Although there is strong evidence in mouse models of obesity that the gut microbiome can be manipulated to target obesity-related metabolic disorders, evidence in humans is scarce. Human studies examining the effects and underlying mechanisms of gut microbiota modulation on host metabolism are currently lacking.
A recent randomized double-blind placebo-controlled trial, led by Dr. Ellen Blaak from the Department of Human Biology at Maastricht University Medical Centre in Maastricht (The Netherlands), has found that a 7-day antibiotic treatment does not affect host metabolism in obese humans in the short term, despite profound changes in gut microbial diversity and composition.
The researchers investigated the effects of broad-spectrum (amoxicillin, n=18) and narrow-spectrum (vancomycin, n=19) antibiotic treatment for 7 days on gut microbiota composition, insulin sensitivity, energy expenditure, substrate oxidation, faecal and plasma bile acids (BAs) and short-chain fatty acids (SCFAs), gut permeability, abdominal subcutaneous adipocyte size, and systemic low-grade inflammation in 35-70-year-old Caucasian obese men with impaired fasting glucose levels and/or impaired glucose tolerance, who were insulin resistant. The placebo group consisted of 19 obese pre-diabetic men without differences in baseline characteristics when compared to both intervention groups. Furthermore, 8 weeks after cessation of antibiotic treatment, gut microbiota composition, insulin sensitivity, faecal energy harvest, and adipocyte size were again determined.
Vancomycin but not amoxicillin treatment altered gut microbiota composition. Vancomycin decreased bacterial diversity and reduced the relative abundance of bacteria from the Firmicutes phylum involved in butyrate production and in BA metabolism. Concomitant with inhibition in SCFA production and BA conversion by vancomycin, plasma and/or faecal concentrations of primary/secondary BAs and SCFAs were also altered. Of note, gut microbiota composition was still affected 8 weeks after cessation of vancomycin treatment. Conversely, amoxicillin treatment did not affect gut microbiota composition after 7 days treatment or at 8 weeks follow-up compared to placebo.
7-day antibiotic treatment did not affect tissue-specific (hepatic and adipose tissue) or peripheral insulin sensitivity. At 8 weeks follow-up, whole-body insulin sensitivity assessed by the homeostasis model assessment of insulin resistance (HOMA-IR) was not altered by antibiotic treatment. In accordance, antibiotics did not affect energy and substrate metabolism, postprandial hormones and metabolites, systemic inflammation, gut permeability, or adipocyte size. Together, these results show that host metabolism remained unchanged at 8-week follow-up, despite deviant gut microbiota composition induced by vancomycin.
To sum up, despite profound changes in gut microbiota composition and plasma/faecal SCFAs and BAs induced by vancomycin, treatment with this antibiotic did not affect host metabolism in obese humans immediately after cessation of treatment, nor at 8 weeks follow-up.
Reijnders D, Goossens GH, Hermes GD, et al. Effects of gut microbiota manipulation by antibiotics on host metabolism in obese humans: a randomized double-blind placebo-controlled trial. Cell Metab. 2016; 24(1):63-74. doi: 10.1016/j.cmet.2016.06.016.
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