The Gut-Brain Axis and Neurological Disorders: Recent Insights and Therapeutic Opportunities

Danella Calina | Youth4Neuro | Dalhousie University | June 25 2025

(Loh et al., 2024)

Table of Contents

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Therapeutic Opportunities and Future Directions

Conclusion

GBA and Central Nervous System (CNS) Disorders

GBA and Parkinson’s Disease (PD)

Introduction

Introduction

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Background Information

• The gut-brain axis (GBA) involves two-way communication between the enteric nervous system (ENS) and the central nervous system (CNS)
• Key Connections: It links the brain’s cognitive and emotional regions with intestinal functions.

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Role of Gut Microbiota

Visual

The Gut-Brain Axis Mechanism

• Role of Gut Microbiota: Gut microbiota, which include bacteria, eukarya, and archaea, play a crucial role in these interactions (Carabotti et al., 2015; Thursby & Juge, 2017).

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(Singh et al., 2023)

Purpose and Overview

• Examine recent discoveries and therapeutic opportunities related to the GBA, especially in neurological disorders like Parkinson’s disease.

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Purpose of the Presentation

Overview of Topics

• Mechanisms of the Gut-Brain Axis
• Impact of Gut Microbiota on CNS Disorders
• Parkinson’s Disease and the GBA
• Therapeutic Opportunities and Future Directions

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(“Parkinson’s Disease: Causes, Symptoms & Treatment”, n.d.)

GBA and CNS Disorders

02

GBA and CNS Disorders

• Gut Microbiota's Role: Critical in maintaining homeostasis; disruptions can lead to CNS disorders.
• Influence on Behavior: Studies show gut microbiota affect anxiety, cognition, pain, and mood (Cryan & Dinan, 2012).

Key Points

(Yuan et al., 2023)

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GBA and CNS Disorders

• Mechanisms of Gut-Brain Signaling:
• Changes in microbial composition
• Vagus nerve signaling
• Immune activation
• Production of specific microbial neuroactive metabolites
• Alterations in tryptophan metabolism (precursor to serotonin)
• Bacterial cell wall sugars (blood brain barrier integrity)

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Relevant Information

(Dantas et al., 2022)

GBA and Parkinson’s Disease (PD)

03

GBA and PD

• Examined the connection between gut microbiota and Parkinson’s disease (PD).

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Mouse Model

Study by Sampson et al. (2016)

• Used mice that overexpress α-synuclein (αSyn), a protein linked to PD neuropathology and genetics (Stefanis, 2012).

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(Sampson et al., 2016)

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(Ray et al., 2021)

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GBA and PD

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• Gut bacteria are necessary for developing motor deficits, αSyn pathology, and microglia activation.
• Antibiotic treatment, which decreases gut microbiota, alleviated symptoms.
• Re-colonization of the gut restored motor deficits and neuroinflammation.
• Mice with microbiota from PD patients exhibited more severe symptoms compared to those with microbiota from healthy individuals.

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Findings

(Sampson et al., 2016)

Therapeutic Opportunities and Future Directions

04

Therapeutic Opportunities and Future Directions

• Potential for treating neurological and gastrointestinal disorders by targeting the gut-brain axis (GBA) (Aljeradat et al., 2024).
• Techniques:
• Deep brain stimulation (DBS)
• Transcranial magnetic stimulation (TMS)
• Vagus nerve stimulation (VNS)
• Effects:
• Modulation of gut microbiota
• Reduction of proinflammatory cytokines
• Enhancement of neurotrophic factors
• Reduction of inflammation
• Alleviation of pain

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Neuromodulation Techniques

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Significant Impact

• Conditions like Parkinson’s disease (PD) and various neuropsychiatric disorders can be significantly impacted by neuromodulation.

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(Aljeradat et al., 2024)

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Therapeutic Opportunities and Future Directions

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• Clinical Trials: Essential to substantiate preclinical findings and confirm effectiveness and safety in human populations.
• Personalized Therapies: Potential for treatments tailored to unique microbiota profiles of individual patients, enhancing therapy effectiveness.
• Emerging Research Areas:
• Novel neuromodulation techniques
• Dietary interventions on the GBA
• Mechanisms by which gut-derived metabolites influence brain function

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Future Directions

(Aljeradat et al., 2024)

Summary of VNS effects on GBA physiology

Conclusion

05

Conclusion

• Plays a crucial role in neurological disorders such as Parkinson’s disease (PD) and Alzheimer’s disease (AD).

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Gut Microbiota

The Gut-Brain Axis

• Significantly influences neurological health by modulating neuroinflammation, neurotrophic factors, and synaptic function (Sampson et al., 2016; Stefanis, 2012).

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Therapeutic Opportunities

• Neuromodulation techniques (DBS, TMS, VNS) and microbiome-targeted therapies show promise in treating neurodegenerative conditions (Aljeradat et al., 2024; Toledo et al., 2022).

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(Aljeradat et al., 2024)

Conclusion

• Continued research is essential to fully understand and harness the therapeutic potential of the GBA.
• Personalized microbiome therapies could enhance treatment effectiveness for neurological conditions.
• Exploring novel neuromodulation techniques and dietary interventions could lead to groundbreaking treatments.

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• Advancements in GBA research hold the potential to revolutionize the treatment of neurological disorders.
• By leveraging the intricate connections between the gut and brain, innovative and effective therapies can be developed to improve patient outcomes and quality of life.

Final Thoughts

Key Takeaways

(Savidge et al., 2007)

References

Aljeradat, B., Kumar, D., Abdulmuizz, S., Kundu, M., Almealawy, Y. F., Batarseh, D. R., Atallah, O., Ennabe, M., Alsarafandi, M., Alan, A., & Weinand, M. (2024, May 17). Neuromodulation and the gut-brain axis: Therapeutic mechanisms and implications for gastrointestinal and neurological disorders. Pathophysiology : the official journal of the International Society for Pathophysiology. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11130832/

Carabotti, M., Scirocco, A., Maselli, M. A., & Severi, C. (2015). The gut-brain axis: Interactions between enteric microbiota, Central and Enteric Nervous Systems. Annals of gastroenterology. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4367209/

Cryan, J. F., & Dinan, T. G. (2012, September 12). Mind-altering microorganisms: The impact of the gut microbiota on brain and behaviour. Nature News. https://www.nature.com/articles/nrn3346

Dantas, A. M., Sack, A. T., Bruggen, E., Jiao, P., & Schuhmann, T. (2022, July 15). The effects of probiotics on risk and time preferences. Nature News. https://www.nature.com/articles/s41598-022-16251-x

Loh, J. S., Mak, W. Q., Tan, L. K. S., Ng, C. X., Chan, H. H., Yeow, S. H., Foo, J. B., Ong, Y. S., How, C. W., & Khaw, K. Y. (2024, February 16). Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases. Nature News. https://www.nature.com/articles/s41392-024-01743-1

Lynch, C. M. K., Nagpal, J., Luczynski, P., Neufeld, K.-A. M., Dinan, T. G., Clarke, G., & Cryan, J. F. (2023, December 7). Germ-free animals: A key tool in unraveling how the microbiota affects the brain and behavior. The Gut-Brain Axis (Second Edition). https://www.sciencedirect.com/science/article/abs/pii/B9780323999717000126

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References

Practo Health Wiki. (n.d.). Parkinson’s disease: Causes, symptoms & treatment. Practo. https://www.practo.com/health-wiki/parkinsons-disease-symptoms-treatment/166/article

Ray, B., Mahalakshmi, A. M., Tuladhar, S., Bhat, A., Srinivasan, A., Pellegrino, C., Kannan, A., Bolla, S. R., Chidambaram, S. B., & Sakharkar, M. K. (2021, May 28). Theory on how α-synuclein aggregates are formed in a step-wise process... | download scientific diagram. frontiers in Cell and Developmental Biology. https://www.researchgate.net/figure/Theory-on-how-a-synuclein-aggregates-are-formed-in-a-step-wise-process-Monomers-can-get_fig2_298908048

Sampson, T., Janssen, S., Thron, T., & Debelius, J. (2016, December 1). Gut microbiota regulate motor deficits and neuroinflammation in a model of parkinson’s disease. Cell. https://pubmed.ncbi.nlm.nih.gov/27912057/

Savidge, T. C., Sofroniew, M. V., & Neunlist, M. (2007, August). Starring roles for astroglia in barrier pathologies of gut and brain. Laboratory investigation; a journal of technical methods and pathology. https://pubmed.ncbi.nlm.nih.gov/17607301/

Singh, H., Chopra, C., Singh, H., Malgotra, V., Wani, A. K., Dhanjal, D. S., Sharma, I., Nepovimova, E., Alomar, S., Singh, R., Sharma, V., & Kuca, K. (2023, November 30). Gut-Brain Axis and alzheimer’s disease: Therapeutic interventions and strategies. Journal of Functional Foods. https://www.sciencedirect.com/science/article/pii/S1756464623005157

Stefanis, L. (2012, February). Α-synuclein in parkinson’s disease. Cold Spring Harbor perspectives in medicine. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281589/

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References

Thursby, E., & Juge, N. (2017, May 16). Introduction to the human gut microbiota. The Biochemical journal. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5433529/

Toledo, A. R. L., Monroy, G. R., Salazar, F. E., Lee, J.-Y., Jain, S., Yadav, H., & Borlongan, C. V. (2022, January 21). Gut–brain axis as a pathological and therapeutic target for neurodegenerative disorders. MDPI. https://www.mdpi.com/1422-0067/23/3/1184

Yuan, C., He, Y., Xie, K., Feng, L., Gao, S., & Cai, L. (2023, September 20). Review of microbiota gut brain axis and innate immunity in inflammatory and infective diseases. Frontiers. https://www.frontiersin.org/articles/10.3389/fcimb.2023.1282431

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Thank you for your attention!