{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T19:36:13Z","timestamp":1791488173987,"version":"4.3.4"},"reference-count":28,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,8,23]],"date-time":"2022-08-23T00:00:00Z","timestamp":1661212800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"China Pharmaceutical University","award":["CPU20180815 HFG"],"award-info":[{"award-number":["CPU20180815 HFG"]}]},{"name":"China Pharmaceutical University","award":["CPU20200228 HFG"],"award-info":[{"award-number":["CPU20200228 HFG"]}]},{"name":"Cooperation Research Project","award":["CPU20180815 HFG"],"award-info":[{"award-number":["CPU20180815 HFG"]}]},{"name":"Cooperation Research Project","award":["CPU20200228 HFG"],"award-info":[{"award-number":["CPU20200228 HFG"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Evidence has demonstrated that either metabolites or intestinal microbiota are involved in the pathogenesis of type 2 diabetes (T2D) and diabetic kidney disease (DKD). To explore the interaction between plasma metabolomics and intestinal microbiome in the progress of T2D-DKD, in the current study, we analyzed metabolomics in the plasma of db\/db mice with liquid chromatography\u2013mass spectrometry and also examined intestinal prokaryotes and entire gut microbiome dysbiosis at the genus level with both 16S rDNA and metagenomic sequencing techniques. We found that Negativibacillus and Rikenella were upregulated, while Akkermansia, Candidatus, Erysipelatoclostridium and Ileibacterium were downregulated in the colon of db\/db mice compared with non-diabetic controls. In parallel, a total of 91 metabolites were upregulated, while 23 were downregulated in the plasma of db\/db mice. The top five upregulated metabolites included D-arabinose 5-phosphate, estrone 3-sulfate, L-theanine, 3\u2032-aenylic acid and adenosine 5\u2032-monophosphate, and the five most significantly downregulated metabolites were aurohyocholic acid sodium salt, calcium phosphorylcholine chloride, tauro-alpha-muricholic acid sodium salt, galactinol and phosphocholine. These plasma metabolites were interacted with intestinal microbiomes, which are mainly involved in the pathways related to the biosynthesis of unsaturated fatty acids, fatty acid elongation, steroid biosynthesis, and D-arginine and D-ornithine metabolism. In the differential metabolites, N-acetyl-L-ornithine, ornithine and L-kyn could be metabolized by the correspondingly differential ontology genes in the intestinal metagenome. The current study thereby provides evidence for a gut\u2013metabolism\u2013kidney axis in the metabolism of db\/db mice, in which the gut microbiome and circulating metabolomics interact, and suggests that information from this axis may contribute to our understanding of T2D and DKD pathogenesis.<\/jats:p>","DOI":"10.3390\/metabo12090775","type":"journal-article","created":{"date-parts":[[2022,8,24]],"date-time":"2022-08-24T00:22:48Z","timestamp":1661300568000},"page":"775","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Interaction between Plasma Metabolomics and Intestinal Microbiome in db\/db Mouse, an Animal Model for Study of Type 2 Diabetes and Diabetic Kidney Disease"],"prefix":"10.3390","volume":"12","author":[{"given":"Chenhua","family":"Wu","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Medicine, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, China"},{"name":"Laboratory of Minigene Pharmacy, School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Fei","sequence":"additional","affiliation":[{"name":"Laboratory of Minigene Pharmacy, School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Xu","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Medicine, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingjun","family":"Tao","sequence":"additional","affiliation":[{"name":"Laboratory of Minigene Pharmacy, School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziqi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Laboratory of Minigene Pharmacy, School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yurong","family":"Wang","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Medicine, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Wu","sequence":"additional","affiliation":[{"name":"Laboratory of Minigene Pharmacy, School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4578-5449","authenticated-orcid":false,"given":"Harvest F.","family":"Gu","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Medicine, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"107843","DOI":"10.1016\/j.diabres.2019.107843","article-title":"Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition","volume":"157","author":"Saeedi","year":"2019","journal-title":"Diabetes Res. 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