The human microbiota has a fundamental role in host physiology and pathology. Gut microbial alteration, also known as dysbiosis, is a condition associated not only with gastrointestinal disorders but also with diseases affecting other distal organs. Recently it became evident that the intestinal bacteria can affect the central nervous system (CNS) physiology and inflammation. The nervous system and the gastrointestinal tract are communicating through a bidirectional network of signaling pathways called the gut-brain axis, which consists of multiple connections, including the vagus nerve, the immune system, and bacterial metabolites and products. During dysbiosis, these pathways are dysregulated and associated with altered permeability of the blood-brain barrier (BBB) and neuroinflammation. However, numerous mechanisms behind the impact of the gut microbiota in neuro-development and -pathogenesis remain poorly understood. There are several immune pathways involved in CNS homeostasis and inflammation. Among those, the inflammasome pathway has been linked to neuroinflammatory conditions such as multiple sclerosis, Alzheimer’s and Parkinson’s diseases, but also anxiety and depressive-like disorders. The inflammasome complex assembles upon cell activation due to exposure to microbes, danger signals, or stress and lead to the production of pro-inflammatory cytokines (interleukin-1β and interleukin-18) and to pyroptosis. Evidences suggest that there is a reciprocal influence of microbiota and inflammasome activation in the brain. However, how this influence is precisely working is yet to be discovered. Herein, we discuss the status of the knowledge and the open questions in the field focusing on the function of intestinal microbial metabolites or products on CNS cells during healthy and inflammatory conditions, such as multiple sclerosis, Alzheimer’s and Parkinson’s diseases, and also neuropsychiatric disorders. In particular, we focus on the innate inflammasome pathway as immune mechanism that can be involved in several of these conditions, upon exposure to certain microbes.

Intestinal microbiota can influence the phenotype and function of immune cell responses through the dissemination of bacterial antigens or metabolites. Diet is one of the major forces shaping the microbiota composition and metabolism, contributing to host homeostasis and disease susceptibility. Currently, nutrition is a complementary and alternative approach to the management of metabolic and neurological diseases and cancer. However, the knowledge of the exact mechanism of action of diet and microbiota on the gut–brain communication is only developing in recent years. Here, we reviewed the current knowledge on the effect of diet and microbiota on the gut–brain axis in patients with two different central nervous system diseases, multiple sclerosis and stroke. We have also highlighted the open questions in the field that we believe are important to address to gain a deeper understanding of the mechanisms by which diet can directly or indirectly affect the host via the microbiota. We think this will open up new approaches to the treatment, diagnosis, and monitoring of various diseases.