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  • Journal article
    Molyneaux PL, Cox MJ, Willis-Owen SAG, Mallia P, Russell KE, Russel A-M, Murphy E, Johnston SL, Schwarte DA, Wells AU, Cookson WOC, Maher TM, Moffatt MFet al., 2014,

    The role of bacteria in the pathogenesis and progression of idiopathic pulmonary fibrosis

    , American Journal of Respiratory and Critical Care Medicine, Vol: 190, Pages: 906-913, ISSN: 1535-4970

    Rationale:Idiopathic pulmonaryfibrosis (IPF)isa progressivelung diseaseof unknown cause that leads to respiratory failure and death within 5 yearsof diagnosis. Overt respiratory infection and immunosuppression carrya high morbidity and mortality, and polymorphisms in genes related toepithelial integrity and host defense predispose to IPF.Objectives: To investigate the role of bacteria in the pathogenesisand progression of IPF.Methods: We prospectively enrolled patients diagnosed with IPFaccording to international criteria together with healthy smokers,nonsmokers, and subjectswithmoderate chronic obstructive pulmonarydisease as control subjects. Subjects underwent bronchoalveolarlavage (BAL), from which genomic DNA was isolated. The V3–V5region of the bacterial 16S rRNA gene was amplified, allowingquantification of bacterial load and identification of communities by 16SrRNA quantitative polymerase chain reaction and pyrosequencing. Measurements and Main Results: Sixty-five patients with IPFhad double the burden of bacteria in BAL fluid compared with 44 controlsubjects. Baseline bacterial burden predicted the rate of decline in lungvolume and risk of death and associated independently with thers35705950 polymorphism of the MUC5B mucin gene, a proven hostsusceptibilityfactorfor IPF. Sequencing yielded912,883 high-quality readsfrom all subjects.WeidentifiedHaemophilus, Streptococcus,Neisseria, andVeillonella spp. to be more abundant in cases than control subjects.Regression analyses indicated that these specific operational taxonomicunits as well as bacterial burden associated independently with IPF.Conclusions: IPF is characterized by an increased bacterial burdenin BAL that predicts decline in lung function and death. Trials ofantimicrobial therapy are needed to determine if microbial burdenis pathogenic in the disease.
  • Journal article
    Venkatesh M, Mukherjee S, Wang H, Li H, Sun K, Benechet AP, Qiu Z, Maher L, Redinbo MR, Phillips RS, Fleet JC, Kortagere S, Mukherjee P, Fasano A, Le Ven J, Nicholson JK, Dumas ME, Khanna KM, Mani Set al., 2014,

    Symbiotic bacterial metabolites regulate gastrointestinal barrier function via the Xenobiotic sensor PXR and toll-like receptor 4

    , Immunity, Vol: 41, Pages: 296-310, ISSN: 1074-7613

    Intestinal microbial metabolites are conjectured to affect mucosal integrity through an incompletely characterized mechanism. Here we showed that microbial-specific indoles regulated intestinal barrier function through the xenobiotic sensor, pregnane X receptor (PXR). Indole 3-propionic acid (IPA), in the context of indole, is a ligand for PXR in vivo, and IPA downregulated enterocyte TNF-α while it upregulated junctional protein-coding mRNAs. PXR-deficient (Nr1i2−/−) mice showed a distinctly “leaky” gut physiology coupled with upregulation of the Toll-like receptor (TLR) signaling pathway. These defects in the epithelial barrier were corrected in Nr1i2−/−Tlr4−/− mice. Our results demonstrate that a direct chemical communication between the intestinal symbionts and PXR regulates mucosal integrity through a pathway that involves luminal sensing and signaling by TLR4.
  • Patent
    Martin FP, Boulange CL, Montoliu Roura I, Collino S, Dumas ME, Holmes E, Rezzi SAD, Nicholson JK, Kochhar Set al., 2014,

    Trimethylamine-N-oxide as biomarker for the predisposition for weight gain and obesity

    , WO2014086604

    The present invention relates generally to the field of nutrition and health. In particular, the present invention relates to a new biomarker, its use and a nnethod that allows it to diagnose the likelihood to resist diet induced weight gain, and/or to be susceptible to a diet induced weight gain. For example, the biomarker may be trimethylamine-N-oxide.
  • Patent
    Martin FP, BOULANGE CL, MONTOLIU ROURA I, COLLINO S, Dumas ME, HOLMES E, REZZI SAD, NICHOLSON JK, KOCHHAR Set al., 2014,

    Isovalerylglycine as biomarker for the predisposition for weight gain and obesity

    , WO2014086605

    The present invention relates generally to the field of nutrition and health. In particular, the present invention relates to a new biomarker, its use and a method that allows it to diagnose the likelihood to resist diet induced weight gain, and/or to be susceptible to a diet induced weight gain. For example, the biomarker may be isovalerylglycine.
  • Patent
    MARTIN FP, Boulange CL, Montoliu Roura I, COLLINO S, Dumas ME, Holmes E, REZZI SAD, Nicholson JK, Kochhar Set al., 2014,

    Hexanoylglycine as biomarker for the predisposition for weight gain and obesity

    , WO 2014/086603

    The present invention relates generally to the field of nutrition and health. In particular, the present invention relates to a new biomarker, its use and a method that allows it to diagnose the likelihood to resist diet induced weight gain, and/or to be susceptible to a diet induced weight gain. For example, the biomarker may be hexanoylglycine.
  • Journal article
    Dumas M-E, Kinross J, Nicholson JK, 2014,

    Metabolic Phenotyping and Systems Biology Approaches to Understanding Metabolic Syndrome and Fatty Liver Disease

    , GASTROENTEROLOGY, Vol: 146, Pages: 46-62, ISSN: 0016-5085
  • Journal article
    Molyneaux PL, Mallia P, Cox MJ, Footitt J, Willis-Owen SAG, Homola D, Trujillo-Torralbo M-B, Elkin S, Kon OM, Cookson WOC, Moffatt MF, Johnston SLet al., 2013,

    Outgrowth of the Bacterial Airway Microbiome after Rhinovirus Exacerbation of Chronic Obstructive Pulmonary Disease

    , AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, Vol: 188, Pages: 1224-1231, ISSN: 1073-449X
  • Journal article
    Cox MJ, Cookson WOCM, Moffatt MF, 2013,

    Sequencing the human microbiome in health and disease

    , HUMAN MOLECULAR GENETICS, Vol: 22, Pages: R88-R94, ISSN: 0964-6906
  • Journal article
    Russell WR, Hoyles L, Flint HJ, Dumas MEet al., 2013,

    Colonic bacterial metabolites and human health

    , Current Opinion in Microbiology

    The influence of the microbial–mammalian metabolic axis is becoming increasingly important for human health. Bacterial fermentation of carbohydrates (CHOs) and proteins produces short-chain fatty acids (SCFA) and a range of other metabolites including those from aromatic amino acid (AAA) fermentation. SCFA influence host health as energy sources and via multiple signalling mechanisms. Bacterial transformation of fibre-related phytochemicals is associated with a reduced incidence of several chronic diseases. The ‘gut–liver axis’ is an emerging area of study. Microbial deconjugation of xenobiotics and release of aromatic moieties into the colon can have a wide range of physiological consequences. In addition, the role of the gut microbiota in choline deficiency in non-alcoholic fatty liver disease (NAFLD) and insulin resistance is receiving increased attention.
  • Journal article
    Duff RM, Simmonds NJ, Davies JC, Wilson R, Alton EW, Pantelidis P, Cox MJ, Cookson WOCM, Bilton D, Moffatt MFet al., 2013,

    A molecular comparison of microbial communities in bronchiectasis and cystic fibrosis

    , EUROPEAN RESPIRATORY JOURNAL, Vol: 41, Pages: 991-993, ISSN: 0903-1936

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