{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T22:37:34Z","timestamp":1790116654803,"version":"4.0.1"},"reference-count":82,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T00:00:00Z","timestamp":1758067200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Science Centre","doi-asserted-by":"publisher","award":["2018\/29\/B\/NZ7\/00809"],"award-info":[{"award-number":["2018\/29\/B\/NZ7\/00809"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"National Science Centre","doi-asserted-by":"publisher","award":["501-1-009-12-20"],"award-info":[{"award-number":["501-1-009-12-20"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Centre of Postgraduate Medical Education","award":["2018\/29\/B\/NZ7\/00809"],"award-info":[{"award-number":["2018\/29\/B\/NZ7\/00809"]}]},{"name":"Centre of Postgraduate Medical Education","award":["501-1-009-12-20"],"award-info":[{"award-number":["501-1-009-12-20"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Apolipoprotein A-IV (ApoA-IV) has been implicated in modulating the gut microbiota. However, chronic high-fat diet (HFD) consumption impairs ApoA-IV signaling and disrupts gut microbial balance, contributing to obesity and insulin resistance. This study aimed to investigate the role of ApoA-IV in shaping the gut microbiota and associated metabolic profiles throughout the lifespan of mice exposed to an HFD. Fecal samples were collected from ApoA-IV knockout (KO) and wild-type mice at five time points for microbiota and metabolite profiling using 16S rRNA gene sequencing and gas chromatography\u2013mass spectrometry, respectively. Lifespan was longest in ApoA-IV-KO mice on a normal diet, while the HFD reduced survival across genotypes. Microbiota analysis revealed diet- and age-dependent shifts, including an elevated Firmicutes\/Bacteroidota ratio, altered abundance of Akkermansia and reduced Monoglobus in ApoA-IV-KO mice on the HFD. Metabolic profiling showed a stronger impact of diet than genotype, with early and persistent increases in branched-chain amino acids and reductions in short-chain fatty acids (SCFAs). ApoA-IV deficiency modulated lifespan microbial and metabolic changes and shaped distinct responses to dietary stress. Despite age-related convergence in microbiota structure, genotype-specific differences in metabolite profiles and SCFA-producing bacteria correlations persisted into old age, demonstrating the lasting impact of ApoA-IV on host metabolic adaptation.<\/jats:p>","DOI":"10.3390\/biology14091278","type":"journal-article","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T07:07:18Z","timestamp":1758092838000},"page":"1278","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Lifetime Changes in Gut Microbiota and Metabolite Composition in High-Fat Diet-Induced Obesity in Apolipoprotein A-IV Gene Knockout Mice"],"prefix":"10.3390","volume":"14","author":[{"given":"Natalia","family":"Zeber-Lubecka","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, 02-781 Warsaw, Poland"},{"name":"Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Kulecka","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, 02-781 Warsaw, Poland"},{"name":"Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0228-7650","authenticated-orcid":false,"given":"Aneta","family":"Balabas","sequence":"additional","affiliation":[{"name":"Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3418-1837","authenticated-orcid":false,"given":"Pawel","family":"Czarnowski","sequence":"additional","affiliation":[{"name":"Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazimiera","family":"Py\u015bniak","sequence":"additional","affiliation":[{"name":"Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michalina","family":"D\u0105browska","sequence":"additional","affiliation":[{"name":"Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerzy","family":"Ostrowski","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, 02-781 Warsaw, Poland"},{"name":"Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6388-2237","authenticated-orcid":false,"given":"Ewa E.","family":"Hennig","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, 02-781 Warsaw, Poland"},{"name":"Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1177\/153537020322801013","article-title":"Regulation of Intestinal and Hypothalamic Apolipoprotein A-IV","volume":"228","author":"Liu","year":"2003","journal-title":"Exp. 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