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

Natalia Vallianou, Maria Dalamaga, Theodora Stratigou, Irene Karampela, Christina Tsigalou, Natalia Vallianou, Maria Dalamaga, Theodora Stratigou, Irene Karampela, Christina Tsigalou

Abstract

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.

Keywords: Antibiotic; Diet; Gut; Infection; Intestine; Metabolic syndrome; Microbiome; Microbiota; Obesity; Prebiotic; Probiotic; Virus.

Conflict of interest statement

Natalia Vallianou, Maria Dalamaga, Theodora Stratigou Irene Karampela. and Christina Tsigalou declare no conflict of interest.

© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Figures

Fig. 1
Fig. 1
Key gut microbiota, metabolite, and functional characteristics associated with obesity. Overall, there is lower microbial richness and diversity as well as lower microbial gene count in obesity compared to normal weight individuals. A plethora of studies has implicated certain microbial species, metabolic and functional characteristics in obesity; nevertheless, findings differ between studies. This list is not complete regarding the totality of altered taxonomic, metabolite, and functional characteristics but represents frequent patterns observed amid studies. Abbreviation list: BCAA: branched-chain amino acid; LPS: lipopolysaccharide; SCFA: short-chain fatty acid; TMAO: trimethyl-amine-N-oxide; ↓ or ↑: reduced or increased abundance in obesity compared to normal-weight individuals
Fig. 2
Fig. 2
Gut dysbiosis triggered by environmental exposures such as diet and antibiotics plays an important role in disrupting molecular metabolism and impacting on obesity outcomes. In obesity, the adipose tissue is infiltrated with inflammatory immune cells that produce high amounts of proinflammatory cytokines and chemokines. The gut barrier is disrupted causing gut antigens and PAMPs such as LPS to enter the tissue and stimulate inflammation. DC: dendritic cells, GABA: gamma aminobutyric acid, Mono: monocytes, PYY: peptide YY, PMNs: polymorphonuclear neutrophils, Th: T helper cells; 5HT: 5-hydroxytryptamine

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