Concurrent Prebiotic Intake Reverses Insulin Resistance Induced by Early-Life Pulsed Antibiotic in Rats

• Published in: Biomedicines Vol. 9; no. 1; p. 66
• Main Authors: Klancic, Teja, Laforest-Lapointe, Isabelle, Wong, Jolene, Choo, Ashley, Nettleton, Jodi E, Chleilat, Faye, Arrieta, Marie-Claire, Reimer, Raylene A
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 12.01.2021; MDPI
• Subjects: antibiotic; Antibiotics; Azithromycin; Body fat; Body weight; Diet; Experiments; Feces; Gene expression; Glucose; gut microbiota; High fat diet; Hyperinsulinemia; Hypothalamus; Insulin; Insulin resistance; Juveniles; Laboratory animals; Metabolism; Microbiota; Obesity; oligofructose; Phenotypes; prebiotic; Prebiotics; Sex differences; Sucrose; Canada; United States > US; antibiotic; prebiotic; insulin resistance; oligofructose; gut microbiota; obesity
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines9010066

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 and increased 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.