Contribution of Gut Bacteria to Liver Pathobiology

Son, Gakuhei; Kremer, Michael; Hines, Ian N.

doi:10.1155/2010/453563

Cited by 131 publications

(102 citation statements)

References 125 publications

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“…Emerging evidence suggests a strong interaction between the gut microbiota and human liver diseases (10,11). Receiving approximately 70% of its blood supply from the intestine through the portal circulation, the liver is the first line of defense against gut-derived antigens (11).…”

Section: Introductionmentioning

confidence: 99%

Gut-Derived Lipopolysaccharide Promotes T-Cell–Mediated Hepatitis in Mice through Toll-Like Receptor 4

Yu¹,

Yan²,

Yang³

et al. 2012

Cancer Prevention Research

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Robust clinical and epidemiologic data support the role of inflammation as a key player in hepatocellular carcinoma (HCC) development. Our previous data showed that gut-derived lipopolysaccharide (LPS) promote HCC development by activating Toll-like receptor 4 (TLR4) expressed on myeloid-derived cells. However, the effects of gut-derived LPS on other types of liver injury models are yet to be studied. The purpose of this study was to determine the importance of gut-derived LPS and TLR4 signaling in a T-cellmediated hepatitis-Con A-induced hepatitis model, which mimic the viral hepatitis. Reduction of endotoxin using antibiotics regimen or genetic ablation of TLR4 in mice significantly alleviate Con A-induced liver injury by inhibiting the infiltration of T lymphocytes into the liver and the activation of CD4 þ T lymphocytes as well as the production of T helper 1 cytokines; in contrast, exogenous LPS can promote Con A-induced hepatitis and CD4 þ T cells activation in vivo and in vitro. Reconstitution of TLR4-expressing myeloid cells in TLR4-deficient mice restored Con A-induced liver injury and inflammation, indicating the major cell target of LPS. In addition, TLR4 may positively regulate the target hepatocellular apoptosis via the perforin/granzyme B pathway. These data suggest that gut-derived LPS and TLR4 play important positive roles in Con A-induced hepatitis and modulation of the gut microbiotia may represent a new avenue for therapeutic intervention to treat acute hepatitis induced by hepatitis virus infection, thus to prevent hepatocellular carcinoma. Cancer Prev Res; 5(9); 1090-102. Ó2012 AACR.

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Section: Introductionmentioning

confidence: 99%

Gut-Derived Lipopolysaccharide Promotes T-Cell–Mediated Hepatitis in Mice through Toll-Like Receptor 4

Yu¹,

Yan²,

Yang³

et al. 2012

Cancer Prevention Research

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“…In addition, 2-oleoylglycerol leads to the release of gut peptides from intestinal L-cells, such as the glucagon-like peptide 2, which is associated with the regulation of gut barrier function [120] . Although some investigations have led to the hypothesis that Gram-negative bacteria may be involved in triggering metabolic endotoxemia and, therefore, in worsening the condition of the intestinal barrier [119][120][121][122][123] , it is plausible that mechanisms other than lipopolysaccharide (LPS) are responsible for this. This is illustrated by the study that showed that Akkermansia muciniphila, a Gramnegative bacterium, decreased metabolic endotoxemia, which was induced by a high-fat diet, through increasing levels of endocannabinoids that control inflammation, the gut barrier and the gut peptide secretion [121] .…”

Section: Gut Permeability: An Unclear Connection Between Altered Gut mentioning

confidence: 99%

Intestinal barrier: A gentlemen’s agreement between microbiota and immunity

Caricilli

Castoldi

Câmara

2014

WJGP

114

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Our body is colonized by more than a hundred trillion commensals, represented by viruses, bacteria and fungi. This complex interaction has shown that the microbiome system contributes to the host's adaptation to its environment, providing genes and functionality that give flexibility of diet and modulate the immune system in order not to reject these symbionts. In the intestine, specifically, the microbiota helps developing organ structures, participates of the metabolism of nutrients and induces immunity. Certain components of the microbiota have been shown to trigger inflammatory responses, whereas others, anti-inflammatory responses. The diversity and the composition of the microbiota, thus, play a key role in the maintenance of intestinal homeostasis and explain partially the link between intestinal microbiota changes and gut-related disorders in humans. Tight junction proteins are key molecules for determination of the paracellular permeability. In the context of intestinal inflammatory diseases, the intestinal barrier is compromised, and decreased expression and differential distribution of tight junction proteins is observed. It is still unclear what is the nature of the luminal or mucosal factors that affect the tight junction proteins function, but the modulation of the immune cells found in the intestinal lamina propria is hypothesized as having a role in this modulation. In this review, we provide an overview of the current understanding of the interaction of the gut microbiota with the immune system in the development and maintenance of the intestinal barrier.© 2014 Baishideng Publishing Group Co., Limited. All rights reserved.Key words: Microbiota; Immune system; Lamina propria; Intestinal barrier Core tip: Each of our bodies is colonized by more than a hundred trillion commensals, which include viruses, bacteria and fungi. The association between microbiota and their hosts is complex and has important repercussions for both. The diversity and the composition of the microbiota thus play a key role in the maintenance of intestinal homeostasis and the induction of immunity. These features partially explain the link between alterations in intestinal microbiota and gut-related disorders in humans. In this review, we provide an overview of the current understanding of the interaction between gut microbiota and the immune system in the development and maintenance of the intestinal barrier.Caricilli AM, Castoldi A, Câmara NOS. Intestinal barrier: A gentlemen's agreement between microbiota and immunity.

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“…Danger signals derived from the microbiome trigger the inflammatory cascade and activate immune cells. 86 Liver and spleen are the major organs that help in removing bacterial toxins and their lipopolysaccharides (LPS) from the blood. 87 Mechanisms that balance the barrier function of the gut and the ability of the liver to detoxify have been studied.…”

Section: Connecting Gut and Livermentioning

confidence: 99%

“…87 Mechanisms that balance the barrier function of the gut and the ability of the liver to detoxify have been studied. 86,88 It was found that gut derived LPS played a significant role in several liver diseases. 89,90 Lu et al observed an increase in inflammatory responses as there was attrition of the protective ability of the liver to detoxify LPS derived from the gut.…”

Section: Connecting Gut and Livermentioning

confidence: 99%