Background
Constipation, defined as infrequent or difficult evacuation of feces [
1], is a worldwide functional gastrointestinal disorder. A systematic review recorded prevalence rates in six different population groups from Asia ranging widely from 11.6% to 29.6% [
2]. In general, constipation appears to be more common in the elderly, women, nonwhites, and persons in lower socio-economic and education classes [
3]. Constipation also significantly impacts health-related quality of life in constipated people [
4]. A primary mechanism for slow-transit constipation is a failure of peristalsis to move luminal contents through the colon results in more time for bacterial degradation of stool solids and more time for salt and water absorption, thus reducing stool frequency and stool weight dramatically [
5]. Medical therapy for constipation contains traditional laxatives and agents. The former can induce defecation or modify stool consistency to make defecation easier, while the latter targets presumed defects in colonic neuromuscular function [
5,
6]. Although a common problem, the treatment of constipation has been far from satisfactory [
7].
Beta-glucans, naturally occurring polysaccharides with poly-branched beta-(1→3)-D-glucans or beta-(1→6)-D-glucose side chains, are a major component of the bran of cereal plant and the cell wall of bacteria and fungi [
8,
9]. A number of studies demonstrate beta-glucans may be beneficial in gastrointestinal disease prevention and health promotion, including reduction of cholesterol absorption and bile acids excretion [
10], fermentation by intestinal bacteria that yields short chain fatty acids [
11], resistance to enteric bacterial and viral infections [
12,
13], stimulation autochthonous
Lactobacillus populations in the colon [
14], and prevention of colorectal cancer by effecting immune and cancer cells [
15]. In addition, early observers suggest that a decreasing prevalence of constipation is associated with an increasing dietary fiber intake, depending on their ability to avoid digestion and absorption in small intestine and to escape bacterial metabolism in colon [
16]. Cummings [
17] has tabulated the efficacy of different fibers in terms of increased fecal weight per gram of administered fiber, including wheat bran, psyllium, cellulose, oats, corn, legumes, and pectin. Psyllium polysaccharide from
Plantago ovate is approved by the FDA for its proven laxative effects as available fiber supplements [
18,
19].
Salecan, produced by
Agrobacterium sp. ZX09, is a novel high molecular, water-soluble extracellular polysaccharide, and its structure is proven to consist of the following repeating unit:→3)-β-D-Glcp-(1→3)-[ β-D-Glcp-(1→3)-β-D-Glcp-(1→3)]3-α-D-Glcp-(1→3)-α-D-Glcp-(1→ [
20]. As a new beta-glucan with special molecular structure, its safety has been demonstrated in the acute and subchronic experiment [
21]. Supplementation with Salecan reduced adiposity and improved glucose tolerance in high-fat diet-fed mice through disturbing bile acid-promoted emulsification in intestine [
22]. Its rheology study indicates that Salecan has a non-Newtonian viscosity behavior, and could be utilized in the food industry [
23]. In the present study, we estimated the laxative effects of Salecan on fecal output and small intestinal transit in normal and two models of drug-induced constipation mice. Our results suggest that Salecan may be used as a hydrophilic laxative for constipation.
Discussion
Constipation is a highly prevalent functional gastrointestinal disorder, affecting the quality of life in constipated persons [
7], and the use of dietary fiber in the prevention and treatment of constipation is a common practice in many countries of the world [
16,
28]. The present study has evaluated laxative effects of Salecan on normal as well as on loperamide- and clonidine-induced constipation mice.
As an agent for functional bowel disorders like diarrhea, loperamide used as constipation inducer is well documented. The drug inhibits intestinal fluid secretion and intestinal motility, leading to delay fecal evacuation time and intestinal luminal transit [
29], and is used to induce a model of spastic constipation. On the other hand, clonidine also has a potent antidiarrheal effect, and has a suppressive effect on gastrointestinal contractions [
30]. This drug can cause a model of atonic constipation. The observed decrease in the number and weight of feces by the treatment with these two drugs indicated induction of constipation in mice. Similar observation was reported by Kakino et al. [
27].
Salecan is an identified extracellular macromolecule from
Agrobacterium sp. ZX09, mainly composed of β-(1→3)-D-glucosidic linkages as the main backbone structure, together with a small portion of α-(1→3)-D-glucosidic linkages [
20]. Salecan is a non-toxic and water-soluble beta-glucan with excellent rheological properties [
21,
23]. Bacterial extracellular polysaccharides (e.g. dextran) can be easily produced and applied in food industry [
31]. Beta-glucans are not digestible due to a lack of the hydrolase in gastrointestinal tract. Furthermore, Salecan increased fecal weight and fecal number in normal mice in present study. Similar observation was reported by Nakamura et al. [
32] where brewer’s yeast cell wall, which was composed mainly of polysaccharides, significantly increased fecal frequency and weight in normal rats. Due to these properties, it is presumed that Salecan has favorable effects on prevention of constipation.
The effects of Salecan on constipation in this study were tested in loperamide- and clonidine-induced constipation mice. The administration of Salecan to the constipated mice was effective in increasing the fecal number and fecal weight, which were indications of the laxative character of Salecan. Unlike clonidine, loperamide also markedly decreased the water content of feces through inhibition of intestinal fluid secretion. Treatment with Salecan significantly raised the fecal water content in loperamide-induced constipation mice. And the SIT time was shortened by the treatment with Salecan in both constipation models. The laxative effectiveness of dietary fibers, as bulk agents, depends on their WHC and swelling force [
5]. Salecan was proved to have a high WHC. It may thus be concluded that the fecal output character was affected by the WHC and swelling force of Salecan in small intestine. This swelling force serves as a stimulus to defecation. Xu et al. [
33] reported that supplementation of the diet with partially defatted flaxseed meal markedly decreased gastrointestinal transit time as well as increased fecal frequency and weight in constipated mice, which was dependent on luminal bulk. In addition, given the fact that soluble fibers may delay nutrients digestion and absorption by absorbing large quantities of water and forming gels in the gastrointestinal tract [
34], Salecan might be possible to prevent the absorption of loperamide and clonidine in this results.
Conclusion
Our results demonstrate that Salecan, as a new structural glucan, alleviates the symptom of loperamide- and clonidine-induced constipation. Because of its easy availability, Salecan could be recommended as a cost-effective alternative for constipation.
Competing interests
The authors declared no conflict of interest.
Authors’ contributions
MYZ substantially contributed to study conception and design, as well as acquisition, analysis, and interpretation of data, drafting and revision of the manuscript. PJ and YBZ participated in the acquisition and analysis of data. AHX conceived of the study conception and design. JPC and YZ was involved in the experiments. PC helped to draft and revise the manuscript. JFZ contributed to study design, drafting and revision of the manuscript, and acquisition of funding. All authors read and approved the final manuscript.