Could the microbiome hold the key to diagnosing and treating biliary tract cancer?

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A recent study published in the journal Microorganisms Exploring the microbiome composition in patients with biliary tract cancer.

Study: Interplay between the human microbiome and biliary tract cancer: implications for pathogenesis and therapy. Image Credit: MR.AUKID PHUMSIRICHAT/

Biliary tract cancer

Cancers of the biliary tract include a wide range of invasive adenocarcinomas, including gallbladder carcinoma and cholangiocarcinoma. Cholangiocarcinoma, often associated with a poor prognosis, can be further classified as intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma.

Incidence rates of biliary tract cancer vary by geographic region and subgroup. In recent years, the global prevalence of ICC has increased from 0.44 to 1.18 cases per 100,000 persons. In contrast to ICC, extrahepatic cholangiocarcinoma increased from 0.95 to 10.2 per 100,000 persons over a 40-year period.

Epidemiological studies have identified multiple risk factors associated with the incidence of cholangiocarcinoma. Some of these risk factors include hepatolithiasis, choledocholithiasis, primary sclerosing cholangitis, cholelithiasis, and bile duct cysts.

Biliary tract cancer and the microbiome

Thousands of microorganisms are present in various organs, including the stomach, skin, liver, and intestines, all of which influence various physiological functions, including immune regulation.

Previous studies have indicated that the gastrointestinal microbiome may be associated with the manifestation of cancer and metabolic disorders. Similarly, next-generation sequencing (NGS) technology has highlighted an association between biliary tract cancer and the microbiome.

Compared to healthy individuals, biliary tract cancer patients exhibit increased levels Enterobacteriaceae and its magnitude Faecalibacterium, ClostridiaAnd Coprococcus.

fecal samples from gallbladder cancer patients also revealed high levels Enterobacteriaceae. Actually, about 50 Enterobacteriaceae Species identified in bile samples from patients were similar to strains identified from stool samples at the operational taxonomic unit (OTU) level.

Previous studies have observed an association between intestinal dysbiosis and the incidence of ICC due to the association between gut microbiota, cytokine profile and bile acids. ICC patients exhibit significant α- and β-variation compared with liver cirrhosis hepatocellular carcinoma and healthy individuals.

High-level has been associated with the ICC Lactobacillus, Actinomyces, Alloscardovia, and Peptostreptococcaceae. Significantly higher glycosodeoxycholic acid and taursodeoxycholic acid (TUDCA) plasma-stool ratios were also observed in ICC. Dietziaceae, PseudomonadaceaeAnd Oxalobacteriaceae Also white ductal tissue has been detected.

Genomic studies have indicated the presence Streptococcus, Enterococcus, Bacteroides, KlebsiellaAnd Pyramidobacter Among the biliary microflora. These bacteria play an important role in the initiation of cholangiocarcinoma; Therefore, these microbes can be used as a biomarker for the condition.

Extrahepatic cholangiocarcinoma has been associated with a reduced level Nesterenkonia But an abundance Methylophyllaceae, Prevotella, Fusobacterium, Actinomyces, Helicobacter pyloriAnd Novosphingobium.

Prolonged inflammation plays an important role in the development of gallbladder cancer, which also affects the bile ducts. The risk of gallbladder cancer increases in the presence of bacterial infection, which can induce chronic inflammation, carcinogenic toxins, and metabolite production.

Fusobacterium nucleatum And Escherichia coli Dominant species identified in bile from patients with gallbladder cancer. presence Salmonella typhi Gallbladder may also affect the onset of gallbladder cancer.

Impact of the host microbe on the diagnosis and treatment of biliary tract cancer

Although immunotherapy is a common approach for the treatment of malignant tumors, its efficacy is significantly influenced by intestinal flora and environmental factors. Many studies have shown that the gut microbiome influences the response to immune checkpoint inhibitors (ICIs). These studies also highlight the link between the gut microbiome and tumor immune resistance.

Strategic use of probiotics to control ICI may play an effective role in controlling harmful bacteria with carcinogenic potential. Early clinical trial reports have indicated a modest response rate to immune checkpoint therapy (ICT) in cholangiocarcinoma.

Taxonomic screening is an important strategy to identify biomarkers that can be used to assess clinical responses to immunotherapy. Altering gut microbial composition and diversity may be an effective strategy for modulating responses to cancer immunotherapy.

The liver-bile acid-microbiota axis plays an important role in gastrointestinal carcinogenesis. Thus, individual changes in plasma bile acid concentration can be used as potential diagnostic biomarkers to differentiate cholangiocarcinoma from benign biliary disease and healthy individuals.

Journal Reference:

  • Yeh, C., Dong, C., Lin, Y., etc (2023) Interplay between the human microbiome and biliary tract cancer: implications for pathogenesis and therapy. Microorganisms 11(10); 2598. doi:10.3390/microorganisms11102598

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