Gut-microbiota prompt activation of natural killer cell on alcoholic liver disease

Gut Microbes. 2023 Dec;15(2):2281014. doi: 10.1080/19490976.2023.2281014. Epub 2023 Nov 21.


The liver is rich in innate immune cells, such as natural killer (NK) cells, natural killer T cells, and Kupffer cells associated with the gut microbiome. These immune cells are dysfunctional owing to alcohol consumption. However, there is insufficient data on the association between immune cells and gut microbiome in alcoholic liver disease (ALD). Therefore, the purpose of this study was to evaluate the effects of probiotic strains on NK cells in ALD patients. In total, 125 human blood samples [control (n = 22), alcoholic hepatitis (n = 43), and alcoholic cirrhosis (n = 60]) were collected for flow cytometric analysis. C57BL/6J mice were divided into four groups (normal, EtOH-fed, and 2 EtOH+strain groups [Phocaeicola dorei and Lactobacillus helveticus]). Lymphocytes isolated from mouse livers were analyzed using flow cytometry. The frequency of NK cells increased in patients with alcoholic hepatitis and decreased in patients with alcoholic cirrhosis. The expression of NKp46, an NK cell-activating receptor, was decreased in patients with alcoholic hepatitis and increased in patients with alcoholic cirrhosis compared to that in the control group. The number of cytotoxic CD56dimCD16+ NK cells was significantly reduced in patients with alcoholic cirrhosis. We tested the effect of oral administration P. dorei and L. helveticus in EtOH-fed mice. P. dorei and L. helveticus improved liver inflammation and intestinal barrier damage caused by EtOH supply and increased NK cell activity. Therefore, these observations suggest that the gut microbiome may ameliorate ALD by regulating immune cells.

Keywords: Alcoholic liver disease; NK cell; gut liver axis; gut microbiota; immune.

MeSH terms

  • Animals
  • Ethanol
  • Gastrointestinal Microbiome*
  • Hepatitis, Alcoholic*
  • Humans
  • Killer Cells, Natural
  • Liver Cirrhosis, Alcoholic
  • Liver Diseases, Alcoholic*
  • Mice
  • Mice, Inbred C57BL


  • Ethanol

Grants and funding

This research was supported by the Hallym University Research Fund, the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF-2019R1I1A3A01060447and NRF-2020R1A6A1A03043026), Korea Institute for Advancement of Technology (P0020622), and Bio Industrial Technology Development Program (20018494) funded by the Ministry of Trade, Industry and Energy (MOTIE, Korea).