The authors declare that they have no competing interests. Mean AUC ROC value for five times repeated, 10-fold cross validation. CAS
ME/CFS samples showed lower relative abundance of Firmicutes (35 %) (Fig. and fit the Fukuda diagnostic criteria [1]. Manage cookies/Do not sell my data we use in the preference centre. 2c, d). Our data supports the hypothesis of increased MT in the ME/CFS group as evidenced by (i) significantly raised levels of plasma LPS and (ii) significantly higher levels of sCD14 and LBP, as indicators of direct LPS stimulation. Because of the frequent occurrence of GI disturbances, as well as these prior reports of abnormalities, we investigated the diversity and composition of the gut microbiota of ME/CFS patients in comparison to healthy individuals. In contrast, we amplified the V4 hypervariable region of the 16S rRNA gene, sequenced amplicons using the MiSeq Illumina platform, obtained an average of many more reads/sample (98,000), and compared the resulting sequences to a different database, the Greengenes non-redundant reference database [31]. Sartor RB. Rev Infect Dis. Machiels K, Joossens M, Sabino J, De Preter V, Arijs I, Eeckhaut V, et al. Sartor RB. Springer Nature. Matto J, Maunuksela L, Kajander K, Palva A, Korpela R, Kassinen A, et al. She examined natural killer cell function and abnormalities in catecholamine response in these patients and then opened a private practice to provide medical support to a growing CFS population in the New York and New Jersey area. Sci Rep. 2015;5:12693. Among the 48 ME/CFS patients in the study, 19 indicated a gradual and 25 stated a sudden onset. This site uses cookies. We amplified 16S rRNA genes (V4 hypervariable region) from bulk DNA using the 515F and 806R primers as previously described [67] prior to sequencing. Res Immunol. Riedl A, Schmidtmann M, Stengel A, Goebel M, Wisser AS, Klapp BF, et al. The replicate PCR reactions were combined and purified using a magnetic bead system (Mag-Bind EZPure, Omega Bio-Tek, Norcross, GA). 2006;55(Pt 5):625–33. (XLSX 61 kb). (q = 0.016), Faecalibacterium prausnitzii (q = 0.014), and Ruminococcus spp.
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Komaroff AL, Buchwald D. Symptoms and signs of chronic fatigue syndrome. 2008;197(3):435–8. Through deep sequencing of bacterial rRNA markers, we identified differences between the gut microbiomes of healthy individuals and patients with ME/CFS. PubMed Within the Firmicutes, at the family level, Ruminococcaceae were lower in the ME/CFS samples (16 vs. 11 % in ME/CFS and healthy individuals respectively) (Fig.
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Levels of hsCRP were higher in the ME/CFS population in comparison to healthy controls (1.38 and 1.21 mg/L, respectively), but the difference was not statistically significant (P = 0.15, Fig. ME/CFS subjects completed the SF-36 form (Additional file 1: Figure S1) and Bell’s Disability scale (Table 1). 2009;2(2):100–2. Maukonen J, Satokari R, Matto J, Soderlund H, Mattila-Sandholm T, Saarela M. Prevalence and temporal stability of selected clostridial groups in irritable bowel syndrome in relation to predominant faecal bacteria. Nature. Giloteaux, L., Goodrich, J.K., Walters, W.A. Please be aware that this might heavily reduce the functionality and appearance of our site. Next, we analyzed the associations among biomarker measurements in the ME/CFS population. Washington, D.C: The National Academies Press; 2015. Article Click to enable/disable _gat_* - Google Analytics Cookie. Infect Immun. 2014;588(22):4223–33. Non-invasive mapping of the gastrointestinal microbiota identifies children with inflammatory bowel disease. Google Scholar. None of the other parameters tested, i.e., sex, BMI, or clinical data revealed clustering (data not shown). Founding members have served on the expert panel that authored the National Academy of Medicine’s 2015 report on ME/CFS, have authored primers on clinical management, have contributed to the CDC’s medical education initiatives, and have served on the Health and Human Services’ CFS Advisory Committee before it was sunsetted in 2018. Values of P < 0.05 were considered statistically significant. PubMed Google Scholar. https://doi.org/10.1186/s40168-016-0171-4, DOI: https://doi.org/10.1186/s40168-016-0171-4. Dr. Dan Peterson – Internal Medicine, NV. Cytokine network analysis of cerebrospinal fluid in myalgic encephalomyelitis/chronic fatigue syndrome.
In addition to detecting significant features, LEfSe also ranks features by effect size, which put features explaining most of the biological difference at top (Segata et al. Mucosal Immunol. Papa E, Docktor M, Smillie C, Weber S, Preheim SP, Gevers D, et al. Additionally, processing microbial sequencing data without including BMI and blood inflammatory marker levels results in 70, 75, and 72 % classification accuracy for genus, species, and OTU-level data respectively (confusion matrices available in Additional file 4: Figure S3). PCR amplicons were quantified using the QuantiT PicoGreen dsDNA Assay Kit (Invitrogen, Carlsbad, CA). If there is damage to the gut mucosa, microbial translocation could increase, altering antimicrobial regulators and dysregulating the innate immune system. Developing therapeutic interventions aimed at reducing local inflammation, restoring gastrointestinal tract immunity and integrity and modifying the intestinal microbiome may ameliorate ME/CFS symptoms in a number of affected patients. You can check these in your browser security settings. Gastroenterology. 2013;339(6120):708–11. Susan M. Levine, M.D. Our analysis showed that within-sample diversity is lower in the ME/CFS specimens compared to controls. 1. We quantified plasma levels of hsCRP, lipopolysaccharides (LPS) as a marker of microbial translocation (MT) and plasma intestinal fatty acid binding protein (I-FABP) as a marker for gastrointestinal tract damage in both groups. Biometrika. Role of lipopolysaccharide (LPS), interleukin-1, interleukin-6, tumor necrosis factor, and dexamethasone in regulation of LPS-binding protein expression in normal hepatocytes and hepatocytes from LPS-treated rats. Regardless of disease state, bacteria belonging to the Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria phyla represented the vast majority of sequences identified. Click to enable/disable Google reCaptcha. Anaerobe.
But this will always prompt you to accept/refuse cookies when revisiting our site. et al. Sinai Hospital, respectively. Two reports suggest altered gut microbiota in ME/CFS patients. All work involving human subjects was approved by the Cornell University Institutional Review Board. 2011;12(6):R60. Gastroenterology. Abnormal immune activation can be caused by translocation of microbes from an inflamed gut [18]. 2007;104(34):13780–5.
Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. Google Scholar. Since these providers may collect personal data like your IP address we allow you to block them here. We thank the subjects for providing samples and information for the study and Lin Lin for technical assistance.
Bell SystTech J. Sokol H, Pigneur B, Watterlot L, Lakhdari O, Bermudez-Humaran LG, Gratadoux JJ, et al. The dynamics of gut-associated microbial communities during inflammation. Briefly, 100 μl of each plasma sample was diluted in 200 μl of β-G-Blocker (Lonza Group Ltd, Allendale, NJ) to eliminate the possibility of false positives. Here, we profiled gut microbial diversity by sequencing 16S ribosomal ribonucleic acid (rRNA) genes from stool as well as inflammatory markers from serum for cases (n = 48) and controls (n = 39). For more information, see the Site Privacy Policy. Pelsers MMAL, Hermens WT, Glatz JFC. Susan M. Levine, M.D., graduated from Albert Einstein School of Medicine in 1981 and completed a residency in Internal Medicine at Montefiore Hospital in the Bronx followed by two fellowships in Infectious Diseases and Allergy and Immunology at Memorial Sloan Kettering Cancer Center and Mt. LEfSe analysis was performed under the following conditions: the α value for the factorial Kruskal-Wallis test among classes was 0.05 and the threshold on the logarithmic LDA score for discriminative features was 2.0. We used both the weighted and unweighted UniFrac distance metrics as measures of between-sample (beta) diversity and applied principal coordinates analysis (PCoA) to visualize patterns of diversity. RL and MH contributed to study design. We also examined a set of inflammatory markers in blood: C-reactive protein (CRP), intestinal fatty acid-binding protein (I-FABP), lipopolysaccharide (LPS), LPS-binding protein (LBP), and soluble CD14 (sCD14). Inflamm Bowel Dis. Endotoxaemia in active Crohn’s disease. Gastroenterology.
36-Item Short Form Health Survey (SF-36) profiles from studies reporting SF-36 scores for individuals with a ME/CFS diagnosis. Study population characteristics. With OTUs collapsed at the species level, the average accuracy was 0.80 with a standard deviation of 0.11. Gut. Within the microbial community cluster, there appears to be no clear difference in beta-diversity between the ME/CFS group and healthy group using both weighted (Additional file 2: Figure S2a) and unweighted (Additional file 2: Figure S2b) UniFrac distance matrices. Results of LPS measured were expressed in picograms per milliliter (1 EU/ml = 100 pg/ml).
Winter SE, Lopez CA, Baumler AJ.
(PDF 1170 kb), Per-sample metadata mapping file used throughout the QIIME pipeline. 2005;54(2):242–9. Hornig M, Montoya JG, Klimas NG, Levine S, Felsenstein D, Bateman L, et al. Gut. PubMed Central Wu X, Ma C, Han L, Nawaz M, Gao F, Zhang X, et al. 2002;122(4):1140–56. Binning sequences using a pairwise identity threshold of 97 %, we obtained an average of 1330 ± 423 operational taxonomic units (OTUs) per sample. 1992;61:1–10. Molecular characterisation of the faecal microbiota in patients with type II diabetes. The distribution of plasma hsCRP, LPS and I-FABP is shown in Fig. 1d, e, Table 2). Qin J, Li Y, Cai Z, Li S, Zhu J, Zhang F, et al. ME/CFS patients had significantly higher plasma LPS levels than healthy individuals (median ME/CFS—119.43 pg/mL vs. controls—74.74 pg/mL, P < 0.0005, Fig. The authors amplified the V5 and V6 hypervariable 16S rRNA regions and sequenced the amplicons using a Roche FLX 454 sequencer, which resulted in an average of only 6000–7000 reads/sample. CAS The cause of ME/CFS is unknown, but gut dysbiosis could be contributing to some of the symptoms and their severity. 4a) and higher relative abundance of Proteobacteria (8 %), due almost entirely to a twofold increase in the Proteobacteria family Enterobacteriaceae (6 vs. 3 % for ME/CFS and healthy individuals, respectively) (Fig. Our results indicate dysbiosis of the gut microbiota in this disease and further suggest an increased incidence of microbial translocation, which may play a role in inflammatory symptoms in ME/CFS. Medication use by persons with chronic fatigue syndrome: results of a randomized telephone survey in Wichita, Kansas. 3a). [11] described higher levels of D-lactic acid producing Enterococcus and Streptococcus spp. Many of the common symptoms reported by ME/CFS patients are characteristic of inflammatory illnesses [15]. Tana C, Umesaki Y, Imaoka A, Handa T, Kanazawa M, Fukudo S. Altered profiles of intestinal microbiota and organic acids may be the origin of symptoms in irritable bowel syndrome. 2002;122(1):44–54. CAS Using this approach, we were able to classify unlabeled samples with some degree of accuracy, as demonstrated by the high AUC ROC value obtained (0.8928) at the genus level. 1986;27(7):814–20. BMI, age, and gender of subjects were recorded. Faith DP.
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