UCLA researchers in the Department of Medicine, have developed a novel approach to prevent and treat age-related cognitive decline and neurodegenerative diseases by modulating the gut microbiome using diet-derived bacterial and metabolite signatures.
BACKGROUND: Diet is a major modifiable determinant of cognitive function and mental health, with growing evidence linking it to both neuropsychiatric and neurodegenerative outcomes. Recent scientific advances have highlighted the significant impact of diet on the composition and function of the intestinal microbiome, shaping microbial composition and metabolic activity. Specific dietary nutrients and microbiome-derived metabolites can influence signaling pathways and neurotransmitter function in both the brain and the microbiome, which in turn can affect cognitive and mood outcomes.
These interactions are thought to be mediated through the brain-gut-microbiome (BGM) system, a complex communication network linking the gastrointestinal system with the central nervous system through hormonal, neural, immune, and microbial pathways. Alterations in microbiome composition have been shown to affect energy metabolism, provoke inflammation, and impair insulin sensitivity, and have been mechanistically linked to type 2 diabetes, obesity, cardiovascular disease, and Alzheimer’s disease.
Despite the substantial evidence connecting diet, the microbiome, and cognitive health, the specific dietary factors and metabolic signatures that define these relationships remain unclear. Thus, there is a critical need for objective biomarkers that accurately reflect dietary patterns and can be integrated with microbiome and neurocognitive measures.
INNOVATION: Researchers at UCLA, led by Dr. Arpana Church, have developed a novel approach for treating and preventing neurodegenerative diseases and age-related cognitive decline by modulating the diet-microbiome-brain axis. They used a novel “foodomics” approach, reconstructing dietary intake profiles directly from untargeted LC-MS/MS metabolomics data, providing an objective alternative to self-reported dietary assessments.
By integrating metabolomics, microbiome sequencing, gut hormone measurements, and brain imaging in a study of healthy human participants, the researchers identified dietary patterns associated with altered gut microbial composition, reduced gray matter volume in cognitive brain regions, neurocognitive impairment, and metabolic dysfunction. These findings enable the development of targeted microbial compositions containing one or more bacterial strains, optionally combined with metabolite or bile acid supplements, to modulate disease-relevant microbiome pathways, and represents a novel precision medicine approach to prevent neurodegenerative disease and improve brain health.
POTENTIAL APPLICATIONS:
ADVANTAGES:
DEVELOPMENT-TO-DATE: This technology has been validated in 111 human participants using untargeted LC-MS/MS metabolomics and 16S rRNA sequencing of fecal samples, paired with structural brain MRI, gut hormone assays, and validated cognitive and psychosocial assessments.
Related Papers (from the inventors only):
Labus JS, Selvaraj K, Pamula S, Zemlin J, Dorrestein P, Church A. Metabolically Derived Dietary Intake: Links to Gut Microbiome Composition, Gut Hormones, Cognitive Markers and Brain Imaging-Derived Phenotypes in Healthy Participants. Digestive Disease Week (DDW) 2025; Abstract Control ID 4243518.
Keywords: Microbiome, gut microbiome, brain-gut-microbiome axis, BGM, neurodegeneration, Alzheimer’s disease, cognitive decline, age-related cognitive decline, dementia, foodomics, metabolomics, probiotic, prebiotic, cognitive health, executive function, sensorimotor network, gray matter, brain imaging, MRI, gut hormones, GLP-1, GIP, C-peptide, insulin resistance, BMI, obesity