Effects of Gut Microbiota Manipulation by Antibiotics on Host Metabolism in Obese Humans: A Randomized Double-Blind Placebo-Controlled Trial

Abstract

Highlights d Vancomycin but not amoxicillin treatment alters human gut microbiota composition d Vancomycin treatment alters short-chain fatty acid and bile acid concentrations d Modulation of adult microbiota by 7-day antibiotics does not affect host metabolism d Host metabolism remained unchanged at 8-week follow-up, despite deviant microbiota

Effects of gut microbiota manipulation onex vivolipolysis in human abdominal subcutaneous adipocytes

“…We demonstrated that oral administration of VANCO or AMOX for 7 days has no major effect on ex vivo β-adrenergic sensitivity in adipocytes derived from obese insulin resistant men. We have previously reported that VANCO but not AMOX treatment markedly reduced microbiota diversity and altered its composition, predominantly by decreasing gram-positive Firmicutes [19]. In the current sub-cohort, microbiota changes were comparable (data not shown).…”

“…In the current sub-cohort, microbiota changes were comparable (data not shown). VANCO treatment for 7 days decreased the abundance of Clostridium clusters XIVa and IV, which was accompanied by a reduced conversion of primary to secondary BAs, and a lower concentration of fecal SCFA [19]. Interestingly, SCFA and BA receptors (i.e.…”

“…The current research was conducted as part of a larger clinical trial on the effect of gut microbiota manipulation on host metabolism [19], In total, 22 overweight and obese (BMI 25–35 kg × m 2 ) Caucasian men between 35–70 years were included in the present study. Detailed inclusion and exclusion criteria have previously been described [19].…”

“…Detailed inclusion and exclusion criteria have previously been described [19]. All subjects gave written informed consent before participation in this trail.…”

“…SCFA or GLP-1 agonists) may indeed affect AT metabolism, it remains to be determined whether modulation of the gut microbiota may provide a strategy to target adipose tissue lipolysis and potentially improve obesity-related metabolic impairments. To this end, we collected adipose tissue biopsies of obese, insulin resistant humans after microbiota manipulation using broad spectrum (amoxicillin; AMOX) and narrow-spectrum (vancomycin; VANCO) antibiotics for 7 days [19], In the collected human adipocytes, we assessed ex vivo basal and β-adrenergically stimulated lipolysis. Targeted gene and protein expression analyses were performed to investigate potential underlying mechanisms that link the gut microbiota with host metabolic processes.…”