Gut microbiota modulates lung fibrosis severity following acute lung injury in mice
Chioma, Ozioma S. S.
Mallott, Elizabeth K. K.
Chapman, Austin
Van Amburg, Joseph C. C.
Wu, Hongmei
Shah-Gandhi, Binal
Dey, Nandita
Kirkland, Marina E. E.
Blanca Piazuelo, M.
Johnson, Joyce
Bernard, Gordon R. R.
Bodduluri, Sobha R. R.
Davison, Steven
Haribabu, Bodduluri
Bordenstein, Seth R. R.
Drake, Wonder P. P.
:
2023-01-13
Abstract
Independent studies demonstrate the significance of gut microbiota on the pathogenesis of chronic lung diseases; yet little is known regarding the role of the gut microbiota in lung fibrosis progression. Here we show, using the bleomycin murine model to quantify lung fibrosis in C57BL/6 J mice housed in germ-free, animal biosafety level 1 (ABSL-1), or animal biosafety level 2 (ABSL-2) environments, that germ-free mice are protected from lung fibrosis, while ABSL-1 and ABSL-2 mice develop mild and severe lung fibrosis, respectively. Metagenomic analysis reveals no notable distinctions between ABSL-1 and ABSL-2 lung microbiota, whereas greater microbial diversity, with increased Bifidobacterium and Lactobacilli, is present in ABSL-1 compared to ABSL-2 gut microbiota. Flow cytometric analysis reveals enhanced IL-6/STAT3/IL-17A signaling in pulmonary CD4 + T cells of ABSL-2 mice. Fecal transplantation of ABSL-2 stool into germ-free mice recapitulated more severe fibrosis than transplantation of ABSL-1 stool. Lactobacilli supernatant reduces collagen 1 A production in IL-17A- and TGF beta 1-stimulated human lung fibroblasts. These findings support a functional role of the gut microbiota in augmenting lung fibrosis severity.