Gut microbiota impact on the peripheral immune response in non-alcoholic fatty liver disease related hepatocellular carcinoma

Abstract

The gut microbiota is reported to modulate the immune response in hepatocellular carcinoma (HCC). Here, we employ metagenomic and metabolomic studies to characterise gut microbiota in patients with non-alcoholic fatty liver disease (NAFLD) related cirrhosis, with or without HCC, and evaluate its effect on the peripheral immune response in an ex vivo model. We find that dysbiosis characterises the microbiota of patients with NAFLD-cirrhosis, with compositional and functional shifts occurring with HCC development. Gene function of the microbiota in NAFLD-HCC supports short chain fatty acid production, and this is confirmed by metabolomic studies. Ex vivo studies show that bacterial extracts from the NAFLD-HCC microbiota, but not from the control groups, elicit a T cell immunosuppressive phenotype, characterised by expansion of regulatory T cells and attenuation of CD8 + T cells. Our study suggest that the gut microbiota in NAFLD-HCC is characterised by a distinctive microbiome/metabolomic profile, and can modulate the peripheral immune response.

Resveratrol Butyrate Esters Inhibit BPA-Induced Liver Damage in Male Offspring Rats by Modulating Antioxidant Capacity and Gut Microbiota

“…Short-chain fatty acids (SCFAs) are the end products of the fermentation of food performed by the intestinal microbiota, with acetic acid, propionic acid, and butyric acid comprising 95% of SCFAs in the human gut [41]. These SCFAs not only serve as a source of energy for the host, but also participate in many metabolic processes in the human body, such as energy metabolism [42], the inflammatory response [43], adipose tissue formation [44], and liver metabolism [45]. In addition, SCFAs are also beneficial in disease treatment, because they can effectively inhibit colon cancer cell proliferation and provide energy to normal colonic epithelial cells [41].…”

Association of Increased Circulating Acetic Acid With Poor Survival in Pseudomonas aeruginosa Ventilator-Associated Pneumonia Patients

“…The high concentration of acetic acid in sinusitis mucus was a risk factor for chronic rhinosinusitis with PA infection ( Cho et al., 2020 ). On the other hand, some clinical studies also found that SCFAs may be detrimental ( Kurilshikov et al., 2019 ; Behary et al., 2021 ). It was reported that SCFAs were associated with poorer clinical outcomes in hepatocellular carcinoma patients ( Behary et al., 2021 ).…”

“…On the other hand, some clinical studies also found that SCFAs may be detrimental ( Kurilshikov et al., 2019 ; Behary et al., 2021 ). It was reported that SCFAs were associated with poorer clinical outcomes in hepatocellular carcinoma patients ( Behary et al., 2021 ). Since most of the protective effects of SCFAs have been found in mice, more clinical studies are needed to clarify the role of SCFAs in bacterial pneumonia.…”

Consideration of Gut Microbiome in Murine Models of Diseases

“…Differences in GM are also associated with non-intestinal conditions via different axes ( Figure 1 ) in human and mouse diseases. For instance, features of the GM are associated with neurodegenerative and neuropsychiatric disorders [ 21 ], such as Parkinson’s [ 22 , 23 ] and Alzheimer’s disease [ 24 ] through the gut–brain axis [ 25 ], respiratory diseases via the gut–lung axis [ 26 , 27 ], liver diseases through the gut–liver axis [ 28 , 29 , 30 , 31 ], cardiovascular diseases [ 32 , 33 ], autoimmune disorders [ 34 , 35 , 36 , 37 ], and others [ 38 ]. In the following subsections, we review the current knowledge of the GM of laboratory mice, and its influence on host health and disease susceptibility through colonization resistance, immune responses, and metabolic pathways.…”