Aryl hydrocarbon receptor activation by Lactobacillus reuteri tryptophan metabolism alleviates Escherichia coli-induced mastitis in mice.
Aryl hydrocarbon receptor activation by Lactobacillus reuteri tryptophan metabolism alleviates Escherichia coli-induced mastitis in mice.
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罗伊氏乳杆菌色氨酸代谢激活芳基碳氢化合物受体可减轻大肠杆菌引起的小鼠乳腺炎
DOI：
10.1371/journal.ppat.1009774
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发表时间：
2021-07
期刊：
影响因子：
6.7
通讯作者：
Zhang N
中科院分区：
文献类型：
--
作者：
Zhao C;Hu X;Bao L;Wu K;Feng L;Qiu M;Hao H;Fu Y;Zhang N
肠道菌群与乳腺炎的发生和发展有关，乳腺炎是哺乳期妇女和雌性动物最严重的疾病之一，但其潜在机制尚未阐明。微生物群色氨酸代谢衍生配体激活芳基碳氢化合物受体（AhR）参与维持宿主体内平衡和抵抗疾病。我们研究了微生物代谢配体激活 AhR 是否会影响小鼠乳腺炎的发展。在这项研究中，我们发现使用 Ficz 激活 AhR 可改善乳腺炎症状，这与限制 NF-κB 激活和增强屏障功能有关。通过干扰肠道微生物群来削弱 AhR 的激活会引发乳腺炎，并在小鼠中处理大肠杆菌 (E. coli) 诱发的乳腺炎。饮食中补充色氨酸可减轻乳腺炎，但肠道微生物群的消除会抑制这种减轻，而给予色氨酸代谢物（包括 IAld 和吲哚，但不包括 IPA）可挽救菌群失调小鼠中的色氨酸效应。补充具有产生 AhR 配体能力的罗伊氏乳杆菌 (L. reuteri) 菌株也以 AhR 依赖性方式改善了大肠杆菌诱导的乳腺炎。这些发现为治疗乳腺炎的新治疗策略提供了证据，并支持源自肠道微生物群的代谢物在改善远端疾病中的作用。
The intestinal microbiota has been associated with the occurrence and development of mastitis, which is one of the most serious diseases of lactating women and female animals, but the underlying mechanism has not yet been elucidated. Aryl hydrocarbon receptor (AhR) activation by microbiota tryptophan metabolism-derived ligands is involved in maintaining host homeostasis and resisting diseases. We investigated whether AhR activation by microbiota-metabolic ligands could influence mastitis development in mice. In this study, we found that AhR activation using Ficz ameliorated mastitis symptoms, which were related to limiting NF-κB activation and enhancing barrier function. Impaired AhR activation by disturbing the intestinal microbiota initiated mastitis, and processed Escherichia coli (E. coli)-induced mastitis in mice. Supplementation with dietary tryptophan attenuated the mastitis, but attenuation was inhibited by the intestinal microbiota abrogation, while administering tryptophan metabolites including IAld and indole but not IPA, rescued the tryptophan effects in dysbiotic mice. Supplementation with a Lactobacillus reuteri (L. reuteri) strain with the capacity to produce AhR ligands also improved E. coli-induced mastitis in an AhR-dependent manner. These findings provide evidence for novel therapeutic strategies for treating mastitis, and support the role of metabolites derived from the intestinal microbiota in improving distal disease.
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