Modulation of gut microbiota contributes to effects of intensive insulin therapy on intestinal morphological alteration in high-fat-diet-treated mice

被引:16
|
作者
Wang, Hongdong [1 ]
Tang, Wenjuan [1 ]
Zhang, Pengzi [1 ]
Zhang, Zhou [1 ]
He, Jielei [1 ]
Zhu, Dalong [1 ]
Bi, Yan [1 ]
机构
[1] Nanjing Univ, Sch Med, Drum Tower Hosp, Dept Endocrinol, 321 Zhongshan Rd, Nanjing 210008, Peoples R China
基金
中国国家自然科学基金;
关键词
Gut microbiota; Type; 2; diabetes; Intestinal morphology; Intensive insulin therapy; BETA-CELL FUNCTION; OXIDATIVE STRESS; STEM-CELLS; SENSITIVITY; GLUCONEOGENESIS; ENTEROENDOCRINE; PROLIFERATION; CHOLESTEROL; LIVER; BILE;
D O I
10.1007/s00592-019-01436-0
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Aims 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. Methods 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. Results 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.' Conclusions 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.
引用
收藏
页码:455 / 467
页数:13
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