# Regulating the crosstalk between Bifidobacterium and the brain: a potential therapeutic strategy for Alzheimer’s disease

**Authors:** Liting Peng, Zhiming Zhang, Yuan Hu, Huijia Chen, Yingru Tian, Hongyan Ling

PMC · DOI: 10.3389/fimmu.2026.1706811 · 2026-02-03

## TL;DR

This paper reviews how Bifidobacterium in the gut may influence Alzheimer’s disease through the gut-brain connection, suggesting a new treatment approach.

## Contribution

The paper systematically reviews Bifidobacterium’s role in Alzheimer’s and its potential as a therapeutic strategy via the gut-microbe-brain axis.

## Key findings

- Bifidobacterium levels are significantly reduced in Alzheimer’s patients.
- Bifidobacterium may influence Alzheimer’s pathology through gut-brain communication.
- Current understanding of Bifidobacterium’s mechanisms in Alzheimer’s remains limited.

## Abstract

Alzheimer’s disease (AD) is a common dementia in the elderly population, typically manifested through symptoms of cognitive impairment (CI) and memory loss. Pathologically, it is characterized by abnormally elevated levels of amyloid-β (Aβ) deposition and tau phosphorylation. Given the rapid rate of population aging, many scientists are investigating AD, focusing on its pathogenic mechanisms and potential treatments. Unfortunately, to date, no highly effective therapeutic strategies have emerged. Intriguingly, multiple studies have revealed alterations in the gut microbiome of individuals with AD, suggesting it may serve as a novel avenue for investigating AD pathogenesis. Bifidobacterium, a pivotal probiotic in the gastrointestinal tract, is crucial in upholding the equilibrium of gut flora. Notably, marked deficiencies in Bifidobacterium have been observed in the guts of AD patients, underscoring the potential of further inquiry into the impact of Bifidobacteria on AD via the gut-microbe-brain axis. However, current research on the mechanisms through which Bifidobacteria can alleviate AD is limited, warranting further investigation. This review examines Bifidobacterial alterations in Alzheimer’s disease patients and the underlying mechanisms, with the aim of evaluating their potential as a therapeutic strategy for Alzheimer’s disease.

## Linked entities

- **Proteins:** MAPT (microtubule associated protein tau)
- **Diseases:** Alzheimer’s disease (MONDO:0004975), dementia (MONDO:0001627)
- **Species:** Bifidobacterium (taxon 1678)

## Full-text entities

- **Genes:** Ffar3 (free fatty acid receptor 3) [NCBI Gene 233080] {aka Gm478, Gpr41}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Htr1b (5-hydroxytryptamine (serotonin) receptor 1B) [NCBI Gene 15551] {aka 5-HT-1B}, Lbp (lipopolysaccharide binding protein) [NCBI Gene 16803] {aka Bpifd2, Ly88}, MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}, Grin1 (glutamate receptor, ionotropic, NMDA1 (zeta 1)) [NCBI Gene 14810] {aka GluN1, GluRdelta1, GluRzeta1, M100174, NMD-R1, NMDAR1}, Hcar2 (hydroxycarboxylic acid receptor 2) [NCBI Gene 80885] {aka Gpr109a, Gpr109b, HM74, Niacr1, PUMA-G, Pumag}, Htr2a (5-hydroxytryptamine (serotonin) receptor 2A) [NCBI Gene 15558] {aka 5-HT-2, 5-HT-2A, E030013E04, Htr-2, Htr2}, Bdnf (brain derived neurotrophic factor) [NCBI Gene 12064], Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, App (amyloid beta precursor protein) [NCBI Gene 11820] {aka Abeta, Abpp, Adap, Ag, Cvap, E030013M08Rik}, Adam10 (a disintegrin and metallopeptidase domain 10) [NCBI Gene 11487] {aka 1700031C13Rik, MADM, kuz, kuzbanian}, H3c7 (H3 clustered histone 7) [NCBI Gene 260423] {aka H3.2-221, H3c13, H3c14, H3c15, H3c2, H3c3}, Dlg4 (discs large MAGUK scaffold protein 4) [NCBI Gene 13385] {aka Dlgh4, PSD-95, PSD95, SAP90, SAP90A}, Ntrk2 (neurotrophic tyrosine kinase, receptor, type 2) [NCBI Gene 18212] {aka GP145-TrkB/GP95-TrkB, Tkrb, trk-B, trkB}, Tlr4 (toll-like receptor 4) [NCBI Gene 21898] {aka Lps, Ly87, Ran/M1, Rasl2-8}, Itgax (integrin alpha X) [NCBI Gene 16411] {aka Cd11c, Cr4, N418}, Mapk8 (mitogen-activated protein kinase 8) [NCBI Gene 26419] {aka JNK, JNK1, Prkm8, SAPK1}, Mapk14 (mitogen-activated protein kinase 14) [NCBI Gene 26416] {aka CSBP2, Crk1, Csbp1, Mxi2, PRKM14, PRKM15}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, Glul (glutamate-ammonia ligase) [NCBI Gene 14645] {aka GS, Glns}, Psen1 (presenilin 1) [NCBI Gene 19164] {aka Ad3h, PS-1, PS1, S182}, Pparg (peroxisome proliferator activated receptor gamma) [NCBI Gene 19016] {aka Nr1c3, PPAR-gamma, PPAR-gamma2, PPARgamma, PPARgamma2}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}
- **Diseases:** intestinal diseases (MESH:D007410), CI (MESH:D003072), memory deficits (MESH:D008569), amyloidosis (MESH:D000686), sleep deprivation (MESH:D012892), dementia (MESH:D003704), endotoxemia (MESH:D019446), neurological decline (MESH:D009461), neurotoxicity (MESH:D020258), AD (MESH:D000544), SAE (MESH:D065166), diabetes mellitus (MESH:D003920), Gut dysbiosis (MESH:D064806), Neuroinflammation (MESH:D000090862), CNS dysfunction (MESH:D002493), liver diseases (MESH:D008107), central nervous system (CNS) inflammation (MESH:D007249), HL (MESH:C538324), neurodegeneration (MESH:D019636), cerebral diseases (MESH:D002539)
- **Chemicals:** acetate (MESH:D000085), pyridoxal phosphate (MESH:D011732), tryptophan (MESH:D014364), glucose (MESH:D005947), 5-HT (MESH:D012701), BAs (MESH:D001464), SCFA (MESH:D005232), Butyric acid (MESH:D020148), LPS (MESH:D008070), butyrate (MESH:D002087), amino acids (MESH:D000596), MSG (MESH:D012970), propionate (MESH:D011422), BB68S (-), bile acids (MESH:D001647), NO (MESH:D009614), GABA (MESH:D005680), inulin (MESH:D007444), glutamate (MESH:D018698), Acetic acid (MESH:D019342), propionic acid (MESH:C029658), lactic acid (MESH:D019344), MDA (MESH:D015104), cortisol (MESH:D006854)
- **Species:** Bifidobacterium breve (species) [taxon 1685], gut metagenome (species) [taxon 749906], Levilactobacillus brevis (species) [taxon 1580], Bacillota (clostridial firmicutes, phylum) [taxon 1239], Thomasclavelia cocleata (species) [taxon 69824], Bifidobacterium animalis (species) [taxon 28025], Acetobacter subgen. Acetobacter (subgenus) [taxon 151157], Collinsella (genus) [taxon 102106], Bifidobacterium dentium (species) [taxon 1689], Bacteroides (genus) [taxon 816], Bifidobacterium longum BORI (strain) [taxon 478445], Homo sapiens (human, species) [taxon 9606], Bifidobacterium (genus) [taxon 1678], Akkermansia muciniphila (species) [taxon 239935], Lachnospira (genus) [taxon 28050], Bifidobacterium angulatum (species) [taxon 1683], Porphyromonas gingivalis (species) [taxon 837], Erysipelothrix (genus) [taxon 1647], Mycobacterium avium (species) [taxon 1764], Bifidobacterium moukalabense (species) [taxon 1333651], Lactococcus lactis (species) [taxon 1358], Candidatus Stoquefichus (genus) [taxon 1470349], Clostridia (class) [taxon 186801], Bifidobacterium ruminantium (species) [taxon 78346], Bifidobacterium adolescentis (species) [taxon 1680], Bifidobacterium merycicum (species) [taxon 78345], Lactococcus lactis subsp. lactis (subspecies) [taxon 1360], Eubacterium (genus) [taxon 1730], Mus musculus (house mouse, species) [taxon 10090], Lacticaseibacillus rhamnosus (species) [taxon 47715], Clostridium sp. MD294 (species) [taxon 97138], Bifidobacterium longum (species) [taxon 216816], Faecalibacterium (genus) [taxon 216851], Bifidobacterium bifidum BGN4 (strain) [taxon 484020]

## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12909532/full.md

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Source: https://tomesphere.com/paper/PMC12909532