1. Antibiotic-induced microbiome perturbations are associated with significant alterations to colonic mucosal immunity in rhesus macaques.
- Author
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Manuzak JA, Zevin AS, Cheu R, Richardson B, Modesitt J, Hensley-McBain T, Miller C, Gustin AT, Coronado E, Gott T, Fang M, Cartwright M, Wangari S, Agricola B, May D, Smith E, Hampel HB, Gale M, Cameron CM, Cameron MJ, Smedley J, and Klatt NR
- Subjects
- Animals, Anti-Bacterial Agents administration & dosage, Anti-Bacterial Agents pharmacokinetics, Bacteria, Biodiversity, Biomarkers, Drug Administration Schedule, Drug Monitoring, Fatty Acids, Volatile metabolism, Feces cytology, Feces microbiology, Gas Chromatography-Mass Spectrometry, Immunophenotyping, Intestinal Mucosa pathology, Macaca mulatta, Neutrophil Infiltration drug effects, Neutrophil Infiltration immunology, T-Lymphocyte Subsets drug effects, T-Lymphocyte Subsets immunology, T-Lymphocyte Subsets metabolism, Tissue Distribution, Anti-Bacterial Agents pharmacology, Colon, Gastrointestinal Microbiome drug effects, Immunity, Mucosal drug effects, Intestinal Mucosa drug effects, Intestinal Mucosa immunology, Intestinal Mucosa microbiology
- 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
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