The intestinal tract is an essential digestive organ of the human body, and damage to the intestinal barrier will lead to various diseases. Functional oligosaccharides are carbohydrates with a low degree of polymerization and exhibit beneficial effects on human intestinal health.
1. Colorectal Cancer
The colon environment, including imbalanced intestinal microflora and mutations in the Wnt signaling pathway are the leading causes of CRC
[1][2]. The current treatments for CRC include chemotherapy, radiotherapy, and surgery, but most of them are accompanied by high-risk complications, and the success rate is limited. Therefore, new early treatment strategies are needed
[3]. The use of functional oligosaccharides in preventing CRC may be promising. Studies show FOS and GOS can reduce the severity of colon cancer in rats and mice induced by 1,2-dimethylhydrazine by reducing the number of colon ACF
[4][5][6]. Researchers have found that low-degree FOS are more effective in treating early colon cancer in mice induced by DMH
[7] and significantly reducing the risk of colon cancer in animal models
[8]. There are two aspects regarding the inhibitory effect of functional oligosaccharides on colorectal cancer. First, functional oligosaccharides affect the homeostasis of intestinal microflora by promoting the growth and colonization of intestinal probiotics and upregulating production of metabolites such as SCFA, which inhibit the proliferation and differentiation of colon tumor cells
[3][9] and regulates exogenous metabolic enzymes that stimulate the activation and metabolism of carcinogens
[10][11]. Furthermore, functional oligosaccharides directly regulate the functions of intestinal GALT and other immune cells, influence gene expression levels of cancer cells, and promote cancer cell apoptosis
[8].
The clinical data also show that functional oligosaccharides have a positive effect on the immunological indexes of colon cancer and microbial flora abundance
[12]. However, some clinical data point out that functional oligosaccharides do not significantly reduce the mortality of colorectal cancer in women after menopause
[1][12]. There is no clear explanation for the structure-activity relationship, dosage, and individual differences of functional oligosaccharides, which may also be the main reason for restricting the clinical trials of functional oligosaccharides in the treatment of colorectal cancer. Therefore, the clinical treatment of CRC with functional oligosaccharides remains unconfirmed. Consequently, research on new technologies such as combining probiotics and functional oligosaccharides as targeted therapeutic agents for colon cancer based on host–guest chemistry is also an aspect worth exploring
[13].
2. Inflammatory Bowel Disease
IBD is a chronic nonspecific gastrointestinal inflammatory disease that destroys the intestinal mucosal structure and floral balance, leading to abnormal systemic biochemical indexes
[14]. The etiology of inflammatory bowel disease is not clear, while comprehensive factors such as intestinal flora, immunity, environment, and gene susceptibility might be involved.
The DSS-induced mouse colitis model is one of the widely recognized models for studying the pathogenesis of IBD and evaluating potential therapeutic methods
[15]. Growing evidence supports the potential of functional oligosaccharides to treat inflammatory diseases, including colitis. FOS and GOS in vitro affect immunity by binding to TLR on monocytes, macrophages, and intestinal epithelial cells and regulating cytokine production and immune cell maturation
[16][17][18][19][20]. In addition, animal models and clinical studies have shown that functional oligosaccharides reduce the intestinal inflammatory response and IBD symptoms
[21][22]. A clinical study focused on enteritis after abdominal radiotherapy (RT) found that FOS supplementation in patients’ daily diet can stimulate the proliferation of
Lactobacilus and
Bifidobacterium, thereby repairing intestinal mucosal damage during RT and preventing the occurrence and development of IBD
[23]. COS treatment upregulates the expression of occludin in the proximal colon of diabetic mice
[24], alleviates DSS-induced mucosal defects in IBD, and protects the intestinal mucosal barrier function of ulcerative colitis mice
[25].
3. Irritable Bowel Syndrome
IBS is a chronic disease affected by stress and eating habits. It is characterized by abdominal pain, mucosal and immune functions, and changes in the intestinal microbial structure. Dietary patterns, the intestinal microbial structure, inflammatory response, and other factors can aggravate the symptoms of irritable bowel syndrome. Dietary interventions are recommended to control the disease due to the efficacy and tolerance of common drug treatments.
Evidence shows that the ecological imbalance of intestinal and mucosal colon microflora in IBS is usually characterized by the reduction of the
Bifidobacterium species
[26][27][28][29]. Some studies have found that supplementing probiotics to regulate intestinal microflora are effective in treating IBS
[30][31]. Some clinical studies have also found that low-dose functional oligosaccharides, such as FOS, can alleviate the symptoms of IBS patients through increasing the concentration of SCFA
[32]. In contrast, a low FODMAP diet has gradually become the standard method for the treatment of IBS worldwide. This method can alleviate the clinical symptoms of IBS patients by limiting the daily intake of short-chain fermentable carbohydrates (low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP)). Studies have consistently proven the clinical efficacy of a low FODMAP diet in patients with IBS
[32]. In fact, the low FODMAP diet has clinical efficacy, but it reduces the abundance of intestinal
Bifidobacterium, which is not conducive to the thorough treatment of IBS patients.
4. Application Prospect of Functional Oligosaccharides in the Intestinal Tract
Glycans generally have complex monosaccharide composition, glycosidic bond type and degree of polymerization, and their structural complexity is much higher than that of proteins and nucleic acids. In the past decade, glycoscience, with the support of governments, has made a lot of progress, and it has revealed the role of glycans in inflammatory responses and immune system regulation, cardiovascular diseases, intestinal diseases, and cancers. A variety of functional oligosaccharides have shown kinds of activities in intestinal barrier protection and repair and have demonstrated the great promise of glycans in intestinal disease treatment. However, the structure-activity relationship and molecular mechanism have not been fully elucidated. Glycan-based products used in related research are often a mixture of glycans with slightly different structural characters and subject to variations in different preparation methods and raw material sources. Recent studies have shown that small changes in the structure of glycans have significant effects on their activities, so the accurate analysis and preparation of glycan products is the key to clarify their structure-activity relationships and develop functional glycan products, for example, structural analysis and pharmacokinetic study of glycans by liquid chromatography-tandem mass spectrometry (LC-MS/MS)
[33]. On the other hand, based on the different activities of different sugar chains, the combination of several different glycans have received more attention and applications
[34][35][36]. In the face of the complex microbial and host environment in the intestinal tract, products containing multiple different glycans will play a greater role. However, there is a lack of in-depth research on the compounding mechanism and synergistic effect of multiple glycan recipes.