Gut Microbiota and Liver Interaction through Immune System Cross-Talk: A Comprehensive Review at the Time of the SARS-CoV-2 Pandemic

Abstract

Background and aims: The gut microbiota is a complex ecosystem containing bacteria, viruses, fungi, yeasts and other single-celled organisms. It is involved in the development and maintenance of both innate and systemic immunity of the body. Emerging evidence has shown its role in liver diseases through the immune system cross-talk. We review herein literature data regarding the triangular interaction between gut microbiota, immune system and liver in health and disease. Methods: We conducted a search on the main medical databases for original articles, reviews, meta-analyses, randomized clinical trials and case series using the following keywords and acronyms and their associations: gut microbiota, microbiome, gut virome, immunity, gastrointestinal-associated lymphoid tissue (GALT), non-alcoholic fatty liver disease (NAFLD), non-alcoholic steato-hepatitis (NASH), alcoholic liver disease, liver cirrhosis, hepatocellular carcinoma. Results: The gut microbiota consists of microorganisms that educate our systemic immunity through GALT and non-GALT interactions. The latter maintain health but are also involved in the pathophysiology and in the outcome of several liver diseases, particularly those with metabolic, toxic or immune-mediated etiology. In this context, gut virome has an emerging role in liver diseases and needs to be further investigated, especially due to the link reported between severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection and hepatic dysfunctions. Conclusions: Changes in gut microbiota composition and alterations in the immune system response are involved in the pathogenesis of metabolic and immune-mediated liver diseases.

Are probiotics effective in reversing non-alcoholic steatohepatitis?

“…The study employed a specific human-like animal model, farnesoid X receptor (FXR) knockout (KO) mice, which presented elevated BAs and developed steatosis and NASH, progressing spontaneously to liver cancer (4). These findings are consistent with previous works showing that inhibition of intestinal FXR signaling reduces obesity, insulin resistance, and fatty liver disease by modulation of hepatic and gut bacteria-mediated BA metabolism, and intestinal ceramide synthesis (6), while reduced expression of FXR has been detected in patients with liver cirrhosis and HCC (3). As BAs are produced by the conversion of hepatic cholesterol through hepatic and gut microbial enzymes, both nutrients and/or GM can affect metabolism and inflammation.…”

“…and HCC presentation and prevention (3). To date, there is only scarce evidence on the efficacy of certain probiotics on liver fat deposition, down-regulation of the inflammatory cascade, improvement of metabolic parameters in animal models (Table 1), and remission of symptoms in patients with ulcerative colitis (2).…”

Complication and Sequelae of COVID-19: What Should We Pay Attention to in the Post-Epidemic Era

“…In addition, more noteworthy was the role of intestinal flora in the development of COVID-19. On the one hand, clinical data indicated the intestinal flora was disordered in patients with COVID-19, which lead to the adverse reactions in the gastrointestinal tract (64,65). On the other hand, the intestinal flora had the potential to promote the activity of antiinflammation cells in the alveolar and inhibit the progression of pneumonia, which is defined as the "gut-lung axis" (66).…”

Diet, Probiotics and Their Impact on the Gut Microbiota during the COVID-19 Pandemic

“…Scarpellini et al [ 20 ] analyzed the interactions of the gut microbiota and the liver mediated by the immune system during the SARS-CoV-2 pandemic, and detected the immunosuppressive effects of alcohol consumption. Ethanol inhibits the NK cell response and depletes other types of lymphoid cells.…”