Dual-pathway mechanisms of plant-derived polysaccharides in ulcerative colitis: integrative roles of microbiota modulation, immune regulation, and barrier restoration.

Chronic inflammation of the colon has been described as an inflammatory condition of the colon that is characterized by recurring flare-ups of the disease (ulcerative colitis). Ulcerative colitis is a complex inflammatory disorder of the colon that is determined by the combination of several mechanisms: abnormal bacterial flora, inappropriate immune response, and the breakdown of the protective lining of the colon. The last 10 years have seen the emergence of plant derived polysaccharides as new biological active compounds with the potential to intervene at the different levels of the disease. Plant derived polysaccharides can be divided into two separate regulatory modes; the first mode of action occurs when the polysaccharides work in collaboration with the microbiota to modify the structure of the microbiota and create a positive environment for the growth of the beneficial bacteria. The second mode of action occurs without the use of the microbiota and works by creating anti-inflammatory signals to regulate the body's immune system and protect the integrity of the intestinal lining. The authors of this paper used a systematic method to identify 103 papers published on the subject of plant derived polysaccharides and their effects on the disease mechanism of ulcerative colitis. The results of the analysis of these papers indicated that the polysaccharides act to reduce the inflammatory process through the downregulation of the three major inflammatory signaling pathways of NF-κB, PI3K/AKT, and JAK/STAT. In addition, the polysaccharides were shown to restore the balance of macrophages and T-cells and increase the production of mucus producing cells and tighten the tight junctions between the intestinal epithelial cells. In recent studies it was found that the metabolic products of the microbes and the intracellular signaling processes are part of a coordinated regulatory network. Therefore, based on the results of the study, plant derived polysaccharides appear to be multi-target modulators of the disease process rather than just acting on one pathway of the disease process. Although the study indicates that there has been significant progress in understanding how the plant derived polysaccharides interact with the disease process, there are still many barriers to overcome before the plant derived polysaccharides can be used as a treatment for ulcerative colitis in humans. These barriers include; the structural heterogeneity of the polysaccharides, the lack of clinical trials evaluating the safety and efficacy of the polysaccharides as a treatment for ulcerative colitis, and the large variation in how individuals respond to changes in the composition of the gastrointestinal tract microbiota. Therefore, this study represents a comprehensive review of the current state of knowledge on the interaction of plant derived polysaccharides with the pathophysiology of ulcerative colitis, and highlights areas of future research necessary to develop polysaccharide based treatments for ulcerative colitis that are safe, effective, and can be translated into the clinic.