Disruption of the Lung Microbiome Early in Life Protects Mice from Systemic Lupus Erythematosus 2260267

Abstract Introduction Systemic lupus erythematosus (SLE) is an incurable autoimmune disease. While the disease is well characterized, the pathogenesis is not clearly understood. It is widely accepted that the gut microbiome plays a role in SLE progression, but there is less data about other mucosal microbiomes, such as in the lung. Methods We administered a mixture of vancomycin, neomycin, ampicillin, and metronidazole (ABX) or phosphate-buffer solution (PBS) via intranasal gavage every 3 days, starting at 4 weeks, until 7 of life (10 administrations) to lupus-prone MRL/lpr mice, collecting urine and weights weekly. At 15 weeks, we euthanized the mice and collected lymph organs, lungs, and kidneys. We extracted bacterial DNA from bronchial alveolar lavage fluid (BALF) and feces and performed bacterial 16S ribosomal sequencing. Results ABX mice had larger mediastinal lymph nodes (MsLN), but more distant lymph organs were the same size. However, ABX mice had decreased protein in their urine, indicating less severe lupus disease. ABX mice had decreased monocytes in their lung and increased CD4+ T cells. In the MsLN, ABX mice had decreased plasmablasts, IL-17-producing B cells, and interferon gamma producing T cells in their MsLN. ABX mice had fewer CD4-CD8- (DN) T cells and monocytes in their spleen. There was no difference in the lung microbiomes when comparing overall microbiota compositions, however, when comparing individual genus and family levels, there were clear differences. Further, when correlating the relative abundance of bacteria to disease parameters, we found that the lung microbiome, indicated by BALF, was more predictive of disease severity than the gut microbiome represented by the feces. Conclusion We found that intranasal antibiotics conferred protection against lupus, and that the lung microbiome was capable of predicting disease outcomes in lupus-prone mice. We believe that further study of the lung microbiome in inflammatory diseases is important, as it is a major site of microbe-host interaction. Funding Source NIH Topic Categories Basic Autoimmunity (BA)