Non-toxigenic Bacteroides fragilis (NTBF) administration reduces bacteria-driven chronic colitis and tumor development independent of polysaccharide A

Abstract

Polysaccharide A (PSA), an immunogenic capsular component of non-toxigenic Bacteroides fragilis (NTBF) strain NCTC 9343, is reported to promote mucosal immune development and suppress colitis. Contrastingly, enterotoxigenic Bacteroides fragilis (ETBF) is highly associated with inflammatory bowel disease (IBD) and colorectal cancer (CRC), rapidly inducing IL-17-dependent murine colitis and tumorigenesis. In specific-pathogen-free (SPF) C57BL/6 wild type (WT) and multiple intestinal neoplasia (Min Apc 716+/− ) mice, we show that sequential treatment of the NTBF strain, 9343, followed by the ETBF strain, 86–5443-2–2 (86), diminished colitis and tumorigenesis. Mice treated simultaneously with 9343 and 86 exhibited both severe colitis and tumorigenesis. Abrogated disease severity in sequentially treated mice was attributed to 9343 strain dominance and decreased IL-17A, but 86 colonization prior to or simultaneous with 9343 mitigated the anti-inflammatory effect of 9343. Remarkably, 9343-mediated protection was independent of PSA, as sequentially treated mice receiving ΔPSA 9343 exhibited similar protection. Further, SPF WT and Min mice colonized with PSA-competent or PSA-deficient 9343 exhibited similar IL-10, IL-17, and IFN-γ responses. Treatment of 86-colonized mice with 9343 failed to disrupt 86 pathogenesis. Our findings demonstrate 9343 colonization, independent of PSA, offers prophylaxis against colitis-inducing 86 but may not be a valid therapy once colitis is established.

Epithelial-microbial diplomacy: escalating border tensions drive inflammation in inflammatory bowel disease

“…37 Intriguingly, B. fragilis also accounts for a majority of Bacteroides infections in the body and the enterotoxigenic B. fragilis (ETBF) strain is a causative pathogen of diarrhea. 102 Recently, Chan et al 103 demonstrated stable colonization of non-enterotoxigenic B. fragilis (NTBF) ameliorated disease severity following ETBF infection, in a PSA-independent manner. This study confirmed that B. fragilis predominance alone can be protective against mucosal inflammation.…”

Glucosylceramide production maintains colon integrity in response toBacteroides fragilistoxin‐induced colon epithelial cell signaling

“…The first, non-toxigenic B. fragilis (NTBF), is a beneficial symbiote that promotes the expansion of anti-inflammatory regulatory T-cells (Treg), while also suppressing pro-inflammatory T-helper 17 (Th17) cells known to aid in colon tumorigenesis. 1,2 The second subtype, enterotoxigenic B. fragilis (ETBF), promotes colitis and colon tumorigenesis through a Th17-dependent mechanism. 3 The main difference between the NTBF and ETBF subtypes is the production of B. fragilis toxin (BFT) by ETBF strains.…”

Demystifying the manipulation of host immunity, metabolism, and extraintestinal tumors by the gut microbiome

“…Notably, the protective effect of nontoxigenic B. fragilis on colitis is partly in a PSA-independent manner by which the bacterial sphingolipid source limits the expansion of colonic iNKT cells. 252,253 The recolonization of Lactobacillus has also been associated with restoring the proportion of Treg cells and activating DCs in broad-spectrum antibiotictreated mice. 254 Cell surface β-glucan/galactan polysaccharides of B. bifidum strain are also assumed to be pivotal ingredients responsible for Treg induction and eliciting anti-inflammatory responses through activating TLR2 on DCs.…”