{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:06:23Z","timestamp":1791230783877,"version":"4.1.0"},"reference-count":77,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,3,21]],"date-time":"2025-03-21T00:00:00Z","timestamp":1742515200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"PMU-Research and Innovation Fund (PMU-RIF)","award":["2023-PRE-008-Altendorfer"],"award-info":[{"award-number":["2023-PRE-008-Altendorfer"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Neuroinflammation, a hallmark of Alzheimer\u2019s disease (AD), is characterized by elevated levels of inflammatory signaling molecules, including cytokines and eicosanoids, as well as increased microglial reactivity, and is augmented by gut microbiota dysbiosis via the gut\u2013brain axis. We conducted a pilot experiment to elucidate the anti-inflammatory effects of dietary omega-3 polyunsaturated fatty acid (\u03c9-3 PUFA) eicosapentaenoic acid (EPA) on the gut microbiota and neuroinflammation. Methods: Female APP\/PS1 mice (TG) and non-transgenic littermates (WT), 13\u201314 months old, were fed a diet supplemented with 0.3% EPA or control chow for 3 weeks. The gut microbiota composition, hippocampal and plasma eicosanoids levels, platelet activation, and microglial phagocytosis, as well as the brain and retinal genes and protein expression, were analyzed. Results: EPA supplementation decreased the percentage of Bacteroidetes and increased bacteria of the phylum Firmicutes in APP\/PS1 and WT mice. Inflammatory lipid mediators were elevated in the hippocampus of the TG mice, accompanied by a reduction in the endocannabinoid docosahexaenoyl ethanolamide (DHEA). Dietary EPA did not affect hippocampal lipid mediators, but reduced the levels of arachidonic-derived 5-HETE and N-arachidonoylethanolamine (AEA) in WT plasma. Moreover, EPA supplementation decreased major histocompatibility complex class II (MHCII) gene expression in the retina in both genotypes, and MHCII+ cells in the hippocampus of TG mice. Conclusions: This pilot study showed that short-term EPA supplementation shaped the gut microbiota by increasing butyrate-producing bacteria of the Firmicutes phylum and decreasing Gram-negative LPS-producing bacteria of the Bacteroidetes phylum, and downregulated the inflammatory microglial marker MHCII in two distinct regions of the central nervous system (CNS). Further investigation is needed to determine whether EPA-mediated effects on the microbiome and microglial MHCII have beneficial long-term effects on AD pathology and cognition.<\/jats:p>","DOI":"10.3390\/nu17071108","type":"journal-article","created":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T04:48:18Z","timestamp":1742791698000},"page":"1108","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Omega-3 EPA Supplementation Shapes the Gut Microbiota Composition and Reduces Major Histocompatibility Complex Class II in Aged Wild-Type and APP\/PS1 Alzheimer\u2019s Mice: A Pilot Experimental Study"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3669-5206","authenticated-orcid":false,"given":"Barbara","family":"Altendorfer","sequence":"first","affiliation":[{"name":"Institute of Molecular Regenerative Medicine, Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-6855-6507","authenticated-orcid":false,"given":"Ariane","family":"Benedetti","sequence":"additional","affiliation":[{"name":"Institute of Experimental Neuroregeneration, Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-8373-6813","authenticated-orcid":false,"given":"Heike","family":"Mrowetz","sequence":"additional","affiliation":[{"name":"Institute of Molecular Regenerative Medicine, Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0164-2537","authenticated-orcid":false,"given":"Sabine","family":"Bernegger","sequence":"additional","affiliation":[{"name":"Institute of Molecular Regenerative Medicine, Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina","family":"Bretl","sequence":"additional","affiliation":[{"name":"Institute of Molecular Regenerative Medicine, Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4716-908X","authenticated-orcid":false,"given":"Julia","family":"Preishuber-Pfl\u00fcgl","sequence":"additional","affiliation":[{"name":"Research Program for Experimental Ophthalmology and Glaucoma Research, Department of Ophthalmology and Optometry, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana Marisa","family":"Bessa de Sousa","sequence":"additional","affiliation":[{"name":"Institute of Molecular Regenerative Medicine, Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja Maria","family":"Ladek","sequence":"additional","affiliation":[{"name":"Research Program for Experimental Ophthalmology and Glaucoma Research, Department of Ophthalmology and Optometry, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6108-8411","authenticated-orcid":false,"given":"Andreas","family":"Koller","sequence":"additional","affiliation":[{"name":"Research Program for Experimental Ophthalmology and Glaucoma Research, Department of Ophthalmology and Optometry, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline","family":"Le Faouder","sequence":"additional","affiliation":[{"name":"MetaToul-Lipidomique Core Facility, I2MC, Inserm 1048, 31432 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9815-1517","authenticated-orcid":false,"given":"Justine","family":"Bertrand-Michel","sequence":"additional","affiliation":[{"name":"MetaToul-Lipidomique Core Facility, I2MC, Inserm 1048, 31432 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Trost","sequence":"additional","affiliation":[{"name":"Research Program for Experimental Ophthalmology and Glaucoma Research, Department of Ophthalmology and Optometry, University Hospital of the Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1653-8046","authenticated-orcid":false,"given":"Ludwig","family":"Aigner","sequence":"additional","affiliation":[{"name":"Institute of Molecular Regenerative Medicine, Paracelsus Medical University, 5020 Salzburg, Austria"},{"name":"Austrian Cluster of Tissue Regeneration, 1200 Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,21]]},"reference":[{"key":"ref_1","unstructured":"(2024). 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