ArticleGut microbes
Age-associated temporal decline in butyrate-producing bacteria plays a key pathogenic role in the onset and progression of neuropathology and memory deficits in 3×Tg-AD mice.
Article in Gut microbes. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed.
- From Dysbiosis to Blood-Brain Barrier Disruption: The Metabolite-Mediated Gut-Brain Axis in Alzheimer's Disease.Molecular neurobiology · 2026Review
- Review
- The Gut Microbiome as a Mechanistic Link Between the Planetary Health Diet and Healthy Aging.Nutrients · 2026Review
- Yogurt and human health across history, culture, and science: Lessons for modern aging populations.The journal of nutrition, health & aging · 2026Review
- Designing fiber-gut microbiome interactions with active learning.Nature chemical biology · 2026Article
- Review
- Akkermansia muciniphila reduces neuroinflammation and Aβ deposition via tryptophan metabolism in the APP/PS1 mouse model of Alzheimer's disease.Alzheimer's research & therapy · 2026Article
- Fish (Alaska Pollock) protein intake attenuates age-related short-term memory decline through gut microbiota modulation.Scientific reports · 2026Article
- Exercise training mitigates age-related cognitive decline by attenuating TMAO-induced inflammation.Scientific reports · 2026Article
- Gut microbiota and brain aging: a comparative review of African and western populations.Frontiers in aging neuroscience · 2026Review
- Gut Microbiota and Bipolar Disorder: Advances in Translational Applications.Current neuropharmacology · 2026Review
- Brain-gut communication and potential applications of microecological treatments in stroke.Frontiers in neuroscience · 2026Review
- Synergistic Regulation of Alzheimer's Disease and Intestinal Microbiota Metabolism Mediated by the Gut-Brain Axis: A Comprehensive Analysis from a Multidisciplinary Perspective.International journal of medical sciences · 2026Review
- Sex-Specific Diet-Microbiota Interactions in Ageing: Implications for Healthy Longevity.Nutrients · 2025Review
- Sodium oligomannate modulates the gut-brain axis to alleviate post-stroke cognitive impairment by restoring butyrate metabolism.Microbiome · 2025Article
- Progress and Perspectives on the Estrogen-Microbiota-Brain Axis in Alzheimer's Disease.Neurochemical research · 2025Review
- Fecal short-chain fatty acids vary by sex and amyloid status.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Impacts of systemic milieu on cerebrovascular and brain aging: insights from heterochronic parabiosis, blood exchange, and plasma transfer experiments.GeroScience · 2025Review
- Intestinal epithelial Dicer1 regulates gut microbiome and Alzheimer's pathology in App-knock-in mice.Alzheimer's research & therapy · 2025Article
- Linkage of circadian rhythm disruptions with Alzheimer's disease and therapeutic interventions.Acta pharmaceutica Sinica. B · 2025Review
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Authors and funding
19 authors.
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Abstract
Alterations in the gut-microbiome-brain axis are increasingly being recognized to be involved in Alzheimer's disease (AD) pathogenesis. However, the functional consequences of enteric dysbiosis linking gut microbiota and brain pathology in AD progression remain largely undetermined. The present work investigated the causal role of age-associated temporal decline in butyrate-producing bacteria and butyrate in the etiopathogenesis of AD. Longitudinal metagenomics, neuropathological, and memory analyses were performed in the 3×Tg-AD mouse model. Metataxonomic analyses showed a significant temporal decline in the alpha diversity marked by a decrease in butyrate-producing bacterial communities and a concurrent reduction in cecal butyrate production. Inferred metagenomics analysis identified the bacterial acetyl-CoA pathway as the main butyrate synthesis pathway impacted. Concomitantly, there was an age-associated decline in the transcriptionally permissive acetylation of histone 3 at lysines 9 and 14 (H3K9/K14-Ac) in hippocampal neurons. Importantly, these microbiome-gut-brain changes preceded AD-related neuropathology, including oxidative stress, tau hyperphosphorylation, memory deficits, and neuromuscular dysfunction, which manifest by 17-18 months. Initiation of oral administration of tributyrin, a butyrate prodrug, at 6 months of age mitigated the age-related decline in butyrate-producing bacteria, protected the H3K9/K14-Ac status, and attenuated the development of neuropathological and cognitive changes associated with AD pathogenesis. These data causally implicate age-associated decline in butyrate-producing bacteria as a key pathogenic feature of the microbiome-gut-brain axis affecting the onset and progression of AD. Importantly, the regulation of butyrate-producing bacteria and consequent butyrate synthesis could be a significant therapeutic strategy in the prevention and treatment of AD.
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