Fecal microbiota transplantation: a promising strategy in preventing the progression of non-alcoholic steatohepatitis and improving the anti-cancer immune response

ABSTRACT

Introduction: Non-alcoholic fatty liver disease (NAFLD) has the potential to progress to hepatocellular carcinoma (HCC). However, limited therapies are currently available for the treatment of advanced HCC, and one must strive to search for novel strategies.

Areas covered: We provide insight on current knowledge related to gut microbiota and NAFLD, summarize the sequence linking obesity to HCC and highlight gut dysbiosis in obesity and its consequences on the liver. We detail the impact of the gut microbiota on immune checkpoint inhibitors, and speculate on the role of fecal microbiota transplantation (FMT) in NAFLD and in improving anti-neoplastic immune response.

Expert Opinion: Manipulation of the gut microbiota seems promising in the secondary prevention of NAFLD/NASH and/or in potentiating anti-cancer immune response, notably by a global ‘resetting’ using FMT. However, the composition of a ‘harmful’ gut microbiome in HCC still needs to be characterized, and the impact of FMT on HCC growth needs to be assessed.

KEYWORDS:

• Cancer
• checkpoint inhibitors
• fecal microbiota transplantation
• gut microbiota
• hepatocellular carcinoma
• immunotherapy
• metabolic syndrome
• non-alcoholic fatty liver disease
• non-alcoholic steatohepatitis
• obesity

Article highlights

• Obesity-related non-alcoholic liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) is expected to become the leading cause of hepatocellular carcinoma (HCC) in the near future.

• Gut dysbiosis in obese individuals leads to increased gut permeability, a systemic pro-inflammatory immune phenotype, and the presence of increased levels of circulating toxic bacterial byproducts, favoring chronic liver inflammation.

• The composition of the gut microbiota has an impact on tumor response to immune checkpoint inhibitors.

• The goal of fecal microbiota transplantation (FMT), from screened healthy donors, is to restore a physiological gut microbiome in individuals with gut dysbiosis.

• With limited therapeutic options in advanced HCC, individual-specific tailored FMT could be interesting in the management of NAFLD/NASH-related liver injury and/or in improving tumor response to new therapies such as immune checkpoint inhibitors.

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Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

Christian Toso was supported by a grant from the Swiss National Science Foundation (PP00P3_165837).