Research article
Partially hydrolyzed guar gum down-regulates colonic inflammatory response in dextran sulfate sodium-induced colitis in mice

https://doi.org/10.1016/j.jnutbio.2005.08.010Get rights and content

Abstract

Partially hydrolyzed guar gum (PHGG), a water-soluble dietary fiber produced by a controlled partial enzymatic hydrolysis of guar gum beans, has various physiological actions. The aim of the present study was to elucidate the beneficial effects of PHGG on colonic mucosal damage and on the inflammatory response in a dextran sulfate sodium (DSS) colitis model. After 2 weeks of prefeeding of PHGG, acute colitis was induced with 8% DSS in female BALB/c mice. Colonic mucosal inflammation was evaluated clinically, biochemically and histologically. Mucosal protein contents and mRNA levels of tumor necrosis factor-α (TNF-α) were determined by immunoassay and reverse transcription polymerase chain reaction. Disease activity scores determined by weight loss, stool consistency and blood in stool in DSS-treated mice were significantly lower in the PHGG-treated mice compared with the control mice. Shortening of the colon was significantly reversed by PHGG. Histological study also showed a reduced infiltration of inflammatory cells, especially neutrophils, and mucosal cell disruption in PHGG-treated mice compared with the control mice. The increases in tissue-associated myeloperoxidase activity and thiobarbituric acid-reactive substances after DSS administration were both significantly inhibited by pretreatment with PHGG. Partially hydrolyzed guar gum also inhibited increases in intestinal TNF-α protein and mRNA expression after DSS administration, respectively. These results suggest that chronic ingestion of PHGG prevents the development of DSS-induced colitis in mice via the inhibition of mucosal inflammatory response.

Introduction

Ulcerative colitis and Crohn's disease are chronic, immunologically mediated diseases. Recent evidence has shown that enteric pathogens including microflora appear to be important in the initiation and reactivation of human inflammatory bowel disease, and may be responsible for chronic inflammation in at least a subset of patients with inflammatory bowel diseases [1]. Therefore, therapeutic alteration of the luminal microenvironment by probiotic, prebiotic and molecular strategies offers great promise for the nontoxic treatment of inflammatory bowel disease. Most notably, a mixture of Bifidobacterium and Lactobacillus [2] and nonpathogenic viable Escherichia coli [3] has proven to prolong remission in cases of ulcerative colitis. In addition, there have been two controlled investigations of oral administration of a short-chain fatty acid (SCFA) substrate (fermentable dietary fiber) in patients with ulcerative colitis. Fernandez-Banares et al. [4] reported the efficacy and safety of dietary fiber from Plantago ovata seeds vs. mesalamine to maintain remission in these patients. Kanauchi et al. [5] also showed that oral administration with germinated barley foodstuff (GBF) made from the aleurone layer and scutellum fractions of malt significantly decreased clinical activity index scores of ulcerative colitis compared with the control group. It is generally accepted that dietary fiber induces the anaerobic bacteria to produce SCFAs, mainly acetate, propionate and butyrate, which are important nutrients for epithelial cells [6]. Moreover, SCFAs, especially butyrate, play an important role in the homeostasis of the colonic mucosa because they stimulate colonic cell proliferation, sodium absorption and increase in mucosal blood flow [7]. Recent findings also showed that butyrate suppressed inflammatory mediator generation by inhibiting nuclear factor-κB and regulated the cell-cycle-related genes by inducing histone hyperacetylation [8].

Guar gum is a water-soluble polysaccharide found in the seeds of guar, a plant indigenous to India, Pakistan and the United States. Guar gum has galactomannan as its main component. It has been shown to be effective in the treatment of hyperlipidemia [9] and postprandial glycemia of diabetes [10]. Because guar gum is extremely viscous, it is very difficult to incorporate it in food in large enough quantities to obtain a physiological effect, so a partially hydrolyzed guar gum (PHGG) is used in beverage form. Partially hydrolyzed guar gum has proved effective in softening and improving the output of feces and in increasing bulking capacities (fecal weight, frequency of defecation and fecal excretory feeling) [11], [12]. Partially hydrolyzed guar gum increased production of Bifidobacterium in the gut [13]. Partially hydrolyzed guar gum also reduced the incidence of diarrhea in septic patients receiving total enteral nutrition and reduced symptoms of irritable bowel syndrome [14], [15]. A multicenter, randomized, open trial in patients with irritable bowel syndrome has demonstrated that PHGG is as effective as a high-fiber diet in improving the core symptoms of irritable bowel syndrome, but is better tolerated by patients [14].

The aim of the present study was to elucidate the effects of PHGG on colonic mucosal damage and on the inflammatory response in a dextran sulfate sodium (DSS) colitis model. Although the pathogenesis of DSS-induced colitis is unclear, its induction may result from the toxic effects of DSS on colonic epithelial cells, alterations of luminal bacterial flora [16] or increases in oxidative and nitrosative stress [17]. In addition, the cytokine expression and histological findings in acute DSS-induced colitis are very similar to those observed in human inflammatory bowel disease [16], [18]. Using this experimental model, GBF showed preventive and therapeutic effects with notable amelioration of severe bloody diarrhea and an attenuation of colonic mucosal damage [19]. In the present study, special attention was paid to the effect of PHGG on DSS-induced intestinal inflammatory response, including neutrophil accumulation and tumor necrosis factor-α (TNF-α).

Section snippets

Chemicals

All chemicals were prepared immediately before use. Thiobarbituric acid (TBA) and 3,3′,5,5′-tetramethylbenzidine were obtained from Wako (Osaka, Japan). 1,1,3,3-Tetramethoxypropane was obtained from Tokyo Kasei (Tokyo, Japan). An enzyme-linked immunosorbent assay kit for mouse TNF-α was obtained from BioSource International (Camarillo, CA). All other chemicals used were of reagent grade.

Partially hydrolyzed guar gum used

The commercial PHGG preparation (SunfiberR) used in this study was a gift from Taiyo Kagaku (Tokyo, Japan).

Effects of PHGG on DAI scores, colon length, and histology

Mice exposed to 8% DSS developed symptoms of acute colitis, with diarrhea being observed first followed by rectal bleeding and severe weight loss. To determine a relevant dose for the study with PHGG, we first performed a dose–response study using mice after 2 weeks of prefeeding of a diet containing PHGG (5%, 10% and 15% of the diet). All three groups significantly reversed shortening of the colon induced by the DSS administration; however, there were no significant differences in its efficacy

Discussion

The present study demonstrates that chronic treatment with PHGG, a water-soluble dietary fiber, attenuates DSS-induced colonic injury and inflammation in mice. In our study, intestinal injury was assessed by a variety of methods including DAI, length of the colon and histology. By each assessment, PHGG treatment significantly inhibited colonic injury. In addition, we showed that MPO activity, TBA-reactive substances and expression of TNF-α gene were enhanced in DSS-induced intestinal

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      In fact, PHGG could elicit constipation relief, modulate gut microbiota [5], and improve symptoms associated with gastrointestinal disorders [6,7]. Additionally, PHGG treatment has been shown to reduce colonic mucosal damage in an animal colitis model [8]. It is well known that lipopolysaccharide (LPS; a major component of the outer membrane of gram-negative bacteria) induces systemic inflammation, and the LPS animal model has several advantages, such as technical ease and high reproducibility of systemic inflammation.

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    This work was supported by grant-in-aid for scientific research (14570493 YN and 15390178 TY) from the Ministry of Education, Culture, Sports, Science and Technology of Japan, by grant from Bio-oriented Technology Research Advancement Institution, and by grant from the Ministry of Agriculture, Forestry and Fisheries of Japan.

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