Serotonin: A mediator of the gut–brain axis in multiple sclerosis

Abstract

Background:The significance of the gut microbiome for the pathogenesis of multiple sclerosis (MS) has been established, although the underlying signaling mechanisms of this interaction have not been sufficiently explored.Objectives:We address this point and use serotonin (5-hydroxytryptamine (5-HT))—a microbial-modulated neurotransmitter (NT) as a showcase to demonstrate that NTs regulated by the gut microbiome are potent candidates for mediators of the gut–brain axis in demyelinating disorders.Methods, Results, and Conclusion:Our comprehensive overview of literature provides evidence that 5-HT levels in the gut are controlled by the microbiome, both via secretion and through regulation of metabolites. In addition, we demonstrate that the gut microbiome can influence the formation of the serotonergic system (SS) in the brain. We also show that SS alterations have been related to MS directly—altered expression of 5-HT transporters in central nervous system (CNS) and indirectly—beneficial effects of 5-HT modulating drugs on the course of the disease and higher prevalence of depression in patients with MS. Finally, we discuss briefly the role of other microbiome-modulated NTs such as γ-aminobutyric acid and dopamine in MS to highlight a new direction for future research aiming to relate microbiome-regulated NTs to demyelinating disorders.

Biochemical Differences in Cerebrospinal Fluid between Secondary Progressive and Relapsing–Remitting Multiple Sclerosis

“…The neurotransmitter serotonin is known to regulate macrophages, T cells, and dendritic cells and is partially modulated by the gut microbiome [44]. A recently suggested hypothesis propose a connection between an unbalanced microbiota and MS pathology, through SS modulation [41]. This is supported by another recent study emphasizing the potential role of tryptophan metabolism by the gut microbiota in neuroinflammation and MS [35].…”

“…The relationship between MS and the serotonergic system (SS), of which serotonin’s main metabolite 5-HIAA is a part, is currently not well understood. Previous studies have shown alterations in the SS in MS patients and underlined the necessity of a deeper characterization of the role of SS in MS pathology [40,41]. Fluoxetine, a candidate drug for repurposing that increases serotonin levels in the CNS, is now clinically tested as a neuroprotective treatment for SPMS patients [42,43].…”

Effect of the probiotic Lactobacillus plantarum IS-10506 on BDNF and 5HT stimulation: role of intestinal microbiota on the gut-brain axis

“…5-HT is released from enterochromaffin cells of the gastric mucosa in response to various stimuli including signals from gut microbiota (15)(16)(17). Although 5-HT is a well-known neurotransmitter that is associated with emotion and behaviour, about 90% of 5-HT in the body is produced in the digestive tract where it is involved in the detection of resource availability and regulation of bowel movement.…”

“…Gut microbiota stimulates host intestinal cells to produce 5-HT. An imbalance of 5-HT in the brain can lead to depression, whereas peripheral dysregulation of this neurotransmitter has been linked to a variety of diseases (1,2,7,12,15,16,(18)(19)(20)(21). In this study we found that treatment with L. plantarum IS-10506 caused an increase in brain 5-HT level in rats relative to the control group.…”

Gut Microbiota: An Effective Factor in the Human Brain and Behavior

“…As trocyte 45 Microbe-associated molecular patterns 46 Major his tocompatibility complex Π 47 Aryl hydrocarbon receptor 48 Indole-3-aldehyde 49 Indole-3-propionic acid 50 T helper 17 51 Interleukin 17A…”