Cancer, Diet and Gut Bacteria

On Monday, I read a little article on Medical Express about a multi-center research study done in Spain, just published in the journal, Nutrients, which took an in-depth look at the association between diet and the development of both breast and colorectal cancer.[i]   Thousands of cases of cancer, as well as healthy controls, were analyzed and the scientists found that those who ate an inflammatory diet (which included a high consumption of red and processed meat, saturated and trans fats, and refined carbohydrates) had twice the risk of developing colorectal cancer than those who ate an anti-inflammatory diet (consisting of predominantly plant-based foods, like vegetables, fruit, legumes and nuts).  Interestingly, they did not find an association with breast cancer.  (They intend to look into this further in the future.)

Ordinarily, while interesting, this wouldn’t merit a blog post from me as it is hardly surprising, but within minutes of finishing reading it, I read a second article, this one out of the Baylor College of Medicine, on the exact same topic:  the relationship of diet to colorectal cancer.[ii]  As it is the 4th most common cancer in the world, well…now this relationship did seem worth reporting to you, especially since there is such synergy between the two studies.

The Baylor researchers, noting this relationship, are actually trying to figure out the mechanism of action.  How does diet influence the risk of this cancer?  These scientists had already shown, in a previous study, that a healthy diet was associated with a decrease in the risk of pancreatic cancer.  They now have taken that research a step further.

It turns out that there is an association between “…diet quality and microbiome composition in the gut mucosa.”  These scientists found that “…a high-quality diet is linked to more potentially beneficial bacteria; while a low-quality diet is associated with an increase in potentially harmful bacteria.”  While this too is hardly shocking, what IS really interesting about this Baylor study is that rather than looking at individual diets, they looked at dietary patterns (I’ll come back to this in a moment), and secondly, they looked directly at the gut bacteria in the mucus lining of the intestines (from consenting adults having colonscopies), as opposed to analyzing fecal samples.  Since the gut bacteria influence, “…nutrient uptake, synthesis of vitamins, energy harvest [i.e. how calories are derived from food and used or stored], chronic inflammation, carcinogen metabolism and the body’s immune and metabolic response…,” well, obviously the microbiome has tremendous influence on the development of disease.

In terms of dietary patterns, they compared the foods the participants ate to the Healthy Eating Index (HEI)-2005, and looked at how particular groups of foods affected the gut bacteria.  Lower scores on the index are given for whole fruits (HEI 1 and HEI 2), while added sugar, trans fats and alcohol are HEI 12s.  They found not only that there were distinct differences for let’s say, HEI 7 (lower Faecalibacterium and Fusobacterium but higher Bacteroides) as compared to, for example, HEI12 (lower Subdoligranulum but higher Escherichia and Fusobacterium), but also that “A lower score for total HEI–2005 was significantly associated with reduced relative abundance of potentially beneficial bacteria but increased potentially harmful bacteria in the colonic mucosa of endoscopically normal individuals.”[iii]

The bacteria in the mucosa are associated directly with both immunity and host-microbiome interaction, apparently more so than fecal bacteria.  These researchers found “…a good-quality diet as the one recommended by the Dietary Guidelines for Americans to be high in fruits, vegetables and whole grains, and low in added sugar, alcoholic beverages and solid fats is associated with higher abundance of beneficial bacteria such as those with anti-inflammatory properties. A poor-quality diet, on the other hand, is associated with more potentially pathogenic bacteria, such as Fusobacteria, which has been linked to colorectal cancer.”

Essentially, they conclude that by affecting the structure of the mucosal microbiome, diet affects immunity, thus inflammatory status…thus the risk of cancer and other chronic diseases.

This of course, completely coincides with the findings of the Spanish scientists, I mentioned early.  And you all know how much I love coincidences!

Going forward, this team wants to look in greater depth at bacterial metabolites (like short chain fatty acids, for example) to see how these affect the growth of tumors, as well as looking how we can modify the gut bacteria using pre- and pro-biotics,  even in those with a poor diet.

In the meantime though – not exactly a news flash: eating a healthy diet seems like a pretty good idea.

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[i] https://medicalxpress.com/news/2019-07-inflammatory-diet-colorectal-cancer.html

[ii] https://www.bcm.edu/news/research/diet-influences-microbiome-colonic-mucosa

[iii] Liu, Y, et. al. Dietary quality and the colonic mucosa – associated gut microbiome in humans. The American Journal of Clinical Nutrition. 2019.  https://doi.org/10.1093/ajcn/nqz139

Yet MORE on Akkermansia, This Time as a Pasteurized Probiotic!

A few weeks back, I shared a post about a recent study that looked at using our old friend, Akkermansia muciniphila (a quick summary of some of the findings re:  this probiotic bacteria are in a postscript below) to improve glucose tolerance and insulin levels.  (I had written about this before once, back last October.) As many of you know, there’s a bi-directional association between poor glucose control and weight gain.  And as I’ve been writing about extensively, obesity is one of the great health epidemics of our time – as is type 2 diabetes and its predecessor, metabolic syndrome. Akkermansia is also one of my biggest interests, as a growing body of research shows it has powerful health effects, including helping with weight loss.

A quick primer on insulin before I proceed.  Firstly, remember that in order to be absorbed and utilized by your body, all carbohydrates – which are just long strings of sugar molecules – must be broken down to individual molecules in your intestines, before making it into your blood stream to feed every cell of your body.  Remember too that insulin is released when those sugars hit your blood, to keep that glucose at a steady level.  Blood sugar, in fact, is incredibly tightly regulated in the body as even a little too much or too little has enormously detrimental effects on us.  To rapidly remove excess glucose from your blood, insulin quickly stores it away in your liver…but if your liver is “full,” it stores it as fat.  If you’ve ever heard of the glycemic index, well, this is essentially the theory behind it:  rapid rises in glucose cause a huge burst of insulin, which then rapidly stores the sugar as fat, so the avoidance of foods that cause this – in favor of foods that cause only slow rises in blood sugar (reducing the need for insulin release) – are thought to be helpful for weight loss.  (That said though, we are learning that because of differences in the composition of gut bacteria, people have entirely different glucose responses to the same foods.  I’ve written about that here. So even this gets to be an awfully complicated picture!)

Anyway, back to Akkermansia and this new research:

After I posted that story, one of my regular followers asked me what “pasteurized” A.municiphila  meant, and I responded that it was heat sterilized.  He wrote back saying, “But won’t that kill the bacteria?”…which yes, I assumed it would and like him, didn’t really understand why dead probiotics would have a beneficial effect.  And that’s been wearing on me…but I simply haven’t had time to do more research into it. (Please, all of you understand – this blog is a labor of love.  I make no money from it…and I already am a single mom caring for a profoundly autistic son…and work 2 “real” jobs as well.  I’m just a little swamped for time!  So Stephen, I’m sorry it’s taken me a couple of weeks to get back to you on that!)

Therefore, though, I was very excited when an article appeared yesterday on Gut Microbiota for Health explaining this phenomenon.[i]

The article was actually written by one of the researchers involved in these studies.  He starts by stating that in 2017, his team found that “…a pasteurized form of A. muciniphila led to a stronger reduction in fat mass development, insulin resistance and dyslipidemia in mice when compared with the live bacterium.”  Since they didn’t know if it would have the same effect in humans, he just led a 3 month long randomized, double-blind, placebo-controlled study (so the gold standard) looking at this in 32 overweight or obese people and found, again, that this heat-inactivated (you read that right:  INACTIVATED) form of A.muciniphila, “…helps to limit the increase of different cardiovascular risk factors in subjects who are overweight and obese.”  How crazy is that?![ii]

The people in the study did not change anything else during the trial, so no diets and no increase in physical activity.  They were then, in randomized fashion, given 100 billion of either live A.muciniphila or this inactivated, pasteurized form.  Only those treated with the latter – the inactive form – had “…lower circulating insulin levels, reduced insulin resistance indices, lower total blood cholesterol and lower circulating dipeptidyl peptidase IV (DPP-IV) when compared with the placebo group. The enzyme DPP-IV has been involved in modulating glucose homeostasis, satiety and emotional-affective behavior.”  So it not only improved glucose control – it also improved feelings of being full?! This inactive form also reduced white blood cell counts (which are apparently elevated in obesity and “associated with glucose intolerance”); AND reduced the amount of proinflammatory byproducts from gut bacteria (lipopolysaccharides, or LPS); AND it reduced liver inflammatory markers.

Wait…what?!  How is this possible?!

Well, they don’t know for sure but…here’s the theory.  They know from previous studies that the outer membrane of A. muciniphila contains a protein called Amuc_1100 which seems to induce many of the benefits associated with giving mice and humans pasteurized A. muciniphila. The researchers therefore believe that this mild heat inactivation, or pasteurization, allows the components of the bacteria’s cell wall greater freedom to exert these benefits.

Both forms of the A. muciniphila were well tolerated, by the way, and as you’ve read on this blog before (see below), the live form also exerts huge benefits.  So…you’ll be happy to read the last sentence of this article:  “Our next steps include planning larger-scale tests and commercializing the bacteria in the form of food supplements.”

Whoopa!

p.s.  As promised, here are just 3, of several, other posts on The Biome Buzz related to Akkermansia muciniphila:

  1.  It appears to have an anti-aging effect as I wrote about here on November 20, 2018.
  2. In May 2018, I wrote about the finding that boosting levels of Akkermansia, via the ketogenic diet, seems to have anti-seizure effects.
  3. Akkermansia may also be beneficial in neurodegenerative diseases, like Alzheimer’s as I wrote about here, in October 2018.

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[i] https://www.gutmicrobiotaforhealth.com/en/akkermansia-muciniphila-helps-improve-features-of-metabolic-syndrome-in-overweight-and-obese-subjects/

[ii] Depommier C, Everard A, Druart C, et al. Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study. Nat Med. 2019. doi: 10.1038/s41591-019-0495-2.

Antibiotics in Early Childhood: The Road to Asthma and Allergy

When my son was just 36 hours old, he was re-hospitalized with a fever and put onto 5 days of IV antibiotics.  (You can read more about his history here.)  He was given more oral antibiotics right before his first birthday. Once I learned about the gut-brain-immune connection, several years later, I began to wonder what effect those antibiotics had had on him, especially in light of his diagnoses with both autism and then, several years later, with inflammatory bowel disease.

As you can imagine, I’ve always followed research into the effects of early introduction of antibiotics closely.  I remember, when Alex was very young, I found myself sitting in a psychiatrist’s waiting room reading an article in a lay publication about the burgeoning realization that there is a relationship between early use of these medications and the development of allergy. And 20 years later, I’m still reading more of the same.  There is a massive amount of evidence at this point.  I’ve addressed this issue several times before on this blog, for example, here – but it’s such an incredibly important topic that I want to keep you up-to-date as the evidence accumulates.

Last night I read a study done at Loyola University’s Medical Center that used a retrospective look at children’s medical charts, between the years of 2007 and 2016, to further delve into this association.[i]  Before I go into their results though, I want to tell you a couple of astounding statistics the paper provides.  Firstly, in spite of the fact that the overuse of antibiotics is known to be detrimental to health, and that there is a relationship between “…early antibiotic exposure and dysbiosis of the gut microbiota [which] may have significant implications for the health of children now and as they grow into adults,”  the use of these medicines continues to grow in hospitals. They are also the “…most frequently dispensed outpatient prescription medication, accounting for approximately 25% of all pediatric medication prescriptions.”  A recent large study showed that 30% of the antibiotics prescribed for respiratory tract infections are unnecessary.  11.5 million antibiotics are prescribed annually for illnesses without a bacterial component.

Unbelievable, right?

The article goes on to state that the first year of life is crucial in the development of a normal bacterial microbiome, and that by 3 years of age, it is fully mature.  Early disruption of the microbiome has been definitively linked with disruptions of the immune system and to the development of atopic (allergic) and inflammatory respiratory diseases, like asthma and allergic rhinitis.  This particular study is meant to add data to the investigation into the question of the timing of the antibiotics and its relationship to these illnesses: “…we hypothesize that children exposed to antibiotics during the first year of life will be more likely to be diagnosed with asthma or allergic rhinitis later in childhood, compared to children not receiving antibiotics during their first year of life.”

The researchers analyzed the data from 7224 children born at the hospital and  once they narrowed it down to those who had at least 2 subsequent visits there, were left with 2398 of them.  Believe it or not, a whopping 44.2% of these children were exposed to antibiotics in their first year!  And in the course of the 9 years covered by this study, the children averaged about 4 rounds of antibiotics.  Exposure to these medicines in their first year was significantly correlated with the development of asthma, but not with allergic rhinitis.  However, there was a significant association of lifetime antibiotics to the development of both diseases.  This, the authors suggest that this may mean that the early developing gut flora “… may still be sensitive to insult as the child grows, or that the insults may be cumulative and irreversible.”  That is, the more antibiotics a child is exposed to in those first early years, the worse the permanent damage, and the greater their chances for developing these diseases during the course of their lives.

In my son’s case, his antibiotic exposure, which of course is just one factor in his medical history that was likely detrimental, did not lead to allergy or asthma, which are the only two illnesses looked at in this research.  I’d bet money though that more such studies, looking at other diseases, will be conducted in the near future.  I’ll read them, of course, and report to you. But…I’m not looking forward to it.

p.s.  Don’t you wonder why the physicians prescribing the antibiotics didn’t have the parents put the babies on infant probiotics or synbiotics (i.e. a combination of pro- and prebiotics)?  Or…if they did, did it have a protective effect at all?  I also wonder how many of these babies were breast fed…???

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[i] Ni, J, Friedman, H, Boyd, BC, McGurn, A, Babinski, P, Markossian, T, Dugas, LR.  Early antibiotic exposure and development of asthma and allergic rhinitis in childhood.  BMC Pediatrics. 2019. 19:225.  https://doi.org/10.1186/s12887-019-1594-4

More on Helminths and the Prevention of Cancer

Last October, I wrote about a study that looked at the effects on cancer of the immune modulation afforded by helminths (intestinal worms), which are the main component of the mammalian macrobiome.  That paper provided a very positive initial review of the mechanisms by which helminths may exert their anti-cancer effect, but obviously, a massive amount of data and studies needed to be done before any conclusions could be drawn.

Previous research has shown that there is a correlation between the lack of a strong Th2 immune response and the development of cancer.  Nowadays, the Th2 family of cytokines (chemical messengers) is associated with allergy (an inappropriate inflammatory response to benign environmental stimuli), but in fact, from an evolutionary stand point, these chemicals are there to keep our helminths in check.  (Some are good, some are bad, and too many of even the benign ones are not good.  Our bodies needed to develop a mechanism of action to deal with their presence in a way as to ensure our survival.) As I have written about before many times (here, as just one example), all mammals on the plant evolved with a macrobiome – our native animal life – as well as the much better known microbiome.  However, in the last 50 to 75 years or so, those of us living in the industrialized world (and our domesticated pets) have effectively been de-wormed.  As the Th2 cytokines also include those which are regulatory, which moderate inflammation, we are now perpetually low in regulatory chemicals and prone to out-of-control inflammation.  Some scientists have now come to believe that the loss of our helminths is one of the biggest factors in our current epidemic of inflammatory diseases, ranging from allergies to autoimmunity to autism to cancer.  Unlike a swift (i.e. acute) “allergic” response, helminths provide a strong and continual stimulation to the Th2 system, which as I said, over months and years, modulates inflammation. De-worming humans is akin to going into a rainforest and removing all the insects.  We abruptly killed off an entire species from our ecosystem.  And humans, like all ecosystems, were in a delicate balance…that we have destroyed.

In May, a new animal study came out looking at the effects of a helminth, H. Nana (which is native to rodents) on cancer. [i] The scientists broke the mice up into 4 groups:

  1. The first group was given DMSO cutaneously (through the skin)
  2. The 2nd group were given only the H.nana
  3. The 3rd group was given another chemical, DMBA, again cutaneously. DMBA is known to induce tumor growth.
  4. The 4th group was given both the helminth, H. Nana, and the cutaneous DMBA.

The chemicals given  the mice did indeed induce tumor growth, and the tumor load, as well as blood levels of various  immune components were assessed by the researchers.

The results showed that the group that had first been colonized by the H.Nana had “…a reduced amount of tumors with smaller size…”  More than that, they found that they had significantly lower levels of proinflammatory immune cells in their blood.  They concluded that the reduction in tumor growth may be due to the increase in certain kinds of immune cells (eosinophils and neutrophils) that they found in the animals.  It is unlikely to be from anything secreted by the H.Nana because the protective effect lastedeven after the mice had eliminated the helminth.

One item of particular interest to me:

As my regular readers know, interleukin-10 (IL-10) is one of the predominant regulatory cytokines that is very much responsible for modulating the inflammatory response and balancing the immune system.  It is also thought to perhaps be associated with cancer, as lowering the inflammatory response may prevent the body from fighting cancer cells effectively.  (That is, an increase in IL-10 for people who already have cancer may be a bad idea.  This thinking , however, is still very controversial as IL-10’s relationship to cancer, should it exist, is poorly understood.)  What these researchers found though is pretty amazing.  The highest levels of IL-10 were found in the mice who were only given the carcinogenic DMBA, and this actually replicated the findings of previous studies!  Those who also had the helminths on board actually had a “significant reduction” in IL-10 levels, even though helminths are usually a potent stimulator of its production.  What does this suggest? It appears that helminths not only do not actually suppress immune response, but instead, seem to modulate it so that it is appropriate for the given situation.  Therefore, in the face of a carcinogen, the helminths stimulate the immune system in such a way as to help it fight cancer – and thus, the reduction in tumor growth seen in this group.  In fact, the tumors induced by DMBA typically start as benign and progress toward carcinoma (cancer).  However,  the few tumors that did grow in the mice with helminths on board did not progress toward malignancy.

That is a major WOW.

According to a 2017 article out of the University of Adelaide, in Australia (which, by the way, has the highest rates of cancer in the world)[ii]:  “…the 10 countries with the lowest opportunities for natural selection (among the “better” countries of the world) are: Iceland, Singapore, Japan, Switzerland, Sweden, Luxembourg, Germany, Italy, Cyprus, and Andorra….The 10 countries with highest opportunities for natural selection (among the “worse off” countries of the world): Burkina Faso, Chad, Central African Republic, Afghanistan, Somalia, Sierra Leone, Democratic Republic of the Congo, Guinea-Bissau, Burundi, and Cameroon.”[iii]

Their explanation , which of course is very likely a part of the picture, is that because we live longer in the industrialized world – ie. we don’t die from acute infections like malaria and the like, have better medical care, and so forth – we get cancer more often.  But it also strikes me that what they call the “worse off” countries are also those where helminth colonization is still the norm.

As I say to you  all the time – there are no simple answers.  The cancer question is undoubtedly going to turn out to be one of those cases where many factors,  from the two I just named, to our food, our chemical exposure, etc. are all a part of the picture.

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[i] Ramos-Martinez, E, et. al. The immune response to Hymenolepis nana in mice decreases tumorigenesis induced by 7,12 dimethylbenz-anthracene.  Cytokine. 2019. 123:154743.  doi.org/10.1016/j.cyto.2019.154743

[ii] https://www.wcrf.org/dietandcancer/cancer-trends/data-cancer-frequency-country

[iii] https://www.sciencedaily.com/releases/2017/10/171011100708.htm

Bloated? A Surprising Culprit May Be to Blame

This morning, I spotted an interesting little piece on Medical Daily entitled, “Bloated?  High-Fiber Foods Are Not to Blame; This Ingredient Is.”[i]  Curious to see what they were suggesting as a possible culprit (after all, bloating is the second most common complaint I hear as a nutritionist, right after constipation, as I mentioned earlier this week), I checked it out.  And I’m glad I did, as I learned something new:  “…it could be that your gut is rebelling against you for eating too much salt.”

Researchers at Johns Hopkins looked at data from a trial conducted back in the 1990s on the DASH diet (“Dietary Approaches to Stop Hypertension-Sodium) and realized that the results pointed to salt causing more bloating than a high-fiber diet, which is usually blamed.  While they are unsure as the exact mechanism of action, they suspect two possibilities:  firstly, salt causes fluid retention which makes digestion less efficient.  Secondly, studies suggest that salt alters the composition of the gut bacteria, leading to more gas production.

Again, this was news to me so I looked for more information.  Sure enough, as just one example, last year a study conducted in Germany showed that high salt consumption kills the probiotic bacteria, Lactobacillus.[ii] Even more remarkable, the high salt diet also triggered the production of proinflammatory immune cells and the mice ended up showing signs of a neurological disease similar to multiple sclerosis, as well as high blood pressure. Giving the mice Lactobacillus normalized both their blood pressure and reduced the production of these inflammatory immune cells.

The scientists then tested this on humans – 12 healthy men.  They doubled their normal salt intake by giving them 6 extra grams of salt per day for 2 weeks and found that, like the mice, most had Lactobacillus eradicated from their guts.  To boot, their blood pressures also increased, as had their production of proinflammatory cells.

Holy cow, right?!

Now even more curious, I took a quick look at the average salt consumption of Americans. According to the Center for Disease Control, the average adult should eat no more than 2.3 grams of salt per day but currently, we consume, on average, 3.4 grams, most of which does not come from the salt shaker on the table:  “…the majority of the sodium Americans consume – more than 70% – is found in processed food and restaurant meals.”[iii]

So yeah, I’m giving you all yet another thing to be aware of in your diet!  Sorry…not sorry!

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[i] https://www.medicaldaily.com/bloated-high-fiber-foods-are-not-blame-ingredient-438291

[ii] https://www.medicalnewstoday.com/articles/322076.php

[iii] https://www.cdc.gov/salt/pdfs/sodium_dietary_guidelines.pdf

The Human Biome and What We Don’t know

My old mentor, a well known functional medicine physician, used to always conclude his talks with a quote by Vaclav Havel:  “Keep the company of those who seek the truth – run from those who have found it.”   I think about that concept every single day, especially when I read any kind of definitive statement about the biome: i.e.  “it’s the chemicals in our food,” or “the rates of obesity continue to grow because people eat too much.”  I’ve pointed out before on this blog that nothing having to do with the human gut biome is simple and the causes of these illnesses are multifactorial.  We have barely started to scrape the surface of a system that involves trillions of organisms, all of which interact with each other, with our bodies, with our food, etc.,  sometimes in ways we have not as yet even discovered, let alone understood.

In this vein, I loved a recent article I read on Medical Express summarizing some of the new biome research going on at the University of Southern California.[i]  It starts by telling the story of a woman – a friend of one of the researchers – with gastrointestinal issues, who tried 3 different kinds of yogurts, looking for relief.  One had worked wonders for a friend of hers…but in her, it caused constipation.  The second caused diarrhea. The third made her feel great.  All the yogurts contained lactobacillus.  Why she should respond so very differently to each, and so very differently from her friend – we have no clue at the moment.   As the article says, “The microbiome is a complex and dynamic system – and as unique to each individual as a fingerprint.”  (I’d be willing to bet every last one of you reading this post has had this exact experience, in some form or another.   You do great on something, a food, a probiotic, a prebiotic, etc. which turns out to be awful for someone else you know.)

The article goes on to discuss both the promise of probiotics (and manipulation of the microbiome)…and the incredible difficulty we’re going to have reaching that promised land.

For example, Dr. James Boedicker of USC, has is working on a mathematical model “…to predict what happens when different species commingle.”  He points out that you can’t just study each species individually, as each species affects every other species in its vicinity.  His group measured the metabolic output of 4 individual species of bacteria:  “If living together has no effect…then the overall metabolic rate would simply be the average of each species’ individual rate.”  On the contrary though, they found that the overall metabolic output was markedly higher than that average.  That is, living together caused enormous changes in how these bacteria behave.

The importance of this kind of finding cannot be understated.  As this article points out, figuring all this out – how the various species affect each other – could explain everything from different responses to probiotics, to different responses to drugs and chemotherapy, and can help us predict what will work and won’t work for each person as the individual he or she is.

And of course, most of the current research concerns only the bacterial microbiome.  We literally know next-to-nothing about the other –omes of the gut (the virome, the mycobiome, the macrobiome, etc.), let alone how all these various organisms affect one another.

Too boot, none of this takes into account the interactions between the organisms of the biome and the food we eat.  Just a week ago or so, I wrote about another new study on personalized nutrition:  “As these researchers point out, we currently have very little information on nutrients that affect gut bacteria. 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.”

As another USC researcher says, “We can determine the microbiome of anything pretty quickly, but we don’t know what it means.”  That pretty much sums things up.

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[i] https://medicalxpress.com/news/2019-06-probiotics-factors-reliably-benefit-health.html

Constipation, Dysbiosis, Autism and a Prebiotic: A New Clinical Trial

The single most common gastrointestinal (GI) complaint I hear as a nutritionist, by a long way, is constipation…and the single best piece of advice I give my clients is “drink more water.”  It never ceases to amaze me how dehydrated most people are.  Invariably, I then  need to say, “and eat more fiber too.”  If you regularly read this blog, you don’t need me to remind you that in the industrialized world, we eat frighteningly low amounts of fiber.  Undoubtedly, this plays a huge role in not just GI issues, but in the negative alterations found in our microbiomes. Remember:  constipation is both the cause AND effect of dysbiosis.  So on this, World Microbiome Day, give some serious consideration to what you can do to improve your inner biome and thus, your, health.

On that note:  as you all know, I am constantly on the lookout for “things you can do now.”  Last night, I read a brand new clinical study done on children with autism, using a prebiotic supplement derived from guar gum (partially hydyolyzed guar gum, PHGG), which is a kind of carbohydrate that comes from the guar plant bean.[i]  The results were actually fairly remarkable and not just for those with autism, but for anyone suffering from constipation.

While I knew that constipation was rampant in the autism population, I was astounded by just how rampant.  One study found that 33.9% of 124 children tested were affected.

This 2 month+ long clinical study was done on 13 children with autism, ages 4-9, all of whom suffered from severe constipation.  9 of the children defecated once per week before the study,  while the other for went twice per week.  (Can you imagine?!)  The gut bacteria and aberrant behaviors were also analyzed before and after the study.

After supplementation with this PHGG prebiotic, “…defecation increased from two times to four times per week in all children.”  There were significant changes to the microbiome as well:  9 bacterial genera “changed significantly.”  Blood levels of inflammatory chemicals, including TNF-α (tumor necrosis factor, which is one of the main pro-inflammatory chemicals in the human body) and interleukin-6 (IL-6) decreased.  And perhaps most exciting of all, there were major decreases in irritability, measured by different autism rating scales.

The scientists were able to determine that it is likely the improvement in constipation that led to the alterations in the gut bacteria.  They point out that it is well established that constipation and gut dysbiosis “…lead to an increase in mucosal permeability (leaky gut…”  Scientists have found an increase in endotoxins (toxins from gut bacteria) in the blood of children with severe autism.  Several years back, in a seminal paper by Jyonouchi et. al,[ii] it was found that bacterial endotoxins caused an increase in the exact same pro-inflammatory chemicals that these Japanese scientists found decreased after treatment with the prebiotic (i.e. TNF-α and IL-6, etc.).  These authors state that their results demonstrate that supplementation with this prebiotic, “…helped decrease the load of endotoxins from the intestine, which in turn resulted in a decreased production of serum [blood] inflammatory cytokines.”  The authors conclude that this decrease in inflammation is likely not only the result of the improvement in constipation and leaky-gut, but this reduction in inflammation:  “…in the present study, although the number of samples from ASD children may be considered relatively small, our results indicate that PHGG supplementation to diets may be a good therapeutic approach for treating ASD symptoms.”

I took a look to see if this prebiotic is available for sale and found that yes, it likely is in different places in the world.  However, to find out if you can buy it where you live, you’d need to contact the company.  As I always ask: if any of you do try it, please let me know how you fare!

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[i] Inoue, R, et. al. Dietary supplementation with partially hydrolyzed guar gum helps improve constipation and gut dysbiosis symptoms and behavioral irritability in children with autism spectrum disorder.  Journal of clinical Biochemical Nutrition. 2019

[ii] Jyonouchi H, Sun S, Le H. Proinflammatory and regulatory cytokine production associated with innate and adaptive immune responses in children with autism spectrum disorders and developmental regression. Journal of Neuroimmunology. 2001; 120: 170–179.

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.)

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  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.