumen produced high concentration of the active retinoids, all-trans-retinoic acid (atRA) and 13-cis retinoic acid (13cisRA), as well as the principal circulating retinoid, retinol. Ablation of anaerobic bacteria significantly reduced retinol, atRA, and 13cisRA, while introducing these bacteria into germ-free mice significantly enhanced retinoids. Remarkably, cecal bacterial supplemented with VA produced active retinoids in vitro, establishing that gut bacteria encode metabolic machinery necessary for multistep conversion of dietary VA into its active forms. Finally, gut bacteria Lactobacillus intestinalis metabolized VA and specifically restored RA levels in the gut of vancomycin-treated mice. Our work establishes vitamin A metabolism as an emergent property of the gut microbiome and lays the groundwork for developing probiotic-based retinoid therapy. Bonakdar, Czuba et al show commensal bacteria perform multistep conversion of dietary vitamin A into retinoic acid, significantly increasing the concentration of vitamin A metabolites in the gut lumen. Vitamin A metabolism is an emergent property of gut microbiome, pointing towards a mechanism by which gut microbes regulate host physiology.
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影响因子：
7.3
作者：
Snyder LM;Arora J;Kennett MJ;Weaver V;Cantorna MT
通讯作者：
Cantorna MT
影响因子：
48
作者：
Callahan BJ;McMurdie PJ;Rosen MJ;Han AW;Johnson AJ;Holmes SP
通讯作者：
Holmes SP
影响因子：
12.2
作者：
Duncan K;Carey-Ewend K;Vaishnava S
通讯作者：
Vaishnava S
影响因子：
32.4
作者：
Hall JA;Grainger JR;Spencer SP;Belkaid Y
通讯作者：
Belkaid Y
DOI：
10.1073/pnas.1116053109
发表时间：
2012-01-10
影响因子：
11.1
作者：
Greenblum, Sharon;Turnbaugh, Peter J.;Borenstein, Elhanan
通讯作者：
Borenstein, Elhanan