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J Endocrinol. 2018 Sep;238(3):231-244. doi: 10.1530/JOE-18-0137. Epub 2018 Jun 25.

Sodium butyrate supplementation ameliorates diabetic inflammation in db/db mice.

Xu YH1,2, Gao CL3,2,4, Guo HL3,2, Zhang WQ3,2, Huang W3,2,4, Tang SS3,2, Gan WJ3,2, Xu Y1,4, Zhou H3,2, Zhu Q3,2.

Author information

1
Faculty of Chinese MedicineMacau University of Science and Technology, Taipa, Macao, China yhxu@must.edu.mo xuyouhua_021@163.com.
2
State Key Laboratory of Quality Research in Chinese MedicineMacau University of Science and Technology, Taipa, Macao, China.
3
Faculty of Chinese MedicineMacau University of Science and Technology, Taipa, Macao, China.
4
Department of EndocrinologyAffiliated Hospital of Southwest Medical University, Luzhou, Sichuan, China.

Abstract

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.

KEYWORDS:

butyrate; endotoxemia; gut barrier; inflammation; type 2 diabetes mellitus

PMID:
29941502
DOI:
10.1530/JOE-18-0137
[Indexed for MEDLINE]

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