Vitamin B12 modulates the transcriptome of the skin microbiota in acne pathogenesis.

Vitamin B12 modulates the transcriptome of the skin microbiota in acne pathogenesis.
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DOI:
10.1126/scitranslmed.aab2009
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发表时间:
2015-06-24
影响因子:
17.1
通讯作者:
Li H
Li H
中科院分区:
医学1区
文献类型:
--
作者:
Kang D;Shi B;Erfe MC;Craft N;Li H

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各种疾病都与人类微生物区系有关,但微生物区系在疾病发病机制中的潜在分子机制往往知之甚少。利用痤疮作为疾病模型,我们的目的是了解皮肤微生物区系在疾病发病机制中对宿主代谢物信号的分子反应。通过元转录分析,我们发现皮肤微生物区系的转录图谱将痤疮患者与健康人区分开来。在痤疮患者中,皮肤细菌痤疮丙酸杆菌中维生素B12的生物合成途径显著下调。我们假设宿主维生素B12调节皮肤微生物区系的活动,并在痤疮发病机制中发挥作用。为了验证这一假设,我们分析了补充维生素B12的健康受试者的皮肤微生物区系。我们发现,补充剂抑制了痤疮假单胞菌中维生素B12生物合成基因的表达,并改变了皮肤微生物区系的转录组。十名受试者中有一人在补充维生素B12一周后长出粉刺。为了进一步了解分子机制,我们揭示了在痤疮假单胞菌培养中补充维生素B12促进了卟啉的产生,这是已知的诱导痤疮炎症的因素。我们的发现提示了痤疮一种新的细菌发病途径,并为补充维生素B12导致痤疮发生的长期临床观察提供了一个分子解释。我们的研究发现,维生素B12是人类的一种基本营养物质,它调节皮肤细菌的转录活动,并提供证据表明,代谢物介导的宿主和皮肤微生物区系之间的相互作用在疾病发展中发挥重要作用。
Various diseases have been linked to the human microbiota, but the underlying molecular mechanisms of the microbiota in disease pathogenesis are often poorly understood. Using acne as a disease model, we aim to understand the molecular response of the skin microbiota to host metabolite signaling in disease pathogenesis. By metatranscriptomic analysis, we found that the transcriptional profiles of the skin microbiota separated acne patients from healthy individuals. The vitamin B12 biosynthesis pathway in the skin bacterium, Propionibacterium acnes, was significantly down-regulated in acne patients. We hypothesized that host vitamin B12 modulates the activities of the skin microbiota and plays a role in acne pathogenesis. To test this hypothesis, we analyzed the skin microbiota in healthy subjects supplemented with vitamin B12. We found that the supplementation repressed the expression of vitamin B12 biosynthesis genes in P. acnes and altered the transcriptome of the skin microbiota. One of the ten subjects studied developed acne one week after vitamin B12 supplementation. To further understand the molecular mechanism, we revealed that vitamin B12 supplementation in P. acnes cultures promoted the production of porphyrins, which are known to induce inflammation in acne. Our findings suggest a new bacterial pathogenesis pathway in acne and provide one molecular explanation for the long-standing clinical observation that vitamin B12 supplementation leads to acne development. Our study discovered that vitamin B12, an essential nutrient in humans, modulates the transcriptional activities of the skin bacteria, and provided evidence that metabolite-mediated interactions between the host and the skin microbiota play essential roles in disease development.
与痤疮相关的人皮肤微生物组中的痤疮丙酸杆菌菌株群体。
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