Do Antibiotics Cause Obesity Through Long-term Alterations in the Gut Microbiome? A Review of Current Evidence.

PURPOSE OF REVIEW

In this review, we summarize current evidence on the association between antibiotics and the subsequent development of obesity through modulation of the gut microbiome. Particular emphasis is given on (i) animal and human studies and their limitations; (ii) the reservoir of antibiotics in animal feed, emerging antibiotic resistance, gut dysbiosis, and obesity; (iii) the role of infections, specifically viral infections, as a cause of obesity; and (iv) the potential therapeutic approaches other than antibiotics to modulate gut microbiome.

RECENT FINDINGS

Overall, the majority of animal studies and meta-analyses of human studies on the association between antibiotics and subsequent development of obesity are suggestive of a link between exposure to antibiotics, particularly early exposure in life, and the development of subsequent obesity as a result of alterations in the diversity of gut microbiota. The evidence is strong in animal models whereas evidence in humans is inconclusive requiring well-designed, long-term longitudinal studies to examine this association. Based on recent meta-analyses and epidemiologic studies in healthy children, factors, such as the administration of antibiotics during the first 6 months of life, repeated exposure to antibiotics for ≥ 3 courses, treatment with broad-spectrum antibiotics, and male gender have been associated with increased odds of overweight/obesity. Early antibiotic exposure in animal models has shown that reductions in the population size of specific microbiota, such as Lactobacillus, Allobaculum, Rikenellaceae, and Candidatus Arthromitus, are related to subsequent adiposity. These data suggest that the loss of diversity of the gut microbiome, especially early in life, may have potential long-term detrimental effects on the adult host gut microbiome and metabolic health. Genetic, environmental, and age-related factors influence the gut microbiome throughout the lifetime. More large-scale, longer-term, longitudinal studies are needed to determine whether changes that occur in the microbiome after exposure to antibiotics, particularly early exposure, are causal of subsequent weight gain or consequent of weight gain in humans. Further well-designed, large-scale RCTs in humans are required to evaluate the effects of administration of antibiotics, particularly early administration, and the subsequent development of overweight/obesity. Therapeutic interventions, such as bacteriophage treatment or the use of probiotics, especially genetically engineered ones, need to be evaluated in terms of prevention and management of obesity.