Antibiotic-induced microbiota depletion impairs the proregenerative response to a biological scaffold
Abstract
Therapeutic biological scaffolds promote tissue repair primarily through the induction of type 2 immunity. However, systemic immunological factors, including aging, sex, and previous infections, can modulate this response. The gut microbiota is a well-established modulator of immune function across organ systems, yet its influence on type 2-mediated repair remains underexplored. Here, we establish a bidirectional relationship between the gut microbiota and biological scaffold-mediated tissue repair. Utilizing a conventionalized germ-free mouse, we demonstrate that scaffold implantation induces compositional and functional changes in the gut microbiome, particularly affecting amino acid biosynthesis. Additionally, in a model of antibiotic-induced microbiota depletion, we show that dysbiosis disrupts key immune regulators of type 2 immunity, including reductions in eosinophils, proregenerative macrophages, and interleukin-4 (IL-4)-producing CD4 + T cells. At 6 wk post–scaffold implantation, we observed a significant decrease in myocytes with centrally located nuclei alongside an upregulation in profibrotic gene expression with antibiotic treatment. These findings provide insights into the influence of the gut microbiota on type 2-mediated tissue repair.
Article Details
Journal Info
Proceedings of the National Academy of Sciences
National Academy of Sciences
Authors (15)
Natalie Rutkowski
Department of Biomedical Engineering, Cellular and Molecular Medicine, or Ophthalmology, Translational Tissue Engineering Center, Johns Hopkins University
Brenda Yang
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
Anna Ruta
Department of Biomedical Engineering, Cellular and Molecular Medicine, or Ophthalmology, Translational Tissue Engineering Center, Johns Hopkins University
Joscelyn C. Mejías
Department of Biomedical Engineering, Cellular and Molecular Medicine, or Ophthalmology, Translational Tissue Engineering Center, Johns Hopkins University
Michael Patatanian
Department of Biomedical Engineering, Cellular and Molecular Medicine, or Ophthalmology, Translational Tissue Engineering Center, Johns Hopkins University
Christopher Cherry
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
Katlin B. Stivers
Department of Biomedical Engineering, Cellular and Molecular Medicine, or Ophthalmology, Translational Tissue Engineering Center, Johns Hopkins University
Shri Ramanujam
Department of Biomedical Engineering, Cellular and Molecular Medicine, or Ophthalmology, Translational Tissue Engineering Center, Johns Hopkins University
Nathan L. Price
Translational Gerontology Branch, National Institute on Aging
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