title: Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome.
abstract: Gastrointestinal disturbances are among symptoms commonly reported by individuals diagnosed with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). However, whether ME/CFS is associated with an altered microbiome has remained uncertain. 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). 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).
  
  
  
  We observed elevated levels of some blood markers for microbial translocation in ME/CFS patients; levels of LPS, LBP, and sCD14 were elevated in ME/CFS subjects. Levels of LBP correlated with LPS and sCD14 and LPS levels correlated with sCD14. Through deep sequencing of bacterial rRNA markers, we identified differences between the gut microbiomes of healthy individuals and patients with ME/CFS. We observed that bacterial diversity was decreased in the ME/CFS specimens compared to controls, in particular, a reduction in the relative abundance and diversity of members belonging to the Firmicutes phylum. In the patient cohort, we find less diversity as well as increases in specific species often reported to be pro-inflammatory species and reduction in species frequently described as anti-inflammatory. Using a machine learning approach trained on the data obtained from 16S rRNA and inflammatory markers, individuals were classified correctly as ME/CFS with a cross-validation accuracy of 82.93 %.
  
  
  
  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.
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Giloteaux
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA.|Department of Microbiology, Cornell University, Ithaca, NY, USA.
authors.forename: Julia K
authors.initials: JK
authors.lastname: Goodrich
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA.|Department of Microbiology, Cornell University, Ithaca, NY, USA.
authors.forename: William A
authors.initials: WA
authors.lastname: Walters
authors.affiliation: Private Practice, New York, NY, USA.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Levine
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA.|Department of Microbiology, Cornell University, Ithaca, NY, USA.
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Ley
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA. mrh5@cornell.edu.
authors.forename: Maureen R
authors.initials: MR
authors.lastname: Hanson
mesh_terms: D000209:Acute-Phase Proteins / Q000378:metabolism; D000328:Adult; D000368:Aged; D001419:Bacteria / Q000145:classification*; D044822:Biodiversity; D002097:C-Reactive Protein / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D016022:Case-Control Studies; D004275:DNA, Ribosomal / Q000032:analysis; D064806:Dysbiosis / Q000175:diagnosis*; D015673:Fatigue Syndrome, Chronic / Q000378:metabolism / Q000382:microbiology*; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism; D005243:Feces / Q000382:microbiology; D005260:Female; D000068536:Bacillota / Q000302:isolation & purification; D000069196:Gastrointestinal Microbiome; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D010802:Phylogeny; D012336:RNA, Ribosomal, 16S / Q000032:analysis*; D017422:Sequence Analysis, DNA / Q000379:methods*; D055815:Young Adult; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D002097:C-Reactive Protein; D002352:Carrier Proteins; D004275:DNA, Ribosomal; D050556:Fatty Acid-Binding Proteins; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D012336:RNA, Ribosomal, 16S; D000099231:Lipopolysaccharide-Binding Protein
keywords: Beta-diversity; Chronic fatigue syndrome; Inflammation; Lipopolysaccharides; Microbial translocation; Microbiome; Myalgic encephalomyelitis