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

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 (SCFA), 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 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. Overall design: 12 female rhesus macaques were treated with antibiotics (n=3/group) including: enrofloxacin (12 mg/kg, n=3, once daily, 9 days), cephalexin (30mg/kg, n=3, once daily, 9 days), paromomycin (25 mg/kg, n=3, twice daily, 9 days), or clindamycin (10 mg/kg, n=3, twice daily, 6 days). Total RNA was collected from biopsies of the colon before (42 and 21 days prior to treatment), during (day 3), and after (days 14, 28, 63 and 119 or 127) the antibiotic treatment for a total of 84 samples that were sequenced for comparing treatments longitudinally.