Regulation of common neurological disorders by gut microbial metabolites

Abstract

The gut is connected to the CNS by immunological mediators, lymphocytes, neurotransmitters, microbes and microbial metabolites. A mounting body of evidence indicates that the microbiome exerts significant effects on immune cells and CNS cells. These effects frequently result in the suppression or exacerbation of inflammatory responses, the latter of which can lead to severe tissue damage, altered synapse formation and disrupted maintenance of the CNS. Herein, we review recent progress in research on the microbial regulation of CNS diseases with a focus on major gut microbial metabolites, such as short-chain fatty acids, tryptophan metabolites, and secondary bile acids. Pathological changes in the CNS are associated with dysbiosis and altered levels of microbial metabolites, which can further exacerbate various neurological disorders. The cellular and molecular mechanisms by which these gut microbial metabolites regulate inflammatory diseases in the CNS are discussed. We highlight the similarities and differences in the impact on four major CNS diseases, i.e., multiple sclerosis, Parkinson’s disease, Alzheimer’s disease, and autism spectrum disorder, to identify common cellular and molecular networks governing the regulation of cellular constituents and pathogenesis in the CNS by microbial metabolites.

Probiotics: Protecting Our Health from the Gut

“…Since patients with PD have ID, it has been suggested that the GM may be a potential regulator of the pathogenesis of the disease [ 61 ]. In an animal model, PD development was associated with a low expression of bacteria belonging to the taxa Bacteroides , Lactobacillus , Prevotella , Peptostreptococcus , and Butyricicoccus , and a substantial increase in the genera Enterobacter and Proteus spp.…”

“…Autism spectrum disorder (ASD) is an early neurodevelopmental disorder with cognitive features, including alterations in communication and social interaction, sensory abnormalities, repetitive behaviors, and variable levels of intellectual disability [ 71 , 72 ]. The etiology of ASD is complex and depends on various genetic and hereditary factors, from changes in chromosome number to maternal age, perinatal hypoxia, and factors related to diet and medication use during fetal pregnancy [ 61 ].…”

“…The main species associated with dysbiosis in ASD are Bacteroides , Barnesiella , Odoribacter , Parabacteroides , Prevotella , Alistipes , Proteus , Shigella , and Parasutterella , which are found in greater abundance in ASD patients. In contrast, the abundance of Bifidobacterium species is significantly reduced [ 61 , 73 , 74 ].…”

Diet Patterns, the Gut Microbiome, and Alzheimer’s Disease

“…Acetate, propionate, and butyrate are among the SCFAs derived mainly from gut microbial fermentation of dietary fibre [63]. SCFA activate G-protein-coupled receptors to modulate neurohumoral gut signalling and exert antimicrobial and anti-inflammatory effects for maintenance of gut integrity and intestinal health [64]. Interestingly, SCFA have direct effects in the brain and may play a role in modulating AD pathogenesis.…”

Gut Microbiome and Metabolome Changes in Mice With Acute Vestibular Deficit

“…Research has shown that the gut microbiota modulates psychiatric conditions by producing neurotransmitters, including gamma-aminobutyric acid (GABA), serotonin, melatonin, histamine, acetylcholine, and catecholamines ( Banerjee et al., 2021 ; Morais et al., 2021 ; Zhou et al., 2022 ). Besides the bioactive neurotransmitters, gut microbes also produce short-chain fatty acids (SCFAs), such as propionate, butyrate, and acetate, which can pass through the blood–brain barrier and influence central nervous system (CNS) function by regulating numerous host enzymes, such as histone deacetylases (HDACs) ( Park and Kim, 2021 ). Duan et al.…”