Research

The gut–brain axis is one of the most active frontiers in neuroscience. Here is where the field stands — and where our work fits in.

  • Gut bacteria can directly influence neurodegeneration. Independent landmark research (Nature, 2019) demonstrated that microbiome composition causally affects ALS progression in animal models — establishing the gut–brain axis as a driver, not just a bystander, in neurodegenerative disease.
  • One-carbon metabolism is a central, underexplored vulnerability in Alzheimer's disease. Our published work identified a specific disruption in mitochondrial one-carbon metabolism across AD models, patient data, and genetic studies — a mechanism the field had largely overlooked.
  • Boosting this pathway is neuroprotective. Across four peer-reviewed publications, our team has shown that restoring one-carbon metabolic flux — via folinic acid, nucleotide supplementation, or NAD⁺ precursors — reduces amyloid pathology, extends lifespan, and improves mitochondrial function in validated disease models.
  • Probiotic delivery is a clinically viable route. Emerging trials (2026) are now testing whether gut-delivered probiotics can produce measurable cognitive benefits in older adults with MCI and Alzheimer's — validating the therapeutic direction 1C-01 is designed to advance.
  • 1C-01 is built on this body of evidence. Our product is not based on general "gut health" claims — it is designed to target a specific, well-characterised metabolic pathway with a growing body of mechanistic and clinical support.

Our Published Research

Five peer-reviewed publications from our team spanning 2021–2025, establishing mitochondrial one-carbon metabolism as a central vulnerability in Alzheimer's disease and demonstrating neuroprotective benefit across multiple model systems.

Publication Author(s) Date Summary PDF
Enhancing mitochondrial one-carbon metabolism is neuroprotective in Alzheimer's disease models Yu Y., Chen C.Z., Celardo I., Tan B.W.Z., Hurcomb J.D., Leal N.S., Popovic R., Loh S.H.Y., Martins L.M. 2024 View Here, we found that a specific mitochondrial process called one-carbon metabolism is disrupted in Alzheimer's disease. Boosting this pathway genetically or by supplementing with folinic acid improved mitochondrial function in both flies and cells. Human data also showed that genes involved in this pathway affect AD risk, suggesting a new treatment direction. PDF
Mitochondrial one-carbon metabolism and Alzheimer's disease Yu Y., Martins L.M. 2024 View Multiple hallmarks of Alzheimer's disease — including amyloid-β accumulation, tau pathology, and age-related oxidative damage — converge on mitochondrial dysfunction, linked to impaired one-carbon metabolism. Five key cellular processes disrupted in AD (redox balance, NAD⁺ availability, mitochondrial function, genome stability, and DNA methylation) are all connected to the one-carbon pathway. SAM, the brain's primary methyl donor and a product of one-carbon metabolism, is severely depleted in AD brains. Enhancing mitochondrial one-carbon metabolism — through folate, folinic acid, or probiotic-based delivery — represents a viable therapeutic strategy for delaying the onset and progression of Alzheimer's disease. PDF
Increased nucleotide metabolism alleviates Alzheimer's disease pathology Yu Y., Miller M.B., Huang A.Y., Tan B.W.Z., Celardo I., Leal N.S., Loh S.H.Y., Martins L.M. 2025 View This study found that PARP1 — a DNA-repair enzyme — is elevated in Alzheimer's patient brains and causally linked to increased AD risk. In a fly model of AD, phosphorylated nucleotides are depleted; restoring nucleotide availability through dietary supplementation or genetic means reduced oxidative DNA damage, improved mitochondrial function, and extended lifespan. The findings point to boosting nucleotide metabolism as a viable dietary or therapeutic strategy to slow AD progression. PDF
Parp mutations protect from mitochondrial toxicity in Alzheimer's disease Yu Y., Fedele G., Celardo I., Loh S.H.Y., Martins L.M. 2021 View We analysed the metabolomic changes in a fly model of AD and identified a decrease of metabolites associated with nicotinamide metabolism, which is critical for mitochondrial function in neurons. We used combined results in flies and humans to show that increasing the bioavailability of NAD+ is neuroprotective. PDF
Distinct forms of amyloid-β moderate sleep duration through NAD⁺-linked redox metabolism in Alzheimer's disease Yu Y., Fedele G., Celardo I., Zhou L., Tan B.W.Z., Loh S.H.Y., Martins L.M. 2025 View Using epidemiological data and fruit fly models, this study shows that sleep disruption changes direction across the course of Alzheimer's disease: people at high AD risk sleep less, while those with a clinical diagnosis sleep more. Different forms of amyloid-beta replicate this bidirectional pattern in flies, with the mechanism linked to NAD⁺-dependent redox metabolism. The findings connect sleep disruption in AD to one-carbon and related metabolic pathways — the same pathways targeted by 1C-01. PDF