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  • Journal article
    Monaghan TM, Biswas RN, Nashine RR, Joshi SS, Mullish BH, Seekatz AM, Miguens Blanco J, McDonald JAK, Marchesi JR, Yau TO, Christodoulou N, Hatziapostolou M, Pučić-Baković M, Vučković F, Klicek F, Lauc G, Xue N, Dottorini T, Ambalkar S, Satav A, Polytarchou C, Acharjee A, Kashyap RSet al., 2021,

    Multiomics profiling reveals signatures of dysmetabolism in urban populations in central India

    , Microorganisms, Vol: 9, Pages: 1-21, ISSN: 2076-2607

    Background: Non-communicable diseases (NCDs) have become a major cause of morbidity and mortality in India. Perturbation of host–microbiome interactions may be a key mechanism by which lifestyle-related risk factors such as tobacco use, alcohol consumption, and physical inactivity may influence metabolic health. There is an urgent need to identify relevant dysmetabolic traits for predicting risk of metabolic disorders, such as diabetes, among susceptible Asian Indians where NCDs are a growing epidemic. Methods: Here, we report the first in-depth phenotypic study in which we prospectively enrolled 218 adults from urban and rural areas of Central India and used multiomic profiling to identify relationships between microbial taxa and circulating biomarkers of cardiometabolic risk. Assays included fecal microbiota analysis by 16S ribosomal RNA gene amplicon sequencing, quantification of serum short chain fatty acids by gas chromatography-mass spectrometry, and multiplex assaying of serum diabetic proteins, cytokines, chemokines, and multi-isotype antibodies. Sera was also analysed for N-glycans and immunoglobulin G Fc N-glycopeptides. Results: Multiple hallmarks of dysmetabolism were identified in urbanites and young overweight adults, the majority of whom did not have a known diagnosis of diabetes. Association analyses revealed several host–microbe and metabolic associations. Conclusions: Host–microbe and metabolic interactions are differentially shaped by body weight and geographic status in Central Indians. Further exploration of these links may help create a molecular-level map for estimating risk of developing metabolic disorders and designing early interventions.

  • Journal article
    Mullish BH, Ghani R, McDonald JAK, Davies F, Marchesi JRet al., 2021,

    Reply to Woodworth, et al.

    , Clin Infect Dis, Vol: 72, Pages: e924-e925
  • Conference paper
    Habboub N, Manousou P, Forlano R, Mullish BH, Frost G, Challis B, Thursz MR, Dumas M-Eet al., 2021,

    Metabolic Profiling of NASH Patients and Healthy Controls to Investigate the Transferability of a Healthy Metabolome Using Faecal Microbiota Transplantation

    , Metabolomics 2021
  • Conference paper
    Miguens Blanco J, Liu Z, Mullish BH, Danckert NP, Alexander JL, Chrysostomou D, Sengupta R, McHugh N, McDonald JAK, Abraham SM, Marchesi JRet al., 2021,

    A Phenomic Characterization of the Gut Microbiota - Associations with Psoriatic Arthritis and Ankylosing Spondylitis

    , World Microbe Forum
  • Journal article
    Brial F, Chilloux J, Nielsen T, Vieira-Silva S, Falony G, Andrikopoulos P, Olanipekun M, Hoyles L, Djouadi F, Neves AL, Rodriguez-Martinez A, Mouawad GI, Pons N, Forslund S, Le-Chatelier E, Le Lay A, Nicholson J, Hansen T, Hyötyläinen T, Clément K, Oresic M, Bork P, Ehrlich SD, Raes J, Pedersen OB, Gauguier D, Dumas M-Eet al., 2021,

    Human and preclinical studies of the host-gut microbiome co-metabolite hippurate as a marker and mediator of metabolic health.

    , Gut, Vol: 70, Pages: 2105-2114, ISSN: 0017-5749

    OBJECTIVE: Gut microbial products are involved in regulation of host metabolism. In human and experimental studies, we explored the potential role of hippurate, a hepatic phase 2 conjugation product of microbial benzoate, as a marker and mediator of metabolic health. DESIGN: In 271 middle-aged non-diabetic Danish individuals, who were stratified on habitual dietary intake, we applied 1H-nuclear magnetic resonance (NMR) spectroscopy of urine samples and shotgun-sequencing-based metagenomics of the gut microbiome to explore links between the urine level of hippurate, measures of the gut microbiome, dietary fat and markers of metabolic health. In mechanistic experiments with chronic subcutaneous infusion of hippurate to high-fat-diet-fed obese mice, we tested for causality between hippurate and metabolic phenotypes. RESULTS: In the human study, we showed that urine hippurate positively associates with microbial gene richness and functional modules for microbial benzoate biosynthetic pathways, one of which is less prevalent in the Bacteroides 2 enterotype compared with Ruminococcaceae or Prevotella enterotypes. Through dietary stratification, we identify a subset of study participants consuming a diet rich in saturated fat in which urine hippurate concentration, independently of gene richness, accounts for links with metabolic health. In the high-fat-fed mice experiments, we demonstrate causality through chronic infusion of hippurate (20 nmol/day) resulting in improved glucose tolerance and enhanced insulin secretion. CONCLUSION: Our human and experimental studies show that a high urine hippurate concentration is a general marker of metabolic health, and in the context of obesity induced by high-fat diets, hippurate contributes to metabolic improvements, highlighting its potential as a mediator of metabolic health.

  • Conference paper
    Barker GF, Pechlivanis A, Bello AT, Chrysostomou D, Mullish BH, Marchesi J, Posma JM, Kinross JM, Nicholson J, O'Keefe SJ, Li JVet al., 2021,

    Aa022 a high-fiber low-fat diet increases fecal levels of lithocholic acid derivative 3-ketocholanic acid

    , Digestive Disease Week, Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S393-S394, ISSN: 0016-5085
  • Journal article
    Hoyles L, Mayneris-Perxachs J, Cardellini M, Latorre J, Davato F, Moreno-Navarette JM, Arnoriaga-Rodriquez M, Serino M, Abbott J, Barton RH, Puig J, Fernandez-Real X, Ricart W, Tomlinson C, Woodbridge M, Gentileschi P, Butcher SA, Holmes E, Nicholson JK, Perez-Brocal V, Moya A, McClain D, Burcelin R, Dumas M-E, Federici M, Fernandez-Real J-Met al., 2021,

    ­Iron status influences non-alcoholic fatty liver disease in obesity through the gut microbiome

    , Microbiome, Vol: 9, Pages: 1-18, ISSN: 2049-2618

    Background: The gut microbiome and iron status are known to play a role in the pathophysiology of non-alcoholic fatty liver disease (NAFLD), although their complex interaction remains unclear.Results: Here, we applied an integrative systems medicine approach (faecal metagenomics, plasma and urine metabolomics, hepatic transcriptomics) in 2 well-characterised human cohorts of subjects with obesity (discovery n = 49 and validation n = 628) and an independent cohort formed by both individuals with and without obesity (n = 130), combined with in vitro and animal models. Serum ferritin levels, as a markers of liver iron stores, were positively associated with liver fat accumulation in parallel with lower gut microbial gene richness, composition and functionality. Specifically, ferritin had strong negative associations with the Pasteurellaceae, Leuconostocaceae and Micrococcaea families. It also had consistent negative associations with several Veillonella, Bifidobacterium and Lactobacillus species, but positive associations with Bacteroides and Prevotella spp. Notably, the ferritin-associated bacterial families had a strong correlation with iron-related liver genes. In addition, several bacterial functions related to iron metabolism (transport, chelation, heme and siderophore biosynthesis) and NAFLD (fatty acid and glutathione biosynthesis) were also associated with the host serum ferritin levels. This iron-related microbiome signature was linked to a transcriptomic and metabolomic signature associated to the degree of liver fat accumulation through hepatic glucose metabolism. In particular, we found a consistent association among serum ferritin, Pasteurellaceae and Micrococcacea families, bacterial functions involved in histidine transport, the host circulating histidine levels and the liver expression of GYS2 and SEC24B. Serum ferritin was also related to bacterial glycine transporters, the host glycine serum levels and the liver expression of glycine transporters. The

  • Conference paper
    Mullish BH, Marchesi J, Pass DA, Michael D, Plummer S, Wang Det al., 2021,

    DAILY PROBIOTIC USE IS ASSOCIATED WITH A REDUCED RATE OF UPPER RESPIRATORY TRACT SYMPTOMS IN OVERWEIGHT AND OBESE PEOPLE

    , Society-for-Surgery-of-the-Alimentary-Tract Annual Meeting at Digestive Disease Week (DDW), Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S150-S150, ISSN: 0016-5085
  • Conference paper
    Radhakrishnan ST, Mullish BH, Gallagher K, Alexander JL, Danckert NP, Blanco JM, Serrano-Contreras JI, Valdivia-Garcia M, Hopkins BJ, Ghai A, Li JV, Marchesi J, Williams HRet al., 2021,

    RECTAL SWABS AS A VIABLE ALTERNATIVE TO FECAL SAMPLING FOR THE ANALYSIS OF GUT MICROBIOME FUNCTIONALITY AS WELL AS COMPOSITION

    , Society-for-Surgery-of-the-Alimentary-Tract Annual Meeting at Digestive Disease Week (DDW), Publisher: W B SAUNDERS CO-ELSEVIER INC, Pages: S733-S733, ISSN: 0016-5085
  • Conference paper
    Martinez-Gili L, Mullish BH, Correia G, Chekmeneva E, Homeffer-Van Der Sluis V, McClure EL, Marchesi J, Gerber G, Bry L, Allegretti JRet al., 2021,

    A distinctive signature of fecal bile acids and other novel metabolites accompanying recurrence after primary clostridioides difficile infection

    , Society for Surgery of the Alimentary Tract Annual Meeting at Digestive Disease Week (DDW), Publisher: Elsevier, Pages: S368-S368, ISSN: 0016-5085

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