The Intestinal Microbiome in Health and Disease (including PD) – Webinar notes

The Intestinal Microbiome in Health and Disease (including PD) – Webinar notes

The Houston Area Parkinson Society (HAPS) presented a webinar this summer on “The Intestinal Microbiome in Health and Disease.”  The speaker was Herbert DuPont, MD, a professor of infectious diseases at the University of Texas School of Public Health.  Stanford Parkinson’s Community Outreach attended the webinar and are sharing our notes. 

The webinar was held on August 15, 2020.  You can find the speaker’s slides on the HAPS website (starting on page 15 of the PDF).

The speaker, Dr. Herbert DuPont is also the chief scientific officer of the Kelsey Research Foundation.  His talk is titled “The Intestinal Microbiome in Health and Disease.” 

Though the Houston Area Parkinson Society hosted the webinar, the talk included very little content specifically about the microbiome and PD.  Dr. DuPont did mention the Scandinavian vagotomy study.  You can read more about that study on our blog here.

A recording of the webinar is available on the HAPS YouTube channel.

Adrian Quintero with Stanford Parkinson’s Community Outreach attended the webinar and shared his notes today.

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“The Intestinal Microbiome in Health and Disease” (speaker’s title)

“The Gut and Parkinson’s with Dr. Herbert DuPont” (host organization’s title)

Hosted by Houston Area Parkinson Society (HAPS) 

August 15th, 2020 

Notes by Adrian Quintero, Stanford Parkinson’s Community Outreach, October 2, 2020

There are more microbes in the body than there are cells in the body.  

Gut-Microbiota Brain Axis 

95% of all of the microbes in the body are in the intestinal tract.  

There is a brain-microbes-gut (GI tract) triad. They are connected through three pathways. 

Nerve Connection   

Messages are hard wired from the gut (primarily orchestrated by microbes) through the Vagus nerve and spinal nerve, which goes up to the brain. The brain sends messages back to the gut controlling blood flow and movement of the intestines.  

Immune Connections 

70% of all immune cells that keep us healthy are in the GI tract. If you have a healthy microbiome, you have a healthy immune system.  

Endocrine (Hormone) Connections 

A hormone is a chemical produced in one part of the body that travels through the body and has a biologic effect (such as insulin made by the pancreas). The largest endocrine organ of the body is actually the gut. The bacteria and GI tract together produce vast amounts of chemicals (such as Serotonin and Dopamine) that go to the brain and determine how you feel.  

100 trillion microbes in the GI tract are orchestrating these processes.  

Microbiome is the term for the totality of the microbes that live in and on our body. This includes bacteria, fungi, and viruses.  

Diet 

“You are what you eat.” Diet is the most important factor in shaping a healthy microbiome.  

What you eat is the composition of your microbiome (for example, if you eat seaweed, you’re going to acquire the microbes that help you digest seaweed).  Dr. DuPont explains that if you have healthy food, you get healthy bacteria.  

The western diet contains too much animal fat, too much sugar, not enough fiber, and contributes to a lot of major health problems. 

Healthy foods that shape microbiome include soluble fiber and insoluble fiber.  

Soluble fiber (dissolves and readily ferments in the colon) 

Soluble grains: oat bran (oatmeal), rye, barley 

Fruits: figs, prunes, plums, berries, apricots, bananas, pears, guavas, avocados 

Vegetables: beans (all kinds), peas, soybeans, broccoli, root vegetables, Brussels sprouts 

Seeds: flax, chia, sunflower, sesame 

Nuts: all nuts – almonds have highest dietary fiber 

Insoluble fiber (provides bulk to stool and resistant starches can be fermented) 

Whole grains, wheat, corn bran, brown rice 

Fruits: avocado, unripe bananas, kiwi, grape and tomato skids 

Vegetables: green beans, peas, potato skins, cauliflower, zucchini, cabbage, celery 

Seeds: flax, chia, sunflower, sesame 

Nuts: all nuts 

Eat at least 2 or 3 items on these lists every day. 

Avoiding Unnecessary Antibiotics 

Children before age 2 receive an average of 2.3 bouts of antibiotics. By the time children reach adulthood they have received an average of 20 courses of antibiotics. Dr. DuPont says that most (about 55%) of antibiotics humans receive are unnecessary.  

Antibiotics Are Not Equal 

Microbiome Wrecking Antibiotics:  

Clindamycin, Zosyn, Unasyn, 3rd and 4th generation cephalosporins, Fluoroquinolones 

Microbiome Preserving Antibiotics: 

Macrolides, Sulfonamides, Trimethoprim-sulfamethoxazole, Pencillins, including penicillin G and V and Amoxicillin, Tetracylines, Nitrofurantoin, Rfaximin, Vancomycin 

Friends and Enemies of a Healthy Microbiome 

Friends 

  • Healthy Diet (fiber and resistant starches) 
  • Broad exposure to people, plants, and animals. (For example: kids that grow up on farms, or are put in daycare centers early in life have fewer infections later in life and fewer allergies because they are exposed to microbes, which we think of as bad, but they are actually good) 

Enemies 

  • Unhealthy diet (Western diet) 
  • Recurrent courses of antibiotics or course of “bad” antibiotics 

Microbiome in Non-CDI Disease Targets for FMT 

The combination of abnormal microbiome plus DNA (genetic predisposition to disease), leads to disease. Whereas your DNA you can’t do anything about, you can do something about microbes.  

Abnormal Microbiome: Links to Illnesses  

Has been shown in such conditions as: 

CDIF 

Lupus, Rheumatoid Arthritis  

Type 2 diabetes 

IBS and IBD 

Allergic disorders and asthma 

Colorectal cancer 

Pathogenesis of Neurodegeneration Process Beginning Years Before Symptoms Begin 

What happens in people with PD, Alzheimer’s, and Multiple Sclerosis? There are brain vascular changes with degeneration of brain cells. People who are likely to get these diseases have a GI tract problem long before they develop their first neurologic symptom. These abnormal microbes alter the immune system and release T-cells. The immune system produces antibody cells and T-cells, which are important for cancer, viruses, and neurodegenerative disorders. The T-cells become activated, which leads to increased permeability of the gut.  Molecules (such as small proteins and peptides) get through the intestinal lining and can get into the blood stream or the Vagus nerve and reach the brain.  

Gut-Brain Connections in Neurodegenerative Disease 

Upregulated immune cells in MS or bacteria products migrating to the brain acting as “prions” produce neurodegeneration. 

With PD, a-synuclein and ubiquitin are some of the small prion-like proteins that get into the brain (through Vagus nerve or blood stream) and begin the process of degeneration. In many people with PD, the GI tract symptoms (such as constipation) occur before any neurological symptoms (sometimes many years before). 

With MS, the T-cells (inflammatory mediators) gain entrance to the brain from the gut (through the blood stream) and upregulate immune process and degeneration of the brain.  

With Alzheimer’s, the process is more like that of PD. Amyloids and peptides are the proteins involved that get into the brain and begin the process of Alzheimer’s. 

All three of these diseases, which end up with brain damage, seem to have their origin in the GI tract, and the microbiome appears to be important in the process.  

Study: Truncal Vagotomy Protects against Development of Parkinson’s Disease 

Prior to the potent drugs we now have for peptic ulcers and heartburn (such as Prilosec), it was common to cut the Vagus nerve (the big nerve between the gut and the brain) to help the stomach make less acid. This is known as a vagotomy.  

In Scandinavian countries, they follow patients from birth to death, and have a large database system that we don’t have here in the US. In Sweden researchers followed patients with PD and looked back in time, as well as following patients who had received vagotomy, and found that vagotomy helped to protect people from getting PD.  

The Future 

Treatment 

Fecal microbiota transplantation (FMT) in reversing a disordered microbiome.  

In Houston, the Kelsey Research Foundation has taken the lead on this work, and has teamed up with University of Texas Houston to develop the program jointly. Every institution in the Texas Medical Center is involved. There are six FDA approvals to treat and, when possible, reverse disease by treating the microbiome.  

Recurrent CDI 

Parkinson’s Disease 

Non-alcoholic fatty liver disease 

Irritable bowel syndrome 

Ulcerative colitis 

HIV infection 

Recurrent UTI caused by Multidrug resistant organisms 

A dose of these microbes (isolated from lower GI tract of healthy individuals) is 6 capsules. Reverse and normalize the microbiome in disease states. 

They studied the mircrobiome of 100 people with PD, and the paper from this study is just now being written.  

They are now completing a critical placebo-controlled trial (giving FMT vs. placebo) in a small number of patients with PD. They are trying to get more money to expand these studies. This treatment itself is very low tech and low cost. The results from the trial will be available in the end of November.  

What About Probiotics? 

Dr. DuPont describes the probiotic industry as “amazing,” but says that these products don’t provide someone with a healthy microbiome. Probiotics contain some millions of bacteria or fungi, but there are a hundred trillion in the lower GI tract. Dr. DuPont says putting some million into a hundred trillion is only a drop in the bucket.  

There are some minor effects, but he says the vast majority of commercial probiotics are not helpful.  

Summary 

  • The body has two genomes- the one you know, and the microbial genome. 
  • Diet controls the microbiome, and together with human DNA, leads to disease.  
  • We can’t change DNA at this point, but we can change diet and microbial genome. 

Conclusions 

  • The intestinal microbiota shaped by diet is a second body genome.  
  • A healthy microbiome is important for: functional central nervous system, immune system, mood and general health. 
  • Healthy diet and avoiding unnecessary antibiotics are key to microbiome health. 
  • Abnormal microbiome is associated with a broad range of diseases and disorders. 
  • Probiotics are not for healthy people and have few and uncertain benefits. But stay tuned! 
  • FMT is a powerful low-tech physiologic means of potentially reversing an abnormal microbiome in disease states.  

Questions and Answers 

Q: Butyrate has been making headlines recently as a new superstar for gut health. In addition to eating Butyrate rich foods, what is your view on taking Butyrate supplements to support gut and brain health? 

Rather than take Butyrate chemically, eating foods that encourage Butyrate producing bacteria is what Dr. DuPont recommends. These bacteria are depressed in people with PD, as has been shown in the 100-person study he did. Butyrate is a short chain fatty acid. They are important in the integrity in the lining of the gut to prevent molecules from getting out of the permeable gut wall.  

Q: I’ve been taking Align OTC, but it’s expensive. Is there a prescription version that costs less?  

Dr. DuPont says don’t buy probiotics, but buy natural fiber instead (in food). You’ll spend less money but get a bigger effect. Remember, probiotics are a drop in the bucket. A prebiotic is what is needed to make the bacteria jump and grow in the right direction. Feed your bacteria and get them built up to high numbers (and that’s with a prebiotic not a probiotic). 

Q: How does alcohol affect the gut when you have PD? 

Alcohol is absorbed in the upper GI tract. It makes calories, but it doesn’t feed the bacteria. It doesn’t hurt you, as long as you don’t have liver damage from it, but it doesn’t help you.  

Q: What about eating yogurt? And with taking probiotics, can you take too much? 

The yogurt should be fermented (a lot of the yogurt in the US is pasteurized). It’s the same problem with the probiotics, and it’s just too few. It’s wonderful in terms of calcium, protein, but it will not improve your microbiome. 

Q: Is there time to be aggressive with treating the gut? 

The connection between the gut and the brain is long term. Trying to get improvement neurologically with diet is probably a long-term proposition.  

Q: Is Linzess helpful? (it stops constipation but causes diarrhea) 

It does not affect the microbiome, but it stops the constipation. Dr. DuPont thinks diet can be more effective, and cheaper, in relieving constipation symptoms than medication, while giving you additional benefits.  

Miralax and these drugs are very important when constipation is a factor, and Dr. DuPont knows it’s needed on occasion. He wonders how much diet can decrease the need for these drugs.  

 Q: Can you get your microbiome tested? If so, how?  

If you look on the Internet, there are places to get your microbiome tested. The problem is to interpret the results. If you look at 100 different people’s stool samples, you’ll have 100 different results. Strict anaerobes are good, and Ecoli organisms are bad. Dr. DuPont himself has not gotten his microbiome tested, but rather eats the diet that is beneficial for it.  

Q: Do you recommend a vegetarian diet? 

Vegetarian diets are great for the microbiome. However, you don’t need to eat vegetarian foods only to have a microbiome. By and large, vegetarians have better microbiomes, as well as better weight and cholesterol.  

Q: I have a fatty liver and now Parkinson’s. Are these associated with an abnormal microbiome? If so, what can I do?  

Fatty liver disease, which is associated with Type 2 diabetes, and obesity, is associated with an abnormal microbiome. Parkinson’s is also associated with an abnormal microbiome. Without a doubt, you are likely to have an abnormal microbiome. What Dr. DuPont recommends is eating as much of the foods that shape the microbiome as you can tolerate.  

Q: Is permeable gut the same as leaky gut? 

Yes, they are exactly the same. 

Q: Who is a good candidate for FMT? Is it currently an available treatment? Is it possible to get the 6 capsules of FMT prior to FDA approval? 

To give a treatment, that is not licensed, requires the FDA to approve. Getting a green light from the FDA to treat a patient is very hard, and takes many months. Currently, his group is the only group doing treatments to treat PD. If, in December, after the last exam of their subjects on their study, they are going to get money to expand the study, they will look for people to be part of the next study. For now, eat healthy foods, and after the first of the year, look to see if they are enrolling subjects. 

Q: Are medications for stomach acid good for bad? What role does stomach acid play in the microbiome?  

Dr. DuPont thinks we use these drugs too much. Stomach acid helps us digest such things as B-12, calcium, and you are more susceptible to diarrhea when you travel if you take antacids (the stomach acid helps to kill any harmful bacteria).  

The microbiome in the gut is different for people who take such medications (PPIs). Look at why you are taking them. If you have a major problem with peptic ulcers, you may have to take them. If you are just taking them because you have bouts of heartburn every few weeks, Dr. DuPont’s opinion is not to take them. He thinks the H2 blockers (like Pepcid) are safer to take if you need to take one from time to time.  

Q: Can attending to your microbiome reserved a disease state or only slow it from future progression?  

Dr. DuPont has talked to neurologists about this. They all think the attention to microbiome would help to slow down progression. Or it may possibly prevent the occurrence in a family member who doesn’t have the disease yet. He doesn’t think we are going to reverse the motor defects in PD. He says the best we can hope is to arrest it and prevent it in people who will develop it in the future.