ALS and the Gut-Brain Axis: A protocol for a systematic review and meta-analysis assessing the relationship between amyotrophic lateral sclerosis, the gut and its microbiome.

Background: ALS is a devastating neurodegenerative disease characterized by progressive loss of motor function. At the time of symptom manifestation, effective treatment options are extremely limited, due in part to the irreversible loss of motor neurons at this late stage of the disease. Recent research has highlighted the involvement of both gut pathology and gut microbiota as important factors in early disease pathogenesis, which may represent an opportunity for early diagnosis and intervention, prior to neurological symptom onset and thus prior to significant motor neuron loss.

Aim: The aim of this review is to perform a comprehensive analysis of the literature to identify potential pre-symptomatic pathological hallmarks of ALS in the gut, including, but not limited to, changes in gut microbiota and protein aggregation.

Methods: This protocol details the strategy for the proposed systematic review and meta-analysis to identify and compare studies assessing gut-related pathological changes in ALS separated in to two analyses assessing (i) gut microbiota and (ii) non-microbiota related pathways, with the ultimate aim of identifying opportunities for early disease detection before neurological symptom onset.