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  • 1
    In: Nature, Springer Science and Business Media LLC, Vol. 600, No. 7889 ( 2021-12-16), p. 472-477
    Abstract: The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-19 1,2 , host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases 3–7 . They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
    RVK:
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    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
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  • 2
    In: Applied and Environmental Microbiology, American Society for Microbiology, Vol. 86, No. 7 ( 2020-03-18)
    Abstract: The objective of this study was to elucidate the effect of intestinal Akkermansia muciniphila bacteria on fatty liver disease. Five-week-old C57BL/6N mice were administered either phosphate-buffered saline (PBS; control) or A. muciniphila at 10 8 to 10 9 CFU/ml, and were fed either a 45% fat diet (high-fat diet [HFD]) or a 10% fat diet (normal diet [ND] ) for 10 weeks. After 10 weeks, the mice were euthanized, and blood and tissue samples, including adipose tissue, cecum, liver, and brain, were immediately collected. Biochemical and histological analyses were conducted, and the expression levels of related factors were compared to determine the antiobesity effects of Akkermansia muciniphila . The gut microbiome was analyzed in fecal samples. Oral administration of A. muciniphila significantly ( P   〈  0.05) lowered serum triglyceride (TG) and alanine aminotransferase (ALT) levels in obese mice. Compared to the non- A. muciniphila -treated group, the expression of SREBP (regulator of TG synthesis in liver tissue) was decreased in the A. muciniphila -treated group. The expression of IL-6 in the liver of obese mice was decreased following the administration of A. muciniphila . Furthermore, alterations in the ratio of Firmicutes to Bacteroidetes and the decrease in bacterial diversity caused by the HFD were restored upon the administration of A. muciniphila . These results indicate that A. muciniphila prevents fatty liver disease in obese mice by regulating TG synthesis in the liver and maintaining gut homeostasis. IMPORTANCE This study investigated the effect of Akkermansia muciniphila on fatty liver disease. Although some research about the effects of A. muciniphila on host health has been published, study of the relationship between A. muciniphila administration and fatty liver, as well as changes in the gut microbiota, has not been conducted. In this study, we demonstrated that A. muciniphila prevented fatty liver disease by regulation of the expression of genes that regulate fat synthesis and inflammation in the liver.
    Type of Medium: Online Resource
    ISSN: 0099-2240 , 1098-5336
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    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2020
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    SSG: 12
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  • 3
    In: Phytochemistry, Elsevier BV, Vol. 172 ( 2020-04), p. 112255-
    Type of Medium: Online Resource
    ISSN: 0031-9422
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    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 2000313-4
    SSG: 12
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