The Amount of Bifidobacterium Genus in Colorectal Carcinoma Tissue in Relation to Tumor Characteristics and Clinical Outcome

Abstract

Evidence indicates a complex link between microbiota, tumor characteristics, and host immunity in the tumor microenvironment. In experimental studies, bifidobacteria appear to modulate intestinal epithelial cell differentiation. Accumulating evidence suggests that bifidobacteria may enhance the antitumor immunity and efficacy of immunotherapy. We hypothesized that the amount of bifidobacteria in colorectal carcinoma tissue might be associated with tumor differentiation and higher immune response to colorectal cancer. Using a molecular pathologic epidemiology database of 1313 rectal and colon cancers, we measured the amount of Bifidobacterium DNA in carcinoma tissue by a quantitative PCR assay. The multivariable regression model was used to adjust for potential confounders, including microsatellite instability status, CpG island methylator phenotype, long-interspersed nucleotide element-1 methylation, and KRAS, BRAF, and PIK3CA mutations. Intratumor bifidobacteria were detected in 393 cases (30%). The amount of bifidobacteria was associated with the extent of signet ring cells (P = 0.002). Compared with Bifidobacterium-negative cases, multivariable odd ratios for the extent of signet ring cells were 1.29 (95% CI, 0.74-2.24) for Bifidobacterium-low cases and 1.87 (95% CI, 1.16-3.02) for Bifidobacterium-high cases (P = 0.01). The association between intratumor bifidobacteria and signet ring cells suggests a possible role of bifidobacteria in determining distinct tumor characteristics or as an indicator of dysfunctional mucosal barrier in colorectal cancer.

Association of autophagy status with amount of Fusobacterium nucleatum in colorectal cancer

“…In contrast, the members of Bifidobacterium genus have been considered to inhibit colorectal carcinogenesis through the prevention of enteropathogenic infection and the inhibition of secondary bile acid production [46][47][48]. Our previous population-based study has shown that intratumoural Bifidobacterium genus may reflect loss of intestinal barrier function in poorly differentiated colorectal cancer [36]. These distinct characteristics of F. nucleatum and Bifidobacterium genus are supported by our results of differing associations with autophagic activity.…”

Intestinal Microbiota in Colorectal Cancer Surgery

“…Bifidobacteria possibly acts as a protective probiotic in CRC, acting by enhancing intestinal epithelial homeostasis [ 137 ]. Kosumi et al [ 138 ] assessed the prognostic potential of Bifidobacterium in a cohort study of 1313 CRC patients. Contrary to the above findings, they reported the detection of Bifidobacterium in 30% of tumors with no statistically significant association between its abundance and survival outcomes or molecular and clinicopatholigical features of CRC.…”

Integration of microbiology, molecular pathology, and epidemiology: a new paradigm to explore the pathogenesis of microbiome‐driven neoplasms

“…These studies provide population‐based evidence for the potential role of the microbiome in mediating the relationship between diet and colorectal carcinogenesis. Studies support the roles of viruses and other bacteria, such as enterotoxigenic Bacteroides fragilis , pks‐positive Escherichia coli , Enterococcus faecalis , Lactobacillus , and Bifidobacterium in colorectal cancer . Therefore, investigation of these bacteria and a microbial community as a whole in relation to the incidence and progression of colorectal cancer is also warranted.…”