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

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],...

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Main Authors: Teja Klancic, Isabelle Laforest-Lapointe, Jolene Wong, Ashley Choo, Jodi E. Nettleton, Faye Chleilat, Marie-Claire Arrieta, Raylene A. Reimer
Format: Article
Language:English
Published: MDPI AG 2021-01-01
Series:Biomedicines
Subjects:
Online Access:https://www.mdpi.com/2227-9059/9/1/66
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author Teja Klancic
Isabelle Laforest-Lapointe
Jolene Wong
Ashley Choo
Jodi E. Nettleton
Faye Chleilat
Marie-Claire Arrieta
Raylene A. Reimer
author_facet Teja Klancic
Isabelle Laforest-Lapointe
Jolene Wong
Ashley Choo
Jodi E. Nettleton
Faye Chleilat
Marie-Claire Arrieta
Raylene A. Reimer
author_sort Teja Klancic
collection DOAJ
description 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 <i>Lactobacillaceae</i> and increased <i>Bacteroidaceae</i> 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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spelling doaj.art-40b106f62f0d4f588dbc24887b8f624f2023-12-03T12:52:35ZengMDPI AGBiomedicines2227-90592021-01-01916610.3390/biomedicines9010066Concurrent Prebiotic Intake Reverses Insulin Resistance Induced by Early-Life Pulsed Antibiotic in RatsTeja Klancic0Isabelle Laforest-Lapointe1Jolene Wong2Ashley Choo3Jodi E. Nettleton4Faye Chleilat5Marie-Claire Arrieta6Raylene A. Reimer7Faculty of Kinesiology, University of Calgary, Calgary, AB T2N 1N4, CanadaDepartment of Physiology & Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, CanadaFaculty of Kinesiology, University of Calgary, Calgary, AB T2N 1N4, CanadaFaculty of Kinesiology, University of Calgary, Calgary, AB T2N 1N4, CanadaFaculty of Kinesiology, University of Calgary, Calgary, AB T2N 1N4, CanadaFaculty of Kinesiology, University of Calgary, Calgary, AB T2N 1N4, CanadaDepartment of Physiology & Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, CanadaFaculty of Kinesiology, University of Calgary, Calgary, AB T2N 1N4, CanadaPulsed 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 <i>Lactobacillaceae</i> and increased <i>Bacteroidaceae</i> 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.https://www.mdpi.com/2227-9059/9/1/66antibioticprebioticoligofructoseinsulin resistanceobesitygut microbiota
spellingShingle Teja Klancic
Isabelle Laforest-Lapointe
Jolene Wong
Ashley Choo
Jodi E. Nettleton
Faye Chleilat
Marie-Claire Arrieta
Raylene A. Reimer
Concurrent Prebiotic Intake Reverses Insulin Resistance Induced by Early-Life Pulsed Antibiotic in Rats
Biomedicines
antibiotic
prebiotic
oligofructose
insulin resistance
obesity
gut microbiota
title Concurrent Prebiotic Intake Reverses Insulin Resistance Induced by Early-Life Pulsed Antibiotic in Rats
title_full Concurrent Prebiotic Intake Reverses Insulin Resistance Induced by Early-Life Pulsed Antibiotic in Rats
title_fullStr Concurrent Prebiotic Intake Reverses Insulin Resistance Induced by Early-Life Pulsed Antibiotic in Rats
title_full_unstemmed Concurrent Prebiotic Intake Reverses Insulin Resistance Induced by Early-Life Pulsed Antibiotic in Rats
title_short Concurrent Prebiotic Intake Reverses Insulin Resistance Induced by Early-Life Pulsed Antibiotic in Rats
title_sort concurrent prebiotic intake reverses insulin resistance induced by early life pulsed antibiotic in rats
topic antibiotic
prebiotic
oligofructose
insulin resistance
obesity
gut microbiota
url https://www.mdpi.com/2227-9059/9/1/66
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