Journal of Molecular and Pharmaceutical Sciences
Volume 5, Numéro 1, Pages 72-84
2026-06-30

Environmental Programming Of The Gut-brain Axis In Multiple Sclerosis: A Phase-dependent Framework



Authors : Bechlem Houria . Merabet Souad . Otmani Khawla . Barhouchi Badra .

Abstract

Research on the gut microbiome in multiple sclerosis (MS) has expanded rapidly but remains limited by two conceptual gaps, insufficient integration of environmental risk factors into gut-brain axis (GBA) models and the tendency to treat microbiome alterations as static disease features. This review proposes an integrated framework in which GBA dysfunction is environmentally programmed and dynamically remodelled across disease progression. We argue that established MS risk factors including Epstein-Barr virus exposure, vitamin D deficiency, cigarette smoking, and biological sex, may influence disease susceptibility partly through sustained effects on intestinal immunity, microbial ecology, and host microbial interactions before clinical onset. Dysbiosis is therefore considered a dynamic biological state shaped by cumulative environmental exposure rather than an isolated characteristic of established disease. We further propose that GBA involvement differs across disease stages, in relapsing-remitting MS, GBA dysfunction may primarily amplify peripheral immune activation, whereas in progressive disease it may contribute to persistent neuroimmune and metabolic stress within the central nervous system. This phase dependent perspective may help explain inconsistencies across microbiome studies and the limited efficacy of current microbiome directed interventions. Future progress will require integrating environmental exposures as biological co-determinants, adopting disease stage stratification, and moving beyond taxonomic profiling toward functional approaches. Such a mechanistic and phase informed framework may improve therapeutic targeting and support earlier intervention strategies in MS.

Keywords

gut-brain axis ; microbiome ; multiple sclerosis ; environmental programming ; disease-stage dynamics ; neuroimmune interactions

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