title: Chronic Repression of mTOR Complex 2 Induces Changes in the Gut Microbiota of Diet-induced Obese Mice.
abstract: Alterations in the gut microbiota play a crucial role in host physiology and metabolism; however, the molecular pathways underlying these changes in diet-induced obesity are unclear. Mechanistic target of rapamycin (mTOR) signaling pathway is associated with metabolic disorders such as obesity and type 2 diabetes (T2D). Therefore, we examined whether changes in the regulation of mTOR signaling induced by diet (a high-fat diet [HFD] or normal-chow diet) and/or therapeutics (resveratrol [a specific inhibitor of mTOR complex 1] or rapamycin [an inhibitor of both mTOR complex 1 and 2]) altered the composition of the gut microbiota in mice. Oral administration of resveratrol prevented glucose intolerance and fat accumulation in HFD-fed mice, whereas rapamycin significantly impaired glucose tolerance and exacerbated intestinal inflammation. The abundance of Lactococcus, Clostridium XI, Oscillibacter, and Hydrogenoanaerobacterium increased under the HFD condition; however, the abundance of these species declined after resveratrol treatment. Conversely, the abundance of unclassified Marinilabiliaceae and Turicibacter decreased in response to a HFD or rapamycin. Taken together, these results demonstrated that changes in the composition of intestinal microbiota induced by changes in mTOR activity correlate with obese and diabetic phenotypes.
authors.affiliation: Department of Life and Nanopharmaceutical Sciences and Department of Biology, Kyung Hee University, Seoul 130-701, Korea.
authors.forename: Mi-Ja
authors.initials: MJ
authors.lastname: Jung
authors.affiliation: Department of Life and Nanopharmaceutical Sciences and Department of Biology, Kyung Hee University, Seoul 130-701, Korea.
authors.forename: Jina
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Life and Nanopharmaceutical Sciences and Department of Biology, Kyung Hee University, Seoul 130-701, Korea.
authors.forename: Na-Ri
authors.initials: NR
authors.lastname: Shin
authors.affiliation: Department of Life and Nanopharmaceutical Sciences and Department of Biology, Kyung Hee University, Seoul 130-701, Korea.
authors.forename: Min-Soo
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Department of Life and Nanopharmaceutical Sciences and Department of Biology, Kyung Hee University, Seoul 130-701, Korea.
authors.forename: Dong-Wook
authors.initials: DW
authors.lastname: Hyun
authors.affiliation: Department of Life and Nanopharmaceutical Sciences and Department of Biology, Kyung Hee University, Seoul 130-701, Korea.
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Yun
authors.affiliation: Department of Life and Nanopharmaceutical Sciences and Department of Biology, Kyung Hee University, Seoul 130-701, Korea.
authors.forename: Pil Soo
authors.initials: PS
authors.lastname: Kim
authors.affiliation: Department of Life and Nanopharmaceutical Sciences and Department of Biology, Kyung Hee University, Seoul 130-701, Korea.
authors.forename: Tae Woong
authors.initials: TW
authors.lastname: Whon
authors.affiliation: Department of Life and Nanopharmaceutical Sciences and Department of Biology, Kyung Hee University, Seoul 130-701, Korea.
authors.forename: Jin-Woo
authors.initials: JW
authors.lastname: Bae
mesh_terms: D000818:Animals; D001419:Bacteria / Q000235:genetics / Q000302:isolation & purification; D001786:Blood Glucose / Q000032:analysis; D003013:Clostridium / Q000235:genetics / Q000302:isolation & purification; D059305:Diet, High-Fat; D000069196:Gastrointestinal Microbiome / Q000187:drug effects; D018149:Glucose Intolerance / Q000517:prevention & control; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood; D007422:Intestines / Q000382:microbiology; D017045:Lactococcus / Q000235:genetics / Q000302:isolation & purification; D008297:Male; D000076222:Mechanistic Target of Rapamycin Complex 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000076225:Mechanistic Target of Rapamycin Complex 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology; D013267:Stilbenes / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D001786:Blood Glucose; D007328:Insulin; D013267:Stilbenes; D000076222:Mechanistic Target of Rapamycin Complex 1; D000076225:Mechanistic Target of Rapamycin Complex 2; D000077185:Resveratrol; D020123:Sirolimus