TY - JOUR
T1 - Antibiotic-induced microbiome perturbations are associated with significant alterations to colonic mucosal immunity in rhesus macaques
AU - Manuzak, Jennifer A.
AU - Zevin, Alexander S.
AU - Cheu, Ryan
AU - Richardson, Brian
AU - Modesitt, Jacob
AU - Hensley-McBain, Tiffany
AU - Miller, Charlene
AU - Gustin, Andrew T.
AU - Coronado, Ernesto
AU - Gott, Toni
AU - Fang, Mike
AU - Cartwright, Michael
AU - Wangari, Solomon
AU - Agricola, Brian
AU - May, Drew
AU - Smith, Elise
AU - Hampel, Hans Benjamin
AU - Gale, Michael
AU - Cameron, Cheryl M.
AU - Cameron, Mark J.
AU - Smedley, Jeremy
AU - Klatt, Nichole R.
N1 - Publisher Copyright:
© 2019, Society for Mucosal Immunology.
PY - 2020/5/1
Y1 - 2020/5/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85076003582&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85076003582&partnerID=8YFLogxK
U2 - 10.1038/s41385-019-0238-1
DO - 10.1038/s41385-019-0238-1
M3 - Article
C2 - 31797911
AN - SCOPUS:85076003582
SN - 1933-0219
VL - 13
SP - 471
EP - 480
JO - Mucosal Immunology
JF - Mucosal Immunology
IS - 3
ER -