Microbiota, cirrhosis, and the emerging oral-gut-liver axis

Acharya, Chathur; Sahingur, Sinem E.; Bajaj, Jasmohan S.

doi:10.1172/jci.insight.94416

Cited by 179 publications

(162 citation statements)

References 107 publications

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“…A link between periodontitis and liver disease is best described in animal models, but clinical evidence is now also emerging . Akinkugbe et al recently reported that periodontitis was an independent risk factor for incident NAFLD, and Yoneda et al found that treatment of periodontitis led to reduction in serum transaminase levels.…”

Section: Discussionmentioning

confidence: 99%

“…Periodontitis could affect the liver by several potential mechanisms. First, in periodontitis, oral bacteria and locally produced proinflammatory cytokines can enter the bloodstream and potentially induce liver damage . Secondly, oral bacteria such as Porphyromonas gingivalis can cause alterations in the gut microbiota, with subsequent decreased expression of tight‐junction proteins in the ileum and increased gut translocation and systemic inflammation .…”

Section: Discussionmentioning

confidence: 99%

“…Experimental periodontitis in animal models has been shown to induce liver damage . A link between periodontitis, oral and gut dysbiosis, and gut permeability has also been described . In non‐alcoholic fatty liver disease (NAFLD) patients, treatment of periodontitis was associated with a reduction in serum transaminase levels .…”

Section: Introductionmentioning

confidence: 99%

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Periodontitis is associated with incident chronic liver disease—A population‐based cohort study

Helenius‐Hietala

Suominen

Ruokonen

et al. 2018

Liver International

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Background & Aims Chronic liver disease is a major health concern worldwide and the identification of novel modifiable risk factors may benefit subjects at risk. Few studies have analyzed periodontitis as a risk factor for liver complications. We studied whether periodontitis is associated with incident severe liver disease. Methods The study comprised 6165 individuals without baseline liver disease who participated in the Finnish population‐based Health 2000 Survey (BRIF8901) during 2000‐2001, a nationally representative cohort. Follow‐up was until 2013 for liver‐related admissions, liver cancer and mortality from National Hospital Discharge, Finnish Cancer Registry and Causes of Death Register, Statistics Finland. Mild to moderate periodontitis was defined as ≥1 tooth with periodontal pocket ≥4 mm deep, and advanced periodontitis as ≥5 teeth with such pockets. Multiple confounders were considered. Results A total of 79 subjects experienced a severe liver event during follow‐up. When adjusted for age, sex and number of teeth, hazards ratios by Cox regression regarding incident severe liver disease were, for mild to moderate periodontitis, 2.12 (95% CI 0.98‐4.58), and, for advanced periodontitis, 3.69 (95% CI 1.79‐7.60). These risk estimates remained stable after additionally adjusting for alcohol use, smoking, metabolic risk, serum gamma‐glutamyltransferase, dental‐care habits, lifestyle and socioeconomic status. Periodontal disease‐associated liver risk was accentuated among subjects with non‐alcoholic fatty liver disease or heavy alcohol use at baseline. Conclusions Periodontitis was associated with incident liver disease in the general population independently of various confounders. As a preventable disease, periodontal disease might present a modifiable risk factor for chronic liver disease.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Periodontitis is associated with incident chronic liver disease—A population‐based cohort study

Helenius‐Hietala

Suominen

Ruokonen

et al. 2018

Liver International

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“…Acharya et al. have mentioned a possibility that the link between the liver and the oral cavity could be via the gut through impaired intestinal permeability that could allow the translocation of bacteria ( Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Selenomas noxia ) and their inflammatory mediators from the oral cavity to the blood circulation …”

Section: Introductionmentioning

confidence: 99%

“…[1][2][3] Multiple studies have reported that periodontal disease may have an impact on systemic disease, such as cardiovascular diseases, atherosclerosis, diabetes, osteoporosis, respiratory infections, cancer, and adverse pregnancy outcomes. [4][5][6] The possible causes of periodontitis-systemic diseases association represent the spread of oral-hematogeneous bacteria 7 and the release of periodontal inflammatory mediators. 4 Few studies have addressed the effects of periodontal disease on liver disease.…”

Section: Introductionmentioning

confidence: 99%

Periodontal disease may induce liver fibrosis in an experimental study on Wistar rats

Meşter

Ciobanu

Taulescu

et al. 2019

Journal of Periodontology

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Background The aim was to assess the effects of periodontal disease in promoting liver fibrosis in a rat model of ligature‐induced periodontitis. Methods Twenty‐four Wistar rats were divided into four groups: control (CTRL), experimental periodontitis group at day 7 (PER7), at day 14 (PER14), at day 21 (PER21). Experimental periodontitis was induced by the placement of a silk ligature around mandibular incisors. The following parameters were assessed: gingival index, tooth mobility; liver status, and portal vein caliber by ultrasound examination; bone retraction, bone mineral density (BMD), bone volume/tissue volume (BV/TV) by micro‐CT analysis; aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT); oxidative stress (malondialdehyde [MDA], reduced glutathione/oxidative glutathione ratio [GSH/GSSG]), and matrix metalloproteinase‐8 (MMP‐8) levels; and histopathological evaluation of periodontal and liver tissues. Results Periodontal parameters showed the development of periodontitis in experimental groups. Micro‐CT results indicates an increase of bone retraction and BMD values and a decrease of BV/TV value in PER groups. Liver fibrosis could not be diagnosed with ultrasound examination in any of the groups. Elevated levels of ASAT and ALAT in PER groups compared with CTRL group were found. MDA have indicated elevated levels and a decrease of GSH/GSSG ratio in PER group compared with the CTRL group. Levels of MMP‐8 have indicated high values in PER21 compared with the other groups. Histological analysis of the periodontal and liver tissues sustains the link between periodontal and hepatic injury. Conclusion This study demonstrates a positive correlation between periodontal lesions and liver disease. Periodontitis may be an independent risk factor for liver fibrosis.

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Liver cirrhosis contributes to the disorder of gut microbiota in patients with hepatocellular carcinoma

et al. 2020

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Background Gut microbiota (GM) of patients with liver cancer is disordered, and syet no study reported the GM distribution of liver cirrhosis‐induced HCC (LC‐HCC) and nonliver cirrhosis‐induced HCC (NLC‐HCC). In this study, we aimed to characterize gut dysbiosis of LC‐HCC and NLC‐HCC to elucidate the role of GM in the pathogenesis of HCC. Methods A consecutive series of fecal samples of patients with hepatitis (24 patients), liver cirrhosis (24 patients), HCC (75 patients: 35 infected by HBV, 25 infected by HCV, and 15 with alcoholic liver disease), and healthy controls (20 patients) were obtained and sequenced on the Illumina Hiseq platform. The HCC group contains 52 LC‐HCC and 23 NLC‐HCC. Bioinformatic analysis of the intestinal microbiota was performed with QIIME and MicrobiomeAnalyst. Results Alpha‐diversity analysis showed that fecal microbial diversity was significantly decreased in the LC group, and there were significant differences in 3 phyla and 27 genera in the LC group vs the other groups (the healthy, hepatitis, and HCC groups). Beta‐diversity analysis showed that there were large differences between LC and the others. Gut microbial diversity was significantly increased from LC to HCC. Characterizing the fecal microbiota of LC‐HCC and NLC‐HCC, we found that microbial diversity was increased from LC to LC‐HCC rather than NLC‐HCC. Thirteen genera were discovered to be associated with the tumor size of HCC. Three biomarkers (Enterococcus, Limnobacter, and Phyllobacterium) could be used for precision diagnosis. We also found that HBV infection, HCV infection, or ALD (alcoholic liver disease) was not associated with intestinal microbial dysbiosis in HCC. Conclusion Our results suggest that GM disorders are more common in patients with LC‐HCC. The butyrate‐producing genera were decreased, while genera producing‐lipopolysaccharide (LPS) were increased in LC‐HCC patients. Further studies of GM disorders may achieve early diagnosis and new therapeutic approaches for HCC patients.

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Microbiota, cirrhosis, and the emerging oral-gut-liver axis

Cited by 179 publications

References 107 publications

Periodontitis is associated with incident chronic liver disease—A population‐based cohort study

Periodontitis is associated with incident chronic liver disease—A population‐based cohort study

Periodontal disease may induce liver fibrosis in an experimental study on Wistar rats

Liver cirrhosis contributes to the disorder of gut microbiota in patients with hepatocellular carcinoma

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