Phytochemicals, Gut-Derived Metabolites, and Cognitive Ageing
Doctoral research bridging nutritional epidemiology, gut microbiome science, and cognitive neuroscience.
Background and rationale
The 2024 Lancet Commission identified 14 modifiable risk factors accounting for approximately 45% of dementia cases globally, converging on oxidative stress and neuroinflammation as shared biological pathways. Dietary phytochemicals are biologically plausible interventions targeting these convergent pathways, but progress has been limited by two persistent obstacles: imprecise measurement of dietary phytochemical intake through food frequency questionnaires, and substantial inter-individual variation in microbial metabolism that determines bioavailability and biological activity. Both can be addressed by using gut-derived phytochemical associated metabolites as objective biomarkers that integrate exposure, absorption, and microbial transformation into a single quantifiable signal.
Foundation: a systematic review and meta-analysis (current)
My PROSPERO-registered systematic review of 16 randomised controlled trials (114 outcome observations, N ≈ 1,700) examined long-term phytochemical interventions on cognitive outcomes in adults aged 50 and older. All five domain-level pooled estimates favoured intervention, with a small but statistically significant effect on global cognition after excluding high-risk-of-bias studies (g = 0.11, p = .022), and zero heterogeneity across six executive function trials (g = 0.14, I² = 0%). A convergent pattern emerged across independent studies: phytochemical interventions preferentially benefited cognitively vulnerable populations rather than healthy controls, supporting their inclusion as candidate components of multidomain dementia prevention strategies. This pattern is consistent with ceiling effects in conventional neuropsychological batteries, which were designed primarily to detect gross impairment and may lack the sensitivity to capture the modest cognitive benefits of dietary phytochemical exposure in cognitively intact older adults.
From the AAIC 2026 poster · click through for the full poster page
Moving forward: UK Biobank metabolomics and cognitive ageing
Exploring the Associations Between Gut Microbial-Linked Plasma Metabolites, Phytochemical-rich food, and Cognitive Function in the UK Biobank
Microbes form a key interface between diet and human physiology. In the gut, microbial metabolism of plant-based foods rich in fibre and phytochemicals produces circulating bioactive metabolites that may influence immune regulation, metabolic health, and cognitive function. However, the role of these gut microbial-linked plasma metabolites in cognitive ageing remains poorly understood in large population cohorts.
This project will investigate how gut microbial-linked plasma metabolites relate to plant-based dietary intake and cognitive function in the UK Biobank. The primary objectives are to: identify circulating metabolites with direct or strong indirect links to gut microbial metabolism; test their cross-sectional and longitudinal associations with cognitive performance and cognitive decline; quantify dietary determinants of these metabolites, with emphasis on phytochemical-rich, fibre-containing foods; and assess inflammatory and cardiometabolic pathways as potential biological mediators using established markers of vascular health, lipid metabolism, hepatic function, and systemic inflammation.
Dietary intake, plasma metabolomics, cognition, genetics, and inflammatory biomarkers will be integrated using multivariable regression, composite metabolite scores, and mediation analyses. Where suitable genetic instruments exist, Mendelian randomisation will be used to test causal consistency between microbial-linked metabolites and cognitive outcomes.
By modelling microbial-linked metabolic intermediates at scale, this research seeks to clarify diet–microbe–metabolite–brain pathways and identify circulating biomarkers relevant to early cognitive decline and long-term cognitive resilience. Unlike prior UK Biobank studies that have examined diet or metabolomics in isolation, this project explicitly models gut microbial-linked plasma metabolites as biological intermediates linking phytochemical-rich dietary intake to cognitive ageing and dementia risk.
- Data source
- UK Biobank (approximately 500,000 participants)
- Candidate metabolites
- Gut microbial-linked, phytochemical-associated metabolites, including urolithins, equol, enterolactone, hippurate, and phenolic acid derivatives
- Outcomes
- Cross-sectional and longitudinal cognitive performance and cognitive decline
- Mediators assessed
- Inflammatory and cardiometabolic pathways: vascular health, lipid metabolism, hepatic function, systemic inflammation
- Analysis
- Multivariable regression, composite metabolite scores, and mediation analysis; Mendelian Randomisation where suitable genetic instruments exist
- Training
- Specialist MR training under Professor Stephen Burgess, University of Cambridge, and the Dementias Platform UK Elementary Academy, University of Oxford
Positioning
The research is consistently framed around the immune mediation pathway connecting peripheral biology to brain outcomes, building on the convergent-pathway argument central to the systematic review. The programme is organised around a novel theoretical framework integrating these mechanisms, which will be introduced formally in the forthcoming manuscript.
I am a member of the GIBA Network and iSTAART, and welcome conversations about publication, collaboration, and shared research interests across nutrition, microbiome, and cognitive ageing.
Key links
- PROSPERO
- CRD420261322655
- Manuscript
- Draft available on request
- ORCID
- 0009-0008-4728-6137