Antibiotic-Induced Alterations in Gut Microbiota Are Associated with Changes in Glucose Metabolism in Healthy Mice
| Autor: | Manoj Gurung, Xiaoxi Dong, Andrey Morgun, Natalia Shulzhenko, Karen N. DSouza, Renee L. Greer, Jia Y. Wu, Richard R. Rodrigues |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
transkingdom networks Microbiology (medical) medicine.medical_specialty medicine.drug_class glucose tolerance Antibiotics lcsh:QR1-502 Carbohydrate metabolism Gut flora Microbiology antibiotics lcsh:Microbiology 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Microbiome Original Research 2. Zero hunger Glucose tolerance test medicine.diagnostic_test Bile acid biology gut microbiota non-obese Neomycin lean biology.organism_classification 3. Good health 030104 developmental biology Endocrinology 030211 gastroenterology & hepatology Akkermansia muciniphila medicine.drug |
| Zdroj: | Frontiers in Microbiology, Vol 8 (2017) Frontiers in Microbiology |
| ISSN: | 1664-302X |
| DOI: | 10.3389/fmicb.2017.02306 |
| Popis: | The gut microbiome plays an important role in health and disease. Antibiotics are known to alter gut microbiota, yet their effects on glucose tolerance in lean, normoglycemic mice have not been widely investigated. In this study, we aimed to explore mechanisms by which treatment of lean mice with antibiotics (ampicillin, metronidazole, neomycin, vancomycin, or their cocktail) influences the microbiome and glucose metabolism. Specifically, we sought to: (i) study the effects on body weight, fasting glucose, glucose tolerance, and fasting insulin, (ii) examine the changes in expression of key genes of the bile acid and glucose metabolic pathways in the liver and ileum, (iii) identify the shifts in the cecal microbiota, and (iv) infer interactions between gene expression, microbiome, and the metabolic parameters. Treatment with individual or a cocktail of antibiotics reduced fasting glucose but did not affect body weight. Glucose tolerance changed upon treatment with cocktail, ampicillin, or vancomycin as indicated by reduced area under the curve of the glucose tolerance test. Antibiotic treatment changed gene expression in the ileum and liver, and shifted the alpha and beta diversities of gut microbiota. Network analyses revealed associations between Akkermansia muciniphila with fasting glucose and liver farsenoid X receptor (Fxr) in the top ranked host-microbial interactions, suggesting possible mechanisms by which this bacterium can mediate systemic changes in glucose metabolism. We observed Bacteroides uniformis to be positively and negatively correlated with hepatic Fxr and Glucose 6-phosphatase, respectively. Overall, our transkingdom network approach is a useful hypothesis generating strategy that offers insights into mechanisms by which antibiotics can regulate glucose tolerance in non-obese healthy animals. Experimental validation of our predicted microbe-phenotype interactions can help identify mechanisms by which antibiotics affect host phenotypes and gut microbiota. |
| Databáze: | OpenAIRE |
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