Fibromyalgia: Yet Another Biome Related Illness

I’ve written before about recent findings that alterations in the gut bacteria are associated with chronic fatigue syndrome (CFS), which is closely related to fibromyalgia.  For those of you unfamiliar, the symptoms of fibromyalgia include wide spread body pain, fatigue, impaired sleep, potentially cognitive difficulties and irritable bowel symptoms.  It affects mostly women (75-90% of people with fibro are women).  In CFS, the main symptom tends to be the fatigue; in fibro, it’s pain.  But there is huge overlap in the illnesses.

So much more work needs to be done, especially considering the staggering numbers of people affected:  2-4% of the world’s population (and some information points to that number being closer to 3-6%)![i]

A paper just published last week in the journal, Pain,[ii] is the first showing alterations in gut bacteria are associated with fibro:  19 different species, in fact (some greater than normal, some less). The study involved a total of 156 people, 77 of whom had fibromyalgia (and all of whom were women).  The scientists used multiple techniques to confirm the findings, and were definitively able to establish that these alterations were not the result of diet, medication, age, physical activity, but purely connected to the illness. In fact, based on the pattern of differences, the researchers could predict whether or not someone has fibromyalgia with 87.8% accuracy.

Says the lead researcher, “We found that fibromyalgia and the symptoms of fibromyalgia—pain, fatigue, and cognitive difficulties—contribute more than any of the other factors to the variations we see in the microbiomes of those with the disease.”[iii]

Two more points of particular interest to me:

Firstly, the severity of the symptoms directly correlated with the degree of bacterial variance.  Secondly, the researchers also found alterations in the levels of butyrate and proprionate, two of the three major anti-inflammatory short chain fatty acids produced by gut bacteria.  The cause of fibro is unknown at present, and those afflicted do not show signs of inflammation in blood tests. However, last year, research at Massachusetts General (Harvard’s teaching hospital) showed that glial cells (the immune cells of the central nervous system and brain) are activated in people with fibro.  That is, their brains are inflamed.  Several years before, in fact, pro-inflammatory cytokines were isolated in the cerebral spinal fluid of sufferers.  Again though – the cause of this inflammation is still unknown.[iv] This new information may have pin pointed the source of that inflammation.

Whether the changes are the cause, or an effect, of the disease is also unknown.  Further studies are planned, thank goodness.  So, as I always say…stay tuned!

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[i] http://www.fmaware.org/about-fibromyalgia/prevalence/

[ii] Minerbi, A, et. al. Altered microbiome composition in individuals with fibromylgia. Pain. 2019.  10.1097/j.pain.0000000000001640

[iii] https://www.futurity.org/fibromyalgia-gut-bacteria-microbiome-2085822-2/

[iv] https://medicalxpress.com/news/2018-09-people-fibromyalgia-inflammation-brain.html

More Steps Forward in Personalized Nutrition

A week ago, I read about another really interesting “personalized nutrition” study[i] again looking at the differences in the way people respond to food. 34 participants kept a record of everything they ate for 17 days, while the researchers looked at stool samples over these 2+ weeks to see how their microbiomes responded to these foods.

While individual biomes did change depending on food choices, the actual nutritional content of food seemed to have little relationship to these changes.  As these researchers point out, we currently have very little information on nutrients that affect gut bacteria.  They used a database that provided information about 50 macro and micro nutrients (fats, carbs and proteins=macro; vitamins and minerals=micro) yet, as they point, “…these nutrient profiles ignore hundreds of additional chemical compounds present even in a single piece of fruit…and many other non-nutritive components of foods such as preservatives and food additives.”[ii]  Really it comes as no surprise that there was little consistency in microbiome changes between people.  That is, microbiome responses to food were completely individualized:  I eat a banana, you eat a banana – our gut bacteria respond completely differently.  Since microbiomes appear to be as individual as fingerprints, and we have no idea how each species reacts to this vast number of substrates (which is essentially defined as the food that makes things grow), this only makes sense.

One more items of particular note:  firstly, two of the people in the study drank only a liquid meal replacement product during the study and yet their microbiomes varied day to day anyway, emphasizing this individuality as well as potentially demonstrating that food is not the only factor to affect our microbes.  (Think about stress, or sleep, etc.!)  In fact, a more varied diet actually led to greater biome stability!

As you all know, I love coincidences, so I was delighted when, directly after reading this research, I found another article from the same day about personalized eating.[iii]  I’ve actually covered this topic before, in February 2018, looking at research out of the Weizmann Institute in Israel on how people have completely different glucose responses to the same food.  It’s so darn interesting, though, and so pertinent to this blog post, it’s more than worth (briefly) repeating.

In 2015, these Israeli researchers conducted a 3-part study looking at how people respond completely metabolically differently to food.  First, they tested glucose levels in 800 participants and confirmed that indeed, glucose levels varied considerably after eating the same food.  They took this information (along with other factors like age and weight, etc.) and created an algorithm to try to predict this glucose response.  They then confirmed the algorithm’s validity in a double blind randomized study in which they created customized diets for the participants using microbiome profiles and their algorithm…and by successfully lowering glucose responses in the participants, provided proof that the algorithm works.

This 2nd article I read that day was about another proof of concept study that was conducted this year, again using the algorithm to predict glucose response to food in 293 people.  The results were actually pretty amazing.  For example, “…serum glucose levels after eating a bagel with cream cheese rose by a low of 6 mg/dL in some individuals (low responders) to a high of 94 mg/dL in others (high responders). And some findings were counter intuitive to commonly held nutritional guidance, as evidenced by blood glucose levels that rose higher after eating a banana than after eating a cookie.”  What’s also quite remarkable is that sometimes, combining foods lowers glucose response.  One of the lead authors of this study points out that, “Sometimes a few almonds added into a certain food mitigated the glycemic response.”

In my previous post on this, I mentioned the company Day Two who is using this algorithm to test personal responses to foods.  Unfortunately, the kit is $499, which I simply cannot afford at the moment.  Otherwise, I’d be more than willing to act as a guinea pig.  If any of you do give it a try, please share!  I’d love to hear from you!

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[i] https://www.news-medical.net/news/20190613/Food-responses-are-governed-by-the-gut-microbiota-finds-new-study.aspx

[ii] Johnson AJ, et al. Cell Host and Microbe 2019;25(6):789-802. doi.org/10.1016/j.chom.2019.05.005.

[iii] https://www.medscape.com/viewarticle/913956#vp_1

Helminth Therapy: A Call to Action

An interesting opinion piece by Dr. William Parker, of Duke University, and colleagues at a couple of Czech Universities, just appeared in Trends in Parasitology.[i]  To summarize, the paper makes two key points:

A.  These scientists hold the belief that the interaction between human and helminth is so complex, that a drug isolated from a single helminth-derived metabolite will never have the same effect as using the whole, living organism.

B. Unfortunately, there is no research at all into what might be the optimal organism to use for helminth therapy. Currently, the 4 organisms currently available were selected because of they are not pathogenic in small doses.  But whether or not they are “the best,” we have no clue.

To share a few high points with you:

  1. The authors emphasize that until recently, helminths were ubiquitous to all humans but now, are essentially entirely absent in developed countries.   And the loss of our native macrobiomes has had, “…dire consequences for human health.”
  2. Epidemiological studies clearly show that the loss of a macrobiome in mammals inversely correlates with the global rise in chronic inflammation-associated diseases (CIADs).  These include allergies; autoimmune diseases like inflammatory bowel diseases, multiple sclerosis, rheumatoid arthritis, type 1 diabetes, etc.; autism; and even many so-called “mental illnesses” like depression and anxiety.

(On a side note, this map is commonly used to illustrate point #2.  As you can see, wherever people still have a macrobiome (i.e. helminths on board), the incidence of autoimmune disease is low.  To read more about this, you might want to check out this post I wrote back in April 2017, about some fascinating research on this topic.)

2019-06-17_16-19-48.jpg

 

  1. More than 40 years ago, Dr. Turton demonstrated that he could reverse seasonal allergies by ingesting benign helminths, which over the years has led to a series of studies in humans and animals demonstrating, over and over, the health benefits of replacing this missing element from our body’s ecosystem.
  2. The authors call helminths “master manipulators” of their host’s immunity, modulating the inflammatory response.
  3. As I mentioned above, these scientists are of the belief that trying to isolate single metabolite from a helminth is in no way a replacement for the whole, living organism: “…we have argued that administration of purified factors cannot recapitulate complex biological relationships that have evolved over hundreds of millions of years.  For this reason, it is anticipated that the use of intact helminths for therapy has substantial and indeed insurmountable advantages over approaches using specific isolated HDecs [helminth derived compounds].”
  4. We already have the ability to isolate and process living helminths under sterile, pharmaceutical-grade laboratory conditions, and regulatory agencies have already approved their use in trials. For example there have already been 14 clinical trials alone testing TSO (Trichuris suis ova, or porcine whip worms) registered with Clinical Trials.gov. There already exists a healthy body of literature on using other helminths in humans.
  5. That said, no one has, as yet, looked at the possibilities of every helminth out there, or tested to see which might be optimal for use in helminth therapy. Like everything having to do with optimizing the human biome, we’ve barely scraped the surface!

From the conclusion of the paper:

“The loss of helminths from the human biome is one of a few key factors that underlie CIADs in modern society, and the necessity of dealing with the root causes of CIADs is increasing as the burden of these diseases rises.”

Take a good look at the graph I used above, to illustrate the rise in autoimmune and neurological diseases in the world, from the American Autoimmune and Related Diseases Association. A couple of weeks ago, I was in the UK giving a talk to the British Association of Naturopathic Practitioners.  These are some of the allergy statistics (from the American Academy of Allergy Asthma and Immunology) that I presented on just 1 slide:

  • Worldwide, the rise in prevalence of allergic diseases has continued in the industrialized world for more than 50 years.
  • Worldwide, allergic rhinitis affects between 10% and 30% of the population.
  • Worldwide, sensitization (IgE antibodies) to foreign proteins in the environment is present in up to 40% of the population.
  • Worldwide, sensitization rates to one or more common allergens among school children are currently approaching 40%-50%.

We in the industrialized world are in a health crisis of mammoth proportion.  Daily though I wonder why no one seems to care.

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[i] Sobotkova, K, et. al.  Helminth Therapy – From the Parasite Perspective.  Trends in Parasitiology. 2019.

Zeroing In On An Inflammatory Bowel Disease Culprit

When Harvard University talks, people listen (including me)!  So I paid particular attention to a fascinating bit of new research out just this week that definitely takes us a step closer to figure out what happens in inflammatory bowel diseases (IBD), in terms of   abnormal bacteria causing an inflammatory reaction in the gut.[i]

We’ve known for a long time that alterations in the bacterial microbiome are associated with inflammatory bowel diseases but the specifics of both species and mechanism of action have been unknown.  Researchers at Harvard though just tracked down the first prime suspect:  Ruminococcus gnavus.

No, I had not heard of it either probably because, ordinarily, it comprises less than 1% of our gut bacteria…and with there being 1000 species or so in the ordinary human, it never leapt to the top of my get-to-know list.

In a previous study though, researchers noted that during flare ups of IBD, this species of bacteria can jump from that less than 1% of the gut microbiome to making up more than 50% ! (How astounding is THAT?!)  The next step, and the subject of this latest research, was to figure out causation.  That is – how do these bacteria exert their detrimental effects?

The scientists grew the bacteria in the lab and then figured out all the molecules they produce, testing to see if any of the metabolites are proinflammatory.  Sure enough, one molecule, a complex sugar (a polysaccharide) made up of glucose and another sugar called rhamnose, caused the release of pro-inflammatory chemicals, including tumor necrosis factor-alpha (TNF-α), a major proinflammatory chemical that is highly associated with autoimmune diseases.  The scientists also identified the gene in the bacteria which is responsible for the production of this polysaccharide. This will allow them to see, in the future, if this gene is over-expressed before a flare up of Crohn’s.

“We found and characterized an inflammatory polysaccharide produced by the gut bacterium Ruminococcus gnavus, populations of which bloom during flares of symptoms in patients with Crohn’s disease. This molecule induces the production of inflammatory cytokines like TNFα…and may contribute to the association between R. gnavus and Crohn’s disease.”[ii]

This research certainly may take us a long way toward figuring out a treatment for IBD, either by targeting the growth of the bacterium, Ruminococcus gnavus, or by targeting its gene, which codes for the polysaccharide.  More than that, this kind of research has demonstrated that it is possible – and potentially highly beneficial – for scientists to comb through suspect bacteria in the human gut, find those associated with disease, and figure out what these might be producing that causes us to get sick.

What does not seem to be explained is what causes these particular bacteria to grow so rapidly prior to a flare up.  I’m sure we’ll read more about this in the future.  I’ll keep an eye out.

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 [i] https://hms.harvard.edu/news/microbiome-malefactor

[ii] Henke, MT, et al. Ruminococcus gnavus, a member of the human gut microbiome associated with Crohn’s disease, produces an inflammatory polysaccharide, Proceedings of the National Academy of Sciences (2019). DOI: 10.1073/pnas.1904099116

Probiotics, Depression and Anxiety: A New Meta-analysis

One of the more common questions I get asked is “what probiotics are good for my condition?”  Believe me, it does not make me happy to have to say, over and over again, “If only we knew.”

I am always glad, therefore, to read something that gives at least a smidge of information on specific species that may help a specified condition.  A couple of weeks ago, Gut Microbiotia for Health published a post about recent research out of Brown University that at least gives us a better idea of what might work for depression and anxiety.[i]  As these are two of the most common illnesses currently affecting those of us in the industrialized world, well…the more we know, the better.

These researchers conducted a meta-analysis of 34 different clinical trials, to try to pinpoint what we currently know.  Such analyses previously done of existing clinical trials have, to date, used too few studies to be of much use and worse, they often combined diagnoses, like depression and anxiety, when looking at outcomes, confusing results.  7 of the trials they looked at tested prebiotics and the other 27 used probiotics or synbiotics (combinations of pro- and pre-biotics).

Results:

They found that using prebiotics alone (for periods ranging from 4 hours to 4 weeks) did not make any difference in the symptoms of anxiety or depression.

However, in the 23 trials that looked at depression and 22 trials that looked at anxiety, the studies showed a trend:  “…the administration of probiotics—including Bifidobacterium longum, Bacillus coagulans, and Lactobacillus alone or in combination with Bifidobacterium—from 8 to 45 weeks led to small but significant antidepressant and antianxiety effects.”

Overall though, these scientists found that improvement was not seen in anxiety or depression using Lactobacillus species alone.  To be effective, they needed to be combined with Bifido species.

One of the things that really struck me was the fact that results are likely worse than they should be because most of the trials were conducted on people who were healthy, not on those with depression or anxiety.  Only 4 of these trials were actually conducted on those affected with these issues, a phenomenon I’ve actually made mention of before in a post I wrote on depression and probiotics back in October of last year.  Why you would test these as treatments for illnesses in people without the illnesses is incomprehensible to me…but what do I know?!  In that October post, which was a general update on what we now know about using probiotics in depression, I also mention (for the 2nd time – this is now the 3rd!) what is still considered one of the most significant studies to date:  an 8 week long double-blind, placebo controlled trial of probiotics on 40 people with major depressive disorder.  In that study, the researchers used 2 billion units each of Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium bifidum. The probiotic made a significant improvement in depressive scores.  Today’s article from Gut Microbiota for Health, also makes note of this particular study.   And notice that in this successful clinical trial, the Lactobacilli were indeed mixed with Bifido bacteria.

Overall, the news is good.  While obviously much more research needs to be done, and we don’t yet know optimal species or doses, we at least know that something out there in this realm seems to work.  As these scientists write, “There is general support for antidepressant and anxiolytic effects of probiotics, but the pooled effects were reduced by the paucity of trials with clinical samples. Additional randomized clinical trials with psychiatric samples are necessary fully to evaluate their therapeutic potential.”[ii]

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[i] https://www.gutmicrobiotaforhealth.com/en/a-new-meta-analysis-of-controlled-clinical-trials-shows-the-antidepressant-and-anxiolytic-potential-of-probiotics/

[ii] Liu, RT, Walsh, RFL, Sheehan, AE.  Prebiotics and probiotics for depression and anxiety: a systematic review and meta-analysis of controlled clinical trials. Neuroscience & Behavioral Reviews. 2019. 102:13-23. https://doi.org/10.1016/j.neubiorev.2019.03.023

Transferring Autism Via Microbiota Transplant: A Clinical Study

In recent years, researchers have found they that by transferring the gut microbiome from animal to animal, they can also transfer particular “disease” states.  Take obesity, for instance – just one example of many – researchers transferred the gut microbiota from lean mice fed a healthy diet to obese ones fed a high fat diet, and showed that the benefits of the healthy diet, in terms of metabolic rate and so forth, could be conferred on the unhealthy rodents:  “Our findings demonstrate that the beneficial effects of diet and exercise are transmissible via FMT [fecal microbiota transplant], suggesting a potential therapeutic treatment for obesity.”[i]

Just a few weeks ago, in fact, I wrote about the semi-successful first attempt to use FMT to treat obese people. (It was semi-successful in that, the treated individuals did not lose weight.  However, their gut microbiota did end up resembling that of thin people.  The study was just a first step and certainly opened up the door to more research going forward.)

For several years now, research has also shown that it is possible to transfer depression via microbiota transplant.  For example, in 2016 a paper was published wherein scientists took the microbiota from depressed humans, and transferred it into rats, inducing, “…behavioral and physiological features characteristic of depression in the recipient animals…”[ii]

Then came Jim Adams and colleagues, at Arizona State University, who used fecal transplant in an open-label study in autism, and found that they could confer an 80% reduction in GI symptoms and also radical improvement in the symptoms of autism in the children:  “…clinical assessments showed that behavioral ASD symptoms improved significantly and remained improved 8 weeks after treatment ended.”[iii]  It was huge news, a couple of months ago, when the follow up study was published by these same scientists, which showed that the gains these children had made were retained 2 years later:  “…most improvements in GI symptoms were maintained, and autism-related symptoms improved even more after the end of treatment.”[iv] (This of course makes perfect sense.  GI symptoms were mostly maintained but of course, would be diet dependent.  And autism symptoms like speech issues require months of therapy to show improvement.  If the microbiota transplant worked, you’d expect the children to be able to learn better and more efficiently, and improve continually over time.)

Having read these, and many other such studies over the years, the latest big biome news in the autism world came as absolutely no surprise to me.  Last week, researchers at the California Institute of Technology reported that the symptoms of autism can be transferred to mice via FMT.[v]  They took germ-free mice, infused them with the gut bacteria from children on the autism spectrum, and low and behold:  “…these mice were less vocal than the mice in the control group.  They also tended to engage in more repetitive behaviors and spent less time interacting with other mice.”[vi]  They also found differences in the brains of the treated mice, including changes in certain molecules (metabolites) which were at lower levels in the “ASD” mice.  These particular metabolites, taurine and 5AV (5-amonovaleric acid) affect the levels of GABA in the brain, a neurotransmitter responsible for calming neurons down after they’ve been stimulated.  Many kinds of seizures, which involve abnormal neuronal excitement, for example, are associated with low levels of GABA.  And abnormal levels of GABA have long been associated with autism spectrum disorders.

The researchers took the research a step further and gave 5AV and taurine to a particular kind of mouse (called BTBR) which has been bred to have autism-like behaviors:  “The study found that treating the mice with either 5AV or taurine led to noticeable decreases in the characteristic ASD-like behaviors…And, when the researchers examined brain activity in these mice, they found a strong link between increases in the levels of 5AV and decreased excitability in the brain.”  To summarize:  giving the mice gut bacteria from children with autism not only caused behavioral changes consistent with autism, but also caused chemical changes in the brain that parallel known alterations found in those on the spectrum.

Yes, I suppose in a way it is big news and headlines around the world were screaming it is a triumph.  Honestly though, the research didn’t really rock my world.  Since before my son was diagnosed, 23+ years ago, we’ve known that alterations in the gut biome are associated with autism, and most likely, the root cause.  On this blog alone, I’ve written now 81 posts on the subject…and my blog is only 2 ½ years old!  And I guess, since I’m all about “things you can do now,” clinical studies, like that of Jim Adams and colleagues that I discuss above, is far more exciting to me.  In that study, the researchers used an oral solution of purified bacteria from healthy donors’ stool, that was mixed into milk or juice. The day that product becomes available, well – then you will see overwhelming excitement from me!

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[i] Lai, Z-L, et. al. Fecal microbiota transplantation confers beneficial metabolic effects of diet and exercise on diet-induced obese mice.  Scientific Reports. 2018; 8(15635).

 

 

[ii] Kelly, JR, et. al. Transferring the blues: depression-associated gut microbiota induces neurobehavioral canges in the rat.  Journal of Psychiatric Research. 2016;82:109-118.

[iii] Kang, DW, et. al. Microbiota transfer therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study.  Microbiome. 2017;5(1):10.

[iv] Kang, DW, et. al. Long-term benefit of microbiota transfer therapy on autism symptoms and gut microbiota.  Scientific Reports. 2019;9(1):5821.

 

[v] Sharon, G, et. al. Human gut microbiota from autism spectrum disorder promote behavioral symtpoms in mice.  Cell. 2019;177:1600-1618. doi.org/10.1016/j.cell.2019.05.004

[vi] https://www.medicalnewstoday.com/articles/325338.php

Stressed? Spend Time Outdoors to Get Your Mycobacterium vaccae

For the last couple of years, I’ve followed the research of a team out of the University of Colorado, who have been looking into treating stress and anxiety by using microbiotic organisms, and have even been exploring the idea of creating a vaccine to prevent PTSD [post traumatic stress disorder] from occurring.  I wrote about this here almost exactly a year ago.

Dr. Lowry and his team have just published another really fascinating paper.[i]  If you remember, in the post I refer to above from last June, he and his team injected mice with a (heat-killed) bacteria called Mycobacterium vaccae, and in doing so were able to prevent the animals from developing anxiety behaviors when exposed to an aggressive male mouse.  The results of that study were quite dramatic, actually.  Not only were the mice much less likely to develop anxiety but they were also 50% less likely to suffer from stress-induced colitis, and showed way less inflammation in blood measures.

Mycobacterium vaccae is found in soil, and I have noted a number of studies over the last number of years that have shown a wide variety of benefits on stress response and more.  (I’ll come back to this in a moment).  In fact, this article suggests that our lack of exposure to it through our lack of exposure to “dirt,” may provide yet more evidence supporting the “hygiene hypothesis” – although all my regular readers know at this point to call it biome depletion!  We in the industrialized world are simply too far removed from our natural habitat and the native organisms that inhabit it and should inhabit us.

In their past research, Dr. Lowry’s group also found that when they vaccinated rodents once per week for 3 weeks with Mycobacterium vaccae, there were much higher levels of anti-inflammatory cytokines in the part of the brain that regulates stress, anxiety and the fight-or-flight response.

In this present study, they tried to figure out how Mycobacterium vaccae actually works to cause this anti-stress response.  They isolated and purified a triglyceride, a fat (called 10(Z)-hexadeconoic acid, for those who want to know!), from the bacterium and had it interact with big immune cells called macrophages (which both human and mice have).  They found that the fatty acid bound to a particular receptor (PPAR, which is crucial in regulating the inflammatory response) and in doing so, blocked the production of pro-inflammatory pathways.  That is, treating the immune cells with the fatty acid made them highly resistant to inflammation.  Says Dr. Lowry:  “’It seems that once the soil bacterium gets inside the immune cell, it releases the anti-inflammatory fatty acid. This then binds to the PPAR and closes down the ‘inflammatory cascade.’”[ii]

As promised, coming back for a moment to other studies looking at Mycobacterium vaccae:  I did a bit of looking around, and found another really interesting article dating from 2010, describing research presented at a microbiology meeting in San Diego.[iii]  Two tidbits from this really struck me as interesting:

  1. Said one of the presenters of the study:  “Mycobacterium vaccae is a natural soil bacterium which people likely ingest or breath in when they spend time in nature.”  You really do have to wonder if the therapeutic effects of being outside, in nature (which have been proven over and over again), are not just mental but physical, in that people are being exposed to these sorts of organisms.  An interesting thought, right?  I remember when this study came out just last year:  “A new report published today reveals that exposure to greenspace reduces the risk of type II diabetes, cardiovascular disease, premature death, preterm birth, stress, and high blood pressure.”[iv]  If you read to the bottom of this little article on Science Daily, it mentions that, “Much of the research from Japan suggests that phytoncides — organic compounds with antibacterial properties — released by trees could explain the health-boosting properties of forest bathing.”  It’s not just the psychological benefits  of relaxing in natural beauty that lead to physical ones…it’s actual exposure to elements found only in nature that improve our health.
  1. The study presented showed that mice fed Mycobacterium vaccae were not only less anxious under various circumstances, but more than that, were able to navigate a maze twice as fast as untreated mice. The results suggest that the organism also plays a role in learning.  Said one of the researchers involved, “’This research suggests that M. vaccae may play a role in anxiety and learning in mammals…It is interesting to speculate that creating learning environments in schools that include time in the outdoors where M. vaccae is present may decrease anxiety and improve the ability to learn new tasks.’”

As far as I can find, this particular species of bacterium is not available commercially.  However, as suggested above – you can likely get exposed to it just by spending some time in nature.  And that’s a pretty good idea for your mental and physical health anyway!

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[i] Smith, DG, et. al.  Identification and characterization of a novel anti-inflammatory lipid isolated from Mycobacterium vaccae, a soil-derived bacterium with immunoregulatory and stress resilience properties.  Psychopharmacology. 2019. https://doi.org/10.1007/s00213-019-05253-9

[ii] https://www.medicalnewstoday.com/articles/325357.php

[iii] https://www.sciencedaily.com/releases/2010/05/100524143416.htm

[iv] https://www.sciencedaily.com/releases/2018/07/180706102842.htm

 

Eat Crickets! Delicious, Nutritious and Great for your Biome, Shows a Clinical Study

A couple of months ago, a friend sent me an article I finally had a chance to read, which describes a double-blind, placebo-controlled crossover study that looked at the effects of eating crickets on health and the gut biome.[i]

Now don’t sit there rolling your eyes – or gagging.  After all, insect parts are in most or all of the processed foods you eat.  It simply can’t be helped.  As long as it’s under a certain percentage – for visual appeal really – the FDA has no issue with it, as the bits are certainly not going to harm you.  So bad news…or good news, depending on your point of view:  you’re likely already eating bits every day.

In reality, insects are a fantastic form of food:  “…insects are a good source of bioavailable animal protein including all essential amino acids, as well as B vitamins, minerals, and essential fatty acids.  Insects also contain relevant levels of crude fiber, most predominately in the form of chitin…”  Chitin is structurally very similar to the indigestible fiber, cellulose, that is derived from plants.

To boot, from an environmental standpoint, insects are markedly better, as they emit far few greenhouse gases, and “…require less land, water, and feed to survive and thrive than traditional livestock.  The result is a significantly lower environmental impact.”

And yes – they taste pretty good too!  I’ve tried cricket chips before.  Delicious!

The study was done on twenty healthy adults, half of whom consumed cricket flour (in a breakfast shake) for 14 days, while the other 10 had the placebo.  After a 2 week washout period, the groups were swapped.  The patients in the trial had blood and stool tested multiple times.

The results:  no adverse events were reported and the gut microbiome was not significantly disturbed. Five kinds of bacteria increased in the experimental groups, including Bifidobacterium animalis, which “…has been shown in clinical studies to improve gastrointestinal function, protect against diarrhea, reduce side effects of antibiotic treatment, and increase resistance to common respiratory infections.”   It also fights against gut pathogens, including E. coli.  A study in pigs also showed it reduces Salmonella infection.  Other studies have demonstrated that it “…may be able to interact with immune cells and have an overall beneficial effect on immune system function.”

Interestingly, “…Lactobacillus reuteri and two other lactic acid producing bacteria were decreased by 3 to 4 fold relative to control…”  The authors suspect that this is because of the changes in the breakfast foods consumed.  That is, the participants were not eating foods that commonly contain reuteri, like yogurt.  Also, because many participants took probiotics before the study, but were off their probiotics during the duration of the study, the initial levels of L.reuteri may have been higher than “normal.”  Obviously, they suggest more research into this.

Other changes of note:  the level of the major inflammatory cytokine, tumor necrosis factor alpha (TNF-alpha), which is highly associated with intestinal inflammation and gut disease (as well as autoimmune diseases), was lower in the cricket-eating groups.  The researchers surmise that this is potentially due to improvements in gut barrier function (i.e. healing of leaky gut), which may prevent bacterial toxins from getting into the blood stream and stimulating an inflammatory response from the immune system.  The increase in Bifidobacterium from the prebiotic cricket flour may also be a factor here, as supplementation with this species “…has been shown to modulate improvements in barrier function.”  The fact that they saw such a significant improvement in TNF levels, in as short a time as 2 weeks,  is really great news: “…the influence of diet on production of inflammatory cytokines like TNF-alpha has been linked with a number of important health endpoints including cancer incidence, cardiovascular disease and major depression.”

This was the first study of its kind (i.e. looking at the effects of eating crickets on health and the microbiome), and certainly, more research is needed.  On the other hand, as the article points out, “…2 billion people spread across 80% of the world’s population in 130 countries” currently eat insects and I’d be willing to bet, there is less inflammatory disease in those places where they are regularly consumed.

Well, call me crazy but…I may soon be adding a bit of cricket flour to my breakfasts!

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[i] Stull, VJ, et. al. Impact of edible cricket consumption on gut microbiota in healthy adults, a double-blind, randomized crossover trial.  Scientific Reports. 2018. 8:10762. DOI:10.1038/s41598-018-29032-2

Two New Articles on Parkinson’s

Two more recent article provide yet more evidence linking gut inflammation to the development of Parkinson’s disease…which my regular readers know, is another of my particular interests, as I have 3 friends already suffering from it.

The first article describes research at the University of Wisconsin.[i]  Like  humans, monkeys with inflamed bowels also show “…chemical alterations similar to abnormal protein deposits in the brains of Parkinson’s patients, lending support to the idea that inflammation may play a key role in the development of the degenerative neurological disorder.”  That is, they found the same kind of abnormal (folded protein), alpha-synuclein, that appears in people.  I’ve written about this several times, like here.

No one yet knows for sure all the functions of alpha-synuclein, but it is found in all neurons. It’s thought to play a role in both the immune system and (mainly) in the central nervous system. In Parkinson’s, for reasons not yet understood, it changes shape and clumps together into masses called Lewy bodies.  When James Parkinson first described the disease in 1817, he also noted that those suffering from it had gastrointestinal issues.  In fact, people with inflammatory bowel diseases are more likely to be diagnosed with Parkinson’s.  It’s been known for many years that inflammation and oxidative stress are likely culprits in the development of the disease.

The fact that the same findings also happen in a completely different species provides yet more confirmation that inflammation in the gut is the primary cause.

The question then, of course, becomes – what is the root cause of this inflammation of the gut tissue?  Dysbiosis of the gut microflora looks more and more likely to be the prime suspect.  I looked through a just-published review of what we know/don’t know about the microbiome in PD out of the University of Washington, and found a few interesting highlights to share:[ii]

  1.  There are fairly well document microbiome abnormalities in PD. They not only have different gut bacteria, but the kinds they have are associated with having motor issues in walking, standing, and so forth.  They also have low levels of anti-inflammatory short chain fatty acids, which are produced by good gut bugs.  And a leaky gut/leaky brain may explain be the trigger for that abnormal alpha-synuclein:   “In a recent study, researchers looked at the relative abundance of Enterobacteriaceae in patients with PD and found that (1) patients had higher levels of these bacteria relative to healthy controls, and (2) the abundance of this family was positively associated with severity of postural instability and gait difficulty. (Analysis of fecal samples from patients with PD reveal decreased proportions of certain species of bacteria like Faecalibacterium prausnitzii as well as decreased levels of the SCFAs acetate, propionate, and butyrate…SCFAs are generally associated with maintaining the blood-intestinal and blood-brain barriers and are one of a select few substances that can cross the blood-brain-barrier. Decreased levels of SCFAs, as is observed in the microbiota of patients with PD then, offers a plausible mechanism for increased gut-blood-brain permeability and secondary exposure of environmental and bacterial triggers thought to induce alpha-synuclein aggregation…”
  2. Recent work in animal models suggests that toxins produced by gut bacteria interact with alpha-synuclein causing it to behave abnormally.
  3. A 2017 study looked at biopsies from children with intestinal inflammation and also, at other patients who’d suffered inflammation from norovirus (a nasty gut virus) and found alpha-synuclein in the intestines that “positively correlated to the degree of inflammation of the intestinal wall.” As the first study I wrote about today suggested, this study too supports the idea that gastrointestinal inflammation and infection as potential factors in the pathogenesis of PD.”  In fact, many studies now support “strong support for the theory that alpha-synuclein is involved in activating inflammation in the gut.”  .
  4. A growing number of studies recently have suggested, in fact, that “viral particles may contribute to neurological pathology.” Remember bacteriophages? – viruses that kill bacteria?  They outnumber the bacteria of our gut (which numbers in the trillions) by a factor of 10!  And they “directly affect not just the populations of bacteria and fungi in the gut but the integrity of the blood-gut barrier as well.”  As this article says, more studies on the potential relationships between bacteriophage infection, gut bacteria alterations and the development of PD is a crucial area of study for the future. I wrote about this in the past, here
  5. “With emerging studies showing an association between PD and the abundance of certain gut microbiota…cultivating healthy gut microbiota with bacteria like Prevotellaceae (a family found to be depleted in the microbiota of patients Autism-Spectrum Disorder and PD believed to maintain healthy gut and blood-brain barriers) and closely monitoring levels of Enterobacteriaceae…may represent novel ways of promoting brain health.” The article goes on to say that diet may be the best way of manipulating gut bacterial species.  For example, a study done on rodents, wherein the animals were given uridine (a substance that is made in the liver and helps with the formation of synaptic connections in the brain) and DHA (an omega 3 fatty acid) found that those animals given the 2 supplements had decreased motor and GI abnormalities. (I mentioned this in a post from 2017). A 2018 study found that being on a ketogenic diet (which is highly anti-inflammatory for the brain) for 16 weeks, dramatically improved brain blood flow in mice, and also increased levels in the gut of our old friend, Akkermansia, as well as Lactobacillus.  It also improved the integrity of the blood-brain barrier.

We still have so much more to learn.  But in looking for things you can do now, it seems that working on reducing inflammation via a healthy diet and a trial of DHA and uridine are more than supported by the current literature.  The above mentioned 2017 paper on mice and diet concluded:  “This is the first study demonstrating beneficial effects of specific dietary interventions, given after full development of symptoms, on a broad spectrum of motor and non-motor symptoms in a mouse model for PD.”[iii]  They gave the mice uridine, DHA and prebiotics:  not exactly arduous…and it seems to me, absolutely worth a try.

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[i] https://news.wisc.edu/inflamed-monkey-guts-produce-parkinsons-related-proteins/

[ii] Fitzgerald, E, Murphy, S, Martinson, HA. Alpha-synuclein pathology and the role of the microbiota in Parkinson’s Disease.  Frontiers in Neuroscience. 2019. https://doi.org/10.3389/fnins.2019.00369

[iii] Perez-Pardo, P, de Jong, EM, Broersen, LM, van Wijk, N, Attali, A, Garssen, J, Kraneveld, AD. Promising effects of neurorestorative diets on motor, cognitive, and gastrointestinal dysfunction after symptoms development in a mouse model of Parkinson’s Disease.  Frontiers in Aging Neuroscience. 2017. 9(57).  doi: 10.3389/fnagi.2017.00057.

Two Stories Today…For the Price of One! Stressed You and Overfed You = Stressed And Overfed Gut Bacteria

Two incredibly cool news stories came out last week and since I can’t decide which to share with you today…I’ll share both.

Story 1:

As you all know, if you regularly read this blog, the exact cause of the current inflammatory epidemic plaguing those of us in the industrialized world is unknown.  We do know that alterations of the human intestinal organisms (biome) IS an issue though, and may well be the main culprit.  That fact is now commonly accepted.

There are different hypotheses that explain the cause of the biome differences:  biome depletion caused by excessive hygiene (i.e. lack of exposure to our normal organisms), the overuse of antibiotics, diet differences, and so forth.  A new, very compelling, idea has just been forwarded by researchers at Kiel University, in Germany:  “The Kiel researchers suggest that an unnatural and particularly comprehensive nutrient supply decouples bacteria from their host organisms, and thus destroys the delicate balance of the microbiome. The, to some extent, over-fed bacteria in the gut thus promote disease development.”[i]

That is:  when you overfeed your gut bugs, they no longer need to eat their normal diets – things produced by you, like metabolites, for example.  They can very happily survive and, in fact overgrow, on the excessive nutrients you are consuming.

These scientists noted that research has shown that it’s not just climate change or overfishing that is killing off coral reefs and algae:  it is the nutrient content of the seawater itself.  “As soon as there is an oversupply of food due to human influences, bacteria living in a community with corals begin to decouple from their hosts. They then no longer feed off the metabolic products of the host, but prefer the richer nutrient supply of the surrounding waters. The balance of the coral microbiome is disrupted…and diseases occur as a result.”

This parallels what we are seeing in humans:  “The nutrient supply in the human gut is also changing along with the civilization-induced changes in eating habits – towards an unbalanced, energy-rich [ie. high calorie] and low-fiber diet. In addition to direct negative health consequences, a permanently high, easy to process supply of nutrients not only affects the human metabolism it feeds, but also the bacterial colonization of the intestine, which is also ‘fed.’”  What has, unfortunately, become an all-too-typical  diet in the industrialized world is not just directly harming our health – it’s harming the health of our gut microbes.  And that, of course, indirectly harms us even further.  Says one of the scientists from Kiel:  “This over-feeding of the bacteria promotes their growth as a whole, and certain species of bacteria proliferate to the detriment of other members of the microbiome in an increased and uncontrolled manner.”

In the not-very-distant human past, food was not readily available as it is for us now.  Periodic fasting was the norm.  To boot, people got GI diseases causing diarrhea more often (from bad food, water, etc.)  Bacterial overgrowth was  kept in check by the circumstances of our lives.  That has all changed…as have our gut bacteria.

Interestingly, even before this research was published, the idea of periodic fasting has gained a great deal of traction in the health community.  It has been shown to reduce inflammation…and perhaps now, we know, in part why that may be so.

2nd story:

Researchers from Bar Ilan University in Israel just published a really interesting paper that shows that high levels of stress not only affect our health directly (i.e. we produce pro-inflammatory cytokines, for example), but directly change our gut bacteria so that they, in turn, stimulate our immune systems increasing “the likelihood that the body would attack itself”…as in autoimmunity.[ii]

The researchers compared the gut bacteria of two groups of mice:  the controls led normal lives.  The experimental group was subjected to daily extreme stress by being threatened by a dominant and aggressive mouse.  After 10 days, the bacteria of the stressed mice had changed:  they had higher levels of various bacteria, including two kinds that are known to be higher in people with multiple sclerosis.  More than that, the bacteria in the stressed mice expressed genes related to “potentially violent traits:  “Microbes with these traits can travel to other parts of the body, including lymph nodes, and elicit an immune response.”  Being subjected to violence led to increased “violence” on the part of the gut bacteria!

And more that: “When the researchers analyzed the lymph nodes of stressed mice, they found an increased abundance of several known pathogenic bacterial species. They also found a higher percentage of effector T cells known to play a role in autoimmunity.”

The gut bacteria not only tipped toward diseased-causing species but some of these “violent” bacteria make their way into your lymph system, which evokes an inflammatory immune response leading to autoimmunity.

Incredible, right?

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[i] https://www.news-medical.net/news/20190516/Over-fed-bacteria-in-the-gut-promote-disease-development.aspx

[ii] https://www.eurekalert.org/pub_releases/2019-05/asfm-hsb051019.php