ArticleBMC systems biology2016
Towards understanding brain-gut-microbiome connections in Alzheimer's disease.
Article in BMC systems biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers, 2 of them syntheses that pooled it.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
96 citing papers in PubMed, 2 syntheses or guidelines pooled it, 173 citations in OpenAlex.
- Pooled it
- Gut microbiota, cognitive frailty and dementia in older individuals: a systematic review.Clinical interventions in aging · 2018Pooled it
- Cognitive-Motor Dual Task Training Synergistically Improves Aging-related Cognitive Dysfunction By Reducing TMAO and Suppressing TXNIP/NLRP3 Pathway.Molecular neurobiology · 2026Article
- Modulating the Gut-Microbiota-Brain Axis in Alzheimer's Disease: Therapeutic Potential of Nutritional and Metabolic Factors.CNS neuroscience & therapeutics · 2026Review
- Gut Microbiota-Derived TMAO Drives MC3T3-E1 Senescence and Osteogenic Dysfunction via cGAS-STING-NF-κB Signaling: Implications for Age-Related Bone Loss.Calcified tissue international · 2026Article
- Differences in gut microbiota composition between ischemic stroke patients and healthy individuals.BMC neurology · 2026Article
- Saccharomyces boulardii Ameliorates LPS-Induced Amyloidogenesis in Rats.Probiotics and antimicrobial proteins · 2025Article
- Altered gut microbiota mediates the association between APOE genotype and amyloid-β accumulation in middle-aged adults.Journal of neurology · 2025Article
- Gut microbial metabolite TMAO impairs cognitive function and induces hippocampal synaptic plasticity decline through modulation of GSK-3β activity.Alzheimer's research & therapy · 2025Article
- In Vitro Neuroprotective Effects of a Mixed Extract of Bilberry,Foods (Basel, Switzerland) · 2025Article
- Gastrointestinal Dysfunction and Low-Grade Inflammation Associate With Enteric Neuronal Amyloid-β in a Model for Amyloid Pathology.Neurogastroenterology and motility · 2025Article
- Salivary trimethylamine N-oxide: a novel non-invasive marker for periodontal inflammation.Clinical oral investigations · 2025Article
- Trimethylamine-N-Oxide (TMAO) as a Rising-Star Metabolite: Implications for Human Health.Metabolites · 2025Review
- Microbiota-Gut-Brain Axis: Mass-Spectrometry-Based Metabolomics in the Study of Microbiome Mediators-Stress Relationship.Biomolecules · 2025Review
- The Role of Gut Microbiota-Derived Trimethylamine N-Oxide in the Pathogenesis and Treatment of Mild Cognitive Impairment.International journal of molecular sciences · 2025Review
- Effects of choline metabolite-trimethylamine N-oxide on immunometabolism in inflammatory bowel disease.Frontiers in immunology · 2025Review
- Thinking outside the brain: Gut microbiome influence on innate immunity within neurodegenerative disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Gut microbial metabolism in Alzheimer's disease and related dementias.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
- Exploring the effect of gut microbiome on Alzheimer's disease.Biochemistry and biophysics reports · 2024Review
- Feeding gut microbes to nourish the brain: unravelling the diet-microbiota-gut-brain axis.Nature metabolism · 2024Review
36 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
2 authors at 1 institution in 1 country.
Funding
Abstract
backgroundAlzheimer's disease (AD) is complex, with genetic, epigenetic, and environmental factors contributing to disease susceptibility and progression. While significant progress has been made in understanding genetic, molecular, behavioral, and neurological aspects of AD, relatively little is known about which environmental factors are important in AD etiology and how they interact with genetic factors in the development of AD. Here, we propose a data-driven, hypotheses-free computational approach to characterize which and how human gut microbial metabolites, an important modifiable environmental factor, may contribute to various aspects of AD. MATERIALS AND
methodsWe integrated vast amounts of complex and heterogeneous biomedical data, including disease genetics, chemical genetics, human microbial metabolites, protein-protein interactions, and genetic pathways. We developed a novel network-based approach to model the genetic interactions between all human microbial metabolites and genetic diseases. We identified metabolites that share significant genetic commonality with AD in humans. We developed signal prioritization algorithms to identify the co-regulated genetic pathways underlying the identified AD-metabolite (brain-gut) connections.
resultsWe validated our algorithms using known microbial metabolite-AD associations, namely AD-3,4-dihydroxybenzeneacetic acid, AD-mannitol, and AD-succinic acid. Our study provides supporting evidence that human gut microbial metabolites may be an important mechanistic link between environmental exposure and various aspects of AD. We identified metabolites that are significantly associated with various aspects in AD, including AD susceptibility, cognitive decline, biomarkers, age of onset, and the onset of AD. We identified common genetic pathways underlying AD biomarkers and its top one ranked metabolite trimethylamine N-oxide (TMAO), a gut microbial metabolite of dietary meat and fat. These coregulated pathways between TMAO-AD may provide insights into the mechanisms of how dietary meat and fat contribute to AD.
conclusionsEmploying an integrated computational approach, we provide intriguing and supporting evidence for a role of microbial metabolites, an important modifiable environmental factor, in AD etiology. Our study provides the foundations for subsequent hypothesis-driven biological and clinical studies of brain-gut-environment interactions in AD.
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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.