1. Antibiotic-induced microbiome perturbations are associated with significant alterations to colonic mucosal immunity in rhesus macaques
- Author
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Ryan Cheu, Michael Cartwright, Alexander S. Zevin, Jeremy Smedley, Ernesto Coronado, Mike Fang, Toni M. Gott, Hans Benjamin Hampel, Drew May, Andrew T. Gustin, Jacob Modesitt, Brian Richardson, Solomon Wangari, Nichole R. Klatt, Jennifer A. Manuzak, Mark J. Cameron, Brian Agricola, Cheryl M. Cameron, Elise Smith, Michael Gale, Charlene Miller, and Tiffany Hensley-McBain
- Subjects
0301 basic medicine ,Colon ,medicine.drug_class ,Immunology ,Antibiotics ,medicine.disease_cause ,Drug Administration Schedule ,Gas Chromatography-Mass Spectrometry ,Immunophenotyping ,Microbiology ,Feces ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,T-Lymphocyte Subsets ,Immunity ,medicine ,Animals ,Immunology and Allergy ,Tissue Distribution ,Microbiome ,Intestinal Mucosa ,Immunity, Mucosal ,Bacteria ,biology ,Clindamycin ,Pathogenic bacteria ,Biodiversity ,Fatty Acids, Volatile ,biology.organism_classification ,Macaca mulatta ,Enterobacteriaceae ,Anti-Bacterial Agents ,Gastrointestinal Microbiome ,030104 developmental biology ,Neutrophil Infiltration ,Drug Monitoring ,Biomarkers ,030215 immunology ,medicine.drug - Abstract
The diverse bacterial communities that colonize the gastrointestinal tract play an essential role in maintaining immune homeostasis through the production of critical metabolites such as short-chain fatty acids (SCFAs) and this can be disrupted by antibiotic use. However, few studies have addressed the effects of specific antibiotics longitudinally on the microbiome and immunity. We evaluated the effects of four specific antibiotics: enrofloxacin, cephalexin, paromomycin, and clindamycin, in healthy female rhesus macaques. All antibiotics disrupted the microbiome, including reduced abundances of fermentative bacteria and increased abundances of potentially pathogenic bacteria, including Enterobacteriaceae in the stool, and decreased Helicobacteraceae in the colon. This was associated with decreased SCFAs, indicating altered bacterial metabolism. Importantly, antibiotic use also substantially altered local immune responses, including increased neutrophils and Th17 cells in the colon. Furthermore, we observed increased soluble CD14 in plasma, indicating microbial translocation. These data provide a longitudinal evaluation of antibiotic-induced changes to the composition and function of colonic bacterial communities associated with specific alterations in mucosal and systemic immunity.
- Published
- 2020