Antibiotic-induced microbiome perturbations are associated with significant alterations to colonic mucosal immunity in rhesus macaques

Jennifer A. Manuzak, Alexander S. Zevin, Ryan Cheu, Brian Richardson, Jacob Modesitt, Tiffany Hensley-McBain, Charlene Miller, Andrew T. Gustin, Ernesto Coronado, Toni Gott, Mike Fang, Michael Cartwright, Solomon Wangari, Brian Agricola, Drew May, Elise Smith, Hans Benjamin Hampel, Michael Gale, Cheryl M. Cameron, Mark J. CameronJeremy Smedley, Nichole R. Klatt

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalMucosal Immunology
DOIs
StateAccepted/In press - Jan 1 2019

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Mucosal Immunity
Microbiota
Macaca mulatta
Anti-Bacterial Agents
Volatile Fatty Acids
Colon
Paromomycin
Bacteria
Cephalexin
Th17 Cells
Clindamycin
Enterobacteriaceae
Gastrointestinal Tract
Immunity
Neutrophils
Homeostasis

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Manuzak, J. A., Zevin, A. S., Cheu, R., Richardson, B., Modesitt, J., Hensley-McBain, T., ... Klatt, N. R. (Accepted/In press). Antibiotic-induced microbiome perturbations are associated with significant alterations to colonic mucosal immunity in rhesus macaques. Mucosal Immunology. https://doi.org/10.1038/s41385-019-0238-1

Antibiotic-induced microbiome perturbations are associated with significant alterations to colonic mucosal immunity in rhesus macaques. / Manuzak, Jennifer A.; Zevin, Alexander S.; Cheu, Ryan; Richardson, Brian; Modesitt, Jacob; Hensley-McBain, Tiffany; Miller, Charlene; Gustin, Andrew T.; Coronado, Ernesto; Gott, Toni; Fang, Mike; Cartwright, Michael; Wangari, Solomon; Agricola, Brian; May, Drew; Smith, Elise; Hampel, Hans Benjamin; Gale, Michael; Cameron, Cheryl M.; Cameron, Mark J.; Smedley, Jeremy; Klatt, Nichole R.

In: Mucosal Immunology, 01.01.2019.

Research output: Contribution to journalArticle

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 & Klatt, NR 2019, 'Antibiotic-induced microbiome perturbations are associated with significant alterations to colonic mucosal immunity in rhesus macaques', Mucosal Immunology. https://doi.org/10.1038/s41385-019-0238-1
Manuzak, Jennifer A. ; Zevin, Alexander S. ; Cheu, Ryan ; Richardson, Brian ; Modesitt, Jacob ; Hensley-McBain, Tiffany ; Miller, Charlene ; Gustin, Andrew T. ; Coronado, Ernesto ; Gott, Toni ; Fang, Mike ; Cartwright, Michael ; Wangari, Solomon ; Agricola, Brian ; May, Drew ; Smith, Elise ; Hampel, Hans Benjamin ; Gale, Michael ; Cameron, Cheryl M. ; Cameron, Mark J. ; Smedley, Jeremy ; Klatt, Nichole R. / Antibiotic-induced microbiome perturbations are associated with significant alterations to colonic mucosal immunity in rhesus macaques. In: Mucosal Immunology. 2019.
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