Toll-like receptor 4 prevents AOM/DSS-induced colitis-associated colorectal cancer in Bacteroides fragilis gnotobiotic mice

Lee, Yen Peng; Huang, Wen Ching; Lin, T.; Chiu, Chien Chao; Wang, Yu-Chih; Chen, Yi Hsun; Hung, Shao Wen; Chuang, Hsiao-Li; Chen, Ter Hsin

doi:10.1177/0960327120954249

Cited by 11 publications

(7 citation statements)

References 36 publications

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“…This may be related to the protective effect of it by inhibiting TNF-α-induced apoptosis and injury. NF-κB is a ubiquitously expressed transcription factor that acts as a critical regulator of immune and in ammatory response and programmed cell death [44]. Our results showed that the NF-κB signaling pathway was slightly activated and it was not statistically signi cant when treatment with B. fragilis alone.…”

Section: Discussionmentioning

confidence: 64%

Protective Effect of Bacteroides fragilis on TNF-α- Induced Inflammatory Changes in Human Colon Epithelial Cells and in Inflammatory Bowel Disease Mouse Model

Niu

et al. 2023

Preprint

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Bacteroides fragilis, one of the potential next-generation probiotics, but its protective mechanism is not yet known. We aimed to characterize the anti-inflammatory effect of B. fragilis and to elucidate its mechanism through in vivo and in vitro experiments. An in vitro model of inflammation by induction of colonic cells with TNF-a, and co-cultured with B. fragilis to detect cell viability, apoptosis and invasive capacity. Furthermore, critical proteins of the TLR/NF-κB pathway and the inflammatory cytokines were measured. For animal trials, C57BL/6J male mice were orally administered B. fragilis or PBS once daily for 21 days. Colitis was induced by drinking 2.5% DSS from days 0 to 7. The mice were weighed daily and rectal bleeding, stool condition and blood in the stool were recorded. We found that B. fragilis treatment alone was harmless and had no effect on cell viability or apoptosis. While predictably TNF-α decreased cell viability and increased apoptosis, B. fragilis attenuated this deterioration. The NF-κB pathway and inflammatory cytokines IL-6, IL-8 and IL-1β activated by TNF-α were also blocked by B. fragilis, which was likely mediated by TLR2. Animal studies showed that B. fragilis ameliorated DSS-induced colitis, as evidenced by weight loss, shortened colon length and enhanced barrier function. The colonic tissue levels of inflammatory cytokines (TNF-α, IL1β, IL6) were decreased and IL-10 was increased as a result of B. fragilisadministration. In conclusion, B. fragilisexhibited anti-inflammatory effects whether in vivo or in vitro, and it may be a potential probiotic agent for improving colitis.

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Section: Discussionmentioning

confidence: 64%

Protective Effect of Bacteroides fragilis on TNF-α- Induced Inflammatory Changes in Human Colon Epithelial Cells and in Inflammatory Bowel Disease Mouse Model

Niu

et al. 2023

Preprint

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“…The positivity rates of ETBF were 67.3%, 72.7% and 100% for colonoscopic biopsy samples from healthy, early, and advanced CRC patients [ 16 ], suggesting a trend of ETBF enrichment with CRC progression. ETBF has also been demonstrated to accelerate CRC development and progression by regulating inflammatory responses [ 17 ], dryness [ 18 ], and polyp formation [ 19 , 20 ]. BFT secretion is one of the main pathways through which ETBF facilitates the CRC development process [ 19 , 21–23 ].…”

Section: Discussionmentioning

confidence: 99%

Entero-toxigenic Bacteroides fragilis contributes to intestinal barrier injury and colorectal cancer progression by mediating the BFT/STAT3/ZEB2 pathway

Yang,

Wang,

et al. 2024

Cell Cycle

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Our previous findings confirmed the high enrichment of Bacteroides fragilis (BF) in fecal samples from patients with colorectal cancer (CRC). The intestinal mucosal barrier is the first defense of the organism against commensal flora and intestinal pathogens and is closely associated with the occurrence and development of CRC. Therefore, this study aimed to investigate the molecular mechanisms through which BF mediates intestinal barrier injury and CRC progression. SW480 cells and a Caco2 intestinal barrier model were treated with entero-toxigenic BF (ETBF), its enterotoxin (B. fragilis toxin, BFT), and non-toxigenic BF (NTBF). Cell counting kit-8, flow cytometry, wound healing and transwell assays were performed to analyze the proliferation, apoptosis, migration, and invasion of SW480 cells. Transmission electron microscopy, FITC-dextran, and transepithelial electrical resistance (TEER) were used to analyze damage in the Caco2 intestinal barrier model. The Azoxymethane/Dextran Sulfate Sodium (AOM/DSS) animal model was established to evaluate the effect of ETBF on intestinal barrier injury and CRC progression in vivo . ETBF and BFT enhanced the viability, wound healing ratio, invasion, and EMT of SW480 cells. In addition, ETBF and BFT disrupted the tight junctions and villus structure in the intestinal barrier model, resulting in increased permeability and reduced TEER. Similarly, the expression of intestinal barrier-related proteins (MUC2, Occludin and Zo-1) was restricted by ETBF and BFT. Interestingly, the STAT3/ZEB2 axis was activated by ETBF and BFT, and treatment with Brevilin A (a STAT3 inhibitor) or knockdown of ZEB2 limited the promotional effect of ETBF and BFT on the SW480 malignant phenotype. In vivo experiments also confirmed that ETBF colonization accelerated tumor load, carcinogenesis, and intestinal mucosal barrier damage in the colorectum of the AOM/DSS animal model, and that treatment with Brevilin A alleviated these processes. ETBF-secreted BFT accelerated intestinal barrier damage and CRC by activating the STAT3/ZEB2 axis. Our findings provide new insights and perspectives for the application of ETBF in CRC treatment.

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“…This may be related to the protective effect of it by inhibiting TNF-α-induced cell injury. NF-κB is a ubiquitously expressed transcription factor that acts as a critical regulator of immune and inflammatory response and programmed cell death 33 . Our results showed that the NF-κB signaling pathway was slightly activated and it was not statistically significant when treatment with B. fragilis ATCC25285 alone.…”

Section: Discussionmentioning

confidence: 99%

Protective effects of a new generation of probiotic Bacteroides fragilis against colitis in vivo and in vitro

He,

Niu,

et al. 2023

Sci Rep

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Bacteroides fragilis, one of the potential next-generation probiotics, but its protective mechanism is not yet known. We aimed to characterize the anti-inflammatory effect of B. fragilisATCC25285 and to elucidate its mechanism through in vivo and in vitro experiments. An in vitro model of inflammation by induction of colonic cells with TNF-a, and co-cultured with B. fragilis to detect cell viability, apoptosis and invasive capacity. Furthermore, critical proteins of the TLR/NF-κB pathway and the inflammatory cytokines were measured. For animal trials, C57BL/6 J male mice were orally administered B. fragilis or PBS once daily for 21 days. Colitis was induced by drinking 2.5% DSS from days 0 to 7. The mice were weighed daily and rectal bleeding, stool condition and blood in the stool were recorded. We found that B. fragilis treatment alone was harmless and had no effect on cell viability or apoptosis. While predictably TNF-α decreased cell viability and increased apoptosis, B. fragilis attenuated this deterioration. The NF-κB pathway and inflammatory cytokines IL-6 and IL-1β activated by TNF-α were also blocked by B. fragilis. Notably, the metabolic supernatant of B. fragilis also has an anti-inflammatory effect. Animal studies showed that live B. fragilis rather than dead strain ameliorated DSS-induced colitis, as evidenced by weight loss, shortened colon length and enhanced barrier function. The colonic tissue levels of inflammatory cytokines (TNF-α, IL-1β, IL-6) were decreased and IL-10 was increased as a result of B. fragilis administration. In conclusion, B. fragilis ATCC25285 exhibited anti-inflammatory effects whether in vivo or in vitro, and it may be a potential probiotic agent for improving colitis.

show abstract

Toll-like receptor 4 prevents AOM/DSS-induced colitis-associated colorectal cancer in Bacteroides fragilis gnotobiotic mice

Cited by 11 publications

References 36 publications

Protective Effect of Bacteroides fragilis on TNF-α- Induced Inflammatory Changes in Human Colon Epithelial Cells and in Inflammatory Bowel Disease Mouse Model

Protective Effect of Bacteroides fragilis on TNF-α- Induced Inflammatory Changes in Human Colon Epithelial Cells and in Inflammatory Bowel Disease Mouse Model

Entero-toxigenic Bacteroides fragilis contributes to intestinal barrier injury and colorectal cancer progression by mediating the BFT/STAT3/ZEB2 pathway

Protective effects of a new generation of probiotic Bacteroides fragilis against colitis in vivo and in vitro

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