Lactobacillus rhamnosus Modulates Lung Inflammation and Mitigates Gut Dysbiosis in a Murine Model of Asthma-COPD Overlap Syndrome

Probiotics Antimicrob Proteins. 2023 Oct 14. doi: 10.1007/s12602-023-10167-2. Online ahead of print.

Abstract

The asthma-COPD overlap syndrome (ACOS) presents lung inflammation similar to both asthma and chronic obstructive pulmonary disease (COPD). Due to the immune response between the lung and gut, it is possible that ACOS individuals present gut dysbiosis. Due to therapeutic limitations in ACOS, Lactobacillus rhamnosus (Lr) have received attention once Lr has been effective in asthma and COPD. However, there is no data about the Lr effect on both lung inflammation and gut dysbiosis in ACOS. Thus, our study investigated the Lr effect on lung inflammation, bronchoconstriction, airway remodeling, and gut dysbiosis in the murine ACOS model. Treated mice with Lr were exposed to HDM and cigarette smoke to induce ACOS. Sixty days after ACOS induction, mice were euthanized. Lung inflammation was evaluated in leukocytes in bronchoalveolar lavage fluid (BALF), airway remodeling, cytokine secretion, and transcription factor expression in the lung. The gut microbiota was assayed by 16S mRNA sequencing from a fecal sample. Leukocyte population, bronchial hyperreactivity, pro-inflammatory cytokines, and airway remodeling were attenuated in Lr-treated ACOS mice. Likewise, IL-4, IL-5, and IL-13, STAT6 and GATA3, as well as IL-17, IL-21, IL-22, STAT3, and RORɣt were reduced after Lr. In addition, IL-2, IL-12, IFN-γ, STAT1, and T-bet as well as IL-10, TGF-β, STAT5, and Foxp3 were restored after the Lr. Firmicutes was reduced, while Deferribacteres was increased after Lr. Likewise, Lr decreased Staphylococcus and increased Mucispirillum in ACOS mice. Lr improves fecal bacterial β-diversity. Our findings show for the first time the Lr effect on lung inflammation and gut dysbiosis in murine ACOS.

Keywords: ACOS; Airway remodeling; Gut dysbiosis; Probiotic; STAT signaling; Th cell cytokines.