# Fish (Alaska Pollock) protein intake attenuates age-related short-term memory decline through gut microbiota modulation

**Authors:** Yuki Murakami, Ryota Hosomi, Genki Tanaka, Hirokazu Murakami, Ayaka Kanto, Takahiro Kimura, Yukio Imamura, Munehiro Yoshida, Kenji Fukunaga

PMC · DOI: 10.1038/s41598-026-38717-y · 2026-02-13

## TL;DR

Eating Alaska pollock protein improves memory in aging mice by changing gut bacteria and reducing brain inflammation.

## Contribution

Shows for the first time that Alaska pollock protein intake can prevent age-related memory decline via gut-brain axis modulation.

## Key findings

- Alaska pollock protein diet improved glucose tolerance and prevented memory decline in SAMP8 mice.
- Promoted growth of beneficial gut bacteria like Lactobacillus and Lachnospiraceae in mice.
- Reduced neuroinflammation and demyelination in the hippocampus of SAMP8 mice.

## Abstract

Dysbiosis leads to decreased intestinal barrier function, causing systemic inflammation and possibly the development of age-related cognitive decline. In this study, we investigated the effect of an Alaska pollack protein (APP) diet on cognitive function, gut microbiota composition, intestinal barrier function, and neuroinflammation in senescence-accelerated mouse prone8 (SAMP8) and senescence-resistant AKR/J (SAMR1) mice. The APP diet produced significant improvements across multiple parameters. It enhanced glucose tolerance in both strains and prevented short-term memory decline in SAMP8 mice. Microbiome analysis revealed that APP intake promoted beneficial bacteria growth, specifically increasing Lactobacillus in SAMR1 and butyrate-producing Lachnospiraceae in SAMP8. Notably, while APP diet increased butyrate-producing bacteria in SAMP8, short-chain fatty acids (SCFAs) analysis showed increased aetate but unchanged butyrate levels, suggesting complex metabolic interactions beyond simple bacterial abundance. Moreover, the APP diet significantly suppressed neuroinflammation in SAMP8, evidenced by decreased proinflammatory cytokine expression, microglia and astrocyte activation, and attenuated demyelination in the hippocampus. These findings suggest that APP intake prevents age-related short-term memory decline through beneficial gut microbiota modulation, and reduced neuroinflammation, supporting the role of the gut-brain axis in cognitive aging.

The online version contains supplementary material available at 10.1038/s41598-026-38717-y.

## Full-text entities

- **Genes:** Slc17a5 (solute carrier family 17 (anion/sugar transporter), member 5) [NCBI Gene 235504] {aka 4631416G20Rik, 4732491M05, AST, ISSD, NSD, SD}, Bcar1 (breast cancer anti-estrogen resistance 1) [NCBI Gene 12927] {aka Cas, Crkas}, Muc6 (mucin 6, gastric) [NCBI Gene 353328], Gpt (glutamic pyruvic transaminase, soluble) [NCBI Gene 76282] {aka 1300007J06Rik, 2310022B03Rik, ALT, ALT1, Gpt-1, Gpt1}, Fcgbp (Fc fragment of IgG binding protein) [NCBI Gene 215384] {aka A430096B05Rik}, Muc17 (mucin 17, cell surface associated) [NCBI Gene 666339] {aka Muc3}, Ffar3 (free fatty acid receptor 3) [NCBI Gene 233080] {aka Gm478, Gpr41}, C1qa (complement component 1, q subcomponent, alpha polypeptide) [NCBI Gene 12259] {aka Adic, C1q}, Lcn2 (lipocalin 2) [NCBI Gene 16819] {aka 24p3, NRL, Sip24}, Muc2 (mucin 2) [NCBI Gene 17831] {aka 2010015E03Rik, MCM, wnn}, Gfap (glial fibrillary acidic protein) [NCBI Gene 14580], Alb (albumin) [NCBI Gene 11657] {aka Alb-1, Alb1, BCL001, BCL002, BPL001}, Cys1 (cystin 1) [NCBI Gene 12879] {aka 2900006B19Rik, Ccap, ck, cpk}, Il10 (interleukin 10) [NCBI Gene 16153] {aka CSIF, If2a, Il-10}, Il4 (interleukin 4) [NCBI Gene 16189] {aka BSF-1, Il-4}, Nefh (neurofilament, heavy polypeptide) [NCBI Gene 380684] {aka NF-H, NF200, Nfh, mKIAA0845}, Cldn1 (claudin 1) [NCBI Gene 12737], Tgfb1 (transforming growth factor, beta 1) [NCBI Gene 21803] {aka TGF-beta1, TGFbeta1, Tgfb, Tgfb-1}, Tff3 (trefoil factor 3, intestinal) [NCBI Gene 21786] {aka ITF, mITF}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Lbp (lipopolysaccharide binding protein) [NCBI Gene 16803] {aka Bpifd2, Ly88}, Cbx8 (chromobox 8) [NCBI Gene 30951] {aka Pc3}, Tjp1 (tight junction protein 1) [NCBI Gene 21872] {aka ZO1}, Mbp (myelin basic protein) [NCBI Gene 17196] {aka Hmbpr, golli-mbp, jve, mld, shi}, Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Bdnf (brain derived neurotrophic factor) [NCBI Gene 12064], Cldn2 (claudin 2) [NCBI Gene 12738], Hcar2 (hydroxycarboxylic acid receptor 2) [NCBI Gene 80885] {aka Gpr109a, Gpr109b, HM74, Niacr1, PUMA-G, Pumag}, Ngf (nerve growth factor) [NCBI Gene 18049] {aka Ngfb, beta-NGF}, App (amyloid beta precursor protein) [NCBI Gene 11820] {aka Abeta, Abpp, Adap, Ag, Cvap, E030013M08Rik}, Agr2 (anterior gradient 2) [NCBI Gene 23795] {aka Agr2h, Gob-4, HAG-2, XAG-2, mAG-2}, Ffar2 (free fatty acid receptor 2) [NCBI Gene 233079] {aka GPCR43, Gpr43}, Iba1 (induction of brown adipocytes 1) [NCBI Gene 114737], Ocln (occludin) [NCBI Gene 18260] {aka Ocl}, Il1a (interleukin 1 alpha) [NCBI Gene 16175] {aka Il-1a}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, Psen1 (presenilin 1) [NCBI Gene 19164] {aka Ad3h, PS-1, PS1, S182}
- **Diseases:** synaptic dysfunction (MESH:C536122), MS (MESH:D009103), impaired spatial working memory (MESH:D008569), cognitive and memory decline (MESH:D003072), ulcerative colitis (MESH:D003093), axonal damage (MESH:D001480), dementia (MESH:D003704), amyloid (MESH:C000718787), ischemic injury (MESH:D017202), sudden death (MESH:D003645), brain inflammation (MESH:D004660), insulin resistance (MESH:D007333), endotoxemia (MESH:D019446), Hyperglycemic (MESH:D006944), neurological damage (MESH:D020196), demyelinating disease (MESH:D003711), SAM (MESH:D004482), learning and memory impairment (MESH:D007859), Diabetes (MESH:D003920), Dysbiosis (MESH:D064806), AD (MESH:D000544), memory decline (MESH:D060825), neurotoxicity (MESH:D020258), neuroinflammation (MESH:D000090862), lipidemia (MESH:D006949), hyperglycemia (MESH:D006943), neurodegeneration (MESH:D019636), central nervous system inflammation (MESH:D007249)
- **Chemicals:** cellulose (MESH:D002482), acetate (MESH:D000085), Tween-20 (MESH:D011136), SCFA (MESH:D005232), Periodic acid (MESH:D010504), D (+)-glucose (MESH:D005947), formalin (MESH:D005557), 4',6-diamidino-2-phenylindole (MESH:C007293), citric acid (MESH:D019343), isobutyrate (MESH:D058610), lipopolysaccharide (MESH:D008070), lipid (MESH:D008055), paraformaldehyde (MESH:C003043), sucrose (MESH:D013395), butyrate (MESH:D002087), cornstarch (MESH:D013213), Propionate (MESH:D011422), helium (MESH:D006371), AIN-93G (-), sodium (MESH:D012964), L-cystine (MESH:D003553), PUFAs (MESH:D005231), soybean oil (MESH:D013024), blood glucose (MESH:D001786), valerate (MESH:D014631), Alcian Blue (MESH:D000423), ethanol (MESH:D000431), water (MESH:D014867), TRIzol (MESH:C411644), isoflurane (MESH:D007530), Choline bitartrate (MESH:D002794), n-3 polyunsaturated fatty acids (MESH:D015525), tributyrin (MESH:C005830), Triton X-100 (MESH:D017830), cuprizone (MESH:D003471), paraffin (MESH:D010232), n-hexane (MESH:C026385)
- **Species:** gut metagenome (species) [taxon 749906], Bacillota (clostridial firmicutes, phylum) [taxon 1239], Bacteroides (genus) [taxon 816], Homo sapiens (human, species) [taxon 9606], Erysipelatoclostridium [taxon 1505663], Agathobacter rectalis (species) [taxon 39491], Gadus chalcogrammus (Alaska pollock, species) [taxon 1042646], Mus musculus (house mouse, species) [taxon 10090], Lactobacillus (genus) [taxon 1578], Pollachius pollachius (pollack, species) [taxon 185739]
- **Cell lines:** 3xTg — Mus musculus (Mouse), Hybridoma (CVCL_C6V6), SAMP8 — Mus musculus (Mouse), Factor-dependent cell line (CVCL_K252), AIN-93 — Homo sapiens (Human), Nephropathic cystinosis, Finite cell line (CVCL_CW96), S2 — Drosophila melanogaster (Fruit fly), Spontaneously immortalized cell line (CVCL_Z232)

## Figures

13 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12976315/full.md

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Source: https://tomesphere.com/paper/PMC12976315