Limosilactobacillus reuteri Attenuates Atopic Dermatitis via Changes in Gut Bacteria and Indole Derivatives from Tryptophan Metabolism.

Abstract

Gut bacteria are closely associated with the development of atopic dermatitis (AD) due to their immunoregulatory function. Indole derivatives, produced by gut bacteria metabolizing tryptophan, are ligands to activate the aryl hydrocarbon receptor (AHR), which plays a critical role in attenuating AD symptoms. Limosilactobacillus reuteri, a producer of indole derivatives, regulates mucosal immunity via activating the AHR signaling pathway. However, the effective substance and mechanism of L. reuteri in the amelioration of AD remain to be elucidated. In this research, we found that L. reuteri DYNDL22M62 significantly improved AD-like symptoms in mice by suppressing IgE levels and the expressions of thymic stromal lymphopoietin (TSLP), IL-4, and IL-5. L. reuteri DYNDL22M62 induced an increase in the production of indole lactic acid (ILA) and indole propionic acid (IPA) via targeted tryptophan metabolic analysis and the expression of AHR in mice. Furthermore, L. reuteri DYNDL22M62 increased the proportions of Romboutsia and Ruminococcaceae NK4A214 group, which were positively related to ILA, but decreased Dubosiella, which was negatively related to IPA. Collectively, L. reuteri DYNDL22M62 with the role of modulating gut bacteria and the production of indole derivatives may attenuate AD via activating AHR in mice.