A metagenomic study of biliary microbiome change along the cholecystitis‐carcinoma sequence

Abstract

Background Gallbladder cancer (GBC) is the most common cancer type of the biliary tract, and an association has been found between chronic calculous cholecystitis (CCC) and an increased incidence of GBC mortality. An understanding of the relationship between CCC and its carcinogenesis may enable us to prevent and cure GBC. In this study, we attempted to explore changes in the microbiome profile that take place during the transition from chronic cholecystitis mucosa to malignant lesions. Results Seven paired human GBC and CCC samples were provided by patients who had undergone laparoscopic cholecystectomy or radical cholecystectomy. Mucosal DNA extraction and metagenomic sequencing were performed to evaluate changes in the microbiota between the two groups. We found that GBC patients and CCC patients shared similar stable and permanent dominant species and showed apparent differences in their biliary microbial composition and gene function. Peptostreptococcus stomatis and Enterococcus faecium may potentially play a role in GBC progression. In addition, the metagenomic species profiles, co‐abundance and co‐exclusion correlations, and CAZyme prevalence showed significant differences between the CCC and GBC groups. Conclusion Our data suggested that changes in the microbiota between CCC and GBC may help deepen our understanding of the complex spectrum of different microbiotas involved in the development of GBC. Although the cohort size was small, this study has presented the first evidence of the existence of an altered biliary microbiota in GBC, which is clearly different from that in CCC patients.

Gallstone Disease, Obesity and the Firmicutes/Bacteroidetes Ratio as a Possible Biomarker of Gut Dysbiosis

“…Based on the analysis of the great number of contradictory results reported in the literature, it is currently difficult to associate specific microbial signatures or the Firmicutes/Bacteroidetes ratio with determining health status and more specifically to consider it as a hallmark of GSD and/or obesity. However, most authors believe that both obesity [ 33 , 34 , 40 , 48 , 64 , 130 ] and GSD [ 5 , 6 , 81 , 103 , 109 , 111 , 117 , 118 , 119 , 120 ] are associated with reduced microbial diversity.Therefore, it is important to look at the overall composition of the gut microbial population structure as an indicator of obesity and obesity-associated pathologies, such as GSD, rather than simply the Firmicutes/Bacteroidetes ratio [ 150 ]. However, in my opinion, it is possible to modify this ratio, e.g., to introduce a coefficient that characterizes BMI, to calculate the ratio not of the Firmicutes phylum, but only of the Clostridia class, and so on.…”

“…During a cholecystectomy, mucosal DNA extraction and metagenomic sequencing were performed to evaluate changes in the microbiota between chronic calculous cholecystitis and gallbladder cancer patients [ 118 ]. At the phylum level, Firmicutes , Bacteroidetes , Actinobacteria , and Proteobacteria were found to be stable in both groups.…”

“…At the phylum level, Firmicutes , Bacteroidetes , Actinobacteria , and Proteobacteria were found to be stable in both groups. The diversity of the biliary microbiota was significantly lower in the calculous cholecystitis group, compared with the gallbladder cancer group [ 118 ].…”

“…So, when analyzing available studies of intestinal and bile microbiota in animals and patients with GSD [ 5 , 6 , 15 , 79 , 80 , 81 , 82 , 92 , 93 , 100 , 102 , 103 , 104 , 105 , 106 , 107 , 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 ] there were no unidirectional changes in the Firmicutes/Bacteroidetes ratio. This situation with opposite results is typical not only for GSD.…”

Functional Characterisation of Bile Metagenome: Study of Metagenomic Dark Matter

“…Up to date, few studies characterised the human biliary metagenome. Song et al [2], performed metagenomic sequencing of the biliary microbiota of individuals who had undergone laparoscopic cholecystectomy or radical cholecystectomy. Shen et al [3], reported metagenomic characterisation of bile samples from patients with gallstone disease.…”