Distinctly altered gut microbiota in the progression of liver disease

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Abstract

Recent studies underscore important roles of intestinal microbiota and the bacterial lipopolysaccharides (LPS) production in the pathogenesis of liver disease. However, how gut microbiota alters in response to the development of steatosis and subsequent progression to nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) remains unclear. We aimed to study the gut microbial changes over liver disease progression using a streptozotocin-high fat diet (STZ-HFD) induced NASH-HCC C57BL/6J mouse model that is highly relevant to human liver disease. The fecal microbiota at various liver pathological stages was analyzed by 16S rDNA gene pyrosequencing. Both UniFrac analysis and partial least squares-discriminant analysis showed significant structural alterations in gut microbiota during the development of liver disease. Co-abundance network analysis highlighted relationships between genera. Spearman correlation analysis revealed that the bacterial species, Atopobium spp., Bacteroides spp., Bacteroides vulgatus, Bacteroides acidifaciens, Bacteroides uniformis, Clostridium cocleatum, Clostridium xylanolyticum and Desulfovibrio spp., markedly increased in model mice, were positively correlated with LPS levels and pathophysiological features. Taken together, the results showed that the gut microbiota was altered significantly in the progression of liver disease. The connection between the gut microbial ecology and the liver pathology may represent potential targets for the prevention and treatment of chronic liver disease and HCC.

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UniFrac: a new phylogenetic method for comparing microbial communities.

Catherine A. Lozupone, Rob Knight (2005)

We introduce here a new method for computing differences between microbial communities based on phylogenetic information. This method, UniFrac, measures the phylogenetic distance between sets of taxa in a phylogenetic tree as the fraction of the branch length of the tree that leads to descendants from either one environment or the other, but not both. UniFrac can be used to determine whether communities are significantly different, to compare many communities simultaneously using clustering and ordination techniques, and to measure the relative contributions of different factors, such as chemistry and geography, to similarities between samples. We demonstrate the utility of UniFrac by applying it to published 16S rRNA gene libraries from cultured isolates and environmental clones of bacteria in marine sediment, water, and ice. Our results reveal that (i) cultured isolates from ice, water, and sediment resemble each other and environmental clone sequences from sea ice, but not environmental clone sequences from sediment and water; (ii) the geographical location does not correlate strongly with bacterial community differences in ice and sediment from the Arctic and Antarctic; and (iii) bacterial communities differ between terrestrially impacted seawater (whether polar or temperate) and warm oligotrophic seawater, whereas those in individual seawater samples are not more similar to each other than to those in sediment or ice samples. These results illustrate that UniFrac provides a new way of characterizing microbial communities, using the wealth of environmental rRNA sequences, and allows quantitative insight into the factors that underlie the distribution of lineages among environments.

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Ganoderma lucidum reduces obesity in mice by modulating the composition of the gut microbiota

Chih-Jung Chang, Chuan-Sheng Lin, Chia-Chen Lu … (2015)

Obesity is associated with low-grade chronic inflammation and intestinal dysbiosis. Ganoderma lucidum is a medicinal mushroom used in traditional Chinese medicine with putative anti-diabetic effects. Here, we show that a water extract of Ganoderma lucidum mycelium (WEGL) reduces body weight, inflammation and insulin resistance in mice fed a high-fat diet (HFD). Our data indicate that WEGL not only reverses HFD-induced gut dysbiosis—as indicated by the decreased Firmicutes-to-Bacteroidetes ratios and endotoxin-bearing Proteobacteria levels—but also maintains intestinal barrier integrity and reduces metabolic endotoxemia. The anti-obesity and microbiota-modulating effects are transmissible via horizontal faeces transfer from WEGL-treated mice to HFD-fed mice. We further show that high molecular weight polysaccharides (>300 kDa) isolated from the WEGL extract produce similar anti-obesity and microbiota-modulating effects. Our results indicate that G. lucidum and its high molecular weight polysaccharides may be used as prebiotic agents to prevent gut dysbiosis and obesity-related metabolic disorders in obese individuals.

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Bacterial tag-encoded FLX amplicon pyrosequencing (bTEFAP) for microbiome studies: bacterial diversity in the ileum of newly weaned Salmonella-infected pigs.

Scot Dowd, Yan. Sun, Randy D Wolcott … (2008)

The microbiota of an animal's intestinal tract plays a vital role in the animal's overall health. There is a surprising scarcity of information on the microbial diversity in the gut of livestock species such as cattle and swine. Here we describe a bacterial 16S-based tag-encoded FLX amplicon pyrosequencing (bTEFAP) method that we have developed as a high-throughput universal tool for bacterial diversity, epidemiology, and pathogen detection studies. This method will allow hundreds of samples to be run simultaneously but analyzed individually or as groups. To test this new methodology, we individually evaluated the bacterial diversity in the ileum of 21 pigs. Ubiquitous bacteria detected in the newly weaned pigs were Clostridium spp., Lactobacillus spp., and Helicobacter spp. Many of the pigs had surprisingly low concentrations of beneficial bacteria such as Bifidobacterium spp. Only four of the pigs were shown to be positive for Salmonella spp. using traditional culture methods. A total of eight pigs were bTEFAP positive for Salmonella spp., including all four of the pigs that had been culture positive. Two of the pigs sampled were also positive for Campylobacter spp. tentative identified as jejuni. Using rarefaction curves modeled with the Richards equation, we estimated the maximum number of unique species level (3% dissimilarity) operational taxonomic units in the ileum of these pigs. These predictions indicated that there may be as many as 821 different species associated with the ileum in pigs. Together these data indicate a powerful potential of this technology in food safety and epidemiological and bacterial diversity applications. Using bTEFAP, we can expect to gain a better understanding of how the microbiome of an animal contributes to its health and well-being.

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Journal

Journal ID (nlm-ta): Oncotarget

Journal ID (iso-abbrev): Oncotarget

Journal ID (publisher-id): Oncotarget

Journal ID (publisher-id): ImpactJ

Title: Oncotarget

Publisher: Impact Journals LLC

ISSN (Electronic): 1949-2553

Publication date Collection: 12 April 2016

Publication date (Electronic): 29 March 2016

Volume: 7

Issue: 15

Pages: 19355-19366

Affiliations

¹ Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China

² University of Hawaii Cancer Center, Honolulu, Hawaii, USA

³ E-institute of Shanghai Municipal Education Committee, Shanghai University of Traditional Chinese Medicine, Shanghai, China

⁴ Key Laboratory of Liver and Kidney Diseases (Ministry of Education), Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China

⁵ Department of Oceanography, University of Hawaii at Manoa, Honolulu, Hawaii, USA

⁶ National Key Laboratory of Animal Nutrition, China Agricultural University, Beijing, China

Author notes

Correspondence to: Wei Jia, wjia@ 123456cc.hawaii.edu

Article

Publisher ID: 8466

DOI: 10.18632/oncotarget.8466

PMC ID: 4991388

PubMed ID: 27036035

SO-VID: 9ec87645-9636-43bd-9663-6bf74f13f943

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Distinctly altered gut microbiota in the progression of liver disease

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Karger: Oncology

Most cited references 25

UniFrac: a new phylogenetic method for comparing microbial communities.

Ganoderma lucidum reduces obesity in mice by modulating the composition of the gut microbiota

Bacterial tag-encoded FLX amplicon pyrosequencing (bTEFAP) for microbiome studies: bacterial diversity in the ileum of newly weaned Salmonella-infected pigs.

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