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

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 (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 Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

Optimizing Secondary Electrospray Ionization High-Resolution Mass Spectrometry (SESI-HRMS) for the Analysis of Volatile Fatty Acids from Gut Microbiome

“…Similarly, we also observed relatively decreased levels of C 2 , C 3 , C 5 , and C 6 VFAs of test groups ( Figure 5 A,B,D,E), which may be led by the considerably reduced OD values ( p < 0.05) after anaerobic incubation of antibiotic-treated cultures for six hours. Among the studied VFAs, C 4 VFA such as butyric acid has received an increased attention because of its beneficial effects on the gut as a key energy source for colonic epithelial cells [ 26 ]. It was also reported to exert various intestinal activities that are involved in modulating intestinal epithelial defense and improving inflammation and intestinal motility [ 41 , 42 , 43 ].…”

“…It has been reported that the extrinsic factors, such as diet and antibiotics, perturbate the gut microbiome community and their metabolites, which may lead to dysbiosis [ 17 , 25 ]. The administration of antibiotics has been widely applied in the treatment and prevention of infectious diseases [ 26 ]. However, fewer studies have been conducted to evaluate the effect of antibiotics on the VFA profiles of the gut microbiota [ 26 , 27 ].…”

“…The administration of antibiotics has been widely applied in the treatment and prevention of infectious diseases [ 26 ]. However, fewer studies have been conducted to evaluate the effect of antibiotics on the VFA profiles of the gut microbiota [ 26 , 27 ].…”

Liver bacterial dysbiosis occurs in SIV-infected macaques and persists during antiretroviral therapy

“…infection have advanced the understanding of gut-driven systemic immune activation and HIV disease progression [24]. The microbiome is in uenced by numerous factors such as age, environment, food and antibiotics [25][26][27][28][29]. With regard to the liver during SIV infection, prior studies have identi ed elevated bacterial loads during SIV infection [30,31], as well as in the context of cART [32], and have shown that bacteria may increase immune cell in ltration [30].…”

Reconstruction and dynamics of human intestinal microbiome observedin situ

“…Fecal microbiome largely represent the last stage of transitions of microbial communities along the GI tract, and as numerous biogeographical analyses revealed the distinction of fecal microbiome from different GI sections 2 , where important biological processes take place. Largely composed of bacteria and archaea from lumen (content), fecal microbiome also indicate poorly on the mucosal microbiome, community at the intimate interface of cross-talk with the host and especially interactions with immune systems 3, 4 . In addition, continual fecal samples are rarely taken within short intervals but mostly daily due to human physiology, which disables investigations into community dynamics with finer resolution, for instance diurnal cycles that are feasible in mouse and have already been shown to be closely linked to host physiological homeostasis 5, 6, 7 .…”