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  1. Article ; Online: Pharmacomicrobiomics

    Marwah Doestzada / Arnau Vich Vila / Alexandra Zhernakova / Debby P. Y. Koonen / Rinse K. Weersma / Daan J. Touw / Folkert Kuipers / Cisca Wijmenga / Jingyuan Fu

    Protein & Cell, Vol 9, Iss 5, Pp 432-

    a novel route towards personalized medicine?

    2018  Volume 445

    Abstract: ABSTRACT Inter-individual heterogeneity in drug response is a serious problem that affects the patient’s wellbeing and poses enormous clinical and financial burdens on a societal level. Pharmacogenomics has been at the forefront of research into the ... ...

    Abstract ABSTRACT Inter-individual heterogeneity in drug response is a serious problem that affects the patient’s wellbeing and poses enormous clinical and financial burdens on a societal level. Pharmacogenomics has been at the forefront of research into the impact of individual genetic background on drug response variability or drug toxicity, and recently the gut microbiome, which has also been called the second genome, has been recognized as an important player in this respect. Moreover, the microbiome is a very attractive target for improving drug efficacy and safety due to the opportunities to manipulate its composition. Pharmacomicrobiomics is an emerging field that investigates the interplay of microbiome variation and drugs response and disposition (absorption, distribution, metabolism and excretion). In this review, we provide a historical overview and examine current state-of-the-art knowledge on the complex interactions between gut microbiome, host and drugs. We argue that combining pharmacogenomics and pharmacomicrobiomics will provide an important foundation for making major advances in personalized medicine.
    Keywords gut microbiome ; drug metabolism ; personalized medicine ; Cytology ; QH573-671 ; Animal biochemistry ; QP501-801
    Language English
    Publishing date 2018-04-01T00:00:00Z
    Publisher SpringerOpen
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Genetic and Microbial Associations to Plasma and Fecal Bile Acids in Obesity Relate to Plasma Lipids and Liver Fat Content

    Lianmin Chen / Inge C.L. van den Munckhof / Kiki Schraa / Rob ter Horst / Martijn Koehorst / Martijn van Faassen / Claude van der Ley / Marwah Doestzada / Daria V. Zhernakova / Alexander Kurilshikov / Vincent W. Bloks / Albert K. Groen / Niels P. Riksen / Joost H.W. Rutten / Leo A.B. Joosten / Cisca Wijmenga / Alexandra Zhernakova / Mihai G. Netea / Jingyuan Fu /
    Folkert Kuipers

    Cell Reports, Vol 33, Iss 1, Pp 108212- (2020)

    2020  

    Abstract: Summary: Bile acids (BAs) are implicated in the etiology of obesity-related conditions such as non-alcoholic fatty liver disease. Differently structured BA species display variable signaling activities via farnesoid X receptor (FXR) and Takeda G protein- ... ...

    Abstract Summary: Bile acids (BAs) are implicated in the etiology of obesity-related conditions such as non-alcoholic fatty liver disease. Differently structured BA species display variable signaling activities via farnesoid X receptor (FXR) and Takeda G protein-coupled BA receptor 1 (TGR5). This study profiles plasma and fecal BAs and plasma 7α-hydroxy-4-cholesten-3-one (C4) in 297 persons with obesity, identifies underlying genetic and microbial determinants, and establishes BA correlations with liver fat and plasma lipid parameters. We identify 27 genetic associations (p < 5 × 10−8) and 439 microbial correlations (FDR < 0.05) for 50 BA entities. Additionally, we report 111 correlations between BA and 88 lipid parameters (FDR < 0.05), mainly for C4 reflecting hepatic BA synthesis. Inter-individual variability in the plasma BA profile does not reflect hepatic BA synthetic pathways, but rather transport and metabolism within the enterohepatic circulation. Our study reveals genetic and microbial determinants of BAs in obesity and their relationship to disease-relevant lipid parameters that are important for the design of personalized therapies targeting BA-signaling pathways.
    Keywords bile acids ; genetics ; gut microbiome ; liver ; enterohepatic circulation ; obesity ; Biology (General) ; QH301-705.5
    Subject code 571
    Language English
    Publishing date 2020-10-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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