Streptococcus, the Predominant Bacterium to Predict the Severity of Liver Injury in Alcoholic Liver Disease

BackgroundNew evidence implies that the imbalance of gut microbiota is associated with the progression of alcoholic liver disease (ALD) and that the composition of gut microbiota is altered in ALD patients. However, the predominant bacterium in patients involved in the progress of ALD has not been identified. The purpose of this study is to investigate the predominant bacterium in the early and end-stages of ALD as well as the relationship between the bacterium and the degree of liver injury.MethodsWe enrolled 21 alcoholic fatty liver (AFL) patients, 17 alcoholic liver cirrhosis (ALC) patients and 27 healthy controls, and sequenced the 16S rRNA gene of their fecal microbiota. The gut microbiota composition and its relationship with the indicators of clinical hepatic function were assessed using canonical correspondence analysis (CCA), spearman correlation heatmap and multivariate association with linear (MaAsLin) Models.ResultsThe composition and structure of gut microbiota changed greatly in different stages of ALD, and the degree of disorder was aggravated with the progression of ALD, even in the early stage. Moreover, the relative abundance of Streptococcus was highly enriched only in patients with ALC (P <0.001), and positively correlated with AST level (P = 0.029). The abundance of Streptococcus distinguished the liver injury of ALC patients from the controls with an area under the receiver-operating characteristic curve (AUC) of 0.877 (P < 0.001).ConclusionsThese findings indicate that the imbalance of gut microbiota exists at the early and end-stages of ALD, and the degree of disorder is aggravated with the progression of ALD. Streptococcus, as the predominant bacterium, may be a microbiological marker to evaluate the severity of liver injury in ALD patients.

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P841 Evaluation of gut microbiota composition in NAFLD with UC pancolitis in clinical remission: a pilot study

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.969 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S650-S651

Author(s):

S Cocciolillo ◽

G De Palma ◽

T Chen ◽

M P Ghali ◽

M Deschenes ◽

...

Keyword(s):

Liver Disease ◽

Pilot Study ◽

Gut Microbiota ◽

Clinical Remission ◽

Transient Elastography ◽

Rrna Gene ◽

Microbiota Composition ◽

Cross Sectional ◽

Alcoholic Fatty Liver ◽

Gut Microbiota Composition

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is the main cause of liver disease in Western countries and is a frequently reported comorbidity in inflammatory bowel disease (IBD). A complex interaction among polygenic predisposition, IBD-specific risk factors, microbiome, multiple environmental and patients’ factors could explain the development of NAFLD in IBD. Gut dysbiosis is increasingly recognised as an important player in NAFLD, as well as in IBD pathogenesis. So far, no study has examined the gut microbiota composition in IBD patients with NAFLD. We aimed to characterise faecal microbiota according to NAFLD status in a pilot cohort of ulcerative colitis (UC) pancolitis in clinical remission. Methods This was a cross-sectional pilot study using transient elastography (TE) with controlled attenuation parameter (CAP) to diagnose NAFLD in UC pancolitis patients in clinical remission, defined as partial Mayo score ≤1. NAFLD was diagnosed non-invasively as CAP ≥248 dB/m. Exclusion criteria included: use of corticosteroids in the last year and antibiotics or probiotics/prebiotics in the last 2 months prior to inclusion; significant alcohol intake (AUDIT-C <5); hepatitis B or C infection. Stool samples were collected within 12 h from TE with CAP evaluation. Gut microbiota composition was analysed by 16S rRNA gene sequencing with Illumina technique. Statistical analysis by NAFLD status was performed using Fisher’s exact or Mann–Whitney’s test as appropriate. Results A total of 11 UC pancolitis patients in clinical remission were included (mean age 53 years, 36.4% male, time since IBD diagnosis 16 years). NAFLD was diagnosed in 7 cases (63.6%, mean CAP 291 dB/m). Patients with pancolitis and NAFLD had higher BMI (mean 31 vs. 22 kg/m2, p = 0.006) as well as waist circumference (mean 100 vs. 81 cm, p = 0.006) compared with those without NAFLD, but no other differences in demographic, clinical or pharmacological parameters were found between pancolitis with or without NAFLD. Patients with pancolitis and NAFLD clustered separately from those without NAFLD, when computing Bray Curtis dissimilarities (tested with Adonis, p = 0.006). In addition, patients with pancolitis and NAFLD presented with decreased bacterial richness (p = 0.017) but not diversity. This was accompanied by a significant increase of Bacteroides spp. relative abundance in faecal samples of patients with pancolitis and NAFLD (q = 0.017). Conclusion This pilot study demonstrates, for the first time, that, in UC pancolitis patients, NAFLD associates with altered gut microbiota composition. Further studies are needed to understand the exact role of gut microbiota in UC pancolitis with NAFLD and to evaluate the use of microbiota-directed approaches for the treatment of NAFLD in these patients.

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Alcoholic Liver Disease: Alcohol Metabolism, Cascade of Molecular Mechanisms, Cellular Targets, and Clinical Aspects

Biomedicines ◽

10.3390/biomedicines6040106 ◽

2018 ◽

Vol 6 (4) ◽

pp. 106 ◽

Cited By ~ 28

Author(s):

Rolf Teschke

Keyword(s):

Liver Disease ◽

Liver Injury ◽

Alcoholic Liver Disease ◽

Molecular Mechanisms ◽

Lipid Peroxides ◽

Sirtuin 1 ◽

Clinical Aspects ◽

Alkoxyl Radical ◽

Alcoholic Fatty Liver ◽

Cyp 2E1

Alcoholic liver disease is the result of cascade events, which clinically first lead to alcoholic fatty liver, and then mostly via alcoholic steatohepatitis or alcoholic hepatitis potentially to cirrhosis and hepatocellular carcinoma. Pathogenetic events are linked to the metabolism of ethanol and acetaldehyde as its first oxidation product generated via hepatic alcohol dehydrogenase (ADH) and the microsomal ethanol-oxidizing system (MEOS), which depends on cytochrome P450 2E1 (CYP 2E1), and is inducible by chronic alcohol use. MEOS induction accelerates the metabolism of ethanol to acetaldehyde that facilitates organ injury including the liver, and it produces via CYP 2E1 many reactive oxygen species (ROS) such as ethoxy radical, hydroxyethyl radical, acetyl radical, singlet radical, superoxide radical, hydrogen peroxide, hydroxyl radical, alkoxyl radical, and peroxyl radical. These attack hepatocytes, Kupffer cells, stellate cells, and liver sinusoidal endothelial cells, and their signaling mediators such as interleukins, interferons, and growth factors, help to initiate liver injury including fibrosis and cirrhosis in susceptible individuals with specific risk factors. Through CYP 2E1-dependent ROS, more evidence is emerging that alcohol generates lipid peroxides and modifies the intestinal microbiome, thereby stimulating actions of endotoxins produced by intestinal bacteria; lipid peroxides and endotoxins are potential causes that are involved in alcoholic liver injury. Alcohol modifies SIRT1 (Sirtuin-1; derived from Silent mating type Information Regulation) and SIRT2, and most importantly, the innate and adapted immune systems, which may explain the individual differences of injury susceptibility. Metabolic pathways are also influenced by circadian rhythms, specific conditions known from living organisms including plants. Open for discussion is a 5-hit working hypothesis, attempting to define key elements involved in injury progression. In essence, although abundant biochemical mechanisms are proposed for the initiation and perpetuation of liver injury, patients with an alcohol problem benefit from permanent alcohol abstinence alone.

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Characterization of Early-Stage Alcoholic Liver Disease with Hyperhomocysteinemia and Gut Dysfunction and Associated Immune Response in Alcohol Use Disorder Patients

Biomedicines ◽

10.3390/biomedicines9010007 ◽

2020 ◽

Vol 9 (1) ◽

pp. 7

Author(s):

Vatsalya Vatsalya ◽

Khushboo S. Gala ◽

Ammar Z. Hassan ◽

Jane Frimodig ◽

Maiying Kong ◽

...

Keyword(s):

Liver Disease ◽

Liver Injury ◽

Alcoholic Liver Disease ◽

Alcohol Withdrawal ◽

Alcohol Use Disorder ◽

Early Stage ◽

Heavy Drinking ◽

Cumulative Effects ◽

Proinflammatory Response ◽

Gut Dysfunction

Heavy alcohol consumption can cause hyperhomocysteinemia, which could be consequential in the proinflammatory response and worsening of the neurobehavioral domains of alcohol use disorder (AUD), such as alcohol withdrawal. We examined the role of heavy drinking, hyperhomocysteinemia, gut dysfunction and inflammation in early-stage alcoholic liver disease (ALD) in AUD patients. A total of 110 AUD patients without clinical manifestations of liver injury were grouped by the serum homocysteine levels (SHL): normal ≤ 13 µmol/L (Group 1 (Gr.1); n = 80), and elevated > 13 µmol/L (Group 2 (Gr.2), n = 30). A comprehensive metabolic panel, SHL, a nutritional assessment, and drinking history assessed by the timeline followback questionnaire were evaluated. A subset analysis was performed on 47 subjects (Gr.1 n = 27; Gr.2 n = 20) for additional measures: Clinical Institute Withdrawal Assessment for Alcohol (CIWA) score, plasma cytokines (interleukin-1β (IL-1β)), gut dysfunction markers (lipopolysaccharide (LPS), and LPS-binding protein (LBP)); 27% of the AUD patients exhibited hyperhomocysteinemia. SHL was significantly associated (p = 0.034) with heavy drinking days (HDD90). Subset analyses showed that the withdrawal ratings were both clinically and statistically (p = 0.033) elevated and significantly associated with hyperhomocysteinemia (p = 0.016) in Gr.2. LBP, IL1-β, SHL, and HDD90 showed significant cumulative effects (adjusted R2 = 0.627) on withdrawal ratings in Gr.2 subset. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly higher in all Gr.2 patients; AUROC showed a fair level of true positivity for ALT (0.676), and AST (0.686). Il1-β, LBP, SHL, and HDD90 showed significant cumulative effects (adjusted R2 = 0.554) on the elevated ALT in Gr.2 subset as well. The gut-brain derived proinflammatory response, patterns of heavy drinking, and hyperhomocysteinemia were closely associated with clinically elevated alcohol withdrawal and elevated liver injury. Hyperhomocysteinemia could have a potential phenotypic marker response indicative of early-stage ALD along with AUD.

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Astaxanthin Prevents Alcoholic Fatty Liver Disease by Modulating Mouse Gut Microbiota

Nutrients ◽

10.3390/nu10091298 ◽

2018 ◽

Vol 10 (9) ◽

pp. 1298 ◽

Cited By ~ 18

Author(s):

Huilin Liu ◽

Meihong Liu ◽

Xueqi Fu ◽

Ziqi Zhang ◽

Lingyu Zhu ◽

...

Keyword(s):

Liver Disease ◽

Liver Injury ◽

Gut Microbiota ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Serum Markers ◽

Alcoholic Fatty Liver ◽

Ethanol Group ◽

The Relationship ◽

Alcoholic Fatty Liver Disease

The development and progression of alcoholic fatty liver disease (AFLD) is influenced by the intestinal microbiota. Astaxanthin, a type of oxygenated carotenoid with strong antioxidant and anti-inflammatory properties, has been proven to relieve liver injury. However, the relationship between the gut microbiota regulation effect of astaxanthin and AFLD improvement remains unclear. The effects of astaxanthin on the AFLD phenotype, overall structure, and composition of gut microbiota were assessed in ethanol-fed C57BL/6J mice. The results showed that astaxanthin treatment significantly relieves inflammation and decreases excessive lipid accumulation and serum markers of liver injury. Furthermore, astaxanthin was shown to significantly decrease species from the phyla Bacteroidetes and Proteobacteria and the genera Butyricimonas, Bilophila, and Parabacteroides, as well as increase species from Verrucomicrobia and Akkermansia compared with the Et (ethanol)group. Thirteen phylotypes related to inflammation as well as correlated with metabolic parameters were significantly altered by ethanol, and then notably reversed by astaxanthin. Additionally, astaxanthin altered 18 and 128 KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways involved in lipid metabolism and xenobiotic biodegradation and metabolism at levels 2 and 3, respectively. These findings suggest that Aakkermansia may be a potential target for the astaxanthin-induced alleviation of AFLD and may be a potential treatment for bacterial disorders induced by AFLD.

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Effects of Tea against Alcoholic Fatty Liver Disease by Modulating Gut Microbiota in Chronic Alcohol-Exposed Mice

Foods ◽

10.3390/foods10061232 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1232

Author(s):

Bangyan Li ◽

Qianqian Mao ◽

Dandan Zhou ◽

Min Luo ◽

Renyou Gan ◽

...

Keyword(s):

Liver Disease ◽

Liver Injury ◽

Gut Microbiota ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Black Tea ◽

Chronic Alcohol ◽

Alcoholic Fatty Liver ◽

Oolong Tea ◽

Alcoholic Fatty Liver Disease

Gut microbiota dysbiosis has been a crucial contributor to the pathogenesis of alcoholic fatty liver disease (AFLD). Tea is a popular beverage worldwide and exerts antioxidant and anti-inflammatory activities, as well as hepatoprotective effects. However, the potential role of gut microbiota regulated by tea in the prevention and management of AFLD remains unclear. Here, the protective effects of oolong tea, black tea, and dark tea on AFLD and its regulation of gut microbiota in chronic alcohol-exposed mice were explored and investigated. The results revealed that tea supplementation significantly prevented liver steatosis, decreased oxidative stress and inflammation, and modulated gut microbiota in chronic alcohol-exposed mice, especially oolong tea and dark tea. However, black tea showed less effectiveness against liver injury caused by alcohol. Moreover, the diversity, structure and composition of chronic alcohol-disrupted gut microbiota were restored by the supplementation of oolong tea and dark tea based on the analysis of gut microbiota. Furthermore, the relationship between liver injury biochemical indicators and gut microbiota indicated that some specific bacteria, such as Bacteroides, Alloprevotella, and Parabacteroides were closely associated with AFLD. In addition, the phytochemical components in tea extracts were measured by high-performance liquid chromatography, which could contribute to preventive effects on AFLD. In summary, oolong tea and dark tea could prevent chronic alcohol exposure-induced AFLD by modulating gut microbiota.

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Ademetionine in patients with liver disease: a review

International Journal of Research in Medical Sciences ◽

10.18203/2320-6012.ijrms20192550 ◽

2019 ◽

Vol 7 (6) ◽

pp. 2482 ◽

Cited By ~ 3

Author(s):

Sanjiv Saigal ◽

Dharmesh Kapoor ◽

Dyotona Sen Roy

Keyword(s):

Liver Disease ◽

Liver Injury ◽

Alcoholic Liver Disease ◽

Biochemical Markers ◽

Fatty Liver Disease ◽

Signs And Symptoms ◽

Drug Induced ◽

Alcoholic Fatty Liver ◽

Drug Induced Liver Injury ◽

Alcoholic Fatty Liver Disease

The aim of the present review is to have an in-depth analysis of the published scientific literature relating to the clinical use of ademetionine in various etiologies of liver disease. Literature search was performed using electronic databases like Pubmed/Medline/others to identify studies on ademetionine in patients with intrahepatic cholestasis, alcoholic liver disease, non-alcoholic fatty liver disease, drug induced liver injury and viral hepatitis. Ademetionine has been studied in various etiologies of liver disease with varying dosing and durations. In patients with chronic and alcoholic liver disease, ademetionine was found to be beneficial in improving liver enzyme levels, increasing glutathione levels, improving signs and symptoms of fatigue, pruritus and jaundice. Positive effects of ademetionine therapy have also been documented in multiple studies in patients with non-alcoholic fatty liver disease, with improvements observed in triglyceride, total cholesterol, alanine transaminase and asprtate transaminase levels and ultrasound grading of fatty change. In patients with drug induced liver injury, improvements were observed in liver biochemical markers and symptoms such as pruritus, fatigue and jaundice. Ademetionine has also been studied in patients with viral hepatitis with improvement in laboratory markers and signs and symptoms. Published data suggest that there is clinical evidence to substantiate the use of ademetionine across indications. Its use has resulted in sustained improvement in biochemical markers; signs and symptoms of liver disease has been observed in both acute and chronic liver disease. Further data is warranted through clinical studies to focus on specific end points of therapy areas, in existing and new indications.

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Metabolic Alteration of Gut Microbiota Is Associated With Host Non-alcoholic Fatty Liver Disease Induced by Pyrethroid in Xenopus Laevis

10.21203/rs.3.rs-484978/v1 ◽

2021 ◽

Author(s):

Meng Li ◽

Tingting Liu ◽

Jiaping Zhu ◽

Mengcen Wang ◽

qiangwei wang

Keyword(s):

Liver Disease ◽

Bile Acid ◽

Gut Microbiota ◽

Fatty Liver ◽

Gut Microbiome ◽

Fatty Liver Disease ◽

16S Rrna Gene Sequencing ◽

Metabolite Profile ◽

Rrna Gene ◽

Alcoholic Fatty Liver

Abstract Background: There is increasing awareness of the significance of the gut microbiome to host health, and a clear relationship has been established between the perturbed gut microbiome and multiple diseases. Cis-bifenthrin, a widely used agricultural pyrethroid insecticide, has been implicated as a cause of hepatotoxicity due to the oxidative stress produced during its metabolism by the liver. Studies have demonstrated the role of gut microbiota in gut-liver axis, it is possible that the perturbation of gut microbiota may also contribute to the toxicity of cis-bifenthrin on the liver.Results: 16S rRNA gene sequencing suggested that cis-bifenthrin exposure significantly perturbed the gut microbiota composition, and metabolomics analysis showed signature metabolic shifts arising from exposure. Moreover, we also found altered functional regulation of lipids in the liver after cis-bifenthrin exposure, and the accumulation of lipid droplets in hepatocytes was observed.Conclusions: Our results suggested cis-bifenthrin exposure disturbed the gut microbiota community and metabolite profile in frogs. Specifically, changes in bile acid metabolites altered bile acid hepatoenteral circulation, which affected lipid metabolism in the liver and ultimately caused the development of fatty liver disease. Our findings reveal novel insights into gut microbiota-host axis in frogs, and the perturbed microbial function provides novel mechanism contributing to cis-bifenthrin-induced toxicity.

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