Background
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with unknown etiology and no effective neuroprotective therapy. The gut microbiome may integrate environmental contributions to neurodegeneration. Recent studies suggest potential gut microbiome differences among ALS patients.
Objectives
We hypothesize that specific microbial species or metabolites contribute to systemic dysbiosis, increasing ALS risk and progression. This study integrates patient clinical data, environmental exposure, dietary recall, microbiome samples, multi-omic analyses, and Bayesian machine learning to identify microbial biomarkers predictive of ALS.
Methods
We will enroll 100 ALS patients along with two controls per patient: a spouse/partner control and a control that is sex, age, and geographical location matched. Data collection includes longitudinal clinical data inputted into the MDA MOVR database, environmental exposures, and dietary recall. Advanced ML approaches will identify microbial markers predictive of ALS risk and progression. Recruitment spans six California regions (San Francisco, Santa Barbara, Santa Rosa, Monterey, Modesto, and Fresno). The UCSF ALS Center, in collaboration with the Muscular Dystrophy Association and the ALS Network, provides care for over 90% of ALS patients in Northern California from Santa Barbara to the Nevada and Oregon borders.
Results
To date, we have enrolled 21 participants of our target 100 ALS patients and corresponding controls. We will present, for the first time preliminary metabolomic analyses comparing ALS patients to spouse/partner controls and to matched non-spouse controls. We will also share enrollment characteristics, including symptom onset, disease progression rates, environmental exposures, and dietary correlations, along with newly developed tools for environmental risk and dietary data collection.
Conclusion
This study aims to identify gut microbiome biomarkers predictive of ALS risk and progression, potentially informing therapeutic development, including microbiome-derived metabolites, targeted antibiotics, or probiotics to slow disease progression.
Addendum
While initial patient clinical recruitment data from this study was previously presented at ALS-MND Meeting 2024, this presentation will mark the first time our gut microbiome analyses will be shared. We continued enrollment since the Montreal meeting and will present novel metabolomic data from our cohort.