Liver Flukes and the Microbiota in Cancer

Tumor development is a multifactorial process, influenced by both specific microbial signature. These findings will require verification in genetic and environmental pressures. A small number of chronic infectious agents have been designated carcinogenic, including viruses (hepatitis B, C and HPV), bacteria (Helicobacter pylori) and parasites (De Martel et al., 2012). Further, general microbial dysbiosis can contribute to the development of some cancers (Garrett, 2015), including in the biliary system (Avilés-Jiménez et al., 2016). In the Southeast Asian countries Thailand, Laos, Vietnam, and Cambodia, the liver fluke Opisthorchis viverrini is endemic, and chronic infection with this trematode is a known risk factor for development of the bile duct cancer cholangiocarcinoma (CCA). Understanding how O. viverrini infection contributes to CCA development or progression could lead to new therapeutic interventions for this notoriously hard to treat disease. Multiple O. viverrini infection-induced pathways have been associated with tumorigenesis, including parasite secretion of a growth factor that facilitates wound healing, angiogenesis and cellular proliferation that contributes to transformation of bile duct cholangiocytes (Smout et al., 2015, 2009) and infection-induced chronic inflammation (Sripa et al., 2012). This is reminiscent of a growing number of inflammation-driven cancers that involve bacterial dysbiosis (Garrett, 2015). However, the local tissue microbiome has been an understudied component of CCA. Recent studies using a small animal model of O. viverrini-induced CCA demonstrated that fluke infection of Syrian golden hamsters altered commensal bacterial communities in the gastrointestinal tract and allowed translocation of several microbes into bile fluid (Plieskatt et al., 2013), indicating that microbial shifts associated with O. viverrini infection may influence CCA. In this issue of EBioMedicine, Chng et al. (Chng et al., 2016) interrogate the microbiome of bile ducts isolated from O. viverrini-naïve and -infected CCA patients and report a number of distinct features in the bacterial composition of local tissues. All bile duct samples from CCA patients, independent of O. viverrini infection, harbor similar microbial communities comprised of taxa typically found in the gut. Based on comparison of these tumor samples to hepatic and gastric tissues of non-CCA patients, the authors suggest the existence of a bile duct-