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

A recent study published within the journal Microorganisms explores 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 / Shutterstock.com

Biliary tract cancer

Biliary tract cancer comprises a big selection of invasive adenocarcinomas, including gallbladder carcinoma and cholangiocarcinoma. Cholangiocarcinoma, often related to a poor prognosis, could be further classified as intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma.

The incidence rate of biliary tract cancer varies based on realms and subgroups. In recent times, the worldwide prevalence of ICC has increased from 0.44 to 1.18 cases per 100,000 individuals. Unlike ICC, extrahepatic cholangiocarcinoma has modestly increased from 0.95 to 10.2 for each 100,000 individuals over a 40-year period.

Epidemiological studies have identified multiple risk aspects related to the incidence of cholangiocarcinoma. A few of these risk aspects include hepatolithiasis, choledocholithiasis, primary sclerosing cholangitis, cholelithiasis, and bile duct cysts.

Biliary tract cancer and the microbiome

Hundreds of microorganisms are present in several 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 can correlate with manifestations of cancer and metabolic disorders. Likewise, next-generation sequencing (NGS) technology has highlighted an association between biliary tract cancer and the microbiome.

In comparison with healthy individuals, patients with biliary tract cancer exhibit increased levels of Enterobacteriaceae and decreased levels of Faecalibacterium, Clostridia, and Coprococcus.

Fecal samples of biliary tract cancer patients have also revealed high levels of Enterobacteriaceae. In reality, about 50% of Enterobacteriaceae species identified within the bile samples of patients were just like strains identified from the fecal sample on the operational taxonomic unit (OTU) level.

Previous studies have observed a relationship between gut dysbiosis and the incidence of ICC, possibly as a consequence of the connection between gut microbiota, cytokine profiles, and bile acid. Patients with ICC exhibit significant α- and β-diversity as in comparison with patients with liver cirrhosis hepatocellular carcinoma and healthy individuals.

ICC has been related to higher levels of Lactobacillus, Actinomyces, Alloscardovia, and Peptostreptococcaceae. Significantly higher glycoursodeoxycholic acid and tauroursodeoxycholic acid (TUDCA) plasma-stool ratios have also been observed in ICC. Dietziaceae, Pseudomonadaceae, and Oxalobacteraceae have also been detected within the bile duct tissues.

Genomic studies have indicated the presence of Streptococcus, Enterococcus, Bacteroides, Klebsiella, and Pyramidobacter inside the biliary microflora. These bacteria play a big role within the onset of cholangiocarcinoma; due to this fact, these microbes might be used as a biomarker for the condition.

Extrahepatic cholangiocarcinoma has been related to a reduced level of Nesterenkonia but an abundance of Methylophilaceae, Prevotella, Fusobacterium, Actinomyces, Helicobacter pylori, and Novosphingobium.

Prolonged inflammation plays a critical role in the event of gallbladder cancer, which also influences the biliary tract. The chance of gallbladder cancer increases within the presence of bacterial infections, which could induce chronic inflammation, carcinogenic toxin, and metabolite production. 

Fusobacterium nucleatum and Escherichia coli are dominant species identified within the bile of gallbladder cancer patients. The presence of Salmonella typhi within the gallbladder might also influence the onset of gallbladder cancer.

The impact of host microbes within the diagnosis and treatment of biliary tract cancer

Although immunotherapy is a standard approach to treating malignant tumors, its efficacy is significantly affected by intestinal flora and environmental aspects. Many studies have shown that the gut microbiome influences the response to immune checkpoint inhibitors (ICI). These studies have also highlighted the association between gut microbiome and tumor immune resistance.

The strategic use of probiotics to control ICI could play an efficient role in controlling harmful bacteria with carcinomic potential. Early clinical trial reports have indicated a modest response rate of immune checkpoint therapy (ICT) in cholangiocarcinoma.

Taxonomic screening is a crucial technique to discover biomarkers that could be used to evaluate clinical responses to immunotherapies. Altering gut microbial composition and variety might be an efficient technique to modulate responses to cancer immunotherapy. 

The liver-bile acid-microbiota axis plays a vital role in gastrointestinal carcinogenesis. Thus, distinct changes in plasma bile acid concentrations might be used as potential diagnostic biomarkers to differentiate cholangiocarcinoma from benign biliary diseases and healthy individuals.