Vitamin B12 coordinates ileal epithelial cell and microbiota functions to resist Salmonella infection in mice.
Vitamin B12 coordinates ileal epithelial cell and microbiota functions to resist Salmonella infection in mice.
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DOI：
10.1084/jem.20220057
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发表时间：
2022-07-04
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影响因子：
--
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维生素 B12 塑造肠道微生物组并支持回肠上皮细胞的线粒体代谢，从而协同调节上皮氧合，控制需氧沙门氏菌感染。这种机械相互作用凸显了这种关键微量营养素在维持肠道稳态以抵抗病原体感染方面的重要性。缺乏维生素 B12 (VB12) 与多种疾病有关，但人们对疾病进展的潜在机制知之甚少。使用多组学方法，我们阐明了回肠上皮细胞 (iEC) 和肠道微生物组对 VB12 饮食限制的反应。在这里，VB12 缺乏损害了 iEC 的转录和代谢程序，并减少了肠道鼠伤寒沙门氏菌 (STm) 感染期间上皮线粒体呼吸和肉毒碱穿梭。粪便微生物和非靶向代谢组学分析发现了与 VB12 缺乏相关的显着变化，包括可能激活 iEC 和短链脂肪酸 (SCFA) 中线粒体 β 氧化的代谢物减少。通过链霉素处理消除产生 SCFA 的微生物会降低 VB12 依赖性 STm 保护。此外，iEC 线粒体功能受损与细胞利用氧气的能力下降相关，导致 VB12 缺陷小鼠中氧依赖性 STm 扩张不受控制。我们的研究结果揭示了以前未被认识的机制，VB12通过这些机制协调回肠上皮线粒体稳态和肠道微生物群来调节上皮氧合，从而控制需氧STm感染。
Vitamin B12 shapes gut microbiome and supports mitochondrial metabolism of ileal epithelial cells to synergistically regulate epithelial oxygenation, controlling aerobic Salmonella infection. This mechanistic interplay highlights the significance of this crucial micronutrient in maintaining intestinal homeostasis against pathogen infections. Deprivation of vitamin B12 (VB12) is linked to various diseases, but the underlying mechanisms in disease progression are poorly understood. Using multiomic approaches, we elucidated the responses of ileal epithelial cells (iECs) and gut microbiome to VB12 dietary restriction. Here, VB12 deficiency impaired the transcriptional and metabolic programming of iECs and reduced epithelial mitochondrial respiration and carnitine shuttling during intestinal Salmonella Typhimurium (STm) infection. Fecal microbial and untargeted metabolomic profiling identified marked changes related to VB12 deficiency, including reductions of metabolites potentially activating mitochondrial β-oxidation in iECs and short-chain fatty acids (SCFAs). Depletion of SCFA-producing microbes by streptomycin treatment decreased the VB12-dependent STm protection. Moreover, compromised mitochondrial function of iECs correlated with declined cell capability to utilize oxygen, leading to uncontrolled oxygen-dependent STm expansion in VB12-deficient mice. Our findings uncovered previously unrecognized mechanisms through which VB12 coordinates ileal epithelial mitochondrial homeostasis and gut microbiota to regulate epithelial oxygenation, resulting in the control of aerobic STm infection.
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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：
3.3
作者：
Ahmad, Shadab;Kumar, K. Anand;Sengupta, Shantanu
通讯作者：
Sengupta, Shantanu
影响因子：
4.2
作者：
Evans, Nicholas P.;Misyak, Sarah A.;Bassaganya-Riera, Josep
通讯作者：
Bassaganya-Riera, Josep
DOI：
10.1073/pnas.120163297
发表时间：
2000-06-06
影响因子：
11.1
作者：
Datsenko, KA;Wanner, BL
通讯作者：
Wanner, BL
影响因子：
6.4
作者：
Cevallos, Stephanie A.;Lee, Jee-Yon;Baumler, Andreas J.
通讯作者：
Baumler, Andreas J.