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Published on: November 16, 2011
Concurrent Prebiotic Intake Reverses Insulin Resistance Induced by Early-Life Pulsed Antibiotic in Rats
Teja Klancic1, Isabelle Laforest-Lapointe2,3, Jolene Wong1
1Faculty of Kinesiology, University of Calgary, Calgary, AB T2N 1N4, Canada.
Insights
Pulsed antibiotic treatment (PAT) in early life can lead to obesity, but co-administering prebiotics may mitigate this risk. Prebiotics reversed antibiotic-induced metabolic dysfunction in a sex-specific manner in rat pups.
Area of Science:
- Microbiology
- Metabolic Health
- Pediatric Health
Background:
- Pulsed antibiotic treatment (PAT) early in life is linked to increased obesity risk.
- Prebiotics are known to reduce fat mass and improve metabolic health.
- The potential of prebiotics to counteract PAT-induced obesity requires investigation.
Purpose of the Study:
- To determine if co-administering prebiotics with PAT can reduce obesity risk in rat pups.
- To investigate the sex-specific effects of PAT and prebiotic intervention on metabolic health.
- To explore the molecular mechanisms underlying PAT-induced metabolic changes and their reversal by prebiotics.
Main Methods:
- Rat pups were assigned to control, antibiotic (azithromycin), prebiotic (oligofructose), or antibiotic + prebiotic groups.
- Pulses of antibiotics and prebiotics were administered during early life.
- Body weight, fat mass, insulin levels, insulin resistance, and gene expression were assessed at 10 weeks.
- Gut microbiota composition was analyzed.
Main Results:
- Antibiotic treatment significantly increased body weight and impaired insulin sensitivity in both male and female rats.
- The negative effects of PAT were more pronounced in males, with increased fat mass and hyperinsulinemia.
- Prebiotic co-administration reversed PAT-induced metabolic dysfunction in a sex-specific manner, normalizing insulin sensitivity in females.
- PAT altered gut microbiota composition, reducing Lactobacillaceae and increasing Bacteroidaceae.
Conclusions:
- Pulsed antibiotic treatment in early life increases obesity risk and impairs metabolic health, with sex-specific effects.
- Co-administering prebiotics with antibiotics can mitigate these adverse effects, particularly in females.
- Prebiotics offer a potential strategy to counteract the long-term metabolic consequences of early-life antibiotic exposure.
Abstract:
Pulsed antibiotic treatment (PAT) early in life increases risk of obesity. Prebiotics can reduce fat mass and improve metabolic health. We examined if co-administering prebiotic with PAT reduces obesity risk in rat pups weaned onto a high fat/sucrose diet. Pups were randomized to (1) control [CTR], (2) antibiotic [ABT] (azithromycin), (3) prebiotic [PRE] (10% oligofructose (OFS)), (4) antibiotic + prebiotic [ABT + PRE]. Pulses of antibiotics/prebiotics were administered at d19-21, d28-30 and d37-39. Male and female rats given antibiotics (ABT) had higher body weight than all other groups at 10 wk of age. The PAT phenotype was stronger in ABT males than females, where increased fat mass, hyperinsulinemia and insulin resistance were present and all reversible with prebiotics. Reduced hypothalamic and hepatic expression of insulin receptor substrates and ileal tight junction proteins was seen in males only, explaining their greater insulin resistance. In females, insulin resistance was improved with prebiotics and normalized to lean control. ABT reduced Lactobacillaceae and increased Bacteroidaceae in both sexes. Using a therapeutic dose of an antibiotic commonly used for acute infection in children, PAT increased body weight and impaired insulin production and insulin sensitivity. The effects were reversed with prebiotic co-administration in a sex-specific manner.
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