PMID- 29941502 OWN - NLM STAT- MEDLINE DCOM- 20190820 LR - 20190820 IS - 1479-6805 (Electronic) IS - 0022-0795 (Linking) VI - 238 IP - 3 DP - 2018 Sep TI - Sodium butyrate supplementation ameliorates diabetic inflammation in db/db mice. PG - 231-244 LID - 10.1530/JOE-18-0137 [doi] AB - Endotoxemia has been recognized to be closely accompanied with type 2 diabetes mellitus (T2DM) and is responsible for many diabetic complications. Recent study suggests the potential role of butyrate, a short-chain fatty acid (SCFA) from microbiota metabolite, on T2DM. Gut-leak is a key event in diabetic-endotoxemia. To investigate if butyrate could ameliorate diabetic-endotoxemia, both in vivo and in vitro experiments were carried out in the present study. The effect of butyrate supplementation on blood HbA1c and inflammatory cytokines were determined in db/db mice; gut barrier integrity and expression of tight junction proteins were investigated both in vivo and in vitro Oral butyrate administration significantly decreased blood HbA1c, inflammatory cytokines and LPS in db/db mice; inflammatory cell infiltration was reduced, and gut integrity and intercellular adhesion molecules were increased as detected by HE staining, immunohistochemistry and Western blot. By gut microbiota assay, ratio of Firmicutes:Bacteroidetes for gut microbiota was reduced by butyrate. In Caco-2 cells, butyrate significantly promoted cell proliferation, decreased inflammatory cytokines' secretion, enhanced cell anti-oxidative stress ability and preserved the epithelial monocellular integrity, which was damaged by LPS. The present findings demonstrated that butyrate supplementation could ameliorate diabetic-endotoxemia in db/db mice via restoring composition of gut microbiota and preserving gut epithelial barrier integrity. CI - (c) 2018 Society for Endocrinology. FAU - Xu, You-Hua AU - Xu YH AD - Faculty of Chinese MedicineMacau University of Science and Technology, Taipa, Macao, China yhxu@must.edu.mo xuyouhua_021@163.com. AD - State Key Laboratory of Quality Research in Chinese MedicineMacau University of Science and Technology, Taipa, Macao, China. FAU - Gao, Chen-Lin AU - Gao CL AD - Faculty of Chinese MedicineMacau University of Science and Technology, Taipa, Macao, China. AD - State Key Laboratory of Quality Research in Chinese MedicineMacau University of Science and Technology, Taipa, Macao, China. AD - Department of EndocrinologyAffiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China. FAU - Guo, Heng-Li AU - Guo HL AD - Faculty of Chinese MedicineMacau University of Science and Technology, Taipa, Macao, China. AD - State Key Laboratory of Quality Research in Chinese MedicineMacau University of Science and Technology, Taipa, Macao, China. FAU - Zhang, Wen-Qian AU - Zhang WQ AD - Faculty of Chinese MedicineMacau University of Science and Technology, Taipa, Macao, China. AD - State Key Laboratory of Quality Research in Chinese MedicineMacau University of Science and Technology, Taipa, Macao, China. FAU - Huang, Wei AU - Huang W AD - Faculty of Chinese MedicineMacau University of Science and Technology, Taipa, Macao, China. AD - State Key Laboratory of Quality Research in Chinese MedicineMacau University of Science and Technology, Taipa, Macao, China. AD - Department of EndocrinologyAffiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China. FAU - Tang, Shan-Shan AU - Tang SS AD - Faculty of Chinese MedicineMacau University of Science and Technology, Taipa, Macao, China. AD - State Key Laboratory of Quality Research in Chinese MedicineMacau University of Science and Technology, Taipa, Macao, China. FAU - Gan, Wen-Jun AU - Gan WJ AD - Faculty of Chinese MedicineMacau University of Science and Technology, Taipa, Macao, China. AD - State Key Laboratory of Quality Research in Chinese MedicineMacau University of Science and Technology, Taipa, Macao, China. FAU - Xu, Yong AU - Xu Y AD - Faculty of Chinese MedicineMacau University of Science and Technology, Taipa, Macao, China yhxu@must.edu.mo xuyouhua_021@163.com. AD - Department of EndocrinologyAffiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China. FAU - Zhou, Hua AU - Zhou H AD - Faculty of Chinese MedicineMacau University of Science and Technology, Taipa, Macao, China. AD - State Key Laboratory of Quality Research in Chinese MedicineMacau University of Science and Technology, Taipa, Macao, China. FAU - Zhu, Quan AU - Zhu Q AD - Faculty of Chinese MedicineMacau University of Science and Technology, Taipa, Macao, China. AD - State Key Laboratory of Quality Research in Chinese MedicineMacau University of Science and Technology, Taipa, Macao, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180625 PL - England TA - J Endocrinol JT - The Journal of endocrinology JID - 0375363 RN - 107-92-6 (Butyric Acid) RN - 9100L32L2N (Metformin) MH - Animals MH - Butyric Acid/*administration & dosage MH - Caco-2 Cells MH - Diabetes Mellitus, Experimental/complications/*drug therapy MH - Diabetes Mellitus, Type 2/complications/drug therapy MH - Drug Therapy, Combination MH - Gastrointestinal Microbiome/drug effects MH - Humans MH - Inflammation/etiology/*prevention & control MH - Intestinal Mucosa/drug effects/microbiology/physiology MH - Male MH - Metformin/administration & dosage MH - Mice MH - Mice, Inbred C57BL OTO - NOTNLM OT - butyrate OT - endotoxemia OT - gut barrier OT - inflammation OT - type 2 diabetes mellitus EDAT- 2018/06/27 06:00 MHDA- 2019/08/21 06:00 CRDT- 2018/06/27 06:00 PHST- 2018/06/07 00:00 [received] PHST- 2018/06/25 00:00 [accepted] PHST- 2018/06/27 06:00 [pubmed] PHST- 2019/08/21 06:00 [medline] PHST- 2018/06/27 06:00 [entrez] AID - JOE-18-0137 [pii] AID - 10.1530/JOE-18-0137 [doi] PST - ppublish SO - J Endocrinol. 2018 Sep;238(3):231-244. doi: 10.1530/JOE-18-0137. Epub 2018 Jun 25.