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Gut microbiota modulates lung fibrosis severity following acute lung injury in mice.

Ozioma S ChiomaElizabeth K MallottAustin ChapmanJoseph C Van AmburgHongmei WuBinal Shah-GandhiNandita DeyMarina E KirklandM Blanca PiazueloJoyce JohnsonGordon R BernardSobha R BodduluriSteven DavisonBodduluri HaribabuSeth R BordensteinWonder P Drake
Published in: Communications biology (2022)
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 TGFβ1-stimulated human lung fibroblasts. These findings support a functional role of the gut microbiota in augmenting lung fibrosis severity.
Keyphrases
  • high fat diet induced
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  • stem cells
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  • lipopolysaccharide induced
  • inflammatory response
  • bone marrow
  • signaling pathway
  • pulmonary fibrosis