biostudies-literatureZeber-Lubecka NCentre of Postgraduate Medical EducationNational Science Centre1278https://www.ebi.ac.uk/biostudies/studies/S-EPMC12467894biostudies-literatureUnknown14(9)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-mass 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 <i>Akkermansia</i> and reduced <i>Monoglobus</i> 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.BiologyLifetime Changes in Gut Microbiota and Metabolite Composition in High-Fat Diet-Induced Obesity in Apolipoprotein A-IV Gene Knockout Mice.PMC12467894501-1-009-12-202018/29/B/NZ7/00809Balabas AOstrowski JKulecka MCzarnowski PDabrowska MHennig EEZeber-Lubecka NPysniak KfalseLifetime Changes in Gut Microbiota and Metabolite Composition in High-Fat Diet-Induced Obesity in Apolipoprotein A-IV Gene Knockout Mice.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-mass 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 <i>Akkermansia</i> and reduced <i>Monoglobus</i> 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.2025-01-01T00:00:00Z2025 Sep2026-05-02T03:12:29.165Z2026-05-02T03:07:52.269ZS-EPMC124678944100742210.3390/biology14091278