{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T16:02:49Z","timestamp":1774454569840,"version":"3.50.1"},"reference-count":38,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Biological Breeding-National Science and Technology Major Project","award":["2023ZD0406301"],"award-info":[{"award-number":["2023ZD0406301"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background and Objectives: Pro-inflammatory diet and high-fat diet (HFD) often coexist in real-world, but their combined impact on the gut\u2013liver axis and potential nutritional countermeasures remain insufficiently studied. This study aimed to evaluate a pro-inflammatory\u2013high-fat composite dietary pattern on the intestine and liver in the population, and to further evaluate the protective potential of astaxanthin (ATX) in complementary experimental systems. Methods: Data from the NHANES 2005\u20132010 were used to construct four composite exposure groups based on the dietary inflammation index (DII) and energy from fat. Survey-weighted regression analyses were performed to examine associations with systemic inflammation and liver injury. Interaction and C-reactive protein (CRP)-mediated effect analyses were conducted. Fifty SD rats were randomly divided into control group, model group induced by HFD combined with inflammatory factors, and low-, medium-, and high-dose Haematococcus pluvialis (HP) intervention groups. Serum lipids, liver enzymes, liver and colon pathology, and inflammatory and oxidative markers were measured in rats. In an in vitro organ-on-chip barrier model, the effect of ATX was observed when colonic barrier damage was induced using palmitic acid and lipopolysaccharides. Results: The high DII combined with HFD showed the largest increases in CRP, liver enzymes, and fatty liver index. A synergistic interaction was observed between DII and HFD, with CRP mediating approximately 20% of the effect. In rat model, HP-derived ATX improved the lipid profile, attenuated hepatic steatosis and oxidative damage, and reduced colonic pro-inflammatory cytokines, while restoration of tight junction proteins was limited. In colon organoid model, ATX showed limited efficacy in improving inflammation and barrier function. Conclusions: The pro-inflammatory\u2013high-fat dietary pattern synergistically exacerbates gut\u2013liver dysfunction. HP-derived ATX alleviates metabolic and inflammation-induced enterohepatic comorbidity, but its effect on repairing barrier structure is limited.<\/jats:p>","DOI":"10.3390\/nu18071048","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T15:34:27Z","timestamp":1774452867000},"page":"1048","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synergistic Effects of a Pro-Inflammatory\u2013High-Fat Composite Dietary Pattern on Gut\u2013Liver Injury and the Therapeutic Potential of Haematococcus pluvialis-Derived Astaxanthin"],"prefix":"10.3390","volume":"18","author":[{"given":"Jing","family":"Feng","sequence":"first","affiliation":[{"name":"Key Laboratory of Public Nutrition and Health, National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Han","sequence":"additional","affiliation":[{"name":"Key Laboratory of Public Nutrition and Health, National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinpeng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Public Nutrition and Health, National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuo","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Public Nutrition and Health, National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9840-3945","authenticated-orcid":false,"given":"Chen","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Public Nutrition and Health, National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rongzi","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Public Nutrition and Health, National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chaoqun","family":"Sun","sequence":"additional","affiliation":[{"name":"Key Laboratory of Public Nutrition and Health, National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liyuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Public Nutrition and Health, National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9643-1897","authenticated-orcid":false,"given":"Junsheng","family":"Huo","sequence":"additional","affiliation":[{"name":"Key Laboratory of Public Nutrition and Health, National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9130-3984","authenticated-orcid":false,"given":"Shi","family":"Shen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Public Nutrition and Health, National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qin","family":"Zhuo","sequence":"additional","affiliation":[{"name":"Key Laboratory of Public Nutrition and Health, National Institute for Nutrition and Health, Chinese Center for Disease Control and Prevention, Beijing 100050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"103043","DOI":"10.1016\/j.arcmed.2024.103043","article-title":"Global Prevalence of Nonalcoholic Fatty Liver Disease: An Updated Review Meta-Analysis comprising a Population of 78 million from 38 Countries","volume":"55","author":"Letafatkar","year":"2024","journal-title":"Arch. 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