Chronic liver disease enables gut Enterococcus faecalis colonization to promote liver carcinogenesis

Iida, Noriho; Mizukoshi, Eishiro; Yamashita, Tatsuya; Yutani, Masahiro; Seishima, Jun; Wang, Ziyu; Arai, Kuniaki; Okada, Hikari; Yamashita, Taro; Sakai, Yoshio; Masuo, Yusuke; Agustina, Rina; Kato, Yukio; Fujinaga, Yukako; Oshima, Masanobu; Honda, Masao; Lebreton, François; Gilmore, Michael S.; Kaneko, Shuichi

doi:10.1038/s43018-021-00251-3

Cited by 39 publications

(23 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The modulation of intestinal microbiota using Lactobacilli strains is an appropriate strategy for reducing pathogenic bacteria, such as Enterococcus faecalis and Escherichia coli . According to recent studies, Enterococcus faecalis colonization in the intestinal tract acts as a key promoter in liver carcinogenesis ( Iida et al, 2021 ; Ray, 2021 ). When intestinal permeability increases due to alcohol intake, Enterococcus faecalis causes damage to hepatocytes ( Llorente et al, 2017 ; Duan et al, 2019 ; Iida et al, 2021 ); however, the ALD that ensues can be prevented by bacteriophages against Enterococcus faecalis ( Duan et al, 2019 ; Çolakoǧlu et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

“…According to recent studies, Enterococcus faecalis colonization in the intestinal tract acts as a key promoter in liver carcinogenesis ( Iida et al, 2021 ; Ray, 2021 ). When intestinal permeability increases due to alcohol intake, Enterococcus faecalis causes damage to hepatocytes ( Llorente et al, 2017 ; Duan et al, 2019 ; Iida et al, 2021 ); however, the ALD that ensues can be prevented by bacteriophages against Enterococcus faecalis ( Duan et al, 2019 ; Çolakoǧlu et al, 2020 ). Further, the ingestion of Lb .…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Probiotic Lactobacilli ameliorate alcohol-induced hepatic damage via gut microbial alteration

Kim¹,

Ahn²,

Kim³

et al. 2022

Front. Microbiol.

View full text Add to dashboard Cite

Alcoholic liver disease (ALD), which includes fatty liver, cirrhosis, steatosis, fibrosis, and hepatocellular carcinoma, is a global health problem. The probiotic effects of lactic acid bacteria (LAB) are well-known; however, their protective effect against ALD remains unclear. Therefore, in this study, our objective was to assess the protective effects of LAB on ALD. To this end, mice were fed either a normal diet or an alcohol diet for 10 days (to induce ALD) accompanied by vehicle treatment (the NC and AC groups) or kimchi-derived LAB (Lactiplantibacillus plantarum DSR J266 and Levilactobacillus brevis DSR J301, the AL group; or Lacticaseibacillus rhamnosus GG, the AG group). Our results showed that mice in the AC group showed significantly higher serum aspartate aminotransferase and alanine aminotransferase levels than those in the normal diet groups; however, their levels in the AL and AG groups were relatively lower. We also observed that the AL and AG groups showed relatively lower interleukin-6 levels than the AC group. Additionally, AC group showed the accumulation of several fat vesicles in the liver, while the AL and AG groups showed remarkably lower numbers of fat vesicles. The relative abundance of Enterococcus feacalis, which showed association with liver injury, significantly increased in the AC group compared with its levels in the normal diet groups. However, the AG group showed a decreased relative abundance in this regard, confirming that LAB exerted an improvement effect on gut microbial community. These findings suggested that via gut microbiota alteration, the ingestion of LAB can alleviate the ill effects of alcohol consumption, including inflammation, liver damage, gut dysbiosis, and abnormal intestinal nutrient metabolism.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Probiotic Lactobacilli ameliorate alcohol-induced hepatic damage via gut microbial alteration

Kim¹,

Ahn²,

Kim³

et al. 2022

Front. Microbiol.

View full text Add to dashboard Cite

show abstract

“…Gram-negative commensal gut bacteria can induce hepatocytes to form a tumour-promoting environment by recruiting immunosuppressive CXCR2 + polymorphonuclear myeloid-derived suppressor cells through TLR4-dependent CXCL1 production, eventually promoting the development of intrahepatic cholangiocarcinoma 54 . Enterococcus faecalis , a species enriched in faecal samples of patients with HCV-related chronic hepatitis, appears to promote liver carcinogenesis via the expression of the metallopeptidase gelE 55. In mice, gelE -positive E. faecalis promoted liver carcinogenesis in a TLR4-dependent manner by increasing gut permeability via its gelatinase activity and elevating plasma lipopolysaccharide that acts on hepatocytes 55.…”

Section: Tumour Microenvironmentmentioning

confidence: 99%

“…Enterococcus faecalis , a species enriched in faecal samples of patients with HCV-related chronic hepatitis, appears to promote liver carcinogenesis via the expression of the metallopeptidase gelE 55. In mice, gelE -positive E. faecalis promoted liver carcinogenesis in a TLR4-dependent manner by increasing gut permeability via its gelatinase activity and elevating plasma lipopolysaccharide that acts on hepatocytes 55. The composition of intratumoural microbiota in hepatocellular carcinoma (HCC) differs according to aetiological factors 56 57 .…”

Section: Tumour Microenvironmentmentioning

confidence: 99%

Cancer as microenvironmental, systemic and environmental diseases: opportunity for transdisciplinary microbiomics science

Inamura

Hamada

Bullman

et al. 2022

Gut

View full text Add to dashboard Cite

Cancer is generally regarded as a localised disease, with the well-established role of the tumour microenvironment. However, the realm of cancer goes beyond the tumour microenvironment, and cancer should also be regarded as a systemic and environmental disease. The exposome (ie, the totality of exposures), which encompasses diets, supplements, smoking, alcohol, other lifestyle factors, medications, etc, likely alters the microbiome (inclusive of bacteria, viruses, archaea, fungi, parasites, etc) and immune system in various body sites and influences tumour phenotypes. The systemic metabolic/inflammatory status, which is likely influenced by exposures and intestinal physiological changes, may affect tissue microenvironment of colorectum and any other organs. Germline genomic factors can modify disease phenotypes via gene-by-environment interactions. Although challenges exist, it is crucial to advance not only basic experimental research that can analyse the effects of exposures, microorganisms and microenvironmental components on tumour evolution but also interdisciplinary human population research that can dissect the complex pathogenic roles of the exposome, microbiome and immunome. Metagenomic, metatranscriptomic and metabolomic analyses should be integrated into well-designed population research combined with advanced methodologies of artificial intelligence and molecular pathological epidemiology. Ideally, a prospective cohort study design that enables biospecimen (such as stool) collection before disease detection should be considered to address reverse causation and recall biases. Robust experimental and observational research together can provide insights into dynamic interactions between environmental exposures, microbiota, tumour and immunity during carcinogenesis processes, thereby helping us develop precision prevention and therapeutic strategies to ultimately reduce the cancer burden.

show abstract

“…The exotoxin-secreting gut bacterium Enterococcus (E.) faecalis is a critical contributor to the progression of alcoholic hepatitis ( 8 ) and pancreatic diseases ( 9 ), and it is also recognized as a key promoter of liver carcinogenesis ( 10 ). This suggests that the monitoring of E. faecalis may be useful in the clinical determination of overall disease status.…”

Section: Introductionmentioning

confidence: 99%

Elevation of enterococcus-specific antibodies associated with bacterial translocation is predictive of survival rate in chronic liver disease

et al. 2022

View full text Add to dashboard Cite

Introduction/purposeThe gut-liver axis contributes to disease progression, a rise in infection rate, organ failure and a poor overall outcome in chronic liver diseases (CLD). Monitoring of the gut-liver axis is critical in understanding disease status, but biomarkers have not been elucidated. The aim of this study is to determine the level of serum antibodies against Enterococcus (E.) faecalis in evaluating patients with CLD, including those treated with rifaximin (a minimally absorbed antibiotic), and in patients with alcohol-associated liver disease (ALD).Materials and methodsWe enrolled 109 CLD patients (cohort 1), 30 hepatic encephalopathy patients treated with rifaximin (cohort 2), 53 inpatients with ALD undergoing alcohol cessation (cohort 3) and 33 healthy subjects. To assess the consequences of E. faecalis translocation, we developed an assay for the detection of a serum antibody against E. faecalis capsular polysaccharide (E.CPS).ResultsSerum E.CPS antibody titer was elevated only in those patients with advanced CLD and ALD. The E.CPS antibody titer was an independent prognostic factor (p < 0.05), while Mac-2 binding protein and albumin-bilirubin score were not independent predictors of survival. The improvement of predictive model in integrated factors was significant [continuous net reclassification index (value 0.699, p < 0.05) and integrated discrimination improvement (value 0.164, p = 0.051)]. Furthermore, rifaximin treatment led to a decrease of serum E.CPS antibody titer resulting in a significantly longer overall rate of survival.ConclusionThe E.CPS antibody titer appears to be a strong predictor of survival in CLD patients. Serum E.CPS levels decrease in CLD patients receiving rifaximin, and may be associated with an overall improvement in rate of survival.

show abstract

Chronic liver disease enables gut Enterococcus faecalis colonization to promote liver carcinogenesis

Cited by 39 publications

References 51 publications

Probiotic Lactobacilli ameliorate alcohol-induced hepatic damage via gut microbial alteration

Probiotic Lactobacilli ameliorate alcohol-induced hepatic damage via gut microbial alteration

Cancer as microenvironmental, systemic and environmental diseases: opportunity for transdisciplinary microbiomics science

Elevation of enterococcus-specific antibodies associated with bacterial translocation is predictive of survival rate in chronic liver disease

Contact Info

Product

Resources

About