Last Updated on September 23, 2018 by Patricia Carter

SUMMARY:  Yesterday, Dec. 1, 2016, a major gut — brain animal study paper published finding for Microbiome:  Parkinson’s begins in the gut, at least in mice.   While this has been kicked around for years, this animal mouse study finally proves the theory.  This post documents the Dec 2016 Parkinson’s mouse study.  You’ll recognize some of the authors:  Rob Knight, Sarkis K. Mazmanian, Ali Keshavarzian, and Kathleen M. Shannon if you follow my work as I have worked with these labs or follow them closely.  If you have or are concerned with brain and cognition, be it autism, MS, cognitive decline, Alzheimer’s, Parkinson’s, depression, etc…  consider extending this papers findings and seriously start looking in your gut for answers to the why in your brain.   I can’t stand that it takes so long for folks to get real and realize that what goes into our body impacts the brain too.  Usually they don’t get it until they have major symptoms of impairment.  It’s also beyond me that folks don’t understand that bowel habits are windows into how our body handles what we put into it.  My pearl there is that you need to know what the Bristol Stool Chart is and how to use its incredibly useful information to learn what your body, especially what your microbiome or those trillions of beasties, thinks about the menu you feed it.  Though the human studies are far off, the writing is on the wall.  if you care about your brain, START fixing your gut.  This post was updated Jan 25 and 26, 2017 to include a webinar and podcast dated Jan 17 and 19, 2017, discussing the Mazmanium study along with insights for diet and the “Parkinson’s” microbiome.  Diets for Parkinson’s was further updated Sept 23, 2018.

The Study full text link is:

Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson’s Disease, Dec 2016 and the PDF is here.  The study looks at if changes in the immune response to gut bacteria could affect neurological outcomes, in particular motor symptoms in Parkinson’s.  The study found that metabolites from the microbiome (this is the exhaust of the trillions of beasties) goes into circulation (it is not known yet if they make it into the brain) and these molecules impacted inflammation in the brain and motor symptoms.

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Parkinson’s General Info

Beyond the obvious physical tremors and difficulty walking, Parkinson’s has an aggregation of a protein called alpha-synuclein (αSyn) within cells in the brain and gut, and the presence of inflammatory molecules called cytokines within the brain.  75% of PD patients have gastrointestinal abnormalities, primarily constipation.

One of the researchers, Mazmanian explains, “The gut is a permanent home to a diverse community of beneficial and sometimes harmful bacteria, known as the microbiome, that is important for the development and function of the immune and nervous systems.  Remarkably, 70% of all neurons in the peripheral nervous system — that is, not the brain or spinal cord — are in the intestines, and the gut’s nervous system is directly connected to the central nervous system through the vagus nerve. Because GI problems often precede the motor symptoms by many years, and because most PD cases are caused by environmental factors, we hypothesized that bacteria in the gut may contribute to PD.”

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Summary of the study

Caltech scientists have discovered for the first time a functional link between bacteria in the intestines and Parkinson’s disease (PD). The researchers show that changes in the composition of gut bacterial populations–or possibly gut bacteria themselves – are actively contributing to and may even cause the deterioration of motor skills that is the hallmark of this disease.  Notably, the transplantation of Parkinson’s microbiome into the mice showed that there is an absence of bacteria within the microbiome of Parkinson’s.  This is a new paradigm in science, that the absence of bacteria in the microbiome can be a risk for disease.  Currently, we think of bacteria as causing symptoms or illness.  Actually there are many protective or beneficial organisms that we need for health.  Future work is the identify those found helpful and those found harmful for the Parkinson’s microbiome.

This NeuroScience News article, Parkinson’s Disease Linked to Gut Microbiome, explains:

• The researchers used mice that overproduce αSyn and display symptoms of Parkinson’s.
• One group of mice had a complex consortium of gut bacteria; the others, called germ-free mice, were bred in a completely sterile environment at Caltech and thus lacked gut bacteria.
• The researchers had both groups of mice perform several tasks to measure their motor skills, such as running on treadmills, crossing a beam, and descending from a pole.
• The germ-free mice performed significantly better than the mice with a complete microbiome.  “This was the ‘eureka’ moment,” says Timothy Sampson, a postdoctoral scholar in biology and biological engineering and first author on the paper. “The mice were genetically identical; both groups were making too much αSyn. The only difference was the presence or absence of gut microbiota. Once you remove the microbiome, the mice have normal motor skills even with the overproduction of αSyn.”  “All three of the hallmark traits of Parkinson’s were gone in the germ-free models,” Sampson says. “Now we were quite confident that gut bacteria regulate, and are even required for, the symptoms of PD. So, we wanted to know how this happens.”
• When gut bacteria break down dietary fiber, they produce molecules called short-chain fatty acids (SCFAs), such as acetate and butyrate. Previous research has shown that these molecules also can activate immune responses in the brain. Thus, Mazmanian’s group hypothesized that an imbalance in the levels of SCFAs regulates brain inflammation and other symptoms of PD. Indeed, when germ-free mice were fed SCFAs, cells called microglia–which are immune cells residing in the brain–became activated. Such inflammatory processes can cause neurons to malfunction or even die. In fact, germ-free mice fed SCFAs now showed motor disabilities and αSyn aggregation in regions of the brain linked to PD.
• In a final set of experiments, Mazmanian and his group collaborated with Ali Keshavarzian, a gastroenterologist at Rush University in Chicago, to obtain fecal samples from patients with PD and from healthy controls. The human microbiome samples were transplanted into germ-free mice, which then remarkably began to exhibit symptoms of PD. These mice also showed higher levels of SCFAs in their feces. Transplanted fecal samples from healthy individuals, in contrast, did not trigger PD symptoms, unlike mice harboring gut bacteria from PD patients.  “This really closed the loop for us,” Mazmanian says. “The data suggest that changes to the gut microbiome are likely more than just a consequence of PD. It’s a provocative finding that needs to be further studied, but the fact that you can transplant the microbiome from humans to mice and transfer symptoms suggests that bacteria are a major contributor to disease.”  
• In other words, signals from gut microbes are required for the neuroinflammatory responses as well as hallmark gastrointestinal and a-synuclein-dependent motor deficits in this [mice] model of Parkinson’s disease.

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What the clinical application of microbiome for Parkinson’s is:

“For many neurological conditions, the conventional treatment approach is to get a drug into the brain. However, if PD is indeed not solely caused by changes in the brain but instead by changes in the microbiome, then you may just have to get drugs into the gut to help patients, which is much easier to do,” Mazmanian says. Such drugs could be designed to modulate SCFA levels, deliver beneficial probiotics, or remove harmful organisms. “This new concept may lead to safer therapies with fewer side effects compared to current treatments.”  —Parkinson’s Disease Linked to Gut Microbiome

What is missing? How about DIET changing the metabolites of the microbiome?!?  

Microbiome: Parkinson’s begins in gut

My favorite listen of Dr. Mazmanian discussing and summarizing his Parkinson’s lab work is at Podcast: Gut Bacteria and Parkinson’s Connection.  As well, listen to the webinar, Gut (Bacteria) Check on Parkinson’s: Role of the Microbiome, which explains tons about the microbiome impact for Parkinson’s.  The discussion on diet impact for Parkinson’s microbiome (beginning at time 30:00) fails to address all of the latest recommendations for microbiome support.  The panel offers no insights for fermented real food (probiotics) impact to the Parkinson’s microbiome based on other disease/probiotic studies.  Their recommendation to increase plant based fiber is sound as that is fuel for the microbiome.  They don’t elaborate however on what are the microbiota accessible carbs (MACs), RS, or prebiotics nor are food examples given.  Their recommendation to eat low saturated red meat fat is sound from a microbiome consideration since the microbiome produces TMA when red meat is ingested (except in a vegan/vegetarian eater).  TMA goes to the liver where TMAO is generated (cardiovascular risk).  Read more on TMAO here.   A huge failing for the panel is that there is no discussion of  what healthy fats to eat.  Read these posts for insights into that:

• Type of Fat Consumed and Breast Cancer Diagnosis for Mediterranean Diet.
• Meet the Fats & Best Salad Dressing Oil, Part 1.
• Soybean Oil, Corn Oil, Diabetes, and Metabolic Syndrome.

Another good Dr. Mazmanian discussion can be heard at: Caltech Researchers Link Parkinson’s Disease to Gut Bacteria. 

The BBC News explains in layman’s terms:  Researchers used mice genetically programmed to develop Parkinson’s as they produced very high levels of the protein alpha-synuclein, which is associated with damage in the brains of Parkinson’s patients.

• Transplanting bacteria from Parkinson’s patients to mice led to more symptoms than bacteria taken from healthy people.
• Dr Timothy Sampson, one of the researchers at the California Institute of Technology, said: “This was the ‘eureka’ moment, the mice were genetically identical, the only difference was the presence or absence of gut microbiota.
• “Now we were quite confident that gut bacteria regulate, and are even required for, the symptoms of Parkinson’s disease.”
• The scientists believe the bacteria are releasing chemicals that over-activate parts of the brain, leading to damage.  The bacteria can break down fibre into short-chain fatty acids. It is thought an imbalance in these chemicals triggers the immune cells in the brain to cause damage.

In conclusion:

Diet changing the metabolites of the microbiome….

• I have written how SCFA metabolites (especially butyrate) increases for IBD (which has a messed up microbiome at diagnosis) using the diet called Specific Carbohydrate Diet (SCD). I mention this diet in particular since it resolves gut functional dysfunction for IBD, and is so powerful, that SCD induces remission for many and allows many to even wean off medication. SCD is also being used for autism with success.  All three conditions (IBD, autism, and PD) have gut functional dysfunction (constipation is prevalent in PD).  As such, SCD may be a starting point for PD type diet tenets.  This post describes SCD including the IBD studies! 
•  As well, IBS is associated with IBD, autism, PD, AND many other conditions including depression, anxiety, MS, T2D, Metabolic Syndrome, and Chronic Fatigue.  The FODMAP diet targets modulating the IBS microbiome dsybiosis, and you can read more on all that at the post, IBS, Microbiome, Fodmaps, Probiotics.  The post also links to the Bristol Stool Chart— that defines what a ‘normal BM’ is, and that is likely not what your GI doctor tells you!
• I also mention another diet called Wahl’s Protocol.  Dr. Wahl talked about her research with Robb Wolf, Episode 252 – Dr. Terry Wahls – Multiple Sclerosis and Autoimmunity, Dec 14, 2014.  She noted that Wahl’s Protocol has been used successfully to treat Parkinson’s as well as:  RA, Lupus, IBD, psoriasis, neurological conditions such as Parkinson’s and  early memory loss/dementia, depression, anxiety, even PTSD (fighter pilots with narcolepsy), traumatic brain injury, as well as diabetes and obesity (to normalize blood sugars), and heart disease atherosclerosis — which is now being looked at as possible autoimmune since it is a gut and inflammation issue (see the whole TMAO issue here).  The How-To book is,“The Wahl’s Protocol, Food As Medicine”.  This protocol recommends eating 9 cups vegetables/fruits each day for for men and tall women (like 6′) and if a petite women, then 4 to 6 cups each day.  The diet also recommends eating a lot of high quality protein.  It can be tweaked to be a more ketogenic diet but reduces protein from the classic high PALEO type diet, to add in vegetables.  In the podcast, Dr. Wahl suggested in order to eat 9 cups of vegetables/fruits a day, to eat 4 cups of whole but to juice the remaining.  She says to not over stuff yourself.  When asked if you can substitute for some vegetables, some low calorie sprouted lentils, her reply did not really answer the question.
• Even cancer diet recommendations are heavy on vegetables and fruits. This Phytonutrients PDF chart from Dana Farber Brigham and Women’s Cancer Center recommends 5 to 10 colorful servings, and note, TWO of those servings are to be cruciferous vegetables for detox — see the bottom of the chart.  
• The Pearl:  There are a lot of healing diets which are actually tweaks of each other, being used by many to manage chronic diseases like IBS, hypertension, atherosclerosis, obesity, autism, dementia, cognition, and Alzheimer’s, and autoimmunity like MS and IBD, AND for aggressive preventative medicine!  These diets target the root cause of the illness, looking at gut microbiome dsybiosis.  These diets have common tenets including being heavy on diverse and colorful vegetables and removal of processed foods, grains, legumes, and dairy which are common gut inflammatories.  Regarding vegs, [Cantinean et al 2018] explains that the more vegs consumed, the more diverse the microbiome, and that is thought to be associated with health and improved immune status since MANY chronic diseases (see below) have changes in microbiome diversity AND composition:  

  

  

  

  

• I first wrote about the Optimal Microbiome Diet From American Gut Data in 2014.  I updated it August 2018 to include the MANY important papers that have since published that link disease to microbiome dsybiosis as well as the 2018 update on the American Gut data, [McDonald et al 2018], which still says to eat 30 different vegs each week for a diverse optimal microbiome!    
• DISEASE CONDITIONS MAY NOT SNOWFLAKE, BUT AN INDIVIDUAL’S MICROBIOME IS!!! Individualized healing diets, long term, can change the microbiome nudging it to health thereby mitigating chronic disease symptoms and inducing remission.  Re-introduction of foods eliminated (or reduced in quantity due to tolerance limits) may even be possible once enough of the microbiome is built up to maintain remission.  For more info, see my services page!

Diet changing the metabolites of the microbiome…. seeing this in real time is amazing.  

Try it.  What do you have to lose?

Best in health thru awareness,

 

♥Last updated: September 23, 2018 at 10:04 am  to add SCD, FODMAP, Wahl’s Protocol, Dana Farber Cancer diet recommendations, and Optimal American Gut info in the “Diet Changing Metabolites of the Microbiome”section.  Prior Jan 25 and 26, 2017 updates added a webinar and podcast dated Jan 17 and 19, 2017, discussing the Mazmanium study along with insights for diet and the Parkinson’s microbiome.  In the  Podcast: Gut Bacteria and Parkinson’s Connection,  dated Jan 17, 2017, Sarkis Mazmanian discusses and summarizes his recent gut bacteria research in the latest episode of our “Getting to a Cure: The Science behind the Search” podcast series.

♥The Jan 19, 2017 update added Michael J. Fox Foundation webinar, Gut (Bacteria) Check on Parkinson’s: Role of the Microbiome.