Mechanisms by Which Probiotic Bacteria Attenuate the Risk of Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the second leading cause of cancer-related deaths worldwide. Chronic infections with hepatitis B virus (HBV) and hepatitis C virus (HCV), alcoholic liver disease (ALD), and non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) are the major extrinsic risk factors of HCC development. Genetic background is pivotal in HCC pathogenesis, and both germline mutations and single nucleotide polymorphism (SNP) are intrinsic risk factors of HCC. These HCC risk factors predispose to hepatic injury and subsequent activation of fibrogenesis that progresses into cirrhosis and HCC. Probiotic bacteria can mitigate HCC risk by modulating host gut microbiota (GM) to promote growth of beneficial microbes and inhibit HCC-associated dysbiosis, thus preventing pathogen-associated molecular patterns (PAMPs)-mediated hepatic inflammation. Probiotics have antiviral activities against HBV and HCV infections, ameliorate obesity and risk of NAFLD/NASH, and their antioxidant, anti-proliferative, anti-angiogenic, and anti-metastatic effects can prevent the HCC pathogenesis. Probiotics also upregulate the expression of tumor suppressor genes and downregulate oncogene expression. Moreover, metabolites generated by probiotics through degradation of dietary phytochemicals may mitigate the risk of HCC development. These multiple anticancer mechanisms illustrate the potential of probiotics as an adjuvant strategy for HCC risk management and treatment.

An Update on the Effectiveness of Probiotics in the Prevention and Treatment of Cancer

“…In particular, probiotics have gained attention due to their ability to modulate cancer signalling (Figure 2) [18]. Notably, probiotics can modulate cancers via the (a) induction of apoptosis [19], (b) inhibition of mutagenic activity [20], (c) downregulation of oncogene expression [21], (d) induction of autophagy [22,23], (e) inhibition of kinases [24], (f) reactivation of tumour suppressors [25], and (g) prevention of metastasis [26]. The anticancer properties of probiotics are mainly attributed to metabiotics (Figure 3).…”

Hepatocellular Carcinoma: How the Gut Microbiota Contributes to Pathogenesis, Diagnosis, and Therapy

“…Feeding Prohep was shown to significantly slow liver cancer growth in mice compared to controls, reducing tumour size and weight by 40%, along with a dramatic decrease in the levels of Th17 cells and the suppression of other angiogenic gene expression in liver tumours ( Li et al, 2016 ). In addition, the antiviral activity of probiotics may reduce the risk of HCC by preventing CHB and CHC ( Thilakarathna et al, 2021 ). Probiotics can upregulate the expression of multiple tumour suppressors and inhibit the expression of oncogenes involved in the pathogenesis of HCC ( Thilakarathna et al, 2021 ).…”

“…In addition, the antiviral activity of probiotics may reduce the risk of HCC by preventing CHB and CHC ( Thilakarathna et al, 2021 ). Probiotics can upregulate the expression of multiple tumour suppressors and inhibit the expression of oncogenes involved in the pathogenesis of HCC ( Thilakarathna et al, 2021 ).…”

Probiotics and live biotherapeutic products aiming at cancer mitigation and patient recover

“…Reaching the liver promotes inflammation by stimulating the immune cells to produce cytokines and chemokines through Toll-like receptors. In this way, the effects of carcinoma can be attenuated through the downregulation of these genes by the action of probiotic strains ( Thilakarathna et al, 2021 ). Probiotic bacteria L. acidophilus and B. bifidum can reduce the expression of oncomirs and the oncogenes BCL2-like 2 and Kristen rat viral sarcoma homolog oncogene through methylation and histone modification processes.…”