Molecular systems biology approaches to investigate mechanisms of gut-brain communication in neurological diseases.

Background: Whilst the incidence of neurological diseases is increasing worldwide, treatment remains mostly limited to symptom management. The gut-brain axis, which encompasses the communication routes between microbiota, gut and brain, has emerged as a crucial area of investigation for identifying new preventive and therapeutic targets in neurological disease.

Methods: Due to the inter-organ, systemic nature of the gut-brain axis, together with the multitude of biomolecules and microbial species involved, molecular systems biology approaches are required to accurately investigate the mechanisms of gut-brain communication. High-throughput omics profiling, together with computational methodologies such as dimensionality reduction or clustering, machine learning, network inference and genome-scale metabolic models, allows novel biomarkers to be discovered and elucidates mechanistic insights.

Results: In this review, the general concepts of experimental and computational methodologies for gut-brain axis research are introduced and their applications are discussed, mainly in human cohorts. Important aspects are further highlighted concerning rational study design, sampling procedures and data modalities relevant for gut-brain communication, strengths and limitations of methodological approaches and some future perspectives.

Conclusion: Multi-omics analyses, together with advanced data mining, are essential to functionally characterize the gut-brain axis and put forward novel preventive or therapeutic strategies in neurological disease.