Parkinson’s Disease and the Microbiome

In early December, the medical headlines were screaming that Parkinson’s disease might start in the gut.  A friend of mine, with the illness, emailed me to show me the news.  I wrote back saying, old news…not realizing that another new article had just come out.

The connection between alterations in the microbiome and Parkinson’s is not new news.  I’ve been reading about this for several years and I learned this morning, upon doing some more research, that actually, scientists have been looking at the connection for about a decade.

The first time I remember reading about a possible connection was in 2014, when I saw this headline on Medical News Today:  “Study links Parkinson’s disease to gut bacteria.”[i] Finnish researchers examined the flora of 72 individuals with Parkinson’s and compared them to matched controls:  “Our most important observation was that patients with Parkinson’s have much less bacteria from the Prevotellaceae family; unlike the control group, practically no one in the patient group had a large quantity of bacteria from this family.”[ii]

In preparation for writing about the research that has just come out, I did some reading this morning and came across a 2011 paper [iii] in the journal PLoS One, that was actually the original predecessor to the this month’s headline news.  Five years ago, researchers had “…hypothesized that PD subjects might exhibit increased intestinal permeability to proinflammatory bacterial products in the intestine.”  After testing a group with Parkinson’s disease versus control, they found that those with Parkinson’s exhibited “…significantly greater intestinal permeability (gut leakiness) than controls.”

According to this paper, the “…pathogenic hallmark of PD is neuronal inclusions termed Lewy bodies whose main component is alpha-synuclein protein.” (Upon further research, I learned that apparently alpha-synuclean is a protein normally found in the brain (and in other tissues a little bit), but in PD patients, it begins to clump together and forms toxic fibers in their brains.  This team of researchers found these Lewy bodies in the nerves in the intestines, which led them to hypothesize that the intestines might indeed be an “early site of PD disease in response to an environmental toxin or pathogen [i.e. bad bacteria].”

The research[iv] that my friend emailed me about is actually confirmation of what this original team had already found.

These researchers had two separate groups of mice with genetic susceptibility to PD because they over-produced this alpha-synuclein:  some were raised in normal, non-sterile cages and the 2nd group was raised in a sterile, germ-free environment.  This latter group showed fewer motor deficits and less of these toxic fibers in their brains.  Interestingly, antibiotic treatment was able to reduce symptoms in the non-sterile, more affected mice, which suggests that the bacterial microbiome was enhancing their symptoms.

The scientists also injected gut bacteria from human PD patients into the germ-free mice, who rapidly deteriorated.

They conclude, “These findings reveal that gut bacteria regulate movement disorders in mice and suggest that alterations in the human microbiome represent a risk factor for PD.”

In snooping around this morning, educating myself, I found a pretty great summary article (now a little dated, as it’s from 2015 and won’t include this latest paper) on the PD/gut connection on the National Parkinson Foundation’s website: “What’s Hot in PD? More Evidence Linking Gut Bacteria to Parkinson’s Disease:  A Guide for Patients.”[v]

Actually, the human biome is what’s hot in pretty much ALL chronic inflammatory disease, as far as I’m concerned. As I have pointed out before, this blog is totally trending.

_________________________________________

[i] http://www.medicalnewstoday.com/articles/286912.php

[ii] Gut microbiota are related to Parkinson’s disease and clinical phenotype, Filip Scheperjans, et al., Movement Disorders, doi:10.1002/mds.26069, published online 5 December 2014,

[iii] Forsyth CB, Shannon KM, Kordower JH, et al. Increased Intestinal Permeability Correlates with Sigmoid Mucosa alpha-Synuclein Staining and Endotoxin Exposure Markers in Early Parkinson’s Disease. Oreja-Guevara C, ed. PLoS ONE. 2011;6(12):e28032. doi:10.1371/journal.pone.0028032.

[iv] Sampson, TR, etc. al.  Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkingon’s disease.  Cell: volume 167, issue 6, p1469-1480, December 2016.

[v] http://www.parkinson.org/find-help/blogs/whats-hot/january-2015

Multiple Sclerosis and the Biome

Today has been “one of those days.”  From the minute I got up this morning, I felt overwhelmed.  There’s just too darn much for one person to do sometimes.

That overwhelmed feeling even leached into my writing this post today.  I sat here for a couple of hours staring at a blank Word doc thinking, “There are just too many things to write about for any one person!”

After a cup of coffee, a deep breath and mental reminder that I can always write again tomorrow  :- )  I’ve decided to talk a little about multiple sclerosis and the biome today.

As Scarlett O’Hara says, “Tomorrow is another day!”

Last week there was a really good online article on the topic of MS, Your Head or Your Gut?[i]  I just love its summary of the importance of the bacterial microbiome:

 “Within the gut bacterial microbiome are genes that not only promote their own survival and growth but also code for products that are indispensable for human health. Gut bacterial products can promote proper gut barrier function by ensuring normal development of the intestinal structures, are involved in the metabolism of therapeutic drugs, limit the composition and density of the gut microbiota by ensuring proper immune system development, and play crucial roles in breaking down complex dietary carbohydrates into short-chain fatty acids (SCFAs). Gut bacteria exert effects on almost every organ in the body and have been shown to affect intestinal blood vessel formation, influence lung anti-viral immunity, reduce synaptic connectivity, and regulate hepatic metabolism, among many other tasks.”

 Incredible, isn’t it?

Anyway, the article goes on to explain that multiple sclerosis is the most common neurological disease in young people, affecting at least 2.3 million people worldwide, and that it is considered a “disease of the western world.”  And there you have it:  yet another inflammatory illness that is linked to alterations in the gut biome through lack of exposure in our excessively hygienic societies.

Those with MS have been found to have lower levels of certain anti-inflammatory gut bacteria which the article explains in detail.  However, as the article states, “Simple introduction of probiotic bacteria through consumption has gained traction in recent years, but without additional intervention those introduced may not be able to successfully colonize the gut.”  That is, simply taking oral probiotics does not ensure that they will actually establish themselves.

But luckily…we have helminths!  According to research done in the last year, the presence of helminths in the gut causes major improvements in the quality of the gut bacteria.  For example, Dr. Loke’s recent work in mice demonstrated that those “…infected with intestinal worms experienced as much as a thousand-fold decrease in Bacteroides — a group of bacterial species linked by past studies to higher risk for IBD [inflammatory bowel disease]. At the same time, the number of Clostridia, a bacterial species known to counter inflammation, increased tenfold.”[ii]  Dr. Loke, a researcher at New York University, points out that while his work was specifically on IBD, this model will likely also apply to other autoimmune diseases, including MS.[iii]

This phenomena may well explain, in part, the results of one of the best in vivo studies[iv] we have to date with helminths.  12 patients with MS and helminth colonies were followed for 4 ½ years.  As compared to the controls (who did not have helminths on board), those with helminths, “…showed a significantly lower number of exacerbations, minimal variation in disability scores, as well as fewer magnetic resonance imagining changes…”

Diet is important for those with MS as well.  What you eat can greatly affect the biome, as you share your meals with all those trillions of little guys.  In fact, harkening back to my last post about sugar in young children’s diets…

Earlier this year, a paper[v] came out about MS in children that found, “… perturbations in the gut microbiome composition were observed, in parallel with predicted enrichment of metabolic pathways associated with neurodegeneration.”

The good news in all this is that there may well be something you can do about MS – work on the health of the biome now!

_____________

[i] http://www.labnews.co.uk/features/head-gut-12-12-2016/

[ii] Deepshika Ramanan, Rowann Bowcutt, Soo Ching Lee, Mei San Tang, Zachary D. Kurtz, Yi Ding, Kenya Honda, William C. Gause, Martin J. Blaser, Richard A. Bonneau, Yvonne AL Lim, P’ng Loke, Ken Cadwell. Helminth infection promotes colonization resistance via type 2 immunity. Science, 2016 DOI: 10.1126/science.aaf3229

[iii] [iii] https://www.sciencedaily.com/releases/2016/04/160414145513.htm

[iv] Correale J, Farez M. Association between parasite infection and immune responses in multiple sclerosis. Annals of Neurology. 2007 Feb;61(2):97-108.

[v] Tremlett, H., Fadrosh, D. W., Faruqi, A. A., Zhu, F., Hart, J., Roalstad, S., Graves, J., Lynch, S., Waubant, E. and the US Network of Pediatric MS Centers (2016), Gut microbiota in early pediatric multiple sclerosis: a case−control study. Eur J Neurol, 23: 1308–1321. doi:10.1111/ene.13026

Sugar, the Microbiome and the Specific Carbohydrate Diet

From my son, Alex’s, earliest days, he had digestive issues.  As an infant, he projectile- vomited daily.  He wouldn’t eat solid foods until he was 9 months old.  By the time he was diagnosed with autism, just after his 2nd birthday, he had frequent diarrhea and a very limited diet, which progressively got worse until he was constantly spewing out one end or the other – or both.  No gastroenterologist took us seriously (attributing his digestive issues to his autism) until he was 8 ½ and the situation was dire.  When he finally underwent a colonoscopy, we discovered that he had colitis and cryptitis (infections in the mucus crypts of the intestines). During the following year, he was loaded with medications which had little positive effect: pentasa and colazal (azulfidine drugs), 6MP (a chemotherapy agent), high doses of steroids, etc.  A year later, things looked no better and his gastroenterologist called me to talk about inserting a feeding tube.

Instead, I chose to put him on a diet I’d learned about several years before from another mom at an autism conference:  the Specific Carbohydrate Diet (SCD).  At that time, I had bought the book Breaking the Vicious Cycle: Intestinal Health Through Diet, by Elaine Gottschall, but as no doctor was recommending such a seemingly radical diet (on the contrary, I was being told to feed him anything he’d eat, as his weight was so incredibly low), I’d put the book aside. That day though, faced with Alex’s worsening health and the looming feeding tube, I decided to give one last diet a 3 month shot before scheduling the surgery.  Without a clue really as to what I was doing, not having even finished the book, Alex was on the diet by the next meal.

With that first meal on SCD, he stopped vomiting. 3 ½ months later, Alex had the first formed bowel movement he had had in years.  By 6 months, his bowels were completely normal.  His next colonoscopy a year later showed no pathology. Alex has never had any bowel issues again and now, at 22 years old, he eats a completely normal, healthy, balanced diet.

That is what the right diet can do.

So how does SCD work?  The theory is beautifully explained by Elaine in her book that saved our lives:

Carbohydrates come in 3 forms:  monosaccharides, single-molecule sugars such as are found in fruit and vegetables; disaccharides (2 sugar molecules joined together – which includes lactose (found in dairy) and table sugar); polysaccharides, or starch (such as wheat, potatoes, etc.)  In order to be absorbed by the small intestine, all carbs need to be broken down into those single-molecules of sugar.  If, for any reason, carbohydrate digestion is impaired, undigested carbohydrates are left sitting in the small intestine supplying a very abundant source of food for bacteria, which eat these sugars.  With such a plentiful food supply around, well-fed bacteria multiply…and multiply…and soon, you’re facing a small intestine bacterial overgrowth (SIBO), leading to a myriad of problems including irritable bowel symptoms, inflammatory bowel disease, etc.

By removing all carbohydrates from the diet except those single-molecules of sugar which do not require digestion (and can, therefore, be immediately be absorbed by the intestines), you starve the bacteria, reducing and normalizing the population. And a normal microbiome – as I’ve been talking about on this blog – means markedly improved health.

Having lived through the Alex’s transformation from SCD (as well as the hundreds of children and adults I worked with in my nutrition practice), I know this first-hand.  For years now, I have extensively written (including my book, We Band of Mothers: Autism My Son & the Specific Carbohydrate Diet and lectured about SCD.

In the last 11 years since my friend, Elaine, died, there has been some truly amazing research showing just how right she was.  (And when it comes to autism, forgeddaboutit, as we say here in New York.  The evidence is overwhelmingly in support of trying the diet on every child with an autism diagnosis!) In fact, every time an article comes out supporting her contentions, my heart rejoices.

So, this morning was a good morning.  I spotted a new article[i] in The Journal of Nutrition about the effects of added sugar early in life on the microbiome.  Different groups of young rats were fed various amount of sugar (as would be found in sugar-sweetened beverages) and fecal samples were taken to analyze the microbial composition.  The researchers concluded that indeed, early-life sugar consumption affects the gut microbiome in the animals.

More on this subject soon as really and truly, you can never say too much about it.  Not when you see the amount of suffering that can be alleviated by the right diet.

So get used to reading a lot more about this!

OLYMPUS DIGITAL CAMERA
With my much loved friend and hero, Elaine Gotschall

___________________________________________

 [i] Noble, EE, Hsu, TM, Johnes, RB, Fodor, AA, Goran, MI, Kanoski, SE.  Early-life sugar consuptiom affects the rat microbiome independently of obesity.  The Journal of Nutrition: 2016 Nov 30.

 

Helminths and the Microbiome

As promised:  more about how the presence of helminths (a macrobiome) in the gut improves the quality of the microbiome.

In 2015, Dr. William Parker of Duke University’s Medical School, published a paper in Gut Microbes called, “Alteration of the rat cecal microbiome during colonization with the helminth Hymenolepis diminuta.”[i]  Dr. Parker and colleagues examined the changes to the bacterial content of the rat intestine when colonized with HDs, a mutualistic (beneficial) helminth native to rodents.  They discovered that there was a profound shift in the species of bacteria:

“Colonization of the rats used in this study with Hymenolepis diminuta cause a substantial shift in the microbial community, primarily characterized by changes in the relative contributions from species within the Firmicutes phylum.  Specifically, colonization with the helminth is associated with increased Clostridia and decreased Bacilli.  The contribution of Bacilli to the microbiome is higher with a Western diet characterized by processed sugars and high fat content whereas some species of Clostridia are known to tighten the epithelial barrier and decrease propensity for allergy.”

 An in vivo Australian study[ii] on those with celiac also occurred in 2015.  Volunteers were given Necator americanus (human hookworm).  The researchers assessed the changes in the microbiota before and after colonization, following a gluten challenge: “Experimental hookworm infection of the trial subjects resulted in maintenance of the composition of the intestinal flora, even after a moderate gluten challenge.  Notably, we observed a significant increase in microbial species richness over the course of the trial…”  That is, the presence of a helminth actually improved the diversity of the microbiome, even after the subjects were exposed to an “inflammatory” substance.

In 2016, Dr. P’ng Loke and colleagues at New York University made a similar discovery.  In this study[iii] the researchers looked at mice colonized with Trichuris suis, a porcine whipworm (thus, a non-native helminth).  They found a thousand-fold decrease in Bacteroids, a group of bacterial species linked to inflammatory bowel disease.  They too found an increase (10-fold)  in the number of Clostridia, a species known to counter inflammation. More than that: these researchers found that “Additionally, we show that individuals from helminth-endemic regions harbor a similar protective microbiota and that deworming treatment reduced levels of Clostridiales and increased Bacteroidales.”

Deworming humans – which has no direct effect on the bacterial content of the gut – nonetheless causes an increase in inflammatory and a decrease in anti-inflammatory bacteria. 

Those of us living in the industrialized world have been “dewormed” simply through lack of exposure.  Other than pin worms (which are very undesirable due to the side effects), we have no way of obtaining a macrobiome other than by supplementing. Call me crazy (everyone else does!), but to me, it seems that to not add helminths back into our biomes is the height of illogic.

__________________

[i] Erin A McKenney, Lauren Williamson, Anne D Yoder, John F Rawls, Staci D Bilbo & William Parker (2015). Alteration of the rat cecal microbiome during colonization with the helminth Hymenolepis diminuta, Gut Microbes, 6:3,182-193, DOI: 10.1080/19490976.2015.1047128

[ii] Paul Giacomin, Martha Zakrzewski, John Croese, Xiaopei Su, Javier Sotillo, Leisa McCann, Severine Navarro, Makedonka Mitreva, Lutz Krause, Alex Loukas, Cinzia Cantacessi (2015). Experimental hookworm infection and escalating gluten challenges are associated with increased microbial richness in celiac subjects. Scientific Reports 5, Article number: 13797. doi:10.1038/srep13797

[iii] Deepshika Ramanan, Rowann Bowcutt, Soo Ching Lee, Mei San Tang, Zachary D. Kurtz, Yi Ding, Kenya Honda, William C. Gause, Martin J. Blaser, Richard A. Bonneau, Yvonne AL Lim, P’ng Loke, Ken Cadwell. Helminth infection promotes colonization resistance via type 2 immunity. Science, 2016 DOI: 10.1126/science.aaf3229

Guest Post: Thoughts on Treating Autism

I am excited to introduce my first guest blogger, Dr. Louise Lindenberg, MD.  I first met Louise 6 years ago, on a trip I made to South Africa, to talk in an autism conference.  I loved her from the minute we met and I accidentally put eye drops into my coffee instead of stevia and gagged.  (It was the jet lag!  Honestly!)

img_0364

Louise is one of, if not the only, doctor in South Africa who is treating children with autism medically.  I know she puts an incredible effort in to keeping herself up-to-date on the latest research and spends a huge amount of time and money coming to the USA every year or two to attend medical conferences here.

Here she shares some thoughts on diet, the biome and autism:

________________

Judy, your blog has motivated me to put a few thoughts down!

Here in South Africa things are not any different to anywhere else in the world. Although we are far away from the Americas, Europe, the East and Australasia, we have managed to catch on to all the conveniences of the industrialized world. Modern westernized lifestyle has also been causing chronic disease here.

Our diets are often just as junky and unhealthy as what you are seeing in the US and Europe. I am often amazed at the dis-empowered parents I see in practice who believe that they are doing good by shoving empty calories into their children’s mouths. I had a discussion with a mother of a young,  autistic child recently, who said that her child had followed an exclusion diet for a period of time. Although it had improved his sleep, behavior and upper respiratory health, they found it difficult to persist, and, in giving up, introduced all sorts of junk food to his diet. Their complaint now is that he refuses to eat perceived “healthy” foods and prefers junk food, which they give him, as they opt out of the confrontation. I don’t believe in placing children on special diets unless indicated for specific reasons, but I am absolutely certain that children should follow a healthy, balanced whole foods, rotation diet.

Taking the diet one step further, I often examine children’s gastrointestinal function. You are what you eat echoes from every corner of the universe, but we need to understand that the food that you give your microbiome to live on determines “who” lives there! With what we know now, we know that those organisms are metabolically active and their byproducts affect human biochemistry and function.

Most of us have caught on to using cultured foods and probiotics nowadays. We also use strain specific probiotics for specific reasons. In our functional medicine realm, we are now adding probiotic yeasts as a necessary complement to our probiotic bacteria. What most of us have omitted until now, is the scope of probiotic – or physiological helminth species. The research is showing rewarding outcomes. As some have alluded to, it seems that: “we need to invite our old friends back”!

We have been trained to think of parasites as “all bad.” We make sure that we de-worm our children regularly – every 6 months. What we are actually doing, is whacking the microbiome in very much the same way as what we do with a course of antibiotics. We need to adjust this frame of mind. We  need to pay better attention to reintroducing the helminth component to the gut microbiome….but first, we need to get our heads around taking worms?! AARGH?! Educating the population about good worms has started!

______________

More on the effect of helminths on the microbiome soon.

The Human “omes”

The importance of the microbiome to human health can’t be overstated, but this is only one part of a much vaster biomic whole.  My guess is that because we know more (as little as that is!) about our resident bacteria at the moment – they have been recognized and studied longer than our other old friends – they are what’s trending.  However, already interest in our mycobiome (fungi), our virome (viruses) and our macrobiome (our native animal life) is growing and I believe we’ll see a lot more research on these in the not-very-distant future.

A few examples:

Back in September, I read an article[i] on Science Daily about recent research into fungal, as well as bacterial, alterations in the guts of those with Crohn’s disease.  Researchers compared the bacteria and fungi in those with and without Crohn’s, within the same families, and found marked differences in both bacteria and fungi.  They were actually able to demonstrate that there is interaction between these that can lead to the inflammation found in IBD.[ii]

Last year, I read a similar article[iii] about the virome.  Research on this is just beginning so at this point, we know next-to-nothing.  However, in this study[iv] the scientists did note a large increase in the variety of viruses in those with IBD.  As one researcher involved in the work said, “”This is the tip of the iceberg…A significant portion of the viral DNA we identified in these patients is unfamiliar to us — it comes from newly identified viruses we don’t know much about. We have a great deal of groundwork to do, including sequencing the genetic material of these viruses and learning how they interact with the gut and gut bacteria, before we can determine if changes in the virome cause these conditions or result from them.”

And then there is my own personal favorite “ome” – the macrobiome.  I first learned about the concept in the New York Times, in August 1999.  I read the article “In Pursuit of Autoimmune Worm Cure”[v], and knew without a shadow of a doubt that I was reading about one of the most important factors in our growing epidemic of inflammatory diseases.

All mammals on earth have native animal life resident in their guts, right along with all those microscopic organisms.  The main type of macrobiotic organism is the helminth – intestinal worms.  The vast majority of humans on the planet still have their native helminths, except for those of us in the industrialized world where (by wearing shoes all the time, using toilets, drinking purified water, etc.) we have eradicated our native macrobiomes.  There is a growing body of evidence demonstrating that the loss of the immune stimulation provided by these organisms is largely responsible for our greatly increased tendency toward inflammatory disease.  Helminths stimulate the production of Th2 cytokines, including regulatory ones – the off switch to the inflammatory system.

By the way, two articles were published in the last years which demonstrate that the presence of helminths causes an increase in anti-inflammatory bacteria and a decrease in pro-inflammatory ones.  More on this in a future post.

Back to 1999: I ripped that article out of the newspaper and it still hangs on the wall of my office.  I stare at it every day as I work.  Reading that article was a major turning point in my life.

The complexity of our inner ecosystem is mind-boggling, isn’t it?  It’s like a vast, interlocking puzzle.  I think that’s why I find it so utterly mesmerizing. We, humans, are giant, walking ecosystems, just teeming with other life forms.  We can’t see them or feel them but without our “omes” we wouldn’t be alive.  AMAZING.

__________________________________

[i] https://www.sciencedaily.com/releases/2016/09/160920151435.htm

[ii] G. Hoarau, P. K. Mukherjee, C. Gower-Rousseau, C. Hager, J. Chandra, M. A. Retuerto, C. Neut, S. Vermeire, J. Clemente, J. F. Colombel, H. Fujioka, D. Poulain, B. Sendid and M. A. Ghannoum. Bacteriome and Mycobiome Interactions Underscore Microbial Dysbiosis in Familial Crohn’s Disease. mBio, September 2016 DOI: 10.1128/mBio.01250-16

[iii] https://www.sciencedaily.com/releases/2015/01/150122132738.htm

[iv] Jason M. Norman, Scott A. Handley, Megan T. Baldridge, Lindsay Droit, Catherine Y. Liu, Brian C. Keller, Amal Kambal, Cynthia L. Monaco, Guoyan Zhao, Phillip Fleshner, Thaddeus S. Stappenbeck, Dermot P.B. McGovern, Ali Keshavarzian, Ece A. Mutlu, Jenny Sauk, Dirk Gevers, Ramnik J. Xavier, David Wang, Miles Parkes, Herbert W. Virgin. Disease-Specific Alterations in the Enteric Virome in Inflammatory Bowel Disease. Cell, 2015; DOI: 10.1016/j.cell.2015.01.002

[v] http://www.nytimes.com/1999/08/31/health/in-pursuit-of-autoimmune-worm-cure.html

Moms Are Always Right

EAT YOUR VEGETABLES!

A couple of days ago, I spotted a remarkable article[i] on Medical Express describing new research into the effects of dietary fiber on the health of the intestine.  The article discusses a new paper[ii] in the journal Cell, written by an international team of researchers showing the impact (in mice) of fiber deprivation the mucosal lining of the intestine.  The mice were raised without any gut microbes at all, and then had 14 strains of bacteria (common in the human intestinal tract) transferred to their intestines.  Some of the mice were also infected with a strain of e.coli that is known to potentially cause gut infections in humans (leading to inflammation and symptoms of diarrhea).

The researchers then looked at the impact of diets with different fiber content, including a diet with none at all. What they found was that when starved of their food source, fiber, “the bacteria began to eat the natural layer of mucus that lines the gut, eroding it to the point where dangerous invading bacteria can infect the colon wall.”  In fact, the researchers noted that in no-fiber conditions, the pathogenic bacteria flourished, and the mice rapidly became symptomatic.

The mice that received a diet consisting of 15% fiber from grains and plants completely maintained their mucus lining.  What’s really amazing is that in these healthy mice, within days of removing fiber, negative changes were apparent: the bacteria began eating away at the mucus lining.

The researchers also noted that the mix of bacteria changed, even day to day, depending on how much fiber the mice were fed.  In low and no fiber conditions, the bacterial strains that thrived were those that produce enzymes which break down the glycoprotenis that make up the mucus lining.

So what’s the take-home message?  DIET MATTERS.  As I said in my post yesterday, in my personal experience, it is one of the single most important components of achieving and maintaining your health.

_____________________________

[i] From http://medicalxpress.com/news/2016-11-high-fiber-diet-gut-microbes-colon.html

[ii] Desai, Mahesh S. et al. A Dietary Fiber-Deprived Microbiota Degrades the Colonic Mucus Barrier and Enhances Pathogen Susceptibility. Cell: Volume 167 , Issue 5 , 1339 – 1353.e21

Diet and Mental Health

Diet Plays Important Role for Mental Health says the Association for Psychological Science in an article published on November 17.[i]

I will refrain from sarcasm here (not even a single “Really?! Who knew?!” (oops…that one just slipped out, darn it!….)) because at least they did write about it and are looking at the science.  This is a sore subject for me.  Why?  I’ll put it this way: after 20+ years in the autism world, I am often asked what the best treatment is for autism in my experience.  The Specific Carbohydrate Diet is still, by far, number one in my book.  I have seen more kids, of all ages and functioning levels, improve via diet than any other treatment.  I left special education, in fact, to work as a nutritionist for a reason. There is nothing like the right diet to improve health, and when I say health, I mean both physical and mental.  And yet….

…the authors of this paper point out that nutrition is not a part of mainstream medicine when it comes to mental health.  I am sure that’s true, unfortunately, but it’s actually far worse than that. Many doctors have told me over the years that they had 1 week of nutrition in their 4 years of medical school. So, nutrition is not actually a part of mainstream physical medicine either.  Are any of asked about our diets in the 5 minutes we have for our annual physicals?

And yet, a healthy diet is probably the single most fundamental source of good health.

This article showcases 5 papers that give a good, broad example of the kinds of crucial information demonstrated by the limited research on this topic.

 The first paper is a large-scale study of the broader Mediterranean lifestyle that includes diet, exercise and social activity.  Looking at almost 12,000 people, the researchers found that each variable independently predicts a lower risk of depression.

 The 2nd article compared 21 children with ADHD to an equal number of matched controls.  The children with ADHD consumed the same amount of essential fatty acids (EFA) and yet, they still showed signs of deficiency.  Also, those with lower EFA intake were also most likely to show greater ADHD symptoms.

 The next paper looked at using the amino acid NAC (n-aceytl-cysteine) to treat obsessive compulsive disorder.  While the study showed no statistical difference between the groups, subgroup analysis did show that those who had OCD symptoms for a shorter period of time did seem to improve.  The researchers recommend retesting with a larger sample size.

The 4th paper was a small (14 adults) 8 week open-label study of the effects of micronutrients (vitamins and minerals) on insomnia.  The participants all reported improvements in insomnia as well as mood, stress and anxiety.

 The final paper was on the relationship of inflammation and depression.  The researchers examined data on diet from over 4000 adults over a 5 year period and found that those with diets that would be considered inflammatory had a markedly increased risk of developing depression.

 I will be writing a lot more about the importance of diet on this blog over time as it is crucial for good health, remembering that of course, diet also directly affects the gut biome…which in turn, directly affects health. In fact, here’s a teaser for my next post:  a recent article in Cell showed that a fiber-deprived gut leads to degradation of the colonic mucosal barrier.  And yes – that is a very bad thing!

[i] From http://www.psychologicalscience.org/news/releases/scientists-explore-how-nutrition-may-feed-mental-health.html#.WDNh3X2GrCF

Probiotics and Cognition

This morning, I read about a really interesting randomized, double-blind study[i] done on 60 patients with Alzheimer’s disease.  30 of the patients were in the control group, and were just given ordinary milk.  The 2nd group of 30 was given milk with a mixture of high-dose probiotics.  The probiotic mixture had four kinds of probiotic bacteria: Lactobacillus acidophilus, L. casei, L. fermentum, and Bifidobacterium bifidum (approximately 400 billion bacteria per species – so a total of around 1.6 trillion organisms).  At the end of the 12 week-long trial, scientists looked at both blood work and cognitive functioning. While the treated group remained significantly cognitively impaired, they did show statistically significant improvement over the controls.  They also noted that blood work improved, including C-reactive protein, which is a marker for inflammation.

This is the first time that probiotics have been proven to improve cognition in humans.

Science Daily, which covered this story, quoted an Alzheimer’s researcher’s (not involved in this study) comments on the paper:

 “This early study is interesting and important because it provides evidence for gastrointestinal (GI) tract microbiome components playing a role in neurological function, and indicates that probiotics can in principle improve human cognition. This is in line with some of our recent studies which indicate that the GI tract microbiome in Alzheimer’s is significantly altered in composition when compared to age-matched controls…”[ii]

The implications of this are huge, obviously.  We know, for example, that the microbiome is altered in autism, and most cases of autism are associated with cognitive deficits.  What other “mental illnesses” associated with cognitive loses then might probiotic therapy help?!

______________________________

[i] Elmira Akbari, Zatollah Asemi, Reza Daneshvar Kakhaki, Fereshteh Bahmani, Ebrahim Kouchaki, Omid Reza Tamtaji, Gholam Ali Hamidi, Mahmoud Salami. Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer’s Disease: A Randomized, Double-Blind and Controlled Trial. Frontiers in Aging Neuroscience, 2016; 8 DOI: 10.3389/fnagi.2016.00256

[ii] From https://www.sciencedaily.com/releases/2016/11/161110162840.htm

The Biome/Brain Connection

We know that the brain and immune system are directly connected. We know that 70% or more of that same immune system is located in the lining of the nose and digestive system.  And we know that the digestive system is directly connected to the brain. While we’ve known much of this for decades (except for those lymphatic vessels connecting the brain to the immune system, as per my last post), what has become one of the hottest areas of research now worldwide is the study of how the non-human living organisms of our biome directly affect the brain.

The human body houses about 100 trillion organisms with their own DNA.  It’s astounding that we are only 10% ourselves as those organisms outnumber our cells 10 to 1. I laughed when I read this article a few weeks ago, “Do Microbes Control Our Mood?”[i] which starts off by saying, “If aliens were to examine a human, they would think we were just slavish organisms designed to feed microbes and carry them around.”

So true!  We do indeed serve our co-inhabitants, housing them, feeding them, and if we’re smart, caring for them. The human biome is now recognized as being so integral to health, it is now considered a bodily organ, just like your heart or liver.

How these organisms affect the brain is a hot topic in science research now.  We do know that they communicate with the brain directly. They also have profound indirect effect on the central nervous system.  For example, they help us fight pathogens (thereby, playing an integral part in immunity, which affects the brain) and they make key vitamins that affect the functioning of the central nervous system.

Just this morning, I came across several new papers on this very subject.  One article in particular blew me away:  “The Gut-Brain Axis, BDNF, NMDA and CNS Disorders.”[ii] This came out just this past Friday, and describes how disruption of the gut biome during development negatively affects BDNF (brain derived neurotrophic factor) and the NMDA receptors, which in turn affect synaptic plasticity and cognitive function.  Let’s simplify this:

  1. BDNF is a protein and a member of the growth factor family.  That is, it affects nerve growth in the brain.
  2. NMDA receptors (often written as NMDAR) are receptors for glutamate. Glutamate is an excitatory neurotransmitter which means it causes neurons to fire.  Abnormalities with this receptor are highly associated with mental disorders including schizophrenia, autism, mood disorders, Huntington’s disease, Alzheimer’s, etc.
  3. Gut microbiota modulate BDNF function in the central nervous system by affecting various processes in the body. For example, healthy gut bacteria create short chain fatty acids, which are highly anti-inflammatory and which cross the blood-brain barrier, affecting various brain chemicals.
  4. In the absence of normal gut bacteria (i.e. a baby that has been given antibiotics early in life, while the brain is still developing), BDNF levels are lowered, which leads to abnormalities in the development of the NMDAR, which leads, in turn, to excessive glutamatergic output.
  5. Excessive glutamatergic output the brain leads to extreme brain hyper-reactivity. (Many anti-seizure medications, in fact, reduce brain glutamate to calm the brain down.)

“In the absence of GI microbes, central BDNF levels are reduced and this inhibits the maintenance of NMDAR production. A reduction of NMDAR input onto GABA inhibitory interneurons causes disinhibition of glutamatergic output which disrupts the central signal-to-noise ratio and leads to aberrant synaptic behaviour and cognitive deficits.”

 So, here we have just 1 potential mechanism whereby altering gut bacteria may affect brain development and cognition.  Within minutes of finding this article, I found this one, published in September, “Cognitive Function and the Microbiome,”[iii] which states:

“Cognition was originally thought to be exclusively regulated by the central nervous system, with long-term potentiation and neurogenesis contributing to the creation and storage of memories, but now other systems, including, for example, the immune system and the intestinal microbiome may also be involved.”

And then I found this one, also just published, “The Central Nervous System and the Gut Microbiome”:[iv]

“…emerging data suggest communication between the gut and the brain in anxiety, depression, cognition, and autism spectrum disorder (ASD). The development of a healthy, functional brain depends on key pre- and post-natal events that integrate environmental cues, such as molecular signals from the gut. These cues largely originate from the microbiome, the consortium of symbiotic bacteria that reside within all animals. Research over the past few years reveals that the gut microbiome plays a role in basic neurogenerative processes such as the formation of the blood-brain barrier, myelination, neurogenesis, and microglia maturation and also modulates many aspects of animal behavior.”

I genuinely believe we are living through a medical revolution, as historically important as when “germs” were first discovered in the 1850s.  I believe we will learn to fix “broken” microbiomes (more on this in future posts), and with all my heart, I hope we learn to fix the CNS damage such unhealthy biomes may have caused.

 

 

[i] https://www.sciencedaily.com/releases/2016/10/161020114611.htm

[ii] Maqsood, R. & Stone, T.W. Neurochem Res (2016) 41: 2819. doi:10.1007/s11064-016-2039-1

[iii] Gareau, M.G. (2016). Chapter Eleven – Cognitive Function and the Microbiome. International Review of Neurobiology. Volume 131, 227-246.

[iv] Sharon, G., Sampson, T.R., Geschwind, D.H., Mazmanian, S.K. (2016). The Central Nervous Ssytem and the Gut Microbiome. Cell 2016  Nov 3;167(4):915-932. doi: 10.1016/j.cell.2016.10.027.

 

Psychobiomics (Part 1): A Little About the Immune System–Brain Connection

I recently did a couple of webinars on the biome for practitioners down in Australia.  In preparing my slides, I came across some amazing (and terrifying) statistics.  According to the CDC in the US, 7.6% of Americans aged 12 and over have had moderate to severe depression in the past 2 weeks.  In Australia, a million people a year (in a population of 23 million – so about 4%) suffer from depression.  The numbers are staggering.  And that is just depression!  What about anxiety disorders:  generalized anxiety disorder, PTSD, panic attacks, OCD (which is a subset of anxiety disorders), bipolar disorder, autism, ADHD, etc.?

Referring back yet again to Sid Baker’s spider web analogy – that everything in the body is interconnected – it is amazing how much information has been discovered in the last couple of years about the immune-CNS-gut connection.  In 2015 an important article was published in the Journal of Experimental Medicine which, for the first time ever, showed that the central nervous system is physically tied in directly to the immune system via a previously unknown system of lymph vessels.[i]

Scientific America had a great summary article of this revolutionary finding:

“Perhaps the most commonly cited division between body and brain concerns the immune system. When exposed to foreign bacteria, viruses, tumors, and transplant tissue, the body stirs up a torrent of immune activity: white blood cells devour invading pathogens and burst compromised cells; antibodies tag outsiders for destruction. Except, that is, in the brain. Thought to be too vulnerable to host an onslaught of angry defensive cells, the brain was assumed to be protected from this immune cascade. However research published this month reported a previously unknown line of communication between our brains and immune systems, adding to a fast-growing body of research suggesting that the brain and body are more connected than previously thought.” [ii]

In a way though it’s strange that anyone would have ever thought the immune system was completely separate from the brain.  Medicine has long recognized “sickness behavior,” for example: when an organism is sick, and inflammatory cytokines are released, the organism conserves energy to use it in the battle against the disease – thus appearing lethargic and enervated.  Back in 2013, I remember reading this blog post from Harvard  Health Publications, “Infection, Autoimmune Disease Linked to Depression,”[iii] which cited an amazing statistic based upon a study of the entire Danish population from 1945 to 1995:  “People who had been treated for a severe infection were 62% more likely to have developed a mood disorder than those who never had one. An autoimmune disease increased the risk by 45%.”

And of course, the connection is bidirectional.  How many of us have gotten sick after a period of extreme psychic stress?  Shingles is a perfect example:  the herpes virus that causes shingles lives in the nerves, but is generally kept dormant by our immune systems.  Stress us out and suddenly, the virus wins out over our suppressed immune system.

So, what does all this have to do with the gut biome?  70% or more of our immune system is in our digestive system as most germs enter through our nose and mouth.  And our body’s co-inhabitants are a crucial part of normal immunity…and also, talk directly to our brains.  Completely coincidently, just before finishing this post, I read about the publication of a new article called “Linking the Human Gut Microbiome to Inflammatory Cytokine Production Capacity.”[iv]  I’ll write more on this, the connection of the gut biome to brain development and health, and other recent research in the near future.

______________________________

[i] Aleksanteri Aspelund, Salli Antila, Steven Proulx, Tine Karlsen, Sinem Karaman, Michael Detmar, Helge Wiig and Kari Alitalo. A dural lymphatic vascular system that drains brain interstitial fluid and macromolecules. The Journal of Experimental Medicine, June 2015 DOI: 10.1084/jem.20142290

[ii] from https://www.scientificamerican.com/article/important-link-between-the-brain-and-immune-system-found/

[iii] from:  http://www.health.harvard.edu/blog/infection-autoimmune-disease-linked-to-depression-201306176397

[iv] Schirmer, Melanie et al.Linking the Human Gut Microbiome to Inflammatory Cytokine Production Capacity. Cell , Volume 167 , Issue 4 , 1125 – 1136.e8

 

What’s in a Name?

Every morning I read through all the latest news on the biome, both micro and macro.  I am excited about the onslaught of new research looking at the gut-brain connection.  As I mentioned in my previous post, this concept was the basis of my very first lesson on chronic illness.  (In my case, my son’s autism was the focus.)  On the other hand, I always feel a deep sense of frustration:  if I was learning about this stuff 20 years ago, why is it only now that the medical establishment is REALLY paying attention?

It was just this morning that I read for the first time that the connection between the gut biome and mental health is finally so well established that scientists have given it a name:  Psychobiotics.

“Now that we know that gut bacteria can speak to the brain—in ways that affect our mood, our appetite, and even our circadian rhythms—the next challenge for scientists is to control this communication. The science of psychobiotics, reviewed October 25 in Trends in Neurosciences, explores emerging strategies for planting brain-altering bacteria in the gut to provide mental benefits and the challenges ahead in understanding how such products could work for humans.”1

 NOW that we know that gut bacteria can speak to the brain?!  Grrrr.  I was told that 2 decades ago, and it wasn’t new news then!   Yes, yes, I know:  science can only progress so fast.  First and foremost, it’s a business – and whatever makes the most money will get the most money, in terms of funding. Secondly though, it’s also true that the human body is so unbelievably complex that it boggles the mind.  Back to Sid Baker’s spider web analogy:  everything in the body affects everything else.  Heaven knows how many processes are occurring through the body and cells at one time, and if one tiny thing goes askew, the entire organism is tipped into imbalance – like dominoes falling. Rationally speaking, I know that inch by inch, scientific knowledge progresses.

Where does that leave us though, who are in the trenches right now, battling incredible suffering in ourselves and/or our children? “If it can’t hurt and it could help, do it,” I’ve told myself for the last 20 years.  And if there’s any doubt about the “hurt” part, put the potential treatment on the risk/reward scale and see how things fall.

About 15 years ago or so, I was at an autism medical conference, and was privileged to see a talk about the gut-brain connection given by Dr. Martha Herbert.  Dr. Herbert is an eminent neurologist at Harvard/Mass General, and has been a huge proponent of, as she says, “the brain being downstream from the gut.”  As she concluded her talk, she acknowledged that we are in the earliest stages of understanding this connection but felt that even then, the evidence was strong enough to support families taking measures to improve the health of the gut biome to treat their children’s autistic symptoms.  “When faced with prolonged scientific uncertainty,” she said, “Use your best judgement.”  I quickly wrote down her exact words ensuring I would never forget them.  Right there, she summed up my philosophy far more eloquently than I ever could.  I’ve lived by that mantra from the day my son was first diagnosed.

But back to where science is today.  Over time, I am looking forward to sharing with you whatever new information comes down the pipeline.  I will also review great stuff that has appeared of the last few years.  No matter who you are, whether or not you are suffering from an illness or are in perfect health and want to stay that way, trying to improve the health of the biome can’t hurt and could help.

_________________________________________________________

1.http://medicalxpress.com/news/2016-10-current-state-psychobiotics.html