Molecular Characterization of the Fecal Microbiota in Patients with Nonalcoholic Steatohepatitis – A Longitudinal Study

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background

The human gut microbiota has profound influence on host metabolism and immunity. This study characterized the fecal microbiota in patients with nonalcoholic steatohepatitis (NASH). The relationship between microbiota changes and changes in hepatic steatosis was also studied.

Methods

Fecal microbiota of histology-proven NASH patients and healthy controls was analyzed by 16S ribosomal RNA pyrosequencing. NASH patients were from a previously reported randomized trial on probiotic treatment. Proton-magnetic resonance spectroscopy was performed to monitor changes in intrahepatic triglyceride content (IHTG).

Results

A total of 420,344 16S sequences with acceptable quality were obtained from 16 NASH patients and 22 controls. NASH patients had lower fecal abundance of Faecalibacterium and Anaerosporobacter but higher abundance of Parabacteroides and Allisonella. Partial least-square discriminant analysis yielded a model of 10 genera that discriminated NASH patients from controls. At month 6, 6 of 7 patients in the probiotic group and 4 of 9 patients in the usual care group had improvement in IHTG (P = 0.15). Improvement in IHTG was associated with a reduction in the abundance of Firmicutes (R ² = 0.4820, P = 0.0028) and increase in Bacteroidetes (R ² = 0.4366, P = 0.0053). This was accompanied by corresponding changes at the class, order and genus levels. In contrast, bacterial biodiversity did not differ between NASH patients and controls, and did not change with probiotic treatment.

Conclusions

NASH patients have fecal dysbiosis, and changes in microbiota correlate with improvement in hepatic steatosis. Further studies are required to investigate the mechanism underlying the interaction between gut microbes and the liver.

Related collections

Most cited references 15

Record: found
Abstract: found
Article: not found

Fast UniFrac: Facilitating high-throughput phylogenetic analyses of microbial communities including analysis of pyrosequencing and PhyloChip data

Micah Hamady, Catherine A. Lozupone, Rob Knight (2009)

Next-generation sequencing techniques, and PhyloChip, have made simultaneous phylogenetic analyses of hundreds of microbial communities possible. Insight into community structure has been limited by the inability to integrate and visualize such vast datasets. Fast UniFrac overcomes these issues, allowing integration of larger numbers of sequences and samples into a single analysis. Its new array-based implementation offers orders of magnitude improvements over the original version. New 3D visualization of principal coordinates analysis (PCoA) results, with the option to view multiple coordinate axes simultaneously, provides a powerful way to quickly identify patterns that relate vast numbers of microbial communities. We demonstrate the potential of Fast UniFrac using examples from three data types: Sanger-sequencing studies of diverse free-living and animal-associated bacterial assemblages and from the gut of obese humans as they diet, pyrosequencing data integrated from studies of the human hand and gut, and PhyloChip data from a study of citrus pathogens. We show that a Fast UniFrac analysis using a reference tree recaptures patterns that could not be detected without considering phylogenetic relationships and that Fast UniFrac, coupled with BLAST-based sequence assignment, can be used to quickly analyze pyrosequencing runs containing hundreds of thousands of sequences, revealing patterns relating human and gut samples. Finally, we show that the application of Fast UniFrac to PhyloChip data could identify well-defined subcategories associated with infection. Together, these case studies point the way towards a broad range of applications and demonstrate some of the new features of Fast UniFrac.

0 comments Cited 415 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Comparative Analysis of Human Gut Microbiota by Barcoded Pyrosequencing

Anders F. Andersson, Mathilda Lindberg, Hedvig Jakobsson … (2008)

Humans host complex microbial communities believed to contribute to health maintenance and, when in imbalance, to the development of diseases. Determining the microbial composition in patients and healthy controls may thus provide novel therapeutic targets. For this purpose, high-throughput, cost-effective methods for microbiota characterization are needed. We have employed 454-pyrosequencing of a hyper-variable region of the 16S rRNA gene in combination with sample-specific barcode sequences which enables parallel in-depth analysis of hundreds of samples with limited sample processing. In silico modeling demonstrated that the method correctly describes microbial communities down to phylotypes below the genus level. Here we applied the technique to analyze microbial communities in throat, stomach and fecal samples. Our results demonstrate the applicability of barcoded pyrosequencing as a high-throughput method for comparative microbial ecology.

0 comments Cited 380 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease.

Zhiping Li, Shiqi Yang, Huizhi Lin … (2003)

Ob/ob mice, a model for nonalcoholic fatty liver disease (NAFLD), develop intestinal bacterial overgrowth and overexpress tumor necrosis factor alpha (TNF-alpha). In animal models for alcoholic fatty liver disease (AFLD), decontaminating the intestine or inhibiting TNF-alpha improves AFLD. Because AFLD and NAFLD may have a similar pathogenesis, treatment with a probiotic (to modify the intestinal flora) or anti-TNF antibodies (to inhibit TNF-alpha activity) may improve NAFLD in ob/ob mice. To evaluate this hypothesis, 48 ob/ob mice were given either a high-fat diet alone (ob/ob controls) or the same diet + VSL#3 probiotic or anti-TNF antibodies for 4 weeks. Twelve lean littermates fed a high-fat diet served as controls. Treatment with VSL#3 or anti-TNF antibodies improved liver histology, reduced hepatic total fatty acid content, and decreased serum alanine aminotransferase (ALT) levels. These benefits were associated with decreased hepatic expression of TNF-alpha messenger RNA (mRNA) in mice treated with anti-TNF antibodies but not in mice treated with VSL#3. Nevertheless, both treatments reduced activity of Jun N-terminal kinase (JNK), a TNF-regulated kinase that promotes insulin resistance, and decreased the DNA binding activity of nuclear factor kappaB (NF-kappaB), the target of IKKbeta, another TNF-regulated enzyme that causes insulin resistance. Consistent with treatment-related improvements in hepatic insulin resistance, fatty acid beta-oxidation and uncoupling protein (UCP)-2 expression decreased after treatment with VSL#3 or anti-TNF antibodies. In conclusion, these results support the concept that intestinal bacteria induce endogenous signals that play a pathogenic role in hepatic insulin resistance and NAFLD and suggest novel therapies for these common conditions.

0 comments Cited 225 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Massimo Federici: Role: Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, USA )

ISSN (Electronic): 1932-6203

Publication date Collection: 2013

Publication date (Electronic): 25 April 2013

Volume: 8

Issue: 4

Electronic Location Identifier: e62885

Affiliations

[1 ]Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong

[2 ]Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong

[3 ]Department of Zoology, University of Oxford, Oxford, United Kingdom

[4 ]Department of Imaging and Interventional Radiology, The Chinese University of Hong Kong, Hong Kong

[5 ]Department of Clinical Oncology, The Chinese University of Hong Kong, Hong Kong

[6 ]School of Life Sciences, The Chinese University of Hong Kong, Hong Kong

University of Tor Vergata, Italy

Author notes

* E-mail: wongv@ 123456cuhk.edu.hk

Competing Interests: Vincent Wai-Sun Wong has been an advisory board member of Roche, Novartis, Gilead and Otsuka, and received paid lecture fees from Roche, Novartis, Abbott Diagnostics and Echosens. Grace Lai-Hung Wong has been an advisory board member of Otsuka, and received paid lecture fees from Echosens and Otsuka. Henry Lik-Yuen Chan has been consultant for Abbott, Bristol-Myers Squibb, Merck, Novartis and Roche, and received paid lecture fees from Abbott, Bristol-Myers Squibb, Echosens, Gilead, Glaxo-Smith-Kline, Merck, Novartis and Roche.This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.

Conceived and designed the experiments: VW HC. Performed the experiments: VW CT TL. Analyzed the data: VW CT TL. Contributed reagents/materials/analysis tools: GW AC WC DY PL HK JY JS HC. Wrote the paper: VW CT TL. Radiological analysis: WC DY CT TL PL HK JY JS HC.

Article

Publisher ID: PONE-D-12-39925

DOI: 10.1371/journal.pone.0062885

PMC ID: 3636208

PubMed ID: 23638162

SO-VID: 7f3d1c51-616f-472f-a010-2c4d5768c3d0

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.

History

Date received : 12 December 2012

Date accepted : 27 March 2013

Page count

Pages: 11

Funding

The work described in this paper was partially supported by the Direct Grant of The Chinese University of Hong Kong (Reference no. 2010.1.042). The additional part of the funding of our study came from the authors’ own team. No additional external funding was received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Molecular Characterization of the Fecal Microbiota in Patients with Nonalcoholic Steatohepatitis – A Longitudinal Study

Read this article at

Abstract

Background

Methods

Results

Conclusions

Related collections

PLOS Climate

Most cited references 15

Fast UniFrac: Facilitating high-throughput phylogenetic analyses of microbial communities including analysis of pyrosequencing and PhyloChip data

Comparative Analysis of Human Gut Microbiota by Barcoded Pyrosequencing

Probiotics and antibodies to TNF inhibit inflammatory activity and improve nonalcoholic fatty liver disease.

Author and article information

Contributors

Journal

Affiliations

Author notes

Article

History

Page count

Funding

Categories

Comments

Comment on this article

Similar content 828

Cited by 147

Most referenced authors 1,323