Gut-lung dysbiosis accompanied by diabetes mellitus leads to pulmonary fibrotic change through the NF-κB signaling pathway.

Abstract Growing evidence shows that the lungs are an unavoidable target organ of diabetic complications. However, the pathological mechanisms of diabetic lung injury are still controversial. This study demonstrated the dysbiosis of the gut and lung microbiome, pulmonary alveolar wall thickening and fibrotic change in streptozotocin (STZ)-induced diabetic mice and antibiotic-induced gut dysbiosis mice compared to controls. In both animal models, the NF-κB signaling pathway was activated in the lungs. Enhanced pulmonary alveolar well thickening and fibrotic change appeared in the lungs of transgenic mice expressing a constitutively active NF-κB mutant compared to wild-type. When lincomycin hydrochloride (LH)-induced gut dysbiosis was ameliorated by fecal microbiota transplant (FMT), enhanced inflammatory response in the intestine, and pulmonary fibrotic change in the lungs were significantly decreased compared to LH-treated mice. Furthermore, the application of FMT and Baicalin could also redress the microbial dysbiosis of the gut and lungs in STZ-induced diabetic mice. Taken together, this study data suggest that multiple as yet undefined factors related to microbial dysbiosis of gut and lungs cause pulmonary fibrogenesis associated with DM through an NF-kB signaling pathway.