The Role of the Microbiome in Liver Cancer

Abstract

Hepatocellular carcinoma (HCC) is the most common malignancy occuring in the context of chronic liver disease and is one of the main causes of cancer-derived death worldwide. The lack of effective treatments, together with the poor prognosis, underlines the urge to develop novel and multidisciplinary therapeutics. An increasing body of evidence shows that HCC associates with changes in intestinal microbiota abundance and composition as well as with impaired barrier function, leading to the release of bacteria and their metabolites to the liver. These factors trigger a cascade of inflammatory responses contributing to liver cirrhosis and constituting an ideal environment for the progression of HCC. Interestingly, the use of bacteriotherapy in human and preclinical studies of chronic liver disease and HCC has been shown to successfully modify the microbiota composition, reducing overall inflammation and fibrosis. In this review, we explore the existing knowledge on the characterisation of the intestinal microbial composition in humans and experimental murine chronic liver disease and HCC, as well as the use of antibiotics and bacteriotherapy as therapeutic options.

The Role of Gut Microbiota-Bile Acids Axis in the Progression of Non-alcoholic Fatty Liver Disease

“…Akkermansia muciniphila , a major propionate-producing bacterium, is recommended as a probiotic and an essential gut symbiont to maintain the metabolism homeostasis and alleviate obesity, diabetes, and liver diseases ( Mokhtari et al, 2017 ; Wang et al, 2019 ). FMT, a GM-altering approach, has been reported to reduce high-fat diet-induced steatosis, increase insulin sensitivity in patients with metabolic syndrome and improve the cognitive performance in cirrhotic patients ( Zhou et al, 2017 ; Moreno-Gonzalez and Beraza, 2021 ). Thus, studying the role of GM in NAFLD and the effect of specific intestinal flora in NAFLD patients will further help to diagnose and stratify patients and find therapeutic targets ( Kolodziejczyk et al, 2019 ).…”

“…Moreover, studies have shown that pathogenic Enterobacteriaceae as well as strains from oral microbiota, such as Veillonella and Streptococcus were enriched in patients with cirrhosis, consistent with the spread of bacteria from the mouth to the gut ( Chen et al, 2011 ; Qin et al, 2014 ; Yu and Schwabe, 2017 ). The GM composition of patients with cirrhosis showed relatively lower levels of Lachnospiraceae, Ruminococcaceae, Clostridialies XIV , and F. prausnitzii and a higher abundance of Bacteroidaceae ( Bajaj et al, 2014 ; Aron-Wisnewsky et al, 2020a ; Moreno-Gonzalez and Beraza, 2021 ). The microbial signature of cirrhosis showed high abundance of Megasphaera, Dialister, Atopobium, Prevotella , and Gallibacterium ( Chen et al, 2016 ; Caussy et al, 2019 ).…”

Diagnostic and Therapeutic Uses of the Microbiome in the Field of Oncology

“…Gut microbes can change primary bile acids to secondary bile acids, leading to DNA damage, depletion in tumor-suppressing micro-DNA, alteration in numbers of NK T cells, and carcinogenesis [ 121 - 123 ]. Obesity resulting in nonalcoholic steatohepatitis (NASH) is also indirectly associated with gut dysbiosis leading to HCC [ 124 ].…”

Relevance of organ(s)-on-a-chip systems to the investigation of food-gut microbiota-host interactions

“…As noted above, the presence of an immune element in the OoC could favour the study of certain inflammatory conditions associated with alterations in the gut microbiota, including a variety of chronic diseases (Beaurivage et al 2020;Moreno-Gonzalez and Beraza 2021). However, the clinical applications of OoC have mainly focussed on understanding the physiological mechanisms underpinning these conditions, as well as studies relating to preclinical drug discovery and efficacy, including compound discovery, target validation, drug permeability, pharmacokinetics and pharmacodynamics (Esch et al 2015;Beaurivage et al 2019;Low et al 2021;Ma et al 2021).…”