Microbiomics, Metabolomics, Predicted Metagenomics, and Hepatic Steatosis in a Population-Based Study of 1,355 Adults
Microbiomics, Metabolomics, Predicted Metagenomics, and Hepatic Steatosis in a Population-Based Study of 1,355 Adults
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DOI：
10.1002/hep.31417
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发表时间：
2021-03-01
期刊：
影响因子：
13.5
通讯作者：
Darwish Murad, Sarwa
中科院分区：
文献类型：
--
作者：
Alferink, Louise J. M.;Radjabzadeh, Djawad;Darwish Murad, Sarwa
背景和目的以前的小型研究已经评估了脂肪变性的肠道微生物组（GM），但缺乏大规模的研究。我们研究了GM多样性和组成、血浆代谢物、预测的功能宏基因组学和脂肪变性之间的关联。方法和结果这是对基于前瞻性人群的鹿特丹研究的横断面分析。我们使用16 S核糖体RNA基因测序，并确定分类使用SILVA参考数据库。α多样性和β多样性计算使用香农多样性指数和Bray-Curtis相异度。使用排列多变量方差分析来检验脂肪变性之间的差异。超声诊断为肝脂肪变性。我们随后使用正则化回归选择属。利用京都基因百科全书和基因组途径，基于GM预测功能宏基因组。使用高通量质子核磁共振评估血清代谢组学。所有的分析都校正了年龄、性别、体重指数、酒精、饮食和质子泵抑制剂。我们纳入了1,355名参与者，其中472人患有脂肪变性。脂肪变性的α多样性较低（P = 1.1中心点10（-9）），而β多样性在脂肪变性分层中变化（P = 0.001）。Lasso选择了37个属，其中三个在调整后仍然显著相关（粪球菌3：β = -65;戈弗罗瘤胃球菌群：β = 62;和细尾瘤胃球菌群：β = 45，Q值= 0.037）。预测的宏基因组分析显示，脂肪变性中存在次级胆汁酸合成和生物素代谢途径，而D-丙氨酸代谢则不存在。代谢谱显示芳香族和支链氨基酸和糖蛋白乙酰基与脂肪变性和R。而这些代谢产物与α多样性和粪球菌3呈负相关。结论我们在大规模上证实了低微生物多样性和粪球菌和Gnavus与脂肪变性的相关性。我们还发现脂肪变性和α多样性共享相反的代谢谱。
Background and Aims Previous small studies have appraised the gut microbiome (GM) in steatosis, but large-scale studies are lacking. We studied the association of the GM diversity and composition, plasma metabolites, predicted functional metagenomics, and steatosis.Approach and Results This is a cross-sectional analysis of the prospective population-based Rotterdam Study. We used 16S ribosomal RNA gene sequencing and determined taxonomy using the SILVA reference database. Alpha diversity and beta diversity were calculated using the Shannon diversity index and Bray-Curtis dissimilarities. Differences were tested across steatosis using permutational multivariate analysis of variance. Hepatic steatosis was diagnosed by ultrasonography. We subsequently selected genera using regularized regression. The functional metagenome was predicted based on the GM using Kyoto Encyclopedia of Genes and Genomes pathways. Serum metabolomics were assessed using high-throughput proton nuclear magnetic resonance. All analyses were adjusted for age, sex, body mass index, alcohol, diet, and proton-pump inhibitors. We included 1,355 participants, of whom 472 had steatosis. Alpha diversity was lower in steatosis (P = 1.1 center dot 10(-9)), and beta diversity varied across steatosis strata (P = 0.001). Lasso selected 37 genera of which three remained significantly associated after adjustment (Coprococcus3: beta = -65; Ruminococcus Gauvreauiigroup: beta = 62; and Ruminococcus Gnavusgroup: beta = 45, Q-value = 0.037). Predicted metagenome analyses revealed that pathways of secondary bile-acid synthesis and biotin metabolism were present, and D-alanine metabolism was absent in steatosis. Metabolic profiles showed positive associations for aromatic and branched chain amino acids and glycoprotein acetyls with steatosis and R. Gnavusgroup, whereas these metabolites were inversely associated with alpha diversity and Coprococcus3.Conclusions We confirmed, on a large-scale, the lower microbial diversity and association of Coprococcus and Ruminococcus Gnavus with steatosis. We additionally showed that steatosis and alpha diversity share opposite metabolic profiles.