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Gut microbiota transmission induces cognitive impairment through amyloid pathology in wild-type mice

Chenyi Yang1, Wei Qi1, Wei Li1

  • 1Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.

Neuroscience
|February 27, 2026
PubMed

Insights

Early-life exposure to Alzheimer's disease (AD) mouse microbiota via co-housing induced gut dysbiosis, amyloid pathology, and cognitive deficits in wild-type mice. Probiotic treatment mitigated these AD-like effects.

Area of Science:

  • Neuroscience
  • Microbiology
  • Genetics

Background:

  • Alzheimer's disease (AD) is the primary cause of dementia, often sporadic and influenced by non-genetic factors like gut microbiota.
  • Early-life microbial transmission between AD transgenic (Tg) and wild-type (WT) mice can cause cognitive issues, but mechanisms are unclear.

Purpose of the Study:

  • To investigate the mechanisms of gut microbiota transfer and its impact on cognitive function and amyloid pathology in WT mice exposed to AD Tg mice during early life.
  • To evaluate the therapeutic efficacy of a specific probiotic intervention.

Main Methods:

  • One-month-old WT mice were co-housed with 5XFAD (AD Tg) mice for three months.
  • Gut microbiota composition was analyzed using 16S rRNA sequencing.
  • Brain amyloid-β 42 (Aβ42) levels were measured using ELISA and a nanoplasmonic sensor.
  • Cognitive function was assessed via Morris water maze and Barnes maze.
  • Probiotic treatment (Lactobacillus reuteri and Bifidobacterium pseudolongum) was administered.

Main Results:

  • WT mice co-housed with AD Tg mice (ADWT) exhibited gut dysbiosis with microbial profiles similar to AD Tg mice.
  • ADWT mice showed elevated brain Aβ42 levels and developed cognitive impairments.
  • Probiotic intervention successfully altered gut microbial composition and reduced Aβ42 levels in the cortex and hippocampus of ADWT mice.

Conclusions:

  • Microbiota transfer via early-life co-housing induces gut dysbiosis, amyloid pathology, and cognitive deficits in WT mice.
  • Targeted probiotic intervention can effectively mitigate these microbiota-driven Alzheimer's disease-like effects.
  • These findings support a non-genetic, microbiota-driven pathway in AD pathogenesis.
Keywords:
Alzheimer’sdiseaseCo-housingmodelCognitive impairmentMicrobialdysbiosisProbiotic intervention

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