Capsular Polysaccharide From Bacteroides fragilis Protects Against Ulcerative Colitis in an Undegraded Form

Abstract

The prominent human symbiont Bacteroides fragilis protects animals from intestinal diseases, such as ulcerative colitis, and its capsular polysaccharide plays a key role in reducing inflammation. B. fragilis strain ZY-312 was isolated from the feces of a healthy breast-fed infant, and the zwitterionic capsular polysaccharide zwitterionic polysaccharide, TP2, was extracted. In rats with 2,4-dinitrobenzenesulfonic acid (DNBS)-induced enteritis, TP2 at an optimal dose of 2.5 mg/kg could significantly alleviate enteritis and reduced the degree of intestinal adhesions, the intestinal ulcer area, and the incidence of ulcers in rats. To understand the underlying mechanism, TP2 was labeled with Fluorescein isothiocyanate and orally administered at a dose of 2.5 mg/kg in rats. TP2 was mainly distributed in the cecum and colorectum, but it was not detected in the blood and other organs except that a compound with a molecular weight greater than that of TP2-FITC was found in liver tissue. During the absorption, distribution, metabolism, and excretion, TP2 was indigestible. These results were further confirmed by investigation in the simulated gastric, intestinal fluid, and colonic fluid with fecal microbiota in vitro, where TP2 remained unaltered at different time points. Furthermore, flora composition was analyzed in simulated colonic fluid with TP2 added and it was found that TP2 increased the abundance of Faecalibacterium, Enterococcus romboutsia, and Ruminococcaceae, whereas the abundance of the phylum Proteobacteria represented by Sutterella, Desulfovibrio, and Enterobacteriaceae was decreased. However, the amount of short-chain fatty acids in the simulated colonic fluid was not changed by intestinal flora post-TP2 addition. In conclusion, these findings confirmed that TP2, a capsular polysaccharide of B. fragilis, protects against ulcerative colitis in an undegraded form.

Intestinal Bacteroides Modulates Systemic Inflammation and the Microbial Ecology in a Mouse Model of CF: Evidence for Propionate and other Short Chain Fatty Acids Reducing Systemic Inflammatory Cytokines

“…Interestingly, capsule from B. fragilis has been shown to have anti-inflammatory effects in a mouse model of ulcerative colitis, an intestinal inflammatory disorder with similarities to CF intestinal manifestations (Zheng et al, 2020).…”

Evaluation of the Effects of Different Bacteroides vulgatus Strains against DSS-Induced Colitis

“…COG4464, which is specific to B. vulgatus 7K1, is responsible for the biosynthesis of capsular polysaccharides. The anti-inflammatory effect of the capsular polysaccharide produced by certain Bacteroides strains has been reported in several studies [ 5 , 10 ]. As the best-studied zwitterionic capsular polysaccharide, polysaccharide A has been confirmed to prevent colitis by inducing the expression of IL-10 in the colon [ 73 ].…”

“…Bacteroides , one of the most abundant genera in the mammalian colon, has been a primary candidate for next-generation probiotics and has attracted considerable attention due to its role in the prevention of a series of metabolic disorders, including obesity [ 1 , 2 ], diarrhea [ 3 ], viral encephalitis [ 4 ], and enteritis [ 5 ]. In particular, the protective effects of Bacteroides on inflammatory diseases in the gut are a hot topic.…”

“…For example, polysaccharide A, a type of capsular polysaccharide present on B. fragilis NCTC 9343, has been reported to alleviate colitis [ 22 ] and colitis-associated colorectal cancer [ 23 ]. Another capsular zwitterionic polysaccharide TP2 from B. fragilis ZY-312 has been reported to protect rats from 2,4-dinitrobenzenesulfonic acid-triggered enteritis by reducing the degree of intestinal adhesion and the area of intestinal ulcers [ 5 ]. Moreover, the sphingolipids of B. fragilis NCTC9343 have been found to attenuate oxazolone-induced experimental colitis [ 24 ].…”

Engineering immunomodulatory nanoplatforms from commensal bacteria-derived polysaccharide A

“…12 Thus, CZPs represent an interesting class of biologically active carbohydrates with potential for generating material constructs with immunomodulatory activity that are applicable for the treatment of diseases or usable as vaccines. 7,13,14 Among the CZPs, PSA from B. fragilis is the most characterized and reported in literature. 15–17 Despite the numerous reports detailing the appealing immunomodulatory prowess of PSA, no groups have dared to imagine the fabrication of this natural biomaterial into particulates.…”