Changes in blood microbiota profiles associated with liver fibrosis in obese patients: A pilot analysis
The early detection of liver fibrosis among patients with nonalcoholic fatty liver disease (NAFLD) is an important clinical need. In view of the suggested role played by bacterial translocation in liver disease and obesity, we sought to investigate the relationship between blood microbiota and liver...
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| Published in | Hepatology (Baltimore, Md.) Vol. 64; no. 6; pp. 2015 - 2027 |
|---|---|
| Main Authors | , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Wolters Kluwer Health, Inc
01.12.2016
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| Subjects | |
| Online Access | Get full text |
| ISSN | 0270-9139 1527-3350 1527-3350 |
| DOI | 10.1002/hep.28829 |
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| Abstract | The early detection of liver fibrosis among patients with nonalcoholic fatty liver disease (NAFLD) is an important clinical need. In view of the suggested role played by bacterial translocation in liver disease and obesity, we sought to investigate the relationship between blood microbiota and liver fibrosis (LF) in European cohorts of patients with severe obesity. We carried out a cross‐sectional study of obese patients, well characterized with respect to the severity of the NAFLD, in the cohort FLORINASH. This cohort has been divided into a discovery cohort comprising 50 Spanish patients and then in a validation cohort of 71 Italian patients. Blood bacterial DNA was analyzed both quantitatively by 16S ribosomal DNA (rDNA) quantitative polymerase chain reaction and qualitatively by 16S rDNA targeted metagenomic sequencing and functional metagenome prediction. Spanish plasma bile acid contents were analyzed by liquid chromatography/mass spectrometry. The 16S rDNA concentration was significantly higher in patients of the discovery cohort with LF. By 16S sequencing, we found specific differences in the proportion of several bacterial taxa in both blood and feces that correlate with the presence of LF, thus defining a specific signature of the liver disease. Several secondary/primary bile acid ratios were also decreased with LF in the discovery cohort. We confirmed, in the validation cohort, the correlation between blood 16S rDNA concentration and LF, whereas we did not confirm the specific bacterial taxa signature, despite a similar trend in patients with more‐severe fibrosis. Conclusion: Changes in blood microbiota are associated with LF in obese patients. Blood microbiota analysis provides potential biomarkers for the detection of LF in this population. (Hepatology 2016;64:2015‐2027). |
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| AbstractList | The early detection of liver fibrosis among patients with nonalcoholic fatty liver disease (NAFLD) is an important clinical need. In view of the suggested role played by bacterial translocation in liver disease and obesity, we sought to investigate the relationship between blood microbiota and liver fibrosis (LF) in European cohorts of patients with severe obesity. We carried out a cross-sectional study of obese patients, well characterized with respect to the severity of the NAFLD, in the cohort FLORINASH. This cohort has been divided into a discovery cohort comprising 50 Spanish patients and then in a validation cohort of 71 Italian patients. Blood bacterial DNA was analyzed both quantitatively by 16S ribosomal DNA (rDNA) quantitative polymerase chain reaction and qualitatively by 16S rDNA targeted metagenomic sequencing and functional metagenome prediction. Spanish plasma bile acid contents were analyzed by liquid chromatography/mass spectrometry. The 16S rDNA concentration was significantly higher in patients of the discovery cohort with LF. By 16S sequencing, we found specific differences in the proportion of several bacterial taxa in both blood and feces that correlate with the presence of LF, thus defining a specific signature of the liver disease. Several secondary/primary bile acid ratios were also decreased with LF in the discovery cohort. We confirmed, in the validation cohort, the correlation between blood 16S rDNA concentration and LF, whereas we did not confirm the specific bacterial taxa signature, despite a similar trend in patients with more-severe fibrosis.The early detection of liver fibrosis among patients with nonalcoholic fatty liver disease (NAFLD) is an important clinical need. In view of the suggested role played by bacterial translocation in liver disease and obesity, we sought to investigate the relationship between blood microbiota and liver fibrosis (LF) in European cohorts of patients with severe obesity. We carried out a cross-sectional study of obese patients, well characterized with respect to the severity of the NAFLD, in the cohort FLORINASH. This cohort has been divided into a discovery cohort comprising 50 Spanish patients and then in a validation cohort of 71 Italian patients. Blood bacterial DNA was analyzed both quantitatively by 16S ribosomal DNA (rDNA) quantitative polymerase chain reaction and qualitatively by 16S rDNA targeted metagenomic sequencing and functional metagenome prediction. Spanish plasma bile acid contents were analyzed by liquid chromatography/mass spectrometry. The 16S rDNA concentration was significantly higher in patients of the discovery cohort with LF. By 16S sequencing, we found specific differences in the proportion of several bacterial taxa in both blood and feces that correlate with the presence of LF, thus defining a specific signature of the liver disease. Several secondary/primary bile acid ratios were also decreased with LF in the discovery cohort. We confirmed, in the validation cohort, the correlation between blood 16S rDNA concentration and LF, whereas we did not confirm the specific bacterial taxa signature, despite a similar trend in patients with more-severe fibrosis.Changes in blood microbiota are associated with LF in obese patients. Blood microbiota analysis provides potential biomarkers for the detection of LF in this population. (Hepatology 2016;64:2015-2027).CONCLUSIONChanges in blood microbiota are associated with LF in obese patients. Blood microbiota analysis provides potential biomarkers for the detection of LF in this population. (Hepatology 2016;64:2015-2027). The early detection of liver fibrosis among patients with nonalcoholic fatty liver disease (NAFLD) is an important clinical need. In view of the suggested role played by bacterial translocation in liver disease and obesity, we sought to investigate the relationship between blood microbiota and liver fibrosis (LF) in European cohorts of patients with severe obesity. We carried out a cross‐sectional study of obese patients, well characterized with respect to the severity of the NAFLD, in the cohort FLORINASH. This cohort has been divided into a discovery cohort comprising 50 Spanish patients and then in a validation cohort of 71 Italian patients. Blood bacterial DNA was analyzed both quantitatively by 16S ribosomal DNA (rDNA) quantitative polymerase chain reaction and qualitatively by 16S rDNA targeted metagenomic sequencing and functional metagenome prediction. Spanish plasma bile acid contents were analyzed by liquid chromatography/mass spectrometry. The 16S rDNA concentration was significantly higher in patients of the discovery cohort with LF. By 16S sequencing, we found specific differences in the proportion of several bacterial taxa in both blood and feces that correlate with the presence of LF, thus defining a specific signature of the liver disease. Several secondary/primary bile acid ratios were also decreased with LF in the discovery cohort. We confirmed, in the validation cohort, the correlation between blood 16S rDNA concentration and LF, whereas we did not confirm the specific bacterial taxa signature, despite a similar trend in patients with more‐severe fibrosis. Conclusion: Changes in blood microbiota are associated with LF in obese patients. Blood microbiota analysis provides potential biomarkers for the detection of LF in this population. (Hepatology 2016;64:2015‐2027). The early detection of liver fibrosis among patients with nonalcoholic fatty liver disease (NAFLD) is an important clinical need. In view of the suggested role played by bacterial translocation in liver disease and obesity, we sought to investigate the relationship between blood microbiota and liver fibrosis (LF) in European cohorts of patients with severe obesity. We carried out a cross‐sectional study of obese patients, well characterized with respect to the severity of the NAFLD, in the cohort FLORINASH. This cohort has been divided into a discovery cohort comprising 50 Spanish patients and then in a validation cohort of 71 Italian patients. Blood bacterial DNA was analyzed both quantitatively by 16S ribosomal DNA (rDNA) quantitative polymerase chain reaction and qualitatively by 16S rDNA targeted metagenomic sequencing and functional metagenome prediction. Spanish plasma bile acid contents were analyzed by liquid chromatography/mass spectrometry. The 16S rDNA concentration was significantly higher in patients of the discovery cohort with LF. By 16S sequencing, we found specific differences in the proportion of several bacterial taxa in both blood and feces that correlate with the presence of LF, thus defining a specific signature of the liver disease. Several secondary/primary bile acid ratios were also decreased with LF in the discovery cohort. We confirmed, in the validation cohort, the correlation between blood 16S rDNA concentration and LF, whereas we did not confirm the specific bacterial taxa signature, despite a similar trend in patients with more‐severe fibrosis. Conclusion: Changes in blood microbiota are associated with LF in obese patients. Blood microbiota analysis provides potential biomarkers for the detection of LF in this population. (H epatology 2016;64:2015‐2027). The early detection of liver fibrosis among patients with nonalcoholic fatty liver disease (NAFLD) is an important clinical need. In view of the suggested role played by bacterial translocation in liver disease and obesity, we sought to investigate the relationship between blood microbiota and liver fibrosis (LF) in European cohorts of patients with severe obesity. We carried out a cross-sectional study of obese patients, well characterized with respect to the severity of the NAFLD, in the cohort FLORINASH. This cohort has been divided into a discovery cohort comprising 50 Spanish patients and then in a validation cohort of 71 Italian patients. Blood bacterial DNA was analyzed both quantitatively by 16S ribosomal DNA (rDNA) quantitative polymerase chain reaction and qualitatively by 16S rDNA targeted metagenomic sequencing and functional metagenome prediction. Spanish plasma bile acid contents were analyzed by liquid chromatography/mass spectrometry. The 16S rDNA concentration was significantly higher in patients of the discovery cohort with LF. By 16S sequencing, we found specific differences in the proportion of several bacterial taxa in both blood and feces that correlate with the presence of LF, thus defining a specific signature of the liver disease. Several secondary/primary bile acid ratios were also decreased with LF in the discovery cohort. We confirmed, in the validation cohort, the correlation between blood 16S rDNA concentration and LF, whereas we did not confirm the specific bacterial taxa signature, despite a similar trend in patients with more-severe fibrosis. Changes in blood microbiota are associated with LF in obese patients. Blood microbiota analysis provides potential biomarkers for the detection of LF in this population. (Hepatology 2016;64:2015-2027). |
| Author | Courtney, Michael Puig, Josep Amar, Jacques Servant, Florence Federici, Massimo Fernández‐Real, José‐Manuel Ortiz, Maria Rosa Serino, Matteo Brunet, Anne‐Claire Burcelin, Rémy Valle, Carine Benyahya, Salah Lelouvier, Benjamin Païssé, Sandrine |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/27639192$$D View this record in MEDLINE/PubMed |
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| Copyright | 2016 by the American Association for the Study of Liver Diseases. 2016 by the American Association for the Study of Liver Diseases |
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| Language | English |
| License | 2016 by the American Association for the Study of Liver Diseases. |
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| Notes | These authors contributed equally. Potential conflict of interest: Dr. Amar consults for, received grants from, and owns stock in Vaiomer. Dr. Courtney is employed by and owns stock in Vaiomer. Dr. Burcelin consults for, received grants from, and owns stock in Vaiomer. Mr. Benyahya is employed by Vaiomer. Dr. Paisse is employed by Vaiomer. Dr. Lelouvier is employed by Vaiomer. Mrs. Valle is employed by Vaiomer. Mrs. Servant is employed by Vaiomer. Dr. Brunet is employed by Vaiomer. The FLORINASH cohort is funded by the European Union as part of the 7th framework programme under grant agreement no. HEALTH‐F2‐2009‐241913. The metagenomic analysis was carried out with the financial support of DAEI (Direction de l'Action Économique et de l'Innovation) of the Midi‐Pyrénées Region, France. This study was supported by the Fondo Europeo de Desarrollo Regional (FEDER) and CIBER de la Fisiopatología de la Obesidad y la Nutrición (CIBERobn), an initiative of the Instituto de Salud Carlos III (ISCIII). ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 |
| OpenAccessLink | https://aasldpubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1002/hep.28829 |
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| PublicationDate | December 2016 2016-12-00 20161201 |
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| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States – name: Hoboken |
| PublicationTitle | Hepatology (Baltimore, Md.) |
| PublicationTitleAlternate | Hepatology |
| PublicationYear | 2016 |
| Publisher | Wolters Kluwer Health, Inc |
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diagnostic accuracy of non‐invasive tests for liver disease severity publication-title: Ann Med doi: 10.3109/07853890.2010.518623 – volume: 34 start-page: 274 year: 2011 ident: hep28829-bib-0003-20241017 article-title: Systematic review: the epidemiology and natural history of non‐alcoholic fatty liver disease and non‐alcoholic steatohepatitis in adults publication-title: Aliment Pharmacol Ther doi: 10.1111/j.1365-2036.2011.04724.x – volume: 31 start-page: 290 year: 2005 ident: hep28829-bib-0011-20241017 article-title: Effect of acute alcohol ingestion prior to burn injury on intestinal bacterial growth and barrier function publication-title: Burns doi: 10.1016/j.burns.2004.09.021 – volume: 24 start-page: 248 year: 2009 ident: hep28829-bib-0007-20241017 article-title: Clinical features and outcomes of cirrhosis due to non‐alcoholic steatohepatitis compared with cirrhosis caused by chronic hepatitis C publication-title: J Gastroenterol Hepatol doi: 10.1111/j.1440-1746.2008.05640.x – volume: 158 start-page: 250 year: 2014 ident: hep28829-bib-0035-20241017 article-title: Conducting a microbiome study publication-title: Cell doi: 10.1016/j.cell.2014.06.037 – volume: 36 start-page: 524 year: 2015 ident: hep28829-bib-0050-20241017 article-title: Nitric oxide in liver diseases publication-title: Trends Pharmacol Sci doi: 10.1016/j.tips.2015.05.001 – volume: 15 start-page: 1148 year: 2005 ident: hep28829-bib-0004-20241017 article-title: Predictors of nonalcoholic steatohepatitis (NASH) in obese patients undergoing gastric bypass publication-title: Obes Surg doi: 10.1381/0960892055002347 – volume: 279 start-page: 284 year: 2014 ident: hep28829-bib-0047-20241017 article-title: Modeling toxicodynamic effects of trichloroethylene on liver in mouse model of autoimmune hepatitis publication-title: Toxicol Appl Pharmacol doi: 10.1016/j.taap.2014.07.003 – volume: 12 start-page: R60 year: 2011 ident: hep28829-bib-0032-20241017 article-title: Metagenomic biomarker discovery and explanation publication-title: Genome Biol doi: 10.1186/gb-2011-12-6-r60 – volume: 15 start-page: 61 issue: Suppl 3 year: 2013 ident: hep28829-bib-0023-20241017 article-title: Metagenome and metabolism: the tissue microbiota hypothesis publication-title: Diabetes Obes Metab – volume: 513 start-page: 59 year: 2014 ident: hep28829-bib-0025-20241017 article-title: Alterations of the human gut microbiome in liver cirrhosis publication-title: Nature doi: 10.1038/nature13568 – volume: 55 start-page: 2005 year: 2012 ident: hep28829-bib-0008-20241017 article-title: The diagnosis and management of non‐alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association publication-title: Hepatology doi: 10.1002/hep.25762 – volume: 29 start-page: 535 year: 2005 ident: hep28829-bib-0042-20241017 article-title: Detection of microbial DNA in the blood of surgical patients 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| SubjectTerms | Bile Cross-Sectional Studies Feces - microbiology Female Hepatology Humans Liver Cirrhosis - blood Liver Cirrhosis - complications Liver Cirrhosis - microbiology Liver diseases Male Microbiota Middle Aged Obesity Obesity - blood Obesity - complications Obesity - microbiology Pilot Projects |
| Title | Changes in blood microbiota profiles associated with liver fibrosis in obese patients: A pilot analysis |
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