Gegen Qinlian Decoction Alleviates Experimental Colitis and Concurrent Lung Inflammation by Inhibiting the Recruitment of Inflammatory Myeloid Cells and Restoring Microbial Balance

Abstract

Objective Ulcerative colitis (UC) as one of the intractable diseases in gastroenterology seriously threatens human health. Respiratory pathology is a representative extraintestinal manifestation of UC affecting the quality of life of patients. Gegen Qinlian Decoction (GQD) is a classical traditional Chinese medicine prescription for UC or acute lung injury. This study was aimed to reveal the therapeutic effect of GQD on UC and its pulmonary complications and uncover its molecular mechanism mediated by myeloid cells and microbiota. Methods Mice with DSS-induced colitis were orally administrated with GQD. Overall vital signs were assessed by body weight loss and disease activity index (DAI). Pulmonary general signs were evaluated by pulmonary pathology and lung function. The mechanism of GQD relieving UC was characterized by detecting myeloid cells (neutrophils, macrophages, inflammatory monocytes, and resident monocytes) in colonic and lung tissues, related inflammatory cytokines, as well as the microbiota in bronchoalveolar lavage fluid (BALF) and feces. Results GQD significantly reduced weight loss, DAI scores, and lung injury but improved the lung function of colitis mice. The DSS-induced colonic and concurrent pulmonary inflammation were also alleviated by GQD, as indicated by the down-regulated expressions of inflammatory cytokines (TNF-α, IL-1β, IL-6, CCR2, and CCL2) and the suppressed recruitment of neutrophils and inflammatory monocytes. Meanwhile, GQD greatly improved intestinal microbiota imbalance by enriching Ruminococcaceae UCG-013 while decreasing Parabacteroides, [Eubacterium]_ fissicatena _group , and Akkermansia in the feces of colitis mice. Expectantly, GQD also restored lung microbiota imbalance by clearing excessive Coprococcus 2 and Ochrobactrum in the BALF of colitis mice. Finally, significant correlations appeared between GQD-mediated specific bacteria and inflammatory cytokines or immune cells. Conclusion GQD could alleviate UC by decreasing excessive inflammatory myeloid cells and cytokines, and reshaping the microbiota between the colon and lung, which contributes to clarifying the mechanism by which GQD ameliorates colitis-associated pulmonary inflammation.

Bifidobacterium animalis subsp. lactis BL-99 ameliorates colitis-related lung injury in mice by modulating short-chain fatty acid production and inflammatory monocytes/macrophages

“…34 In our previous study, we found inflammatory monocyte and macrophage infiltration in colitis-induced lung injury, in agreement with our present findings. 9 Moreover, we further found that the high doses of probiotic BL-99 effectively inhibited the infiltration of inflammatory cells in the lungs of colitis mice. Immediately, we proceeded towards exploring the regulation between the gut microbes and metabolites on inflammatory cells.…”

“…Inflammatory (Inflam) monocytes were identified as CD45 + CD11b + CD11c − Ly6C hi , and macrophages were identified as CD45 + CD11b + F4/80 + cells. 9,24 Single-cell suspensions were kept at 4 °C, and nonspecific binding was blocked by an anti-Fc receptor-blocking antibody (anti-CD16/32) before the cell surface was stained with fluorescently conjugated antibodies. The cells were then stained with PB anti-mouse CD45, PE-Cy5 anti-mouse CD11b, FITC anti-mouse CD11c, APC-Cy7 anti-mouse Ly6C, and F4/80 anti-mouse AF700.…”

“…8 Our previous study has also proved that the DSS-colitis mice exhibit significant lung inflammation and a higher proportion of lung inflammatory monocytes than controls. 9 On the other hand, intestinal microbiota and microbial metabolites are also involved in maintaining immune homeostasis in distal mucosal sites, especially in the lungs. 3,10 We have previously found that intestinal microbial diversity and composition in mice with colitis and concurrent lung inflammation are dramatically different from those in their controls.…”

“…3,10 We have previously found that intestinal microbial diversity and composition in mice with colitis and concurrent lung inflammation are dramatically different from those in their controls. 9 Short-chain fatty acids (SCFAs), as important microbial metabolites from the microbial fermentation of dietary fiber, are also a major bridge for metabolic and immune signaling within the gut-lung axis. 11 Mice with LPS-induced acute lung injury are accompanied by a reduction in gut microbiota diversity and a decrease in SCFAproducing bacteria.…”

“…20 In our previous study, we also observed lung pathological damage and a decrease in lung function in UC mice. 9 In this study, we used a DSS-induced experimental colitis mouse model to explore the prophylactic effect of BL-99 on colitis-related lung inflammation and its microbial and immunological mechanisms. This research will provide reliable experimental evidence for the clinical search for probiotics for the treatment of pulmonary complications of colitis.…”