Bifidobacterium longum mediated tryptophan metabolism to improve atopic dermatitis via the gut-skin axis.

Bifidobacterium longum mediated tryptophan metabolism to improve atopic dermatitis via the gut-skin axis.
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长双歧杆菌通过肠 - 皮肤轴介导色氨酸代谢,进而改善特应性皮炎。

DOI:
10.1080/19490976.2022.2044723
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发表时间:
2022-01
期刊:
影响因子:
12.2
通讯作者:
Lu W
Lu W
中科院分区:
医学2区
文献类型:
--
作者:
Fang Z;Pan T;Li L;Wang H;Zhu J;Zhang H;Zhao J;Chen W;Lu W

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肠道微生物的紊乱通过异常的免疫反应影响过敏性疾病,包括哮喘、特应性皮炎(AD)。据报道,一些双歧杆菌物种和菌株通过调节患者的免疫-微生物相互作用来改善AD。然而,双歧杆菌中有效的代谢产物和缓解AD的机制仍有待阐明。本研究旨在探讨长双歧杆菌改善阿尔茨海默病的微生物代谢产物及其作用机制。基于鸟枪宏基因组测序和UHPLC Q-Exactive-MS靶向体内外代谢实验,我们重点研究了色氨酸代谢和吲哚衍生物,它们是芳香烃受体(AHR)的内源性配体。吲哚-3-甲醛(I3 C),B的色氨酸代谢产物。在动物实验和临床实验中,荜茇CCFM 1029激活AHR介导的免疫信号通路以改善AD症状。B。Longum CCFM 1029上调色氨酸代谢并增加I3 C以抑制异常T辅助2型免疫应答,但这些益处被AHR拮抗剂CH 223191消除。此外,B. Longum CCFM 1029重塑了AD患者的肠道微生物组成,增加了粪便和血清I3 C,并维持了与肠道微生物群色氨酸代谢相关的钩端螺旋体的丰度。结果表明,基于肠-皮轴的相互作用,B. Longum CCFM 1029上调色氨酸代谢并产生I3 C以激活AHR介导的免疫应答,从而减轻AD症状。吲哚衍生物是色氨酸的微生物代谢产物,可能是双歧杆菌通过AHR信号通路缓解AD的潜在代谢产物。
Gut microbial disturbance affects allergic diseases including asthma, atopic dermatitis (AD) via the aberrant immune response. Some Bifidobacterial species and strains have been reported to improve AD via modulating immune-microbe interactions in patients. However, the effective metabolites and mechanism of alleviating AD in bifidobacteria remain to be elucidated. This study aimed to explore the microbial metabolite and mechanism of Bifidobacterium longum to improve AD. Based on shotgun metagenomic sequencing and UHPLC Q-Exactive-MS targeted metabolic experiments in vitro and in vivo, we focused on tryptophan metabolism and indole derivatives, which are endogenous ligands for aryl hydrocarbon receptor (AHR). Indole-3-carbaldehyde (I3C), a tryptophan metabolite of B. longum CCFM1029 activated AHR-mediated immune signaling pathway to improve AD symptoms in animal and clinical experiments. B. longum CCFM1029 upregulated tryptophan metabolism and increased I3C to suppress aberrant T helper 2 type immune responses, but these benefits were eliminated by AHR antagonist CH223191. Furthermore, B. longum CCFM1029 reshaped gut microbial composition in AD patients, increased fecal and serum I3C, and maintained the abundance of Lachnospiraceae related to tryptophan metabolism of gut microbiota. The results suggested that based on the interactions of the gut-skin axis, B. longum CCFM1029 upregulated tryptophan metabolism and produced I3C to activate AHR-mediated immune response, alleviating AD symptoms. Indole derivates, microbial metabolites of tryptophan, may be the potential metabolites of bifidobacteria to alleviate AD via the AHR signaling pathway.
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