Targeting Gut Dysbiosis and Microbiome Metabolites for the Development of Therapeutic Modalities for Neurological Disorders

Abstract

The gut microbiota, composed of numerous species of microbes, works in synergy with the various organ systems in the body to bolster our overall health and well-being. The most well-known function of the gut microbiome is to facilitate the metabolism and absorption of crucial nutrients, such as complex carbohydrates, while also generating vitamins. In addition, the gut microbiome plays a crucial role in regulating the functioning of the central nervous system (CNS). Host genetics, including specific genes and single nucleotide polymorphisms (SNPs), have been implicated in the pathophysiology of neurological disorders, including Parkinson’s disease (PD), Alzheimer’s disease (AD), and autism spectrum disorder (ASD). The gut microbiome dysbiosis also plays a role in the pathogenesis of these neurodegenerative disorders, thus perturbing the gut-brain axis. Overproduction of certain metabolites synthesized by the gut microbiome, such as short-chain fatty acids (SCFAs) and p-cresyl sulfate, are known to interfere with microglial function and trigger misfolding of alpha-synuclein protein, which can build up inside neurons and cause damage. By determining the association of the gut microbiome and its metabolites with various diseases, such as neurological disorders, future research will pave the way for the development of effective preventive and treatment modalities.

Unveiling the Journey from the Gut to the Brain: Decoding Neurodegeneration–Gut Connection in Parkinson’s Disease

“…Administration of gut microenvironment modifying agents may afford neuroprotection by regulating the gut–brain axis, controlling gut dysbiosis. Probiotic supplementation containing a variety of microbes can effectively alleviate symptoms of PD by addressing various cellular and molecular processes such as oxidative stress, apoptosis, and inflammatory and anti-inflammatory pathways. − Although it is not obligatory that these gut modifying agents can solely cure PD, if given in conjunction with existing medication, they can enhance gut health, reducing the possible risk of PD associated with gut disturbances. In this review, we attempt to delineate the body first hypothesis of the origin of PD; specifically focusing on the gut–-microbiome–brain axis and agents modifying the pathology, mainly the functional foods, such as biotics, approach and fecal microbiome transplantation (FMT) procedures that are performed in preclinical settings.…”

Targeting the blood–brain barrier to delay aging-accompanied neurological diseases by modulating gut microbiota, circadian rhythms, and their interplays

“…The gut microbiota continuously exchanges nutrients, genetic material, and metabolites with the host throughout its life cycle which regulates the homeostasis in the host, including brain function and blood–brain barrier (BBB) integrity 11 . In individuals with neurological disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), stroke, and multiple sclerosis (MS), circadian rhythm disturbances and gut microbiota dysbiosis are common symptoms 12 , 13 , 14 . Accumulating data suggest that either circadian rhythms or gut dysbiosis contribute to aging-accompanied neurological diseases (AAND) 15 .…”

Modulation of Gut Microbiome as a Therapeutic Modality for Auditory Disorders

“…The gut microbiome refers to the collection of fungi, viruses, and bacteria residing inside the gastrointestinal (GI) tract [1][2][3][4]. These organisms provide great benefits in maintaining the health and normal physiological function of the human body.…”