4.7 Article

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

期刊

BIOMEDICINES
卷 9, 期 1, 页码 -

出版社

MDPI
DOI: 10.3390/biomedicines9010066

关键词

antibiotic; prebiotic; oligofructose; insulin resistance; obesity; gut microbiota

资金

  1. Canadian Institutes of Health Research [PJT-159626]
  2. Vanier Canada Graduate Scholarship
  3. Alberta Innovates Health Solutions Doctoral Scholarship
  4. Eye's High Doctoral Scholarship
  5. Alberta Children Hospital Research Institute Postdoctoral Fellowship
  6. Natural Sciences and Engineering Research Council Undergraduate Summer Research Award
  7. Alberta Children's Hospital Research Institute Graduate Studentship
  8. Dean's Doctoral Scholarship (Kinesiology)
  9. Alberta Children's Hospital Research Institute scholarship

向作者/读者索取更多资源

Pulsed antibiotic treatment early in life increases the risk of obesity, while co-administering prebiotics can reduce fat mass and improve metabolic health. Antibiotic treatment had negative effects on body weight and insulin sensitivity, which were reversed with prebiotic co-administration, especially in a sex-specific manner.
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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