Early-life exposure to antibiotics and excess body weight in childhood and adolescence: A systematic review and meta-analysis.

BACKGROUND: The association between early-life exposure to antibiotics and overweight/obesity is unclear. We conducted a systematic review and meta-analysis to address this issue. METHODS: We searched PubMed, Web of Science, Scopus, and grey literature from inception to August 10, 2022, for cohort studies investigating the association between early-life exposure to antibiotics and weight outcomes. Two independent reviewers screened studies for eligibility, extracted data, assessed risk of bias, and examined the certainty of the evidence. Random-effects meta-analyses was used for pooling the data. The review was registered in PROSPERO, CRD42021265417. RESULTS: We included 42 studies and data from 28 of them were pooled in the quantitative synthesis. Overall antenatal (OR 1.10, 95% CI 1.04-1.16; 518,095 children, very low certainty) and second trimester (OR 1.11, 95% CI 1.08-1.14, 248,469 children, low certainty) exposure to antibiotics were associated with increased risk of overweight/obesity in childhood/adolescence. Overall early postnatal antibiotic exposure was also associated with increased likelihood of overweight/obesity in childhood/adolescence (OR 1.09, 95% CI 1.05-1.12, 1,488,316 children, very low certainty). The magnitude of the association increased from exposure to one (OR 1.07, 95% CI 1.00-1.15, 512,954 children) to four or more courses of antibiotics (OR 1.31, 95% CI 1.17-1.46, 543,627 children). CONCLUSION: Antenatal and early postnatal exposure to antibiotics is associated increased likelihood of overweight/obesity, although the findings are limited by the very low certainty of evidence. We highlight the need for homogeneous prospective studies addressing potential confounding factors to further explore the link between exposure to antibiotics and the risk of excess body weight.

The effect of long-term exposure to nonylphenol at environmentally relevant levels on mouse liver and adipose tissue.

Exposure to the xenoestrogen nonylphenol (NP) during critical windows of development leads to metabolic abnormalities in adult life. However, less is known about NP exposure outside the developmental period on metabolic outcomes. We investigated the effect of prolonged exposure to NP after sexual maturity and at environmentally relevant concentrations below the 'no observable adverse effects level' (0.5 and 2.5 mg/kg/d). Male Swiss mice fed a normal-fat diet exposed to 2.5 mg/kg/d NP showed reduced weight gain and hepatic fat content. In male and female C57BL/6 mice fed a high-fat diet, NP exposure modified the mRNA levels of estrogen receptor α (Esr1) and adipose lineage markers in a sexually dimorphic and adipose depot-dependent pattern. Moreover, in primary female but not male stromal vascular cells from C57BL/6 mouse inguinal WAT induced to differentiate into adipocytes, NP upregulated Fabp4 expression. Low-level exposure to NP outside critical developmental windows may affect the metabolic phenotype distinctly. DATA AVAILABILITY STATEMENT: All data not included in the manuscript, such as raw results, are available upon request and should be addressed to AAA.