parkinsons

Microbiome: Parkinson’s begins in gut

SUMMARY:  Yesterday, Dec. 1, 2016, a major gut — brain animal study paper published finding for Microbiome: Parkinson’s begins in gut, at least in mice.  While this has been kicked around for years, this animal mouse study finally proves the theory, and 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, 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.

The Study full text link:

Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson’s DiseaseDec 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.

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.”

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.
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

lightbulb2What 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:

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.

lightbulb2In conclusion:

I have written how SCFA (especially butyrate) increases for IBD (which has a messed up microbiome at diagnosis) using the diet called Specific Carbohydrate Diet (SCD).  SCD induces remission for many with IBD and allows many to even wean off medication.  SCD is also used for autism with success.  In fact, the healing diets are used by many to manage chronic disease and autoimmunity, and for aggressive preventative medicine!  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: January 26, 2017 at 9:27 am  To add in the Jan 19, 2017 Michael J. Fox Foundation webinar, Gut (Bacteria) Check on Parkinson’s: Role of the Microbiome, along with my insights into what the panelist recommends for the diet – Parkinson’s microbiome.

The prior update Jan 25, 2017 added the  Podcast: Gut Bacteria and Parkinson’s Connection  interview of Sarkis Mazmanian which is dated Jan 17, 2017.  Mazmanium 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.

3 thoughts on “Microbiome: Parkinson’s begins in gut”

  1. Podcast: Gut Bacteria and Parkinson’s Connection, Jan 2017, https://www.michaeljfox.org/foundation/news-detail.php?podcast-gut-bacteria-and-parkinson-connection&utm_content=buffer9b42f&utm_medium=social&utm_source=linkedin.com&utm_campaign=buffer

    Sarkis Mazmanian, PhD, the Luis B. and Nelly Soux Professor of Microbiology and Heritage Medical Research Institute Investigator at the California Institute of Technology, discusses his recent gut bacteria research in the latest episode of our “Getting to a Cure: The Science behind the Search” podcast series. Read more about Dr. Mazmanian’s study. “We have a rich nervous system in the gut, known as the enteric nervous system,” says Mazmanian. “We’d like to know how bacteria in the gut interact with the enteric nervous system to try and understand how those interactions affect outcomes in the brain. Those neurons in the gastrointestinal tract are connected to our central nervous system [brain and spinal cord] through a network of nerves.”

    Pathology supports that constipation gut dysfunction begins before Parkinson’s symptoms manifest. That gives a window for intervention to modify microbiome and address before disease manifests. Slow down or stop progression of Parkinson’s perhaps.

    Discusses animal model research.

Now I'd like to hear your thoughts... comments are always welcome!