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Title: Alterations in the relative abundance of Faecalibacterium prausnitzii correlate with changes in fecal calprotectin in patients with ileal Crohn’s disease: a longitudinal study [Increasing abundance of Faecalibacterium prausnitzii associated with a reduced degree of intestinal inflammation in Crohn’s disease: A longitudinal study]

Abstract

Objectives: Crohn’s disease is characterized by a gut dysbiosis with decreased abundance of butyrate producers such as Faecalibacterium prausnitzii. Although F. prausnitzii secretes anti-inflammatory molecules, few studies have addressed the importance of F. prausnitzii in a longitudinal setting. We aimed to examine the relationship between temporal profiles of F. prausnitzii, the C. leptum group, overall butyrate production, and inflammatory activity. Material and methods: Fecal samples ( n = 59) were collected every third month from nine patients with ileal Crohn’s disease. The abundance of F. prausnitzii and C. leptum was quantified relative to the total amount of bacteria using quantitative-PCR. To assess butyrate production of gut microbiota, gene copy numbers of the butyryl-CoA:acetate-CoA transferase (BCoAT) gene were quantified by qPCR. The inflammatory activity was defined by fecal (f)-calprotectin. Results: No correlation between the relative abundance of F. prausnitzii, the C. leptum group, or copy numbers of the BCoAT gene, and f-calprotectin was observed in the total sample set. By analyzing alterations between consecutive samples, a negative correlation between changes in the relative abundance of F. prausnitzii and f-calprotectin was observed ( R = 0.39; p = .009). Changes in C. leptum ( R = 0.18, p = .23) and numbermore » of copies of the BCoAT gene ( R = 0.12; p = .42) did not correlate with f-calprotectin. Conclusions: There was an inverse correlation between temporal changes in the relative abundance of F. prausnitzii, but not overall butyrate producing capacity, and changes in inflammatory activity in ileal Crohn’s disease. These findings indicate that F. prausnitzii may play a role in gut homeostasis, even though causality is still to be demonstrated.« less

Authors:
ORCiD logo [1];  [1];  [2]; ORCiD logo [3];  [3];  [2];  [1];  [1]
  1. Örebro Univ., Örebro (Sweden)
  2. Karolinska Institutet, Stockholm (Sweden)
  3. Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1543275
Report Number(s):
PNNL-SA-139272
Journal ID: ISSN 0036-5521
Grant/Contract Number:  
AC05-76RL01830
Resource Type:
Accepted Manuscript
Journal Name:
Scandinavian Journal of Gastroenterology
Additional Journal Information:
Journal Volume: 54; Journal Issue: 5; Journal ID: ISSN 0036-5521
Publisher:
Taylor & Francis
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; Faecalibacterium prausnitzii; crohn's disease; Calprotectin; butyrate; dysbiosis

Citation Formats

Björkqvist, Olle, Repsilber, Dirk, Seifert, Maike, Brislawn, Colin J., Jansson, Janet K., Engstrand, Lars, Rangel, Ignacio, and Halfvarson, Jonas. Alterations in the relative abundance of Faecalibacterium prausnitzii correlate with changes in fecal calprotectin in patients with ileal Crohn’s disease: a longitudinal study [Increasing abundance of Faecalibacterium prausnitzii associated with a reduced degree of intestinal inflammation in Crohn’s disease: A longitudinal study]. United States: N. p., 2019. Web. doi:10.1080/00365521.2019.1599417.
Björkqvist, Olle, Repsilber, Dirk, Seifert, Maike, Brislawn, Colin J., Jansson, Janet K., Engstrand, Lars, Rangel, Ignacio, & Halfvarson, Jonas. Alterations in the relative abundance of Faecalibacterium prausnitzii correlate with changes in fecal calprotectin in patients with ileal Crohn’s disease: a longitudinal study [Increasing abundance of Faecalibacterium prausnitzii associated with a reduced degree of intestinal inflammation in Crohn’s disease: A longitudinal study]. United States. doi:10.1080/00365521.2019.1599417.
Björkqvist, Olle, Repsilber, Dirk, Seifert, Maike, Brislawn, Colin J., Jansson, Janet K., Engstrand, Lars, Rangel, Ignacio, and Halfvarson, Jonas. Wed . "Alterations in the relative abundance of Faecalibacterium prausnitzii correlate with changes in fecal calprotectin in patients with ileal Crohn’s disease: a longitudinal study [Increasing abundance of Faecalibacterium prausnitzii associated with a reduced degree of intestinal inflammation in Crohn’s disease: A longitudinal study]". United States. doi:10.1080/00365521.2019.1599417. https://www.osti.gov/servlets/purl/1543275.
@article{osti_1543275,
title = {Alterations in the relative abundance of Faecalibacterium prausnitzii correlate with changes in fecal calprotectin in patients with ileal Crohn’s disease: a longitudinal study [Increasing abundance of Faecalibacterium prausnitzii associated with a reduced degree of intestinal inflammation in Crohn’s disease: A longitudinal study]},
author = {Björkqvist, Olle and Repsilber, Dirk and Seifert, Maike and Brislawn, Colin J. and Jansson, Janet K. and Engstrand, Lars and Rangel, Ignacio and Halfvarson, Jonas},
abstractNote = {Objectives: Crohn’s disease is characterized by a gut dysbiosis with decreased abundance of butyrate producers such as Faecalibacterium prausnitzii. Although F. prausnitzii secretes anti-inflammatory molecules, few studies have addressed the importance of F. prausnitzii in a longitudinal setting. We aimed to examine the relationship between temporal profiles of F. prausnitzii, the C. leptum group, overall butyrate production, and inflammatory activity. Material and methods: Fecal samples (n = 59) were collected every third month from nine patients with ileal Crohn’s disease. The abundance of F. prausnitzii and C. leptum was quantified relative to the total amount of bacteria using quantitative-PCR. To assess butyrate production of gut microbiota, gene copy numbers of the butyryl-CoA:acetate-CoA transferase (BCoAT) gene were quantified by qPCR. The inflammatory activity was defined by fecal (f)-calprotectin. Results: No correlation between the relative abundance of F. prausnitzii, the C. leptum group, or copy numbers of the BCoAT gene, and f-calprotectin was observed in the total sample set. By analyzing alterations between consecutive samples, a negative correlation between changes in the relative abundance of F. prausnitzii and f-calprotectin was observed (R = 0.39; p = .009). Changes in C. leptum (R = 0.18, p = .23) and number of copies of the BCoAT gene (R = 0.12; p = .42) did not correlate with f-calprotectin. Conclusions: There was an inverse correlation between temporal changes in the relative abundance of F. prausnitzii, but not overall butyrate producing capacity, and changes in inflammatory activity in ileal Crohn’s disease. These findings indicate that F. prausnitzii may play a role in gut homeostasis, even though causality is still to be demonstrated.},
doi = {10.1080/00365521.2019.1599417},
journal = {Scandinavian Journal of Gastroenterology},
number = 5,
volume = 54,
place = {United States},
year = {2019},
month = {3}
}

Journal Article:
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Figures / Tables:

Table 1 Table 1: Thermal profiles for quantitative PCR

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Works referenced in this record:

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Dysbiosis, inflammation, and response to treatment: a longitudinal study of pediatric subjects with newly diagnosed inflammatory bowel disease
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    Works referencing / citing this record:

    Role of the faecal stream in the maintenance of Crohn's colitis.
    journal, March 1985


    Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
    journal, December 2001


    Impaired butyrate oxidation in ulcerative colitis is due to decreased butyrate uptake and a defect in the oxidation pathway*
    journal, January 2012

    • De Preter, Vicky; Arijs, Ingrid; Windey, Karen
    • Inflammatory Bowel Diseases, Vol. 18, Issue 6
    • DOI: 10.1002/ibd.21894

    Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients
    journal, October 2008

    • Sokol, H.; Pigneur, B.; Watterlot, L.
    • Proceedings of the National Academy of Sciences, Vol. 105, Issue 43
    • DOI: 10.1073/pnas.0804812105

    Dynamics of the human gut microbiome in inflammatory bowel disease
    journal, February 2017

    • Halfvarson, Jonas; Brislawn, Colin J.; Lamendella, Regina
    • Nature Microbiology, Vol. 2, Issue 5
    • DOI: 10.1038/nmicrobiol.2017.4

    The use of next generation sequencing in the diagnosis and typing of respiratory infections
    journal, August 2015


    Fecal Acetate Is Inversely Related to Acetate Absorption from the Human Rectum and Distal Colon
    journal, October 2003

    • Vogt, Janet A.; Wolever, Thomas M. S.
    • The Journal of Nutrition, Vol. 133, Issue 10
    • DOI: 10.1093/jn/133.10.3145

    Toward an Integrated Clinical, Molecular and Serological Classification of Inflammatory Bowel Disease: Report of a Working Party of the 2005 Montreal World Congress of Gastroenterology
    journal, January 2005

    • Silverberg, Mark S.; Satsangi, Jack; Ahmad, Tariq
    • Canadian Journal of Gastroenterology, Vol. 19, Issue suppl a
    • DOI: 10.1155/2005/269076

    Diversity, metabolism and microbial ecology of butyrate-producing bacteria from the human large intestine
    journal, May 2009


    Comparative analysis of fecal DNA extraction methods with phylogenetic microarray: Effective recovery of bacterial and archaeal DNA using mechanical cell lysis
    journal, May 2010

    • Salonen, Anne; Nikkilä, Janne; Jalanka-Tuovinen, Jonna
    • Journal of Microbiological Methods, Vol. 81, Issue 2
    • DOI: 10.1016/j.mimet.2010.02.007

    Universality of human microbial dynamics
    journal, June 2016

    • Bashan, Amir; Gibson, Travis E.; Friedman, Jonathan
    • Nature, Vol. 534, Issue 7606
    • DOI: 10.1038/nature18301

    Correlation Between Concentrations of Fecal Calprotectin and Outcomes of Patients With Ulcerative Colitis in a Phase 2 Trial
    journal, January 2016


    Determinants of Reduced Genetic Capacity for Butyrate Synthesis by the Gut Microbiome in Crohn’s Disease and Ulcerative Colitis
    journal, October 2017

    • Laserna-Mendieta, Emilio J.; Clooney, Adam G.; Carretero-Gomez, Julián F.
    • Journal of Crohn's and Colitis, Vol. 12, Issue 2
    • DOI: 10.1093/ecco-jcc/jjx137

    Active Crohnʼs disease and ulcerative colitis can be specifically diagnosed and monitored based on the biostructure of the fecal flora
    journal, January 2008

    • Swidsinski, Alexander; Loening-Baucke, Vera; Vaneechoutte, Mario
    • Inflammatory Bowel Diseases, Vol. 14, Issue 2
    • DOI: 10.1002/ibd.20330

    Degree of colitis correlates with microbial composition and cytokine responses in colon and caecum of Gαi2-deficient mice
    journal, May 2016

    • Rangel, Ignacio; Ganda Mall, John Peter; Willén, Roger
    • FEMS Microbiology Ecology, Vol. 92, Issue 7
    • DOI: 10.1093/femsec/fiw098

    Dynamics of metatranscription in the inflammatory bowel disease gut microbiome
    journal, January 2018

    • Schirmer, Melanie; Franzosa, Eric A.; Lloyd-Price, Jason
    • Nature Microbiology, Vol. 3, Issue 3
    • DOI: 10.1038/s41564-017-0089-z

    A Pyrosequencing Study in Twins Shows That Gastrointestinal Microbial Profiles Vary With Inflammatory Bowel Disease Phenotypes
    journal, December 2010


    Low counts of Faecalibacterium prausnitzii in colitis microbiota
    journal, January 2009

    • Sokol, H.; Seksik, P.; Furet, J. P.
    • Inflammatory Bowel Diseases, Vol. 15, Issue 8
    • DOI: 10.1002/ibd.20903

    phyloseq: An R Package for Reproducible Interactive Analysis and Graphics of Microbiome Census Data
    journal, April 2013


    Faecalibacterium prausnitzii Produces Butyrate to Maintain Th17/Treg Balance and to Ameliorate Colorectal Colitis by Inhibiting Histone Deacetylase 1
    journal, May 2018

    • Zhou, Lixing; Zhang, Mingming; Wang, Yuming
    • Inflammatory Bowel Diseases, Vol. 24, Issue 9
    • DOI: 10.1093/ibd/izy182

    Dysbiosis of the faecal microbiota in patients with Crohn's disease and their unaffected relatives
    journal, January 2011


    Twin studies reveal specific imbalances in the mucosa-associated microbiota of patients with ileal Crohnʼs disease
    journal, January 2009

    • Willing, Ben; Halfvarson, Jonas; Dicksved, Johan
    • Inflammatory Bowel Diseases, Vol. 15, Issue 5
    • DOI: 10.1002/ibd.20783

    Reduced Abundance of Butyrate-Producing Bacteria Species in the Fecal Microbial Community in Crohn's Disease
    journal, January 2016

    • Takahashi, Kenichiro; Nishida, Atsushi; Fujimoto, Takehide
    • Digestion, Vol. 93, Issue 1
    • DOI: 10.1159/000441768

    Classification of Inflammatory Bowel Disease
    journal, January 1989


    Dysbiotic gut microbiota causes transmissible Crohn's disease-like ileitis independent of failure in antimicrobial defence
    journal, April 2015


    Dysbiosis, inflammation, and response to treatment: a longitudinal study of pediatric subjects with newly diagnosed inflammatory bowel disease
    journal, July 2016


    The gut microbiota of siblings offers insights into microbial pathogenesis of inflammatory bowel disease
    journal, January 2017


    Potential beneficial effects of butyrate in intestinal and extraintestinal diseases
    journal, January 2011


    Characteristics of Faecal Microbiota in Paediatric Crohn’s Disease and Their Dynamic Changes During Infliximab Therapy
    journal, November 2017

    • Wang, Yizhong; Gao, Xuefeng; Ghozlane, Amine
    • Journal of Crohn's and Colitis, Vol. 12, Issue 3
    • DOI: 10.1093/ecco-jcc/jjx153

    The prognostic significance of faecal calprotectin in patients with inactive inflammatory bowel disease
    journal, July 2016

    • Zhulina, Y.; Cao, Y.; Amcoff, K.
    • Alimentary Pharmacology & Therapeutics, Vol. 44, Issue 5
    • DOI: 10.1111/apt.13731

    The Treatment-Naive Microbiome in New-Onset Crohn’s Disease
    journal, March 2014


    The presence of the anti-inflammatory protein MAM, from Faecalibacterium prausnitzii , in the intestinal ecosystem
    journal, December 2015