2021 Q1 Review:
Parkinson’s & the Gut 
by Martha Carlin

 

The promising area of gut-brain research has continued despite likely slower progress due to the impact of the 2020 Pandemic on many aspects of research. It will be some time before we fully understand how much research was redirected from current focus on microbiome in Parkinson’s to research areas devoted to the virus. Scientific research areas like the microbiome lend themselves to rapid changes in direction because the gut microbiome ties to every aspect of human health.  

A Few Interesting Parkinson’s
Microbiome Papers from this Quarter

Lorente-Picón M, Laguna A. New Avenues for Parkinson's Disease Therapeutics: Disease-Modifying Strategies Based on the Gut Microbiota. Biomolecules. 2021 Mar 15;11(3):433. doi: 10.3390/biom11030433. PMID: 33804226; PMCID: PMC7998286.

 

Evidence is piling up on the effects of gut microbiota in disease development and progression, another front of action has opened up in relation to the potential usage of microbiota-based therapeutic strategies in treating gastrointestinal alterations and possibly also motor symptoms in PD. This review provides an update on the different strategies that are in the front line of expiration  (i.e., antibiotics; probiotics; prebiotics; synbiotics; dietary interventions; fecal microbiota transplantation, live biotherapeutic products), and discusses the opportunities and challenges the field of microbiome research in PD is facing. 

 

Liang Y, Cui L, Gao J, Zhu M, Zhang Y, Zhang HL. Gut Microbial Metabolites in Parkinson's Disease: Implications of Mitochondrial Dysfunction in the Pathogenesis and Treatment. Mol Neurobiol. 2021 Apr 6. doi: 10.1007/s12035-021-02375-0. Epub ahead of print. PMID: 33825149.

This paper reviews the research in mitochondrial dysfunction in Parkinson’s disease and recent research regarding microbial metabolites such as short chain fatty acids and the connection between gut dysfunction in Parkinson’s pathology.  Discussion includes how mitochondrial function is influenced by microbial metabolites and the mechanisms that may be responsible for progressive loss of dopaminergic neurons.  Later this year,  The BioCollective will advance our understanding of probiotic metabolites impact on mitochondria through a collaboration with Dr. Daniel Paredes at Denver University.  

Lerner A, Benzvi C. "Let Food Be Thy Medicine": Gluten and Potential Role in Neurodegeneration. Cells. 2021 Mar 30;10(4):756. doi: 10.3390/cells10040756. PMID: 33808124.

This narrative review expands on various aspects of the gluten-gut-brain axes events, mechanisms and pathways that connect wheat and gluten consumption to neurodegenerative disease. Gluten induced dysbiosis, increased intestinal permeabillity, enteric and systemic side effects, cross-reactive antibodies, and the sequence of homologies between brain antigens and gluten are highlighted. This combination may suggest molecular mimicry, alluding to some autoimmune aspects between gluten and neurodegenerative disease. The proverb of Hippocrates coined in 400 BC, "let food be thy medicine," is critically discussed in the frame of gluten and potential neurodegeneration evolvement.

 

Miller AL, Bessho S, Grando K, Tükel Ç. Microbiome or Infections: Amyloid-Containing Biofilms as a Trigger for Complex Human Diseases. Front Immunol. 2021;12:638867. Published 2021 Feb 26. doi:10.3389/fimmu.2021.638867

This paper from the journal Frontiers in Immunology discusses how the microbiome or infections produce amyloid contain biofilms which may be a trigger for many complex human diseases including Parkinson’s.  Specific bacteria discussed in the context of Parkinson’s are E.coli, Pseudomonas, and Prophyromonas and other Gram-negative bacteria as we age.  The paper also discusses the involvement of bacterial amyloids in autoimmune diseases.  Recent research in Parkinson’s continues to support autoimmune characteristics of the disease.  Many patients with Parkinson’s also suffer from co-morbid diagnosis of other autoimmune diseases such as IBS, diabetes and thyroid disease.  

Rudzki L, Stone TW, Maes M, Misiak B, Samochowiec J, Szulc A. Gut microbiota-derived vitamins - underrated powers of a multipotent ally in psychiatric health and disease. Prog Neuropsychopharmacol Biol Psychiatry. 2021 Apr 20;107:110240. doi: 10.1016/j.pnpbp.2020.110240. Epub 2021 Jan 9. PMID: 33428888.

This paper from the journal Progress in neuro-psychopharmacology & biological psychiatry discusses the importance of B-vitamins in Parkison’s, Alzheimer’s and various psychiatric disorders such as depression.  While B Vitamins are typically acquired from our food, deficiencies are not uncommon.  See my previous blog post on the importance of B Vitamins in Parkinson’s.  The majority of gut bacteria along with bacteria in fermented foods possess the genetic tools to synthesize B vitamins.  The paper discusses growing evidence of the importance of intestinal bacteria and microbiome health to the synthesis of these important brain health vitamins. 

 

Aho VTE, Houser MC, Pereira PAB, Chang J, Rudi K, Paulin L, Hertzberg V, Auvinen P, Tansey MG, Scheperjans F. Relationships of gut microbiota, short-chain fatty acids, inflammation, and the gut barrier in Parkinson's disease. Mol Neurodegener. 2021 Feb 8;16(1):6. doi: 10.1186/s13024-021-00427-6. PMID: 33557896; PMCID: PMC7869249.

Parkinson’s microbiome research pioneer Dr. Filip Scheperjans in the journal Molecular neurodegeneration continues to advance his research reporting on sex-dependent changes in the microbiome of PD patients and increases in the inflammatory gut biomarker calprotectin and decreases in short chain fatty acids which have been linked with gut barrier integrity in other research. 

 

A Few Interesting Parkinson’s
Disease and Probiotics Papers

Castelli V, d'Angelo M, Quintiliani M, Benedetti E, Cifone MG, Cimini A. The emerging role of probiotics in neurodegenerative diseases: new hope for Parkinson's disease? Neural Regen Res. 2021 Apr;16(4):628-634. doi: 10.4103/1673-5374.295270. PMID: 33063712.

 

This review discusses the potential use of probiotics for Parkinson’s disease prevention or treatment or as adjuvant therapy, confirming that gut microbiota modulation influences different pro-survival pathways. The review covers how probiotic bacteria not only modulate host immune responses but also create a healthy gut environment through the balancing of the intestinal microflora. Ingestion of probiotics may restore the composition of the gut microflora to a state more favorable for beneficial microorganisms (Boon Wong et al., 2018; Romo-Araiza et al., 2018)
 

Tan AH, Lim SY, Chong KK, A Manap MAA, Hor JW, Lim JL, Low SC, Chong CW, Mahadeva S, Lang AE. Probiotics for Constipation in Parkinson Disease: A Randomized Placebo-Controlled Study. Neurology. 2021 Feb 2;96(5):e772-e782. doi: 10.1212/WNL.0000000000010998. Epub 2020 Oct 12. PMID: 33046607.
 

This study showed that multistrain probiotics treatment was effective for constipation in PD. Further studies are needed to investigate the long-term efficacy and safety of probiotics in PD, as well as their mechanisms of action.

I am excited to see the continuous progress in understanding how gut health impacts Parkinson’s and many other chronic diseases. Expanding research to the microbiome continues to offer much promise. As people with Parkinson’s begin to understand more how their lifestyle choices can impact this vital “organ” there is hope that this knowledge will lead to more focus in the medical community on how health can be supported and changed more readily with diet, nutrition and lifestyle. 

 

My goal is to educate and provide resources for people with Parkinson’s and their partners that may help effect behavior change to improve their overall health outcome and give them better lives every day.  

 

At The BioCollective we continue our focus looking for potential biomarkers in the microbiome data so that we may one day turn people back from the path of disease. During the first quarter of 2021, we presented early diagnostic biomarkers with our academic partners to several groups and began work on two publications.  

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