| Budget Amount *help |
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2018: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2017: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
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| Outline of Final Research Achievements |
We found the decreased Faecalibacterium Prausnitzii (FP) abundance, hyper-intestinal permeability and high plasma endotoxin level in NAFLD patients with advanced fibrosis. In a mouse NAFLD model, the FP administration improved the intestinal barrier function and eventually prevented from developing not only liver dysfunctions but also dyslipidaemia, insulin resistance and atherosclerosis. Here we show that the high level of plasma choline that was attributable to an impaired hepatic choline uptake could travel back into the colon under the leaky gut condition. This efflux of choline increased trimethylamine which was biotransformed by intestinal microbiota and plasma level of trimethylamine-N-oxide, subsequently promoting atherosclerosis. Thus, this study implicated a novel therapeutic approach; improvement of intestinal barrier function by the FP administration as a central management for NAFLD.
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