Reimer, Raylene A.Klančič, Teja2019-09-252019-09-252019-09-18Klančič, T. (2019). Early life antibiotic and prebiotic exposure: impact on gut microbiota, metabolism and obesity risk (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.http://hdl.handle.net/1880/111062Background: Obesity is a complex disease with multiple contributing factors including the gut microbiota. Antibiotics, when administered early in life, disrupt gut microbiota development and thereby increase the risk of obesity, whereas dietary agents such as prebiotics, reduce obesity risk via several pathways including microbiota-dependent mechanisms. Objective: This dissertation examines how antibiotics when administered with/without prebiotics, alter metabolic, microbial and anthropometric outcomes in rodents and humans. Specifically, the objectives were to: 1) assess the impact of indirect (maternal) antibiotic exposure with prebiotic co-administration on obesity risk in dams and their offspring; 2) determine the impact of direct antibiotic/prebiotic exposure in young rat pups on obesity risk and other metabolic parameters; 3) analyze available human birth cohort data from the All Our Families (AOF) study and explore the association between maternal antibiotic exposure and infant BMI z scores. Methods: 1) Sprague-Dawley rats consumed antibiotic and/or prebiotic during their 3rd week of pregnancy and lactation and their offspring were challenged with a high-fat high-sugar (HFS) diet from 9-17 weeks of age; 2) Rat pups were administered three pulses of azithromycin with/without prebiotic diet and weaned onto a HFS diet; 3) Using the AOF dataset, the association between infant BMI z score and maternal antibiotic use during pregnancy or during birth was examined. In the animal studies, body composition, gut microbiota composition, and metabolic outcomes were examined in dams and their offspring. In the human cohort, the association between antibiotic use during birth (intrapartum, n=1303)/during pregnancy (n=1943) and infant BMI z-score was investigated. Results: 1) Maternal antibiotic use during pregnancy/lactation impairs metabolism and postpartum weight loss in dams and increases obesity risk in their offspring, which was prevented with prebiotic co-administration; 2) Direct administration of azithromycin increased body weight and impaired insulin production/sensitivity. Prebiotic co-administration normalized the impairments; 3) Intrapartum antibiotic exposure might contribute to the development of child overweight/obesity at 1 year of age. Conclusion: Our results provide evidence for the ability of prebiotic co-administration with antibiotics to prevent metabolic impairments and obesity in rats. Future clinical trials should investigate whether this is also possible in humans.engUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.microbiotaprebioticsantibioticsobesityearly lifeEducation--SciencesMicrobiologyBiophysics--MedicalHuman Developmentdoctoral thesis10.11575/PRISM/37124