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Pro-Inflammatory Commensal Bacteria Linked to Colorectal Cancer
The link between gut inflammation and neoplasia involves enterotoxigenic strains of Bacteroides fragilis (ETBF) in the microbiome that harbor the B. fragilis toxin gene, which induces pro-inflammatory cytokines. However, the possible role of nontoxigenic B. fragilis (NTBF) strains in the development of colon polyps is unclear. Kordahi and colleagues examined the histology, mucosal microbiota, and molecular signatures in biopsy samples from 40 patients (age range, 40–75) undergoing routine colonoscopies. Evaluable specimens were polyp-free (PF) or had tubular adenomatous polyps (TAP) or sessile serrated polyps (SSP).
Cytokine studies revealed higher concentrations of a pro-inflammatory cytokine (IL-12p40) in TAP and SSP tissues and higher concentrations of an anti-inflammatory cytokine (IL-10) in PF tissue. Tissue from patients with TAP and SSP was enriched for B. fragilis as compared with tissue from PF patients. In vitro experiments showed that NTBF isolates from polyps induced significantly more pro-inflammatory cytokines than NTBF from PF tissue. Finally, NTBF from patients with polyps activated the TLR4 receptor and expressed glycosyltransferase, an enzyme involved in lipopolysaccharide biosynthesis. The glycosyltransferase gene was present in NTBF from 88% of patients with TAP, 100% of patients with SSP, and 11% of PF patients.
Comment
This series of experiments in colon tissue samples supports a strong link between NTBF and activation of TLR4 via lipopolysaccharide in patients with premalignant TAP and SSP. Along with host genetics and environmental exposures to teratogens through diet and other means, the properties of B. fragilis in the microbiome may play an important role in the development of colon cancer. Further studies are needed to examine what determines the establishment of pro-inflammatory B. fragilis strains in the gut microbiome.
Citation(s)
Author:
Kordahi MC et al.
Title:
Genomic and functional characterization of a mucosal symbiont involved in early-stage colorectal cancer.
Source:
Cell Host Microbe
2021
Oct
13; [e-pub].
(Abstract/FREE Full Text)
Empfohlen von
George Sakoulas, MD