Enteric bacteria have been implicated

Enteric bacteria have been implicated in cancer progression of the gut (Louis et al., 2014; Schwabe and Jobin, 2013). Their increased abundance in bile duct tissues could promote tumorigenesis in a similar manner. Indeed, the data in this study supports an increase in the microbial production of carcinogens such as bile acids (Yoshimoto et al., 2013) and ammonia (Louis et al., 2014) in the altered microbiome of OVa tissues. On the basis of these results, we propose a model involving (i) O. viverrini mediated introduction of specific enteric microbes into the bile duct, (ii) subsequent alterations in the metabolic output of bile duct tissue microbiomes, and (iii) increased levels of potentially carcinogenic metabolites, culminating in a tissue microenvironment primed towards malignant transformation. Recent data from a work that found elevated levels of bile acids in CCA patients, lends further support to this model (Jusakul et al., 2012). A recent study (Sivan et al., 2015) demonstrated a role for gut-dwelling Bifidobacteria in promoting systemic antitumor immunity. Further studies are thus needed to evaluate the role of increased Bifidobacteria in bile duct tissues with respect to OVa carcinogenesis. Apart from O. viverrini, Opisthorchis felineus and sinensisClonorchis are also known to infect the biliary tract. Indeed, C. sinensis infection is known as a risk factor for CCA (Tyson and El-Serag, 2011). Comparing microbiome alterations in biliary tissues associated with O. viverrini and C. sinensis infections could further clarify the commonalities and role of the biliary tissue microbiome in parasite-associated CCA. Our study demonstrates that microbiomes of internal human gingerol are highly variable in composition but specialized to their respective distinct niches. The biological reciprocity between the human host and the tissue microbiome can influence the regulation of specific physiological processes. Taken together, the data in this study supports the notion that compositional shifts in the tissue microbiome following parasite infection can enable an altered microenvironment to drive tumorigenesis. Indeed, Bongers et al. (Bongers et al., 2014) and others have shown tumor development to be sustained by the crosstalk between the genetics of the host and the corresponding specific microbiome. The results in this work provide observational evidence for this model but further functional work is needed in the context of CCA carcinogenesis. In addition, as the study pools data from three different countries, other confounding clinical or epidemiological factors (such as the origin of OVa CCA samples in Thailand) could explain observed difference in OVa vs non-OVa CCA microbiomes. Additional samples from other regions of the world and an integrated approach that combines information about host genetics (e.g. by sequencing the tumor genome), functional output (e.g. from proteomics and metabonomics) and environmental factors (e.g. microbiome profiling) is thus likely needed to dissect host and microbiome contributions to tumorigenesis.
Disclosure of Potential Conflict of Interest
Author Contributions
Introduction Human immunodeficiency virus (HIV) is a chronic inflammatory disease, in which numerous structural (enterocyte apoptosis and the loss of epithelial integrity), functional (errors in the production of mucin/IgA), and immunological (loss of sub-mucosal lymphocytes) defects contribute to an excess risk of mortality (Buzón et al., 2010; Mutlu et al., 2014; McGrath et al., 2015). It has recently been shown that HIV infection also induces a compositional shift in the gut microbiota, with enrichment for bacterial populations, genes and functional capabilities that are either pro-inflammatory or potentially pathogenic, and whose abundance correlated with immune status (McHardy et al., 2013; Vujkovic-Cvijin et al., 2013; Mutlu et al., 2014; Vázquez-Castellanos et al., 2015). However, imbalances in gut bacteria have been found to be different in patients undergoing highly active antiretroviral therapy (ART) compared to untreated patients (Vázquez-Castellanos et al., 2015). This raises the question of whether the gut ecosystem contributes to chronic inflammation and disease progression (Vujkovic-Cvijin et al., 2013; Vázquez-Castellanos et al., 2015) but also to immune recovery, although these patients are still characterized by residual inflammation and excess mortality (Vujkovic-Cvijin et al., 2013; Somsouk et al., 2014; Vázquez-Castellanos et al., 2015).