Antibiotics gut microbiome and metabolome - Long-Term study
Background: Antibiotics disrupt the gut bacterial composition and function, but antibiotic intake frequencies-associated disruptions are unclear. Furthermore, it is unknown to what extent probiotics or fecal microbiota transplantation (FMT) as recovery aids normalize the gut microbial function. Results: We observed significant changes in concentrations of urinary host-microbial co-metabolites and fecal amino acids (AAs) at 8-12 and 12-24 hours, respectively, following a single oral dose of vancomycin and ciprofloxacin (VC). No changes in the small intestinal bacterial composition were observed; relative abundances of Bacteroidaceae, Muribaculaceae and Tannerellaceae families in the caecum, colon and feces were reduced, along with increased caecal counts of Lactobacillaceae, Peptostreptococcaceae, Erysipelotrichaceae and Clostridiaceae families. Notably, VC-induced fecal bacterial changes were distinct from those in the cecum and colon. Next, we compared microbiomic changes induced by three courses of VC given at regular (every 3 weeks, VCr) or irregular (1-3 weeks between VC courses, VCi) frequencies. VCr exerted stronger suppression on the alpha-diversity and bacterial metabolism of AAs and host-microbial cometabolites during antibiotic treatment. Throughout the 3-week recovery, VCr exhibited slower normalization of fecal bacterial alpha-diversity compared to VCi without profound urinary and fecal metabolic differences between the two groups. Furthermore, we found significantly reduced concentrations of jejunal and ileal luminal AAs and choline in VCi and increased levels of jejunal cholic acid and large intestinal 5-aminovalerate (5-AV) in both VCi and VCr groups compared to the controls. We next reported probiotics or autologous FMT (aFMT) used between VC courses impacted fecal bacterial profiles during subsequent VC treatments, evidenced by higher relative abundances of Lactobacillaceae and Akkermansiaceae in aFMT compared to natural recovery. In the recovery phase, aFMT and probiotics promoted quicker normalization of fecal AAs and partially suppressed VC-induced increases in colonic 5-AV concentrations, but did not lead to full metabolic recovery and showed little impact on the VCi-induced changes in the small intestinal environment.  Conclusion: Our study highlighted impact of antibiotic intake frequencies on the fecal microbiome and intestinal luminal metabolome. The partial metabolic normalization by aFMT and probiotics following antibiotics highlight the necessity for tailored and novel recovery approaches to address long-term dysbiosis.
Background: Antibiotics disrupt the gut bacterial composition and function, but antibiotic intake frequencies-associated disruptions are unclear. Furthermore, it is unknown to what extent probiotics or fecal microbiota transplantation (FMT) as recovery aids normalize the gut microbial function. Results: We observed significant changes in concentrations of urinary host-microbial co-metabolites and fecal amino acids (AAs) at 8-12 and 12-24 hours, respectively, following a single oral dose of vancomycin and ciprofloxacin (VC). No changes in the small intestinal bacterial composition were observed; relative abundances of Bacteroidaceae, Muribaculaceae and Tannerellaceae families in the caecum, colon and feces were reduced, along with increased caecal counts of Lactobacillaceae, Peptostreptococcaceae, Erysipelotrichaceae and Clostridiaceae families. Notably, VC-induced fecal bacterial changes were distinct from those in the cecum and colon. Next, we compared microbiomic changes induced by three courses of VC given at regular (every 3 weeks, VCr) or irregular (1-3 weeks between VC courses, VCi) frequencies. VCr exerted stronger suppression on the alpha-diversity and bacterial metabolism of AAs and host-microbial cometabolites during antibiotic treatment. Throughout the 3-week recovery, VCr exhibited slower normalization of fecal bacterial alpha-diversity compared to VCi without profound urinary and fecal metabolic differences between the two groups. Furthermore, we found significantly reduced concentrations of jejunal and ileal luminal AAs and choline in VCi and increased levels of jejunal cholic acid and large intestinal 5-aminovalerate (5-AV) in both VCi and VCr groups compared to the controls. We next reported probiotics or autologous FMT (aFMT) used between VC courses impacted fecal bacterial profiles during subsequent VC treatments, evidenced by higher relative abundances of Lactobacillaceae and Akkermansiaceae in aFMT compared to natural recovery. In the recovery phase, aFMT and probiotics promoted quicker normalization of fecal AAs and partially suppressed VC-induced increases in colonic 5-AV concentrations, but did not lead to full metabolic recovery and showed little impact on the VCi-induced changes in the small intestinal environment.  Conclusion: Our study highlighted impact of antibiotic intake frequencies on the fecal microbiome and intestinal luminal metabolome. The partial metabolic normalization by aFMT and probiotics following antibiotics highlight the necessity for tailored and novel recovery approaches to address long-term dysbiosis.
Cardiff University, School of Biosciences