ArticleeLife2021
Microbiota-derived short chain fatty acids modulate microglia and promote Aβ plaque deposition.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05601856 (Gut Microbiome and Blood Indices in Patients With AD and Their Spousal Caregivers), which is not on this map. Cited by 224 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Gut Microbiome and Blood Indices in Patients With AD and Their Spousal Caregivers
Who cites it
224 citing papers in PubMed, 1 synthesis or guideline pooled it, 309 citations in OpenAlex.
- Gut microbiome dysbiosis in Alzheimer's disease and mild cognitive impairment: A systematic review and meta-analysis.PloS one · 2023Pooled it
- Nutritional regulation of gut-brain immune crosstalk across the lifespan.Gut microbes · 2026Review
- Short-chain fatty acid-producing commensals: Key modulators of AD neuroinflammation via the microbiota-gut-brain axis.Current research in microbial sciences · 2026Review
- Mechanisms of Brain Aging and Their Links to Alzheimer's and Parkinson's Disease Pathology.International journal of molecular sciences · 2026Review
- From Dysbiosis to Blood-Brain Barrier Disruption: The Metabolite-Mediated Gut-Brain Axis in Alzheimer's Disease.Molecular neurobiology · 2026Review
- Effects ofFoods (Basel, Switzerland) · 2026Article
- The neuroimmune network in Alzheimer's and Parkinson's diseases: from mechanistic insights to biomarker-guided immunotherapies and clinical translation.Inflammopharmacology · 2026Review
- Immune dysregulation and gut microbiota: Connection to health and disease development.Neural regeneration research · 2026Article
- The Gut-Immune-Brain Axis in Aging: Integrating Immunosenescence, Inflammaging, and Neuroinflammation for Precision Medicine.Medical sciences (Basel, Switzerland) · 2026Review
- TDP-43-immunity-microbiota axis in amyotrophic lateral sclerosis: A potential pathogenic mechanism.Neural regeneration research · 2026Article
- Short-Chain Fatty Acid-Dependent Neuroimmune Regulation in Autism Spectrum Disorder Pathogenesis.The European journal of neuroscience · 2026Review
- Select microbial metabolites promote tau aggregation in a murine tauopathy model.Nature communications · 2026Article
- From Leaky Gut to a Vulnerable Brain: Obesity-Associated Gut Barrier Failure in Colorectal Cancer and Cognitive Dysfunction.Nutrients · 2026Review
- Neonatal gut Bifidobacterium associates with indole-3-lactic acid levels in blood and risk of ADHD at age 10.Molecular psychiatry · 2026Article
- Review
- Gut-Derived Metabolic Imbalance in Autism Spectrum Disorder: Toward the Concept of a Metabolic Subtype.Nutrients · 2026Review
- Diet-Microbiome-Brain Axis and Mental Health: Biological Mechanisms and Nutritional Implications.Nutrients · 2026Review
- Microbiota as a regulator of brain vulnerability across lifespan and disease contexts.Journal of neuroinflammation · 2026Review
- Gut-brain axis in health and brain disease.Chinese medical journal · 2026Review
- Effects and Mechanisms of Probiotics, Prebiotics, Synbiotics, and Postbiotics for the Prevention and Management of Alzheimer's Disease: A Narrative Review.Antioxidants (Basel, Switzerland) · 2026Review
164 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 5 institutions in 3 countries.
Funding
Abstract
Previous studies have identified a crucial role of the gut microbiome in modifying Alzheimer's disease (AD) progression. However, the mechanisms of microbiome-brain interaction in AD were so far unknown. Here, we identify microbiota-derived short chain fatty acids (SCFA) as microbial metabolites which promote Aβ deposition. Germ-free (GF) AD mice exhibit a substantially reduced Aβ plaque load and markedly reduced SCFA plasma concentrations; conversely, SCFA supplementation to GF AD mice increased the Aβ plaque load to levels of conventionally colonized (specific pathogen-free [SPF]) animals and SCFA supplementation to SPF mice even further exacerbated plaque load. This was accompanied by the pronounced alterations in microglial transcriptomic profile, including upregulation of ApoE. Despite increased microglial recruitment to Aβ plaques upon SCFA supplementation, microglia contained less intracellular Aβ. Taken together, our results demonstrate that microbiota-derived SCFA are critical mediators along the gut-brain axis which promote Aβ deposition likely via modulation of the microglial phenotype.
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Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.