title: Untangling the relationship between diet and visceral fat mass through blood metabolomics and gut microbiome profiling.
abstract: Higher visceral fat mass (VFM) is associated with an increased risk for developing cardio-metabolic diseases. The mechanisms by which an unhealthy diet pattern may influence visceral fat (VF) development has yet to be examined through cutting-edge multi-omic methods. Therefore, our objective was to examine the dietary influences on VFM and identify gut microbiome and metabolite profiles that link food intakes to VFM.
  
  
  
  In 2218 twins with VFM, food intake and metabolomics data available we identified food intakes most strongly associated with VFM in 50% of the sample, then constructed and tested the 'VFM diet score' in the remainder of the sample. Using linear regression (adjusted for covariates, including body mass index and total fat mass), we investigated associations between the VFM diet score, the blood metabolomics profile and the fecal microbiome (n=889), and confirmed these associations with VFM. We replicated top findings in monozygotic (MZ) twins discordant (⩾1 s.d. apart) for VFM, matched for age, sex and the baseline genetic sequence.
  
  
  
  Four metabolites were associated with the VFM diet score and VFM: hippurate, alpha-hydroxyisovalerate, bilirubin (Z,Z) and butyrylcarnitine. We replicated associations between VFM and the diet score (beta (s.e.): 0.281 (0.091); P=0.002), butyrylcarnitine (0.199 (0.087); P=0.023) and hippurate (-0.297 (0.095); P=0.002) in VFM-discordant MZ twins. We identified a single species, Eubacterium dolichum to be associated with the VFM diet score (0.042 (0.011), P=8.47 × 10-5), VFM (0.057 (0.019), P=2.73 × 10-3) and hippurate (-0.075 (0.032), P=0.021). Moreover, higher blood hippurate was associated with elevated adipose tissue expression neuroglobin, with roles in cellular oxygen homeostasis (0.016 (0.004), P=9.82x10-6).
  
  
  
  We linked a dietary VFM score and VFM to E. dolichum and four metabolites in the blood. In particular, the relationship between hippurate, a metabolite derived from microbial metabolism of dietary polyphenols, and reduced VFM, the microbiome and increased adipose tissue expression of neuroglobin provides potential mechanistic insight into the influence of diet on VFM.
authors.affiliation: Department of Twin Research and Genetic Epidemiology, Kings College London, London, UK.
authors.forename: T
authors.initials: T
authors.lastname: Pallister
authors.affiliation: Department of Twin Research and Genetic Epidemiology, Kings College London, London, UK.
authors.forename: M A
authors.initials: MA
authors.lastname: Jackson
authors.affiliation: Department of Twin Research and Genetic Epidemiology, Kings College London, London, UK.
authors.forename: T C
authors.initials: TC
authors.lastname: Martin
authors.affiliation: Department of Twin Research and Genetic Epidemiology, Kings College London, London, UK.
authors.forename: C A
authors.initials: CA
authors.lastname: Glastonbury
authors.affiliation: Department of Nutrition, Norwich Medical School, University of East Anglia, Norwich, UK.
authors.forename: A
authors.initials: A
authors.lastname: Jennings
authors.affiliation: Department of Twin Research and Genetic Epidemiology, Kings College London, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Beaumont
authors.affiliation: Metabolon Inc., Durham, NC, USA.
authors.forename: R P
authors.initials: RP
authors.lastname: Mohney
authors.affiliation: Department of Twin Research and Genetic Epidemiology, Kings College London, London, UK.
authors.forename: K S
authors.initials: KS
authors.lastname: Small
authors.affiliation: Department of Nutrition, Norwich Medical School, University of East Anglia, Norwich, UK.
authors.forename: A
authors.initials: A
authors.lastname: MacGregor
authors.affiliation: Department of Twin Research and Genetic Epidemiology, Kings College London, London, UK.
authors.forename: C J
authors.initials: CJ
authors.lastname: Steves
authors.affiliation: Department of Nutrition, Norwich Medical School, University of East Anglia, Norwich, UK.
authors.forename: A
authors.initials: A
authors.lastname: Cassidy
authors.affiliation: Department of Twin Research and Genetic Epidemiology, Kings College London, London, UK.
authors.forename: T D
authors.initials: TD
authors.lastname: Spector
authors.affiliation: Department of Twin Research and Genetic Epidemiology, Kings College London, London, UK.
authors.forename: C
authors.initials: C
authors.lastname: Menni
authors.affiliation: Department of Twin Research and Genetic Epidemiology, Kings College London, London, UK.|Academic Rheumatology Clinical Sciences Building, University of Nottingham, Nottingham City Hospital, Nottingham, UK.
authors.forename: A M
authors.initials: AM
authors.lastname: Valdes
mesh_terms: D000328:Adult; D001663:Bilirubin; D015415:Biomarkers / Q000378:metabolism; D001769:Blood / Q000378:metabolism*; D002087:Butyrates; D002331:Carnitine / Q000031:analogs & derivatives; D004032:Diet; D004435:Eating; D005243:Feces / Q000382:microbiology; D005260:Female; D005638:Fruit; D000069196:Gastrointestinal Microbiome / Q000502:physiology; D005914:Globins / Q000378:metabolism; D006626:Hippurates; D006706:Homeostasis; D006801:Humans; D007211:Indoles; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D008297:Male; D055432:Metabolomics; D009419:Nerve Tissue Proteins / Q000378:metabolism; D000078787:Neuroglobin; D009752:Nutritional Status; D010084:Oxidation-Reduction; D000069466:Red Meat; D006113:United Kingdom; D014631:Valerates; D014675:Vegetables; D015014:Yogurt
chemical_list: D015415:Biomarkers; D002087:Butyrates; D006626:Hippurates; D007211:Indoles; D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D014631:Valerates; C035864:2-hydroxyisovaleric acid; C427065:butyrylcarnitine; C015292:indolepropionic acid; D005914:Globins; C011369:threonic acid; D001663:Bilirubin; D002331:Carnitine; C030514:hippuric acid