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

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 mech...

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Main Authors: Zhifeng Fang, Tong Pan, Lingzhi Li, Hongchao Wang, Jinlin Zhu, Hao Zhang, Jianxin Zhao, Wei Chen, Wenwei Lu
Format: Article
Language:English
Published: Taylor & Francis Group 2022-12-01
Series:Gut Microbes
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Online Access:https://www.tandfonline.com/doi/10.1080/19490976.2022.2044723
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author Zhifeng Fang
Tong Pan
Lingzhi Li
Hongchao Wang
Jinlin Zhu
Hao Zhang
Jianxin Zhao
Wei Chen
Wenwei Lu
author_facet Zhifeng Fang
Tong Pan
Lingzhi Li
Hongchao Wang
Jinlin Zhu
Hao Zhang
Jianxin Zhao
Wei Chen
Wenwei Lu
author_sort Zhifeng Fang
collection DOAJ
description 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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spelling doaj-art-9e439da1afaf4e5f97b3e5ec00cfa8b72025-08-20T03:21:40ZengTaylor & Francis GroupGut Microbes1949-09761949-09842022-12-0114110.1080/19490976.2022.2044723Bifidobacterium longum mediated tryptophan metabolism to improve atopic dermatitis via the gut-skin axisZhifeng Fang0Tong Pan1Lingzhi Li2Hongchao Wang3Jinlin Zhu4Hao Zhang5Jianxin Zhao6Wei Chen7Wenwei Lu8State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, ChinaState Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, ChinaState Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, ChinaState Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, ChinaState Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, ChinaState Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, ChinaState Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, ChinaState Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, ChinaState Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, ChinaGut 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.https://www.tandfonline.com/doi/10.1080/19490976.2022.2044723Bifidobacterium longumtryptophan metabolismgut-skin axisaryl hydrocarbon receptorsindole-3-carbaldehydeatopic dermatitis
spellingShingle Zhifeng Fang
Tong Pan
Lingzhi Li
Hongchao Wang
Jinlin Zhu
Hao Zhang
Jianxin Zhao
Wei Chen
Wenwei Lu
Bifidobacterium longum mediated tryptophan metabolism to improve atopic dermatitis via the gut-skin axis
Gut Microbes
Bifidobacterium longum
tryptophan metabolism
gut-skin axis
aryl hydrocarbon receptors
indole-3-carbaldehyde
atopic dermatitis
title Bifidobacterium longum mediated tryptophan metabolism to improve atopic dermatitis via the gut-skin axis
title_full Bifidobacterium longum mediated tryptophan metabolism to improve atopic dermatitis via the gut-skin axis
title_fullStr Bifidobacterium longum mediated tryptophan metabolism to improve atopic dermatitis via the gut-skin axis
title_full_unstemmed Bifidobacterium longum mediated tryptophan metabolism to improve atopic dermatitis via the gut-skin axis
title_short Bifidobacterium longum mediated tryptophan metabolism to improve atopic dermatitis via the gut-skin axis
title_sort bifidobacterium longum mediated tryptophan metabolism to improve atopic dermatitis via the gut skin axis
topic Bifidobacterium longum
tryptophan metabolism
gut-skin axis
aryl hydrocarbon receptors
indole-3-carbaldehyde
atopic dermatitis
url https://www.tandfonline.com/doi/10.1080/19490976.2022.2044723
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