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Fecal microbiome analysis as a diagnostic test for diverticulitis

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Abstract

Disease-specific variations in intestinal microbiome composition have been found for a number of intestinal disorders, but little is known about diverticulitis. The purpose of this study was to compare the fecal microbiota of diverticulitis patients with control subjects from a general gastroenterological practice and to investigate the feasibility of predictive diagnostics based on complex microbiota data. Thirty-one patients with computed tomography (CT)-proven left-sided uncomplicated acute diverticulitis were included and compared with 25 control subjects evaluated for a range of gastrointestinal indications. A high-throughput polymerase chain reaction (PCR)-based profiling technique (IS-pro) was performed on DNA isolates from baseline fecal samples. Differences in bacterial phylum abundance and diversity (Shannon index) of the resulting profiles were assessed by conventional statistics. Dissimilarity in microbiome composition was analyzed with principal coordinate analysis (PCoA) based on cosine distance measures. To develop a prediction model for the diagnosis of diverticulitis, we used cross-validated partial least squares discriminant analysis (PLS-DA). Firmicutes/Bacteroidetes ratios and Proteobacteria load were comparable among patients and controls (p = 0.20). The Shannon index indicated a higher diversity in diverticulitis for Proteobacteria (p < 0.00002) and all phyla combined (p = 0.002). PCoA based on Proteobacteria profiles resulted in visually separate clusters of patients and controls. The diagnostic accuracy of the cross-validated PLS-DA regression model was 84 %. The most discriminative species derived largely from the family Enterobacteriaceae. Diverticulitis patients have a higher diversity of fecal microbiota than controls from a mixed population, with the phylum Proteobacteria defining the difference. The analysis of intestinal microbiota offers a novel way to diagnose diverticulitis.

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Acknowledgments

We thank all the physicians and nurses in the participating centers (Academic Medical Center, Amsterdam; Meander Medical Center, Amersfoort; and Kennemer Gasthuis Hospital, Haarlem) for the accrual of patients and performing rectal swabs. We thank Malieka Degen for performing DNA isolation and the IS‐pro procedure on all fecal samples.

Conflict of interest

Financial support: The DIABOLO trial, from which the diverticulitis patient cohort was derived, was funded by the Netherlands Organisation for Health Research and Development of the Dutch Ministry of Health (ZonMw no. 171002303) and by the Dutch Gastrointestinal and Liver Foundation (MLDS no. WO08-54). The sponsors of the study had no role in the study design, data collection, data analysis, data interpretation, or writing of the manuscript.

Potential competing interest: AEB and PHS are involved in the IS-pro technology platform development. The other authors declare that no disclosures exist.

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Authors and Affiliations

  1. Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands

    L. Daniels & M. A. Boermeester

  2. Department of Medical Microbiology and Infection Control, VU University Medical Center, P.O. Box 7057, 1007 MB, Amsterdam, The Netherlands

    A. E. Budding, A. Eck & P. H. Savelkoul

  3. Department of Surgery, Spaarne Hospital, Hoofddorp, The Netherlands

    N. de Korte

  4. Department of Clinical Epidemiology and Biostatistics, VU University Medical Center, Amsterdam, The Netherlands

    J. A. Bogaards

  5. Department of Surgery, Kennemer Gasthuis Hospital, Haarlem, The Netherlands

    H. B. Stockmann

  6. Department of Surgery, Meander Medical Center, Amersfoort, The Netherlands

    E. C. Consten

  7. Department of Medical Microbiology, Maastricht University Medical Center, Maastricht, The Netherlands

    P. H. Savelkoul

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  1. L. Daniels
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  2. A. E. Budding
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Correspondence to A. E. Budding.

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Daniels, L., Budding, A.E., de Korte, N. et al. Fecal microbiome analysis as a diagnostic test for diverticulitis. Eur J Clin Microbiol Infect Dis 33, 1927–1936 (2014). https://doi.org/10.1007/s10096-014-2162-3

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  • DOI: https://doi.org/10.1007/s10096-014-2162-3

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