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Microbiome-Targeted Therapies for CNS Disorders
The human microbiome, a complex and diverse community of microorganisms inhabiting our bodies, plays a significant role in health and disease. Recent research has provided ample evidence that modifications of this biome have implications for Central Nervous System (CNS) disorders. Based on this understanding, microbiome-targeted therapies are being explored as novel strategies for managing these disorders.
Creative Biolabs focuses on the promising potential of microbiome-targeted therapies for CNS disorders, providing a research platform and expertise for CNS drug discovery.
| Services | What We Do | Advantages |
|---|---|---|
| STEMOD™ Advanced Drug Discovery Service | We develop integrated technology platforms to provide one-stop CNS drug discovery services, including drug development targeting the microbiome. |
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| Custom CNS Disease Modeling Services | Our platform can provide reliable customized models, including but not limited to Alzheimer's disease models, Huntington's disease models, and Parkinson's disease models. |
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| Primary Cell Lines | We offer the development of neuroscience-based primary cell lines and related customized products. |
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The Gut-Brain Axis: A Bi-Directional Communication System
The gut-brain axis refers to the two-way communication between the gut and the brain involving neural, hormonal and immune signaling. The gut microbiome, which consists of trillions of bacteria, viruses, fungi and other microorganisms, plays a key role in regulating this complex interaction. Communication occurs through multiple pathways, including the vagus nerve, immune system mediators, and microbial metabolites.
Fig. 1 Gut–brain–microbiome (GBM) interactions.1
From early life through adulthood, the gut microbiota influences the development and function of the central nervous system. In infancy, gut microbial colonization is critical for the maturation of the immune system and the establishment of balance in the gut-brain axis. Dysregulation of this axis is associated with a range of central nervous system disorders, including neurodevelopmental conditions, mood disorders and neurodegenerative diseases.
Microbiome's Impact on CNS Disorders
The human microbiome refers to the trillions of tiny microbial creatures, including bacteria, viruses, fungi, and others, inhabiting our bodies. These microbe communities are typically categorized by their location, with the gut microbiome being the most extensively studied. The gut microbiome performs a plethora of functions, such as aiding in digestion, educating our immune systems, and producing metabolites. Remarkably, this network also communicates with the brain via diverse pathways, known as the gut-brain axis.
Fig. 2 Disruption of gut microbiota can lead to the progression of various CNS disorders.2
Emerging research links alterations in the microbiome to CNS disorders.
- Gut microbiota imbalances, termed dysbiosis, are seen consistently in ASD, schizophrenia, and major depressive disorder (MDD) subjects. Some specific bacterial species seem to be depleted in ASD, while others are elevated. It's proposed that these changes may contribute to symptoms through the gut-brain axis.
- Dysbiosis is noted in Parkinson's and Alzheimer's disease, where specific bacterial profiles relate with disease measures. The mechanisms through which these altered gut bacteria profiles contribute to neurodegeneration are multiple, including increased intestinal permeability, abnormal immune responses, and production of detrimental metabolites, ultimately leading to neuroinflammation, neuronal damage, and impaired brain function.
Microbiome-Targeted Therapies
Given the impact of the microbiome on CNS disorders, it stands as a potential therapeutic target. Our focus will be on microbiome-targeted therapies, including probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and bacteriophage therapy.
| Microbiome-targeted Therapies | Descriptions | Disease areas |
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| Probiotics | Probiotics are live bacteria that, when administered adequately, yield health benefits. Lactobacillus and Bifidobacterium species are commonly used probiotics shown to exhibit neuroprotective effects, reduce inflammation, and improve cognitive symptoms in preclinical models of depression, ASD, and Alzheimer's. |
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| Prebiotics | Prebiotics are non-digestible food substances that promote the growth of beneficial gut bacteria. By enhancing species that produce essential metabolites like short-chain fatty acids (SCFAs), prebiotics could potentially improve brain health. Examples of prebiotics include fructooligosaccharides (FOS), galactooligosaccharides (GOS), and polyphenols. Indeed, early studies suggest that prebiotics can improve stress response, memory, and mood. |
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| Synbiotics | Synbiotics are a combination of probiotics and prebiotics, administered together for synergistic effects. There is preliminary evidence that synbiotics can improve markers of inflammation, stress, and cognitive function in CNS disorders. |
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| Fecal microbiota transplantation (FMT) | FMT refers to the transplantation of gut microbiota from a healthy donor into a recipient, aimed at re-establishing the healthy gut ecosystem. Studies on rodents have demonstrated that FMT can modify behavior and brain chemistry, suggesting exciting future possibilities for FMT in treating CNS disorders. |
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| Bacteriophages | Bacteriophages, or viruses that infect and kill bacteria, can selectively target detrimental bacterial species. This strategy effectively rebalances the gut microbiota, reducing inflammation and neurodegeneration in preclinical models. |
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| Microbial Metabolites and Psychobiotics | Microbial metabolites, such as short-chain fatty acids (SCFAs), produced by gut bacteria, can impact CNS function. Psychobiotics, a term coined for live microorganisms with mental health benefits, may act by producing neuroactive substances. Research is focused on understanding how these compounds influence brain health and exploring their therapeutic potential. |
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| Dietary Interventions | The role of diet in shaping the gut microbiome is well-established. Dietary interventions, including personalized nutrition plans and specific diets like the Mediterranean diet, are being studied for their impact on CNS disorders. Nutritional strategies that promote a healthy gut microbiome could potentially complement existing therapeutic approaches. |
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Microbiome-targeted therapies aim to restore the gut microbiome's balance, thus reestablishing optimum gut-brain axis function. They are a rapidly evolving field in medical science. They hold boundless potential in developing effective treatments for CNS disorders such as Alzheimer's disease, Parkinson's disease, stroke, multiple sclerosis, autism, and anxiety disorders.
Challenges and Future Perspectives
While the potential of microbiome-targeted therapies for CNS disorders is exciting, several challenges must be navigated to translate research findings into effective clinical interventions.
- Microbiome Variability: The diversity and individual variability of the human microbiome pose challenges in identifying universal therapeutic strategies. What works for one individual may not be effective for another, necessitating personalized approaches.
- Long-Term Effects and Safety: The long-term effects of altering the gut microbiome are not fully understood. Safety concerns, potential side effects, and unintended consequences must be thoroughly investigated to ensure the well-being of individuals undergoing microbiome-targeted therapies.
However, ongoing research and advanced tools in genomics, metabolomics, and bioinformatics are enabling a deeper understanding of the microbiome's intricacies. Specific advanced techniques, such as
- Single-cell RNA sequencing
- CRISPR technology
They are potentially potent tools to manipulate the gut microbiome and derive therapeutic benefits.
The study of microbiome-targeted therapies continues to grow, gradually proving the gut-brain axis disruption's role in pathogenesis and progression of CNS disorders. Although clear clinical guidelines and standardized treatments are yet to fully evolve, the journey towards personalized microbiome-targeted therapies is underway, culminating in potentially ground-breaking interventions in the field of neurotherapeutics.
At Creative Biolabs, we remain at the forefront of this scientific avant-garde, dedicated to contributing to these evolving understandings and applications. Fueled by our expertise in neuroscience and microbiology, we are committed to supporting researchers and healthcare providers in harnessing the power of the microbiome. Together, we aspire to unravel the innumerable possibilities this burgeoning field promises in revolutionizing the future of managing CNS disorders.
References
- Mayer, Emeran A., et al. "The gut–brain axis." Annual Review of Medicine 73 (2022): 439-453.
- Ma, Qianquan, et al. "Impact of microbiota on central nervous system and neurological diseases: the gut-brain axis." Journal of neuroinflammation 16.1 (2019): 1-14.
For Research Use Only. Not For Clinical Use.