Live Biotherapeutics Drug Discovery Service for Huntington's Disease
Overview
Huntington's disease (HD) is a neurodegenerative disease caused by trinucleotide amplification of the HTT gene, which is expressed in the brain and the whole body, including the intestinal epithelium and enteric nervous system. Symptoms of HD include uncontrolled body movements, facial expressions, weight loss, personality changes, psychological disorders, and apathy. An important function of gut microbiota is the production of metabolites to maintain host metabolic homeostasis as well as the formation of the gut-brain axis. It has been established that gut microbiota are key modulators for the bi-directional communication between the gut and the brain, also known as the gut-brain axis. Intestinal microbiota has been shown to influence neurodevelopment, brain function, and behavior. The study of the microbiome is the trend of HD research. Recent studies on the role of gut microbiota and their metabolites have opened up new branches in the field of HD. Metabolites of microorganisms have the potential to modulate the pathogenesis of HD. Short-chain fatty acids (SCFAs) can affect the immune system and reduce inflammation in the CNS and peripheral nerves.
Mouse Models of HD
Animal models of HD provide us with tools to study the mammalian microbiome and its possible impact on disease progression. Much of the knowledge of HD pathogenesis has come from the use of model systems, the most common of which is the mouse model. HD mouse models were generated by knock-in or transgenic approaches.
Gut Microbiota in HD
The community of microorganisms that colonize the gut, and their activity (gut microbiome), have been shown to influence brain function. More recently, gut microbiome disruption has been consistently shown in both preclinical and clinical HD, even before the onset of motor symptoms. Understanding gene-environment-gut interactions in HD mice can guide novel therapeutic approaches and may have beneficial effects on other neurodegenerative diseases associated with dysbiosis. Gut microbiota studies in HD patients not only expand our understanding of host-microbiome interactions but may also provide more insights into understanding the early and systemic manifestations of HD.
Fig.1 The gut microbiota's composition and neurodegenerative disorders.1
Microbiota-based Treatments
Probiotic therapy and fecal microbiota transplantation (FMT) are two major microbial-related therapies that are currently used as adjunctive treatments for neurological diseases. Oral administration of mixed or single strains of probiotics as effective adjuvant therapy has shown promising results. Bifidobacterium and Lactobacillus are commonly used in probiotic preparations because these bacteria are often used to improve people's condition and are classified as GRAS (generally defined as safe) for human consumption.
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Research Article
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Faecal microbiota transplant ameliorates gut dysbiosis and cognitive deficits in Huntington's disease mice.2
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References
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Khatoon, Saima, et al. "Effects of gut microbiota on neurodegenerative diseases." Frontiers in Aging Neuroscience 15 (2023): 1145241.
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Gubert, Carolina, et al. "Faecal microbiota transplant ameliorates gut dysbiosis and cognitive deficits in Huntington's disease mice." Brain Communications 4.4 (2022): fcac205.
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Distributed Under Open Access license CC BY 4.0, without modification.
For Research Use Only. Not intended for use in food manufacturing or medical procedures (diagnostics or therapeutics). Do Not Use in Humans.
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