<i>Bifidobacterium longum</i> mediated tryptophan metabolism to improve atopic dermatitis via the gut-skin axis

Abstract

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 <i>Bifidobacterium longum</i> to improve AD. Based on shotgun metagenomic sequencing and UHPLC Q-Exactive-MS targeted metabolic experiments <i>in vitro</i> and <i>in vivo</i>, 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 <i>B. longum</i> CCFM1029 activated AHR-mediated immune signaling pathway to improve AD symptoms in animal and clinical experiments. <i>B. longum</i> 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, <i>B. longum</i> CCFM1029 reshaped gut microbial composition in AD patients, increased fecal and serum I3C, and maintained the abundance of <i>Lachnospiraceae</i> related to tryptophan metabolism of gut microbiota. The results suggested that based on the interactions of the gut-skin axis, <i>B. longum</i> 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.