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In this study, the regulation and mechanism associated with the co-administration of the two were first studied using T2DM rats, induced by a high fat diet (HFD) and streptozocin (STZ) injection. Results demonstrate that, compared to those with DSW or FPS alone, the orally administered combination of DSW and FPS (CDF), especially the high dose (H-CDF), could preferably inhibit weight loss, decrease levels of fasting blood glucose (FBG) and lipids, and improve hepatopancreatic pathology and the abnormal Akt\/GSK-3\u03b2 signaling pathway. The fecal metabolomics data show that H-CDF could regulate the abnormal levels of metabolites mainly through the regulation of linoleic acid (LA) metabolism, bile acid (BA) metabolism, and other related pathways. Moreover, H-CDF could adjust the diversity and richness of bacterial flora and enrich bacterial groups, such as Lactobacillaceae and Ruminococcaceae UCG-014. In addition, Spearman correlation analysis illustrated that the interaction between the gut microbiota and BAs plays an essential role in the action of H-CDF. In the ileum, H-CDF was verified to inhibit activation of the farnesoid X receptor (FXR)\u2013fibroblast growth factor 15 (FGF15) pathway, which is regulated by the microbiota\u2013BA\u2013axis. In conclusion, H-CDF enriched Lactobacillaceae and Ruminococcaceae UCG-014, thereby changing BA metabolism, linoleic acid metabolism, and other related pathways, as well as enhancing insulin sensitivity and improving glucose and lipid metabolism.<\/jats:p>","DOI":"10.3390\/ph16030462","type":"journal-article","created":{"date-parts":[[2023,3,20]],"date-time":"2023-03-20T07:06:37Z","timestamp":1679295997000},"page":"462","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A Combination of Deep-Sea Water and Fucoidan Alleviates T2DM through Modulation of Gut Microbiota and Metabolic Pathways"],"prefix":"10.3390","volume":"16","author":[{"given":"Shan","family":"He","sequence":"first","affiliation":[{"name":"College of Pharmaceutical Science, Shandong University of Traditional Chinese Medicine, Jinan 250355, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Bing","family":"Peng","sequence":"additional","affiliation":[{"name":"Biology Institute, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250103, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Lei","family":"Zhou","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Science, Shandong University of Traditional Chinese Medicine, Jinan 250355, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9399-4635","authenticated-orcid":false,"given":"Xian-Jun","family":"Fu","sequence":"additional","affiliation":[{"name":"Institute for Literature and Culture of Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan-Hua","family":"Sun","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Science, Shandong University of Traditional Chinese Medicine, Jinan 250355, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen-Guo","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute for Literature and Culture of Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,20]]},"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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