Year-end Sale % OFF 
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.
Highlights
The composition of the gut microbiota is influenced by the genetic background, immune status, age, sex and diet of the host[8]
We previously showed that oral administration of mucin-degrading Akkermansia muciniphila, which is markedly more abundant in metformin-treated high-fat diet (HFD)-fed mice, resulted in improved glucose homeostasis and reduced adipose tissue inflammation via its ability to induce goblet cells in the intestine and regulatory T cells in adipose tissue[14]
Since metformin is a key regulator of Mechanistic target of rapamycin (mTOR) signaling, the present study examined whether the mechanisms underlying host central energy metabolism, which are controlled by differential regulation of the mTOR pathway, involve changes in the composition of gut microbiota
Summary
The composition of the gut microbiota is influenced by the genetic background, immune status, age, sex and (especially) diet of the host[8]. Because over-activation of mTOR complex 1 (mTORC1) signaling by excessive energy intake plays a crucial role in metabolic disorders[17], mTOR inhibitors such as rapamycin (23,27-epoxy-3H-pyrido[2,1-c][1,4]oxaazacyclohentriacontine), metformin (1,1-dimethylbiguanide hydrochloride) and resveratrol (3,4′,5-trihydroxy-trans-stilbene) are used to treat those suffering from obesity and T2D14,18,19. Several studies have shown increased activation of AMPK in the liver, muscle and colon tissue of germ-free mice that are resistant to HFD-induced obesity, suggesting that the intestinal microbiota may modulate AMPK activation in the host[20,21] These findings raise the possibility that changes in mTOR signaling may have both direct and indirect effects on the intestinal microbiota, which in turn would contribute to obese and diabetic phenotypes. The results show that resveratrol and rapamycin have marked effects on the mTOR signaling activity and metabolic marker expression and on the composition of gut microbiota, suggesting that specific microbial groups correlate with the pathophysiological phenotypes associated with obesity and T2D
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
