Gut-Brain Axis Targeting Therapies Study

Background of Gut-Brain Axis Targeting Therapies Study

The gut microbiome is a complex large community resident in the gastrointestinal tract, especially the colon. Microbial secretions and metabolites, such as short-chain fatty acids (SCFAs), 5-hydroxytryptamine, vitamins, and lipopolysaccharides (LPS), have a significant impact on the host via several pathways, including gut-brain axis. Gut-brain axis is a bidirectional communication system connecting both gut and brain across the intestinal epithelial barrier (IEB) and blood-brain barrier (BBB) by neural, neuroendocrine, immune, and metabolic systems. Alzheimer's disease (AD) is a common progressive neurodegenerative disorder, that usually occurs in the aged population. The progression of AD is intimately related to the gut microbiome. The alteration of metabolism and immune status of the patients during the progression of AD leads to gut microbial dysbiosis and thus imbalance of microbial secretions and metabolites, which exacerbate AD progression via gut-brain axis. The potential gut-brain axis-targeted therapies against AD encompass carbohydrates, probiotics, and dietary measures that can regulate the gut microbial dysbiosis. Creative Biolabs offers researchers in vivo, in vitro, and ex vivo assays to inquire into the mechanisms of action (MoAs) of AD related to gut-brain axis, which drive the development of anti-AD drugs targeting gut-brain axis.

Gut-Brain Axis MoA in AD

The gut microbiota composition and microbial fermentation are affected by diet, probiotics, pathogens, and medications. IEB and BBB are essential for the function of gut-brain axis, as their selective permeability separates the pathogen from the host, which plays a critical role in immune recognition and maintaining immune homeostasis. The gut dysbiosis alters the IEB permeability, which leaks microbial secretions or metabolites out of the gastrointestinal tract and triggers peripheral circulation inflammation. The inflammation activates peripheral monocytes that cross the BBB into the brain producing a large amount of pro-inflammatory cytokines and activating glia, which ultimately leads to neuroinflammation in AD. Microbial secretions and metabolites can also directly cross the barriers into the brain participating in neurotransmitter signaling (such as GABA and dopamine) or neuroinflammation (such as LPS). In addition, microbial metabolites such as SCFAs are involved in enzyme biosynthesis, supplementary energy metabolism, signal transmission, or neuroepigenetics. Furthermore, microbial metabolites can stimulate vagus nerve or enteric nervous system (ENS), which regulate the neural immune function and affect gut physiology and brain cognition behavior.

Fig.1 The microbiota-gut-brain axis regulatory pathways involved in AD pathology. (Zhong, 2021)

Creative Biolabs has a long-standing dedication to offering a series of gut-brain axis targeting therapies study services that meet your requirements in research and preclinical drug development. The assays used to study gut-brain axis targeting therapies in AD are mainly involved in assays to study neuroinflammation, such as cytokine release assay, lipopolysaccharide (LPS)-induced inflammation assay, and nitric oxide production assay. We have advanced platforms and tools that enable accurate high throughput data for the assays. Please don't hesitate to contact us for your gut-brain axis targeting therapies study in AD.

Reference

1. Zhong, S.; et al. Functional roles of the microbiota-gut-brain axis in Alzheimer's disease: Implications of gut microbiota-targeted therapy. Translational Neuroscience. 2021, 12 (1): 581-600.