Modulation of gut microbiota contributes to effects of intensive insulin therapy on intestinal morphological alteration in high-fat-diet-treated mice
Disturbance of intestinal homeostasis promotes the development of type 2 diabetes. Although intensive insulin therapy has been shown to promote extended glycemic remission in newly diagnosed type 2 diabetic patients through multiple mechanisms, its effect on intestinal homeostasis remains unknown.
This study evaluated the effects of intensive insulin therapy on intestinal morphometric parameters in a hyperglycemic mice model induced by high-fat diet (HFD). 16S rRNA V4 region sequencing and multivariate analysis were utilized to evaluate the structural changes of gut microbiota.
HFD-induced increases in the lengths of villus, microvillus and crypt depth were significantly reversed after intensive insulin therapy. Moreover, intestinal proliferation was notably decreased after intensive insulin therapy, whereas intestinal apoptosis was further increased. Importantly, intensive insulin therapy significantly shifted the overall structure of the HFD-disrupted gut microbiota toward that of mice fed a normal diet and changed the gut microbial composition. The abundances of 54 operational taxonomic units (OTUs) were changed by intensive insulin therapy. Thirty altered OTUs correlated with two or more intestinal morphometric parameters and were designated ‘functionally relevant phylotypes.’
For the first time, our data indicate that intensive insulin therapy recovers diabetes-associated gut structural abnormalities and restores the microbiome landscape. Moreover, specific altered ‘functionally relevant phylotypes’ correlates with improvement in diabetes-associated gut structural alterations.
KeywordsGut microbiota Type 2 diabetes Intestinal morphology Intensive insulin therapy
This work was supported by the National Natural Science Foundation of China Grant Awards (81770819, 81570737, 81370947, 81570736, 81500612, 81400832, 81600637, 81600632 and 81703294), the National Key Research and Development Program of China (2016YFC1304804 and 2017YFC1309605), the Jiangsu Provincial Key Medical Discipline (ZDXKB2016012), the Key Project of Nanjing Clinical Medical Science, Jiangsu Province Key Research and Development Program (BE2016606), the Jiangsu Provincial Medical Talent (ZDRCA2016062), the Natural Science Foundation of Jiangsu Province of China (BK20170125), the Jiangsu Provincial Medical Youth Talent (QNRC2016020, QNRC2016019 and QNRC2016018), the Medical Scientific Research Foundation of Jiangsu Province of China (Z201610 and Q2017006), the Science and Technology Project of Administration of Traditional Chinese Medicine of Jiangsu Province of China (YB2015072), the Six Talent Peaks Project of Jiangsu Province of China (WSN-165 and SWYY-091), the Fundamental Research Funds for the Central Universities (021414380444, 021414380092, 021414380208, 021414380160, 021414380142, 021414380279, 021414380296 and 021414380317), the Nanjing Science and Technology Development Project (ZKX16036, YKK16105 and 201605019) and the Nanjing Health Youth Talent (QRX17123).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All animal studies were conducted according to guidelines established by the Research Animal Care Committee of Drum Tower Hospital Affiliated to Nanjing University Medical School.
For this type of study informed consent is not required.
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