The rapid scientific interest in gut microbiota (GM) has coincided with a global increase in the prevalence of infectious and non-infectivous liver diseases. GM, which is also called “the new virtual metabolic organ”, makes axis with a number of extraintestinal organs, such as kidneys, brain, cardiovascular, and the bone system. The gut-liver axis has attracted greater attention in recent years. GM communication is bi-directional and involves endocrine and immunological mechanisms. In this way, gut-dysbiosis and composition of “ancient” microbiota could be linked to pathogenesis of numerous chronic liver diseases such as chronic hepatitis B (CHB), chronic hepatitis C (CHC), alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), development of liver cirrhosis, and hepatocellular carcinoma (HCC). In this paper, we discuss the current evidence supporting a GM role in the management of different chronic liver diseases and potential new therapeutic GM targets, like fecal transplantation, antibiotics, probiotics, prebiotics, and symbiotics. We conclude that population-level shifts in GM could play a regulatory role in the gut-liver axis and, consequently, etiopathogenesis of chronic liver diseases. This could have a positive impact on future therapeutic strategies.

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Although profoundly studied, etiology of pancreatic cancer (PC) is still rather scant. Exposure to cadmium (Cd), a ubiquitous metal associated with well-established toxic and carcinogenic properties, has been hypothesized to one putative cause of PC. Hence, we analyzed recently published observational studies, meta-analyses, and experimental animal and in vitro studies with the aim of summarizing the evidence of Cd involvement in PC development and describing the possible mechanisms. Consolidation of epidemiological data on PC and exposure to Cd indicated a significant association with an elevated risk of PC among general population exposed to Cd. Cadmium exposure of laboratory animals was showed to cause PC supporting the findings suggested by human studies. The concordance with human and animal studies is buttressed by in vitro studies, although in vitro data interpretation is problematic. In most instances, only significant effects are reported, and the concentrations of Cd are excessive, which would skew interpretation. Previous reports suggest that oxidative stress, apoptotic changes, and DNA cross-linking and hypermethylation are involved in Cd-mediated carcinogenesis. Undoubtedly, a significant amount of work is still needed to achieve a better understanding of the Cd involvement in pancreatic cancer which could facilitate prevention, diagnosis, and therapy of this fatal disease.

Pancreatic cancer (PC) is insidious with a high mortality rate due to the lack of symptomology prior to diagnosis. Mitochondrial involvement in PC development is becoming accepted, and exposure to cadmium (Cd) is suspected of being a risk factor for the development of PC; however, the mechanisms involved remain unclear. In this study, we examined the role of Cd as a mitochondrial toxicant and whether alterations in mitochondrial function may be an underlying cause for the development of PC. In this study, cadmium chloride (CdCl 2 )-mediated toxicity in hTERT-HPNE and AsPC-1 pancreatic cell lines was determined by MTT assay. We also investigated the release of LDH and the generation of free radicals. Mitochondrial toxicity assays were performed in media containing glucose (25 mM) or galactose (10 mM) and following exposure to CdCl 2 (0-100 μ M) followed by MTT assay. For the confirmation of mitochondrial toxicity, we measured the release of ATP following exposure to CdCl 2 . Initial experiments confirmed that exposure to CdCl 2 did not reduce the viability of either cell line until a concentration of >10 μ M was used. Non-linear analysis of the response curves revealed lethal concentration 50% (LC 50 ) values for CdCl 2 in the HPNE cells of 77 μ M compared to 42 μ M in the AsPC-1 cells (P<0.01). The CdCl 2 -mediated mitochondrial toxic effects were greater in the HPNE cells, suggesting a heightened sensitivity to the effects of CdCl 2 , not due to elevated oxidative stress. Increased mitochondrial toxic sensitivity was indicated by a 73.4% reduction in IC 50 values in the HPNE cells cultured in galactose compared to culture in glucose media, whereas the AsPC-1 cells exhibited a 58.8% reduction in IC 50 values. In addition, the higher concentration of CdCl 2 elicited a significant cell-dependent effect on ATP release in both cell lines, suggestive of CdCl 2 being a mitochondrial toxicant. Cell survival was unaffected following exposure to low concentrations of CdCl 2 ; however, exposure did alter mitochondrial function (control cells > tumor cells). Therefore, the findings of this study indicate that the mitochondria may be a site of action for cadmium in promoting tumor development.