Multiomics Analysis Reveals the Impact of Microbiota on Host Metabolism in Hepatic Steatosis

被引:42
作者
Zeybel, Mujdat [1 ,2 ,3 ,4 ]
Arif, Muhammad [5 ,13 ,14 ]
Li, Xiangyu [5 ]
Altay, Ozlem [5 ]
Shi, Mengnan [5 ]
Akyildiz, Murat [1 ]
Saglam, Burcin [1 ]
Gonenli, Mehmet Gokhan [1 ]
Yigit, Buket [1 ]
Ulukan, Burge [1 ]
Ural, Dilek [6 ]
Shoaie, Saeed [5 ,7 ]
Turkez, Hasan [8 ]
Nielsen, Jens [9 ]
Zhang, Cheng [5 ,10 ]
Uhlen, Mathias [5 ]
Boren, Jan [11 ,12 ]
Mardinoglu, Adil [5 ,7 ]
Yang, Hong [5 ]
机构
[1] Koc Univ, Sch Med, Dept Gastroenterol & Hepatol, TR-34010 Istanbul, Turkey
[2] Nottingham Univ Hosp NHS Trust, NIHR Nottingham Biomed Res Ctr, Nottingham NG5 1PB, England
[3] Univ Nottingham, Nottingham NG5 1PB, England
[4] Univ Nottingham, Sch Med, Nottingham Digest Dis Ctr, Nottingham NG7 2UH, England
[5] KTH Royal Inst Technol, Sci Life Lab, SE-17121 Stockholm, Sweden
[6] Koc Univ, Sch Med, TR-34010 Istanbul, Turkey
[7] Kings Coll London, Fac Dent Oral & Craniofacial Sci, Ctr Host Microbiome Interact, London SE1 9RT, England
[8] Ataturk Univ, Fac Med, Dept Med Biol, TR-25240 Erzurum, Turkey
[9] Chalmers Univ Technol, Dept Biol & Biol Engn, SE-41296 Gothenburg, Sweden
[10] Zhengzhou Univ, Sch Pharmaceut Sci, Minist Educ, Key Lab Adv Drug Preparat Technol, Zhengzhou 450001, Henan, Peoples R China
[11] Univ Gothenburg, Dept Mol & Clin Med, SE-41345 Gothenburg, Sweden
[12] Sahlgrenska Univ Hosp Gothenburg, SE-41345 Gothenburg, Sweden
[13] NIAAA, Lab Cardiovasc Physiol & Tissue Injury, NIH, Rockville, MD 20852 USA
[14] NIAAA, Sect Fibrot Disorders, NIH, Rockville, MD 20852 USA
基金
欧盟地平线“2020”;
关键词
gut and oral metagenomics; metabolic dysfunction-associated fatty liver disease; metabolomics; multiomics analysis; proteomics; systems biology; systems medicine; FATTY LIVER-DISEASE; INTESTINAL MICROBIOTA; GUT MICROBIOME; DIET; INFLAMMATION; OBESITY; NAFLD; ACID; ASSOCIATION; INCREASES;
D O I
10.1002/advs.202104373
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Metabolic dysfunction-associated fatty liver disease (MAFLD) is a complex disease involving alterations in multiple biological processes regulated by the interactions between obesity, genetic background, and environmental factors including the microbiome. To decipher hepatic steatosis (HS) pathogenesis by excluding critical confounding factors including genetic variants and diabetes, 56 heterogenous MAFLD patients are characterized by generating multiomics data including oral and gut metagenomics as well as plasma metabolomics and inflammatory proteomics data. The dysbiosis in the oral and gut microbiome is explored and the host-microbiome interactions based on global metabolic and inflammatory processes are revealed. These multiomics data are integrated using the biological network and HS's key features are identified using multiomics data. HS is finally predicted using these key features and findings are validated in a follow-up cohort, where 22 subjects with varying degree of HS are characterized.
引用
收藏
页数:20
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