Propionate Ameliorates Dextran Sodium Sulfate-Induced Colitis by Improving Intestinal Barrier Function and Reducing Inflammation and Oxidative Stress.

Ling-Chang Tong,Li-Chao Zhang,Zhi-Bin Wang,Yue Wang,Ding-Feng Su,Ling Li,Wei-Ye Liu,Sheng Sun

doi:10.3389/fphar.2016.00253

Abstract

Propionate is a short chain fatty acid that is abundant as butyrate in the gut and blood. However, propionate has not been studied as extensively as butyrate in the treatment of colitis. The present study was to investigate the effects of sodium propionate on intestinal barrier function, inflammation and oxidative stress in dextran sulfate sodium (DSS)-induced colitis mice. Animals in DSS group received drinking water from 1 to 6 days and DSS [3% (w/v) dissolved in double distilled water] instead of drinking water from 7 to 14 days. Animals in DSS+propionate (DSS+Prop) group were given 1% sodium propionate for 14 consecutive days and supplemented with 3% DSS solution on day 7–14. Intestinal barrier function, proinflammatory factors, oxidative stress, and signal transducer and activator of transcription 3 (STAT3) signaling pathway in the colon were determined. It was found that sodium propionate ameliorated body weight loss, colon-length shortening and colonic damage in colitis mice. Sodium propionate significantly inhibited the increase of FITC-dextran in serum and the decrease of zonula occludens-1 (ZO-1), occludin, and E-cadherin expression in the colonic tissue. It also inhibited the expression of interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α) mRNA and phosphorylation of STAT3 in colitis mice markedly, reduced the myeloperoxidase (MPO) level, and increased the superoxide dismutase and catalase level in colon and serum compared with DSS group. Sodium propionate inhibited macrophages with CD68 marker infiltration into the colonic mucosa of colitis mice. These results suggest that oral administration of sodium propionate could ameliorate DSS-induced colitis mainly by improving intestinal barrier function and reducing inflammation and oxidative stress via the STAT3 signaling pathway.

Highlights

Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, is a group of chronic inflammatory disorders of the gastrointestinal tract characterized by intestinal inflammation and mucosal damage (Quetglas et al, 2015)
There was no significant difference in body weight, colon length, histological evaluation, and histological score between control and propionate groups
We found that sodium propionate inhibited the down-regulation of tight junction proteins such as zonula occludens-1 (ZO-1), occludin, and E-cadherin, and improved the impaired intestinal barrier function induced by dextran sulfate sodium (DSS)

Summary

Introduction

Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, is a group of chronic inflammatory disorders of the gastrointestinal tract characterized by intestinal inflammation and mucosal damage (Quetglas et al, 2015). SCFAs, predominantly acetate, propionate, and butyrate, are produced in the colonic lumen by anaerobic fermentation of undigested carbohydrates, crude fibers, and polysaccharides (Bolognini et al, 2016). The physiological effects of SCFAs have been well documented, which include reducing the production of proinflammatory factors (Huang and Wu, 1997; Meijer et al, 2010), enhancing intestinal barrier function (Mariadason et al, 1997, 1999; Peng et al, 2007; Suzuki et al, 2008; Van Deun et al, 2008; Elamin et al, 2013), inhibiting oxidative stress (Hamer et al, 2009, 2010), and preventing colon carcinogenesis (Clausen et al, 1991; Hijova and Chmelarova, 2007) in vitro, in vivo, and in animals. Most previous studies mainly focused on butyrate, and few studies have devoted their efforts to other SCFAs such as propionate, it is abundant as butyrate in the gut and blood

Objectives

Methods

Results

Conclusion