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. 2013 Feb;43(2):139-46.
doi: 10.1111/j.1872-034X.2012.01088.x. Epub 2012 Sep 13.

Role of gut microbiota in liver diseases

Yasuhiro Miyake  1 , Kazuhide Yamamoto
Affiliations

Role of gut microbiota in liver diseases (V体育官网)

Yasuhiro Miyake et al. Hepatol Res. 2013 Feb.

Abstract

The liver constantly encounters food-derived antigens and bacterial components such as lipopolysaccharide translocated from the gut into the portal vein. Bacterial components stimulate Toll-like receptors (TLR), which are expressed on Kupffer cells, biliary epithelial cells, hepatocytes, hepatic stellate cells, endothelial cells and dendritic cells and recognize specific pathogen-associated molecular patterns. The signaling of TLR to its main ligand triggers inflammation. Usually, in order to protect against hyperactivation of the immune system and to prevent organ failure by persistent inflammation, TLR tolerance to repeated stimuli is induced. In chronic liver diseases, a breakdown in TLR tolerance occurs. Furthermore, Kupffer cells, hepatic stellate cells and natural killer T cells are key components of innate immunity VSports手机版. Decreased numbers and impaired ability of these cells lead to failures in immune tolerance, resulting in persistent inflammation. Recently, the activation of inflammasome was revealed to control the secretion of pro-inflammatory cytokines such as interleukin-1β in response to bacterial pathogens. Innate immunity seems to be an important contributor to the pathogenesis of fatty liver disease and autoimmune liver disease. Recently, probiotics were reported to affect various liver diseases via shifts in gut microbiota and the stability of intestinal permeability. However, many unresolved questions remain. Further analysis will be needed to gain a more comprehensive understanding of the association of innate immunity with the pathogenesis of various liver diseases. .

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Conflict of interest statement

Conflict of interest

none.

Figures

Figure 1
Figure 1. The dose and strain dependent effects of probiotics on HF diet-induced obesity, insulin resistance and hepatic steatosis
WT C57BL/6 mice were fed either ND or HF diet and some of HF fed mice were also treated with high dose VSL#3 (HF+hi VSL#3), or low dose VSL#3 (HF+lo VSL#3), or antibiotics (HF+anti) or high dose of B. infantis (HF+hi B infantis), or continue ND or HF diet. (A) Animal weight; (B) Glucose tolerance tests; (C) serum insulin level; (D) Insulin resistance measured by HOMA-IR; (E) Hepatic triglyceride content; (F) Representative H&E of liver histology. * p<0.05 vs HF diet group.
Figure 2
Figure 2. The dose and strain dependent effect of probiotics on hepatic NKT cells
Animals were treated as described in Fig. 1. Hepatic mononuclear (HMNC) cells were isolated and labeled with various surface markers. (A) A representative dot plot of NKT cell staining (gated on total HMNC); (B) Means ± SD of three independent experiments (n=5 per group). * p<0.05 vs HF diet group.
Figure 3
Figure 3. Probiotic antigens stimulate NKT cells in vitro and in vivo
(A) Bacterial glycolipids extracted were co-cultured with NKT hybridoma. IL-2 released by NKT hybridoma indicates their activation. 1 = media only; 2 = aAPCs only; 3 = aAPCs loaded with low dose VSL#3 extract; 4 = aAPCs loaded with high dose VSL#3 extract; 5 = aAPCs loaded with high dose VSL#3 extract plus α-GalCer; 6 = aAPCs loaded with low dose B. infantis extract; 7 = aAPCs loaded with high dose B. infantis extract; 8 = aAPCs loaded with high dose B. infantis extract plus α-GalCer; and 9 = aAPCs loaded α-GalCer. (B) Lipid extracts from VSL#3 or B.Infantis, or α-Galcer (2 µg/mouse) were injected to C57BL6 wt mice fed normal diet. After 24 hours, the animals were sacrificed and their hepatic NKT cells were evaluated as described in Fig 2. Means ± SD of the percentages of hepatic NKT cells (gated on CD3+ and CD1d Tetramer+) among HMNCs are shown (n=5 per group). (C) A representative histogram of NKT cell proliferation assay. HMNCs were labeled with CFSE and stimulated with aAPCs loaded with VSL#3 lipid extract or unloaded empty beads. *p<0.025, #p<0.002 vs control.
Figure 4
Figure 4. Disrupting TLR4 signaling did not protect mice from HF diet-induced NAFLD
Wild type and TLR4 knock out C57BL6 mice were fed ND or HF diet for 12 weeks. (A) Hepatic NKT cell content; (B) Animal weight; (C) Glucose tolerance tests; (D) Insulin resistance as measured by HOMA-IR; (E) Representative H&E staining of liver histology; (F) Hepatic triglyceride content. Results were means ± SD (n=5 per group)
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