Using gut neuron health as a predictive indicator of neurodegenerative disease

Neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis are typically diagnosed only after substantial neuronal loss has already occurred, highlighting the urgent need for earlier predictive biomarkers. Emerging evidence suggests that the gastrointestinal (GI) tract may provide a valuable window into the earliest stages of these diseases. GI dysfunction, microbial dysbiosis, and the accumulation of neurodegenerative disease-associated protein aggregates have all been observed in the gut years or even decades before the onset of classical neurological symptoms. This review highlights how the gut-brain axis provides multiple biological pathways through which gut pathology may influence central nervous system health. Neural connections, microbial metabolites, endocrine signaling, immune system interactions, and systemic factors such as aging, oxidative stress, and inflammation collectively link GI and neurological function. Importantly, misfolded proteins associated with neurodegeneration, including alpha-synuclein, Tau, and TDP-43, have been detected in GI tissues prior to clinical disease onset, suggesting that gut neuron health may serve as an early indicator of future neurodegenerative risk. From a diagnostic perspective, the accessibility of the GI tract offers significant advantages over central nervous system sampling. Routine colon biopsies, stool samples, and blood-based analyses provide minimally invasive opportunities to detect early molecular and cellular changes associated with neurodegeneration. Together, these approaches could enable the identification of predictive biomarkers that capture disease-related pathology long before neurological symptoms emerge. Overall, shifting the focus from a purely brain-centred view of neurodegeneration to a systemic perspective that includes gut health may open new opportunities for earlier detection, improved risk stratification, and ultimately more effective therapeutic intervention in neurodegenerative diseases.