Gut Health and Dysbiosis
by Robert L, Jan 4, 2022
I used to think of my long term abdominal pain, gas, belching, constipation, or “irritable bowel syndrome” as just annoyances. If they became really bad, I could always go to the doctor to get antibiotics. As it turns out, these gut symptoms were an indication of dysbiosis, which often precedes Cervical Dystonia, Parkinson’s Disease, Alzheimer’s Disease , and many other systemic diseases by years. Even worse, excessive antibiotic use can lead to dysbiosis .
What is dysbiosis?
Our bodies are home to trillions of bacteria in thousands of species, mostly located in our small and large intestines. These bacteria together as a whole are called the microbiome or microbiota. According to the Harvard School of Medical Health, the microbiome is labeled as a “supporting organ”, because it plays so many key roles in promoting the smooth daily operations of the human body .
Dysbiosis is an imbalance of the bacterial levels in the microbiome, which can lead to inflammation (immune system activation), excess absorption of toxins or incompletely digested proteins, anda biochemical level changes in the blood. Over time, these can drive systemic disease mechanisms such as an increase in oxidative stress damage to neurons, neurotransmitters, and neuronal structures  and neuroinflammation. These alterations predispose us to a variety of neurodegenerative diseases, including PD, Alzheimer’s disease, and multiple sclerosis . Specifically in dystonia and PD:
- In 2021, a landmark study showed that a whopping 51% of isolated dystonia patients had a specific type of dysbiosis . In patients with this dysbiosis, compared against age-matched controls:
- Out of 1500+ measured blood biochemical levels, more than 200 were significantly altered.
- Short chain fatty acid (SCFA) producers such as Lachnospiraceae were significantly increased.
- Phenylalanine, tyrosine, and tryptophan biosynthesis, and purine and sulfur metabolism, all associated to neurotransmitter metabolism, were more active. (Dopamine is made from tyrosine and serotonin is made from tryptophan.)
- Vitamin B6 metabolization, important for detoxification, was decreased.
- Other studies show that 70-80% of PD patients have constipation and 24% show symptoms of irritable bowel syndrome (IBS), both of which can be indicators of dysbiosis .
- A meta-review of several Parkinson’s Disease dysbiosis studies shows wide variations in the microbiome due to local diets. However, several things were noted in common , even with dietary differences:
- In the microbiome, SCFA-producers Roseburia, Faecalibacterium, and Lachnospiraceae were decreased.
- Increases in Akkermansia, which degrades the intestinal protective mucin layer.
- In several studies, microbiome “reconstruction” using fecal microbiota transplantation (FMT) has shown promise in relieving symptoms of Parkinson’s and other systemic diseases. Note that FMT will likely take many more years of clinical trials to become a widely recommended therapeutic treatment . Although we take no position whether it is wise to pursue participation in clinical trials, FMT data indicates that correcting dysbiosis could result in reduced neurologic symptom intensity.
- In a 2021 study, 11 PD patients received FMT, which greatly altered their microbiome, reduced constipation, and improved both motor and non-motor symptoms of PD . Small intestine bacterial overgrowth (SIBO), which can result in excessive burping, was also reduced.
The evidence points strongly to the benefits of correction of dysbiosis indicated by constipation, IBS, excessive burping, or stool testing. Microbiome reconstruction in PD using dietary modifications and probiotics has been tried in several studies. Although the studies generally show a benefit, they are usually performed with a small number of strains of bacteria, and are not individualized nor is diet usually modified or vitamin D deficiencies corrected. So for best results it is important to consult with a healthcare provider trained in dysbiosis correction and the maintenance of a healthy microbiome.
There are many potential mechanisms how dysbiosis could contribute to neurodegenerative disease, and motor conditions such as CD and PD.
- Altered SCFA production can contribute to neurologic disorders.
- Butyric acid has a protective effect against some toxins, resulting in improved motor performance and less dopaminergic degeneration in substantia nigra and striatum . Butyrate is also needed to protect the health of the intestine , e.g. against “leaky gut”.
- Propionic acid showed clear neuroprotective properties after toxin-induced damage, and also increased neurite outgrowth from neurons .
- However, overproduction of SCFAs is not necessarily good, potentially due to overstimulation of the immune system . Overabundance of SCFA producers may also crowd out of other types of beneficial bacteria.
- Altered dopamine production / metabolism can contribute to motor disorders.
- Contrary to popular belief, more dopamine is not always a good thing. Consider cocaine, which increases dopamine concentrations in the brain, which then alters sleep and eating patterns, and leads to brain damage.
- Excess dopamine can more easily oxidize to dopamine o-quinone, aminochrome and 5,6-indolequinone. These toxic chemicals cause oxidative stress, damage mitochondria, and induce growth of misfolded alpha-synuclein clusters, contributing to PD .
- Excess dopamine can be especially toxic when there are also toxic metal (e.g. manganese, lead, etc.) deposits in the basal ganglia. There is a complex interaction which I will write about separately.
- Some bacteria can generate p-cresol and HPHPA. These biochemicals can bind to and inactivate Dopamine Beta Hydroxylase (DBH), inhibiting the conversion of dopamine to norepinephrine in the brain. This results in increased dopamine and reduced norepinephrine and epinephrine, needed for the brain to control heart rate and breathing. Therefore:
- P-cresol has been shown to increase autism-like behaviors due to dopamine alterations .
- People with hereditarily insufficient DBH often develop childhood autonomic disorders such as POTS (low blood pressure when first standing up). POTS is also common among PD patients, so correcting dysbiosis could potentially help reduce any POTS symptoms caused by p-cresol production.
- The bacteria in the mouth, which cause tooth decay, can have a major connection to the gut microbiome and neuroinflammation .
- Dysbiosis can alter levels of GABA, the primary neurotransmitter for inhibiting unintended movement .
- Perhaps not surprisingly, the normal target of Deep Brain Stimulation therapy in both PD and CD is the GPi, the GABA center of the basal ganglia.
Thirty years ago, the most common way to treat gut bacterial overgrowths was with broad-spectrum antibiotics. However, it is now shown that antibiotics can lead to dysbiosis, by wiping out the bacterial diversity that exists in the gut. In fact, sometimes, pathogenic bacteria such as Clostridium Difficile can come back stronger after antibiotics because there are no longer so many species competing for food . Clostridium Difficile, along with all spore-producing bacteria, can survive outside the body for weeks in the form of spores, and repopulate the gut after antibiotics are completed. Some bacteria can also survive antibiotics by producing biofilms, or biochemical “houses” that a colony of bacteria build to protect themselves .
Today, reconstruction of the microbiome with dysbiosis or antibiotic use is a hot topic of research. The new theory is generally to accept that the microbiome will always contain some pathogenic bacteria. In a healthy gut, there are not enough of these pathogenic bacteria to cause any disease. Also in a healthy gut, the “good” bacteria are balanced and there is not an overabundance of any bacteria crowding out other important bacteria. This balance is controlled by a combination of genetics, diet, the immune system, the brain, toxins, and the gut itself, when it is healthy. Also, herbicides or pesticides from foods or other exposures can act like antibiotics, altering the microbiome.
My research shows that the microbiome can be difficult to reconstruct from dysbiosis, and keep it from eventually reverting back to where it started. It is important to get professional help and testing, and to understand the importance of things like diet.
I got help from two naturopathic doctors (NDs), but you can also look for help from functional medicine, integrative, or holistic MDs. There are also some nutritionists and MDs who have written books about healthy diets for the mind, autism spectrum disorder, and ADHD, which can be relatively inexpensive ways to learn more. The genetics and dysbiosis common in ASD, CD, and PD can have a relationship in dopamine production and metabolism, metals retention, and oxidative stress pathways. In fact, many children with ASD also have dysbiosis  and dystonic movement patterns.
Tools Providers Often Use to Fight Dysbiosis
Testing: Testing options for the microbiome and dysbiosis have greatly increased in the past few years. Testing can include testing for bacterial overgrowths, bacterial genetic capabilities (metabolomics), levels of important chemicals, and susceptibility of detected bacterial overgrowths to both antibiotics and herbal formulations. Tests from reputable, established labs in the US include:
Antibacterials: These are substances, often herbal, that can help reduce growth of certain bacteria, to help bring the microbiome back in balance. These are typically less powerful than antibiotics, and also less disruptive. It is important to work with your practitioner on these for proper effect and to minimize side effects.
Probiotics: Probiotics are beneficial bacteria to repopulate the gut, especially with antibacterial or after antibiotic usage. There are many studies showing that even probiotics with a small number of species can help modify the microbiome, reduce inflammation, reduce PD symptoms, and help improve mood (even in healthy individuals) .
Note there are two basic categories of probiotics. The probiotics which contain only “soil based” or “spore-producing” bacteria generally do not require refrigeration and survive stomach acids easily. Other probiotics generally require refrigeration for a decent shelf life. If a product does not state whether it requires refrigeration or not, I usually avoid it.
My NDs asked me to take a variety of probiotics, often recommending specific brands. There can be quality issues with probiotics  so I generally stuck to manufacturers which they had vetted in the past. I ordered all my refrigeration-required products through Wellevate, or other providers that offered express shipping with ice packs.
Fermented Foods: Fermented foods like yogurt, cheese, and pickled foods also can contain naturally occuring probiotics. However, some people may have inflammatory reactions to the histamines in fermented foods, so it’s important to discuss with your healthcare provider.
Prebiotics: Prebiotics are various types of foods for beneficial bacteria. Resistant starch made from potato fiber has been shown to increase colonic butyrate SCFA production , often found short in PD, and possibly in some cases of CD. My ND prescribed Paleofiber RS, a combination of fiber and resistant starch.
Diet: The diet can have a significant influence on gut microbiota in PD, and diets such as the Mediterranean diet may be beneficial . Diet is such a large subject I will cover it in another article. However, I will say here that reducing heavy metals in the diet (contaminated fish, brown rice grown in certain areas, etc.) is important in all neurologic disease. Also, it is important to limit sugars, especially if they cause excessive burping or gas, which can be a sign of small intestine bacterial overgrowth (SIBO).
Vitamin D: Vitamin D (VitD) is involved in immune cell differentiation, gut microbiota modulation, gene transcription, and intestinal wall barrier integrity, and deficiency can be associated with reduced butyrate production . It is not surprising vitamin D deficiency is common in PD and almost all systemic disease.
NAC: NAC (and vitamin C) are supplements that can help break down dysbiosis biofilms . NAC is also an antioxidant and a precursor to glutathione, so it can convey a variety of benefits in systemic disease, when properly used.
2. Dias V, Junn E, Mouradian MM. The role of oxidative stress in Parkinson’s disease. J Parkinsons Dis. 2013;3(4):461-491. doi:10.3233/JPD-130230
3. Doroszkiewicz J, Groblewska M, Mroczko B. The Role of Gut Microbiota and Gut-Brain Interplay in Selected Diseases of the Central Nervous System. Int J Mol Sci. 2021;22(18):10028. Published 2021 Sep 17. doi:10.3390/ijms221810028
4. Ma L, Keng J, Cheng M, et al. Gut Microbiome and Serum Metabolome Alterations Associated with Isolated Dystonia. mSphere. 2021;6(4):e0028321. doi:10.1128/mSphere.00283-21
5. Nishiwaki H, Ito M, Ishida T, Hamaguchi T, Maeda T, Kashihara K, Tsuboi Y, Ueyama J, Shimamura T, Mori H, Kurokawa K, Katsuno M, Hirayama M, Ohno K. Meta-Analysis of Gut Dysbiosis in Parkinson’s Disease. Mov Disord. 2020 Sep;35(9):1626-1635. doi: 10.1002/mds.28119. Epub 2020 Jun 18. PMID: 32557853.
6.Kuai XY, Yao XH, Xu LJ, Zhou YQ, Zhang LP, Liu Y, Pei SF, Zhou CL. Evaluation of fecal microbiota transplantation in Parkinson’s disease patients with constipation. Microb Cell Fact. 2021 May 13;20(1):98. doi: 10.1186/s12934-021-01589-0. PMID: 33985520; PMCID: PMC8120701.
7. Jena R, Jain R, Muralidharan S, Yanamala VL, Zubair Z, Kantamaneni K, Jalla K, Renzu M, Alfonso M. Role of Gastrointestinal Dysbiosis and Fecal Transplantation in Parkinson’s Disease. Cureus. 2021 Oct 25;13(10):e19035. doi: 10.7759/cureus.19035. PMID: 34853754; PMCID: PMC8608042.
8. Fang X. Microbial treatment: the potential application for Parkinson’s disease. Neurol Sci. 2019 Jan;40(1):51-58. doi: 10.1007/s10072-018-3641-6. Epub 2018 Nov 10. PMID: 30415447.
9. Metzdorf J, Tönges L. Short-chain fatty acids in the context of Parkinson’s disease. Neural Regen Res. 2021;16(10):2015-2016. doi:10.4103/1673-5374.308089
10. Qiao CM, Sun MF, Jia XB, Li Y, Zhang BP, Zhao LP, Shi Y, Zhou ZL, Zhu YL, Cui C, Shen YQ. Sodium Butyrate Exacerbates Parkinson’s Disease by Aggravating Neuroinflammation and Colonic Inflammation in MPTP-Induced Mice Model. Neurochem Res. 2020 Sep;45(9):2128-2142. doi: 10.1007/s11064-020-03074-3. Epub 2020 Jun 16. PMID: 32556930.
11. Liu H, Wang J, He T, et al. Butyrate: A Double-Edged Sword for Health?. Adv Nutr. 2018;9(1):21-29. doi:10.1093/advances/nmx009
12. Segura-Aguilar J, Paris I, Muñoz P, Ferrari E, Zecca L, Zucca FA. Protective and toxic roles of dopamine in Parkinson’s disease. J Neurochem. 2014 Jun;129(6):898-915. doi: 10.1111/jnc.12686. Epub 2014 Mar 18. PMID: 24548101.
13. Darkoh C, Plants-Paris K, Bishoff D, DuPont HL. Clostridium difficile Modulates the Gut Microbiota by Inducing the Production of Indole, an Interkingdom Signaling and Antimicrobial Molecule. mSystems. 2019 Mar 19;4(2):e00346-18. doi: 10.1128/mSystems.00346-18. PMID: 30944877; PMCID: PMC6426650.
14. Pascucci T, Colamartino M, Fiori E, et al. P-cresol Alters Brain Dopamine Metabolism and Exacerbates Autism-Like Behaviors in the BTBR Mouse. Brain Sci. 2020;10(4):233. Published 2020 Apr 13. doi:10.3390/brainsci10040233
15. González-Sanmiguel J, Schuh CMAP, Muñoz-Montesino C, Contreras-Kallens P, Aguayo LG, Aguayo S. Complex Interaction between Resident Microbiota and Misfolded Proteins: Role in Neuroinflammation and Neurodegeneration. Cells. 2020;9(11):2476. Published 2020 Nov 13. doi:10.3390/cells9112476
16. Dutta SK, Verma S, Jain V, et al. Parkinson’s Disease: The Emerging Role of Gut Dysbiosis, Antibiotics, Probiotics, and Fecal Microbiota Transplantation. J Neurogastroenterol Motil. 2019;25(3):363-376. doi:10.5056/jnm19044
17. US National Institutes of Health, Probiotics: What You Need To Know, https://www.nccih.nih.gov/health/probiotics-what-you-need-to-know
18. Uyar GÖ, Yildiran H. A nutritional approach to microbiota in Parkinson’s disease. Biosci Microbiota Food Health. 2019;38(4):115-127. doi:10.12938/bmfh.19-002
19. Battistini C, Ballan R, Herkenhoff ME, Saad SMI, Sun J. Vitamin D Modulates Intestinal Microbiota in Inflammatory Bowel Diseases. Int J Mol Sci. 2020;22(1):362. Published 2020 Dec 31. doi:10.3390/ijms22010362
20. Eroshenko D, Polyudova T, Korobov V. N-acetylcysteine inhibits growth, adhesion and biofilm formation of Gram-positive skin pathogens. Microb Pathog. 2017 Apr;105:145-152. doi: 10.1016/j.micpath.2017.02.030. Epub 2017 Feb 22. PMID: 28237766.
21. Yang Q, Liang Q, Balakrishnan B, Belobrajdic DP, Feng QJ, Zhang W. Role of Dietary Nutrients in the Modulation of Gut Microbiota: A Narrative Review. Nutrients. 2020;12(2):381. Published 2020 Jan 31. doi:10.3390/nu12020381
22. Griffiths, J.A., Mazmanian, S.K. Emerging evidence linking the gut microbiome to neurologic disorders. Genome Med 10, 98 (2018). https://doi.org/10.1186/s13073-018-0609-3
23. Zhu F, Li C, Chu F, Tian X, Zhu J. Target Dysbiosis of Gut Microbes as a Future Therapeutic Manipulation in Alzheimer’s Disease. Front Aging Neurosci. 2020;12:544235. Published 2020 Oct 6. doi:10.3389/fnagi.2020.544235
24. Francino MP. Antibiotics and the Human Gut Microbiome: Dysbioses and Accumulation of Resistances. Front Microbiol. 2016;6:1543. Published 2016 Jan 12. doi:10.3389/fmicb.2015.01543
25. Baxter NT, Schmidt AW, Venkataraman A, Kim KS, Waldron C, Schmidt TM. Dynamics of Human Gut Microbiota and Short-Chain Fatty Acids in Response to Dietary Interventions with Three Fermentable Fibers. mBio. 2019;10(1):e02566-18. Published 2019 Jan 29. doi:10.1128/mBio.02566-18