Gut microbiota dysbiosis and the therapeutic potential of dietary polysaccharides: A literature review

Abstract

The gut microbiota is a community of trillions of beneficial bacteria residing in the colon. Non digestible fibers are complex polysaccharides found in plants, fungi, and bacteria, and the human body cannot digest them on its own, so they reach the colon intact. The gut microbiota ferments these polysaccharides using their own enzymes, to produce short-chain fatty acids (SCFAs). The most important SCFAs is butyrate, which strengthens the intestinal barrier by increasing tight junction proteins, and alleviates inflammation by inhibiting the NF-κB pathway. Dysbiosis occurs due to antibiotics, environmental toxins, an unhealthy diet, or pathogenic organisms. Dysbiosis is characterized by loss of microbial diversity, a decrease in butyrate-producing bacteria, and an increase in pathogenic bacteria. These changes cause increased intestinal permeability through decreased tight junction proteins and a decreased mucin layer, allowing LPS, TMAO, and bacteria to translocate into the blood, activating NF-κB with elevated inflammatory cytokines (TNF-α, IL-6, and IL-1β). This leadsto chronic diseases fatty liver disease, atherosclerosis, heart failure; and nervous system diseases such as Alzheimer's, Parkinson's and depression. In the dextran sodium sulfate model (DSS), an animal model of ulcerative colitis (UC), these same mechanisms cause colon shortening, bleeding, diarrhea, and an elevated disease activity index. Here comes the role of natural polysaccharides from various sources (plant; fungal-derived, bacterial-derived, and animal-derived,), which act as effective prebiotics that reprogram the microbiota toward a healthy state by increasing Akkermansia, Lactobacillus, and butyrate-producing bacteria and reducing pathogenic bacteria. Polysaccharides act through mechanisms including butyrate production, which fuels colonic cells and inhibits HDAC and NF-κB; strengthens the intestinal barrier by increasing ZO-1, occludin, claudin-1, and mucin 2 and increasing goblet cells; inhibits inflammation by reducing TNF-α, IL-6, IL-1β, and IL-17 and increasing IL-10 and TGF-β, and improves antioxidants while reducing oxidative stress. All 18 studies collected confirmed a uniform pattern of improvement, independent of the source of polysaccharides and instead dependent on structural features that enhance colonic delivery and slow fermentation for SCFA production, most notably low molecular weight (LMW), branched structure, and sulphated groups. Therefore, polysaccharides have been demonstrated to represent a promising multi-target strategy for managing DSS-induced UC and its associated liver, cardiovascular, and neurological diseases through restoring eubiosis, repairing the intestinal barrier, and modulating immunity, which is known as the microbiota-barrier-immunity axis.