Murine gut microbiota dysbiosis via enteric infection modulates the foreign body response to a distal biomaterial implant
Abstract
The gut microbiota influences systemic immunity and the function of distal tissues, including the brain, liver, skin, lung, and muscle. However, the role of the gut microbiota in the foreign body response and fibrosis is largely unexplored. To investigate this connection, we perturbed the homeostasis of the murine gut microbiota via infection with the pathogenic bacterial species enterotoxigenic Bacteroides fragilis (ETBF) and implanted particulate material (mean particle size <600 μm) of the synthetic polymer polycaprolactone (PCL) into a distal muscle injury. ETBF infection in mice led to increased neutrophil and γδ T cell infiltration into the PCL implant site. ETBF infection alone promoted systemic inflammation, increased levels of neutrophils in lymphoid tissues, and altered skeletal muscle gene expression. At the PCL implant site, we found significant changes in the transcriptome of sorted stromal cells between infected and control mice, including differences related to ECM components such as proteoglycans and glycosaminoglycans. However, we did not observe ETBF-induced differences in fibrosis levels. These results demonstrate the ability of the gut microbiota to mediate long-distance effects such as immune and stromal responses to a distal biomaterial implant.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (22)
Brenda Yang
Department of Biomedical Engineering, Cellular and Molecular Medicine, or Ophthalmology, Translational Tissue Engineering Center, Johns Hopkins University
Natalie Rutkowski
Department of Biomedical Engineering, Cellular and Molecular Medicine, or Ophthalmology, Translational Tissue Engineering Center, Johns Hopkins University
Anna Ruta
Department of Biomedical Engineering, Cellular and Molecular Medicine, or Ophthalmology, Translational Tissue Engineering Center, Johns Hopkins University
Elise Gray-Gaillard
Department of Biomedical Engineering, Cellular and Molecular Medicine, or Ophthalmology, Translational Tissue Engineering Center, Johns Hopkins University
David R. Maestas
Department of Biomedical Engineering, Cellular and Molecular Medicine, or Ophthalmology, Translational Tissue Engineering Center, Johns Hopkins University
Sean H. Kelly
Department of Biomedical Engineering, Cellular and Molecular Medicine, or Ophthalmology, Translational Tissue Engineering Center, Johns Hopkins University
Kavita Krishnan
Department of Biomedical Engineering, Cellular and Molecular Medicine, or Ophthalmology, Translational Tissue Engineering Center, Johns Hopkins University
Xinqun Wu
Department of Medicine, Johns Hopkins University School of Medicine
Shaoguang Wu
Allen Chen
Department of Biomedical Engineering, Zanvyl Krieger Mind/Brain Institute, Johns Hopkins University
Joscelyn C. Mejías
Department of Biomedical Engineering, Cellular and Molecular Medicine, or Ophthalmology, Translational Tissue Engineering Center, Johns Hopkins University
Joshua S. T. Hooks
Department of Biomedical Engineering, Cellular and Molecular Medicine, or Ophthalmology, Translational Tissue Engineering Center, Johns Hopkins University
Isabel Vanderzee
Department of Biomedical Engineering, Cellular and Molecular Medicine, or Ophthalmology, Translational Tissue Engineering Center, Johns Hopkins University
Patricia Mensah
Department of Biomedical Engineering, Cellular and Molecular Medicine, or Ophthalmology, Translational Tissue Engineering Center, Johns Hopkins University
Nazmiye Celik
Department of Biomedical Engineering, Cellular and Molecular Medicine, or Ophthalmology, Translational Tissue Engineering Center, Johns Hopkins University
Marie Eric
Department of Biomedical Engineering, Cellular and Molecular Medicine, or Ophthalmology, Translational Tissue Engineering Center, Johns Hopkins University
Peter Abraham
Department of Biomedical Engineering, Cellular and Molecular Medicine, or Ophthalmology, Translational Tissue Engineering Center, Johns Hopkins University
Ada Tam
Department of Oncology and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine
Franck Housseau
Department of Oncology and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine
Drew M. Pardoll
Department of Oncology and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine
Cynthia L. Sears
Jennifer H. Elisseeff
Department of Biomedical Engineering, Cellular and Molecular Medicine, or Ophthalmology, Translational Tissue Engineering Center, Johns Hopkins University