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      Gut Microbiota’s Relationship with Liver Disease and Role in Hepatoprotection by Dietary Natural Products and Probiotics

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          Abstract

          A variety of dietary natural products have shown hepatoprotective effects. Increasing evidence has also demonstrated that gut microorganisms play an important role in the hepatoprotection contributed by natural products. Gut dysbiosis could increase permeability of the gut barrier, resulting in translocated bacteria and leaked gut-derived products, which can reach the liver through the portal vein and might lead to increased oxidative stress and inflammation, thereby threatening liver health. Targeting gut microbiota modulation represents a promising strategy for hepatoprotection. Many natural products could protect the liver from various injuries or mitigate hepatic disorders by reverting gut dysbiosis, improving intestinal permeability, altering the primary bile acid, and inhibiting hepatic fatty acid accumulation. The mechanisms underlying their beneficial effects also include reducing oxidative stress, suppressing inflammation, attenuating fibrosis, and decreasing apoptosis. This review discusses the hepatoprotective effects of dietary natural products via modulating the gut microbiota, mainly focusing on the mechanisms of action.

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          Gut microbiota profiling of pediatric NAFLD and obese patients unveiled by an integrated meta-omics based approach.

          There is evidence that non-alcoholic fatty liver disease (NAFLD) is affected by gut microbiota. Therefore, we investigated its modifications in paediatric NAFLD patients using targeted-metagenomics (MG) and metabolomics (MB). Stools were collected from 61 consecutive patients diagnosed with NAFL, NASH, or obesity and 54 healthy subjects (CTRLs), matched in a case-control fashion. Operational taxonomic units were pyrosequenced targeting 16S ribosomal RNA and volatile organic compounds (VOCs) determined by solid-phase micro-extraction GC-MS. The α-diversity was highest in CTRLs followed by obese, NASH, NAFL patients and β-diversity distinguished between patients and CTRLs, but not NAFL and NASH. Compared to CTRLs, in NAFLD patients Actinobacteria were significantly increased and Bacteroidetes reduced. There were no significant differences amongst NAFL, NASH, and obese groups. Overall NAFLD patients had increased levels of Bradyrhizobium, Anaerococcus, Peptoniphilus, Propionibacterium acnes, Dorea, Ruminococcus and reduced proportions of Oscillospira and Rikenellaceae compared to CTRLs. After reducing MG and MB data dimensionality, multivariate analyses indicated Oscillospira decrease in NAFL and NASH groups, and Ruminococcus, Blautia, and Dorea increase in NASH patients compared to CTRLs. Of the 292 VOCs, 26 were up- and 2 down-regulated in NAFLD patients. Multivariate analyses found that combination of Oscillospira, Rickenellaceae, Parabacteroides, Bacteroides fragilis, Sutterella, Lachnospiraceae, 4-methyl-2-pentanone, 1-butanol, and 2-butanone could discriminate NAFLD patients from CTRLs. Univariate analyses found significantly lower levels of Oscillospira and higher levels of 1-pentanol and 2-butanone in NAFL compared to CTRLs. In NASH, lower levels of Oscillospira were associated with higher abundance of Dorea, Ruminococcus and higher levels of 2-butanone, 4-methyl-2-pentanone compared to CTRLs.
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            Fecal microbiome and volatile organic compound metabolome in obese humans with nonalcoholic fatty liver disease.

            The histopathology of nonalcoholic fatty liver disease (NAFLD) is similar to that of alcoholic liver disease. Colonic bacteria are a source of many metabolic products, including ethanol and other volatile organic compounds (VOC) that may have toxic effects on the human host after intestinal absorption and delivery to the liver via the portal vein. Recent data suggest that the composition of the gut microbiota in obese human beings is different from that of healthy-weight individuals. The aim of this study was to compare the colonic microbiome and VOC metabolome of obese NAFLD patients (n = 30) with healthy controls (n = 30). Multitag pyrosequencing was used to characterize the fecal microbiota. Fecal VOC profiles were measured by gas chromatography-mass spectrometry. There were statistically significant differences in liver biochemistry and metabolic parameters in NAFLD. Deep sequencing of the fecal microbiome revealed over-representation of Lactobacillus species and selected members of phylum Firmicutes (Lachnospiraceae; genera, Dorea, Robinsoniella, and Roseburia) in NAFLD patients, which was statistically significant. One member of phylum Firmicutes was under-represented significantly in the fecal microbiome of NAFLD patients (Ruminococcaceae; genus, Oscillibacter). Fecal VOC profiles of the 2 patient groups were different, with a significant increase in fecal ester compounds observed in NAFLD patients. A significant increase in fecal ester VOC is associated with compositional shifts in the microbiome of obese NAFLD patients. These novel bacterial metabolomic and metagenomic factors are implicated in the etiology and complications of obesity. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.
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              Gut-liver axis in alcoholic liver disease.

              Alcoholic liver disease (ALD) has been among the leading causes of cirrhosis and liver-related death worldwide for decades. Early discoveries in alcoholic liver disease identified increased levels of bacterial endotoxin in the portal circulation, suggesting a role for gut-derived toxins in ALD. Indeed, alcohol consumption can disrupt the intestinal epithelial barrier and result in increased gut permeability that increasingly is recognized as a major factor in ALD. Bacterial endotoxin, lipopolysaccharide, is a prototypic microbe-derived inflammatory signal that contributes to inflammation in ALD through activation of the Toll-like receptor 4. Recent studies also have shown that alcohol consumption is associated with alterations in the gut microbiome, and the dysbalance of pathogenic and commensal organisms in the intestinal microbiome may contribute to the abnormal gut-liver axis in ALD. Indeed, bacterial decontamination improves ALD both in human and animal models. This short review summarizes recent findings and highlights emerging trends in the gut-liver axis relevant to ALD.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                08 October 2018
                October 2018
                : 10
                : 10
                : 1457
                Affiliations
                [1 ]Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Guangdong Engineering Technology Research Center of Nutrition Translation, Department of Nutrition, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China; mengx7@ 123456mail2.sysu.edu.cn (X.M.); liya28@ 123456mail2.sysu.edu.cn (Y.L.)
                [2 ]School of Chinese Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China; u3003781@ 123456connect.hku.hk
                [3 ]Department of Food Science & Technology, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai 200240, China; renyougan@ 123456sjtu.edu.cn
                [4 ]South China Sea Bioresource Exploitation and Utilization Collaborative Innovation Center, Sun Yat-sen University, Guangzhou 510006, China
                Author notes
                [* ]Correspondence: lihuabin@ 123456mail.sysu.edu.cn ; Tel.: +86-20-873-323-91
                [†]

                These authors contribute equally to this paper.

                Author information
                https://orcid.org/0000-0001-7246-2069
                https://orcid.org/0000-0002-4162-1511
                https://orcid.org/0000-0003-2332-8554
                Article
                nutrients-10-01457
                10.3390/nu10101457
                6213031
                30297615
                f85d105b-5f75-45cd-87f2-988682a686f1
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 30 August 2018
                : 26 September 2018
                Categories
                Review

                Nutrition & Dietetics
                gut microbiota,natural products,probiotics,hepatoprotection,mechanisms
                Nutrition & Dietetics
                gut microbiota, natural products, probiotics, hepatoprotection, mechanisms

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