Insomnia? Your Gut Bacteria May Be to Blame

And now for a subject I hate even thinking about:  sleep.  Unlike most people, I dread going to sleep at night.  I’m a terrible sleeper:  I wake up over and over, sometimes falling back to sleep quickly, but all too often, not.  I can’t tell you how often the thought,“Will this night never end” has gone through my head.

Anyone who is a bad sleeper totally understands why sleep deprivation was used as a form of torture.

I’ve been reading a lot, over the last few years, about the ties between sleep and inflammation/inflammatory diseases. An article a few days ago really caught my eye. It turns out that pro-inflammatory cytokines like interleukin-6 seem to be the link between sleep and the gut microbiome: you can thank your depleted biome for that bad night’s sleep, which results in higher levels of these inflammatory chemicals.[i]

We know that during deep sleep, the brain cleanses itself. Lack of deep-sleep time, in the short-term, is associated with stress and psychological problems.  In the long term, it is associated with cancer, cardiovascular disease, autoimmune illnesses, and more.

26 male subjects had their sleep habits measured (average bed time, wake time, total time in bed, total time actually asleep, length of time to fall asleep, number of awakenings, and so forth).  They also donated saliva and stool samples, in order for the researchers to track the relationships.

Sleep efficiency and total sleep time are positively associated with bacterial microbiome diversity and richness.  (“Sleep efficiency is the percentage of time spent asleep while in bed.”[ii])  Wake after sleep time was negatively associated with bacterial diversity. (So, the less diverse your bacterial microbiome, the more time you spend not sleeping after those night wakings.  (I’m in trouble.))  The researchers conclude:  “We found that microbiome diversity…was positively correlated with sleep efficiency, and total sleep time, and was negatively correlated with the sleep fragmentation.”  In other words, those with richer and more diverse microbiomes slept better.  And since better sleep means better health, those who don’t sleep well are caught in a vicious cycle.  So yeah – those of us with poor sleep were also found to have higher levels of pro-inflammatory IL-6:  “…high daytime serum concentrations of IL-6 is associated with poor sleep quality.  In addition, increased IL-6 levels are associated with fragmented sleep in mice.  IL-6 is also an important factor in sleep regulation as sleep onset often coincides with increased circulating IL-6 and IL6 remains high during the night.”

(For those of you unfamiliar with IL-6, dysregulation of this pro-inflammatory cytokine is highly associated with autoimmune diseases like rheumatoid arthritis, juvenile arthritis, osteoporosis, and psoriasis.  It’s considered critical in the initiation of autoimmunity.)

A few especially interesting notes:

  1. The researchers did not find a correlation between stress biomarkers, IL-6 and biome diversity:  “…it appears the link between gut microbiome diversity and IL-6 is not mediated or influenced by stress despite the well-developed link between high IL-6 concentrations and stress.”  That does not mean, of course, that stress does not play a huge role in sleep problems or in gut biome health.
  2. Those with better sleep and increased gut bacterial diversity, not surprisingly, did better on tests of abstract thinking/brain function.
  3. This study included only men but the news for women is not good:  “…we would expect similar, or even more pronounced, findings in women since the consequences of sleep loss accumulate more quickly in women compared to men and women are at a higher risk than men for sleep loss-related mortality.”
  4. The research showed that the richness of Bacteroidetes and Firmicutes were positively associated with sleep efficiency.  Apparently, these two phyla have been “…previously associated sleep quality in humans, and there is growing evidence that members of these phyla may modulated circadian rhythm and food intake, both of which impact sleep quality.”  Another phylum, Actinobacteria, was negatively correlated with the number of awakenings.  That is, the higher the amount, the fewer times people wake up during the night.  (However, these findings need to be confirmed by further studies as there is contrasting evidence in the medical literature.)  We’ll have to watch the growing research in this area.

The take-away  message is that there most certainly is an association between bacterial microbiome diversity and sleep quality, as well as inflammation.  And, as I mentioned above, while the IL-6 levels were not directly associated with stress, loss of gut bacterial diversity IS associated with stress, as well as many other factors. Once again, we are left with little direction as to how to break out of the vicious cycle (bad sleep leads to bad health and bad health leads to bad sleep).  Working on improving diet, stress reduction, exercise, and so forth are, for the moment, our only options.

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[i] Smith, R. P., Easson, C., Lyle, S. M., Kapoor, R., Donnelly, C. P., Davidson, E. J., … Tartar, J. L. (2019). Gut microbiome diversity is associated with sleep physiology in humans. Plos One14(10). doi: 10.1371/journal.pone.0222394

[ii] https://www.hypersomniafoundation.org/glossary/sleep-efficiency/

The Bacterial Microbiome and Non-Native Fiber: A Halloween Tale

Today is Halloween here in the United States, so I figure it’s the perfect day for a super scary post about fiber.

2019-10-31_13-28-17

Not kidding.  This has me terrified.

Dr. Liping Zhao is a professor in the Department of Biochemistry and Microbiology at Rutgers University in the USA who conducts research on how food impacts the bacterial microbiome, and how it can be used to improve human health.  For example, his team have discovered how a high fiber diet can benefit those with type 2 diabetes.

An article on Gut Microbiota for Health describes a recent interview with Dr. Zhao, conducted at a huge international summit on the microbiome, down in Miami, Florida.[i]

You know, from reading my blog, that fiber may be the most crucial factor in gut microbiome health.  According to Dr. Zhao, however, fiber is not just fiber.  It is critically important that you consume the fiber that was a part of your traditional diet, with which your ancestors co-evolved for thousands of years.

His reason?  He has found that there is a core group of bacteria that essentially act as a “foundation for better health” in each of us, and that core group requires certain fibers as food to maintain itself (and to protect us against the growth of pathogenic bacteria).

Says Dr. Zhao:  “If you are born in a Mediterranean country, better to keep your Mediterranean diet…Over generations, your family has been eating a traditional local diet, so the bacteria you take from your parents, and particularly from your mother, have been feeding on that same diet. That’s why our bacteria are most likely using the same nutrients.”  He goes on to state that moving to another country, adopting a ‘foreign’ diet with its different kinds and amounts of fiber, can be extremely problematic in that this may change your core bacteria, and leave you open to the growth of pathogenic ones.

And how’s this for creepy?  Even staying at home and regularly eating foods from other parts of the world can cause issues!

Dr. Zhao also points out that it’s not only what you eat, but also, how you cook it.  For example, in the Mediterranean, pasta and risotto are eaten al dente, which leads to their starch content being less digestible by us, humans; thus, their fiber is more available for the gut’s bacteria.

Dr. Zhao’s statements don’t completely surprise me.  Some of you may remember that back in November, 2018, I wrote about what happens to the immigrant microbiome when people  move to the United States[ii]:

 “Researchers looked at people from Southeast Asia and found that there was a significant reduction in the diversity of gut microbes with each subsequent generation, culminating with their microbiota resembling those of Americans of European origin. The dominant species of the recent immigrants was Prevotella but that changed remarkably quickly to Bacteroides. Prevotella is important in the digestion of high fiber foods, which are much more predominant in an Asian diet (as opposed to the “western” diet, which is heavy in sugar, fat and protein). Dan Knights, a co-author of the study, points to the change in diet as a key factor in this loss of diversity which changes within just a few months: “People began to lose their native microbes almost immediately after arriving in the U.S. The loss of diversity was quite pronounced: Just coming to the USA, just living in the USA, was associated with a loss of about 15 percent of microbiome diversity….The change in diet, and the loss of microbial diversity, was clearly associated with an increase in obesity and diabetes.”

And there you have it:  people move to a new country, start to eat the native diet meaning that fiber amounts and types change…and the next thing you know, they are suffering from some inflammatory disease or another.

So…scary, right?!

p.s.  Cue haunted house music:  the camera pans down, in a dark room full of eerie shadows, to find Judy sitting down at the table to scarf down her beloved vegetable korma with a side of naan bread and a mango lassi….

Man eats cauliflower spicy curry with rice and naan bread

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[i] https://www.gutmicrobiotaforhealth.com/en/why-the-fiber-in-your-traditional-diet-could-be-the-most-beneficial-for-your-gut-microbiota/

[ii] tps://www.news-medical.net/news/20181104/Migration-affects-gut-microbiota-which-in-turn-affects-health-find-researchers.aspx?fbclid=IwAR0UpAWiDnA2dhi1UfvMh6wlfgc7Rdu-U7pGrTYPT3y5tN7jleFpmYIH54k

The Gut Bacteria and Sunshine Connection

There were several big news stories last week in the biome world.   One I posted on the Biome Buzz’ Facebook page last Thursday (the 24th) is about how experiments (in a rodent model) demonstrate that the gut bacteria play a significant role in controlling our brains’ fear and anxiety responses.  The 2nd was a really interesting study done by Canadian researchers on the relationship of sunlight exposure to the gut microbiome.  As you know, sun exposure is our primary means of creating vitamin D (it’s virtually impossible to get enough through diet alone, unless you use supplements), which has tremendous impact on our immune system’s functioning.

The study had 21 female subjects, who were given three 60-second full body exposures to ultraviolet light band B (UVB) in the course of a week.  The women donated blood and fecal samples at the beginning and the end of the study which the researchers use to measure both vitamin D levels and gut bacterial diversity.  9 of the subjects had taken vitamin D for 3 months, during the winter; the other 12 had not.  20 of the 21 women had “adequate” vitamin D levels prior to the UVB exposure.

In those women who had not taken vitamin D supplements, there were both a 10% increase in blood vitamin D levels, but also, significantly, marked increases in gut bacterial diversity.

Said the senior researcher on this study:  “Prior to UVB exposure, these women had a less diverse and balanced gut microbiome than those taking regular vitamin D supplements…UVB exposure boosted the richness and evenness of their microbiome to levels indistinguishable from the supplemented group, whose microbiome was not significantly changed.”[i]

The mechanism of action is, as yet, unknown, but this scientist goes on to say that,  “It is likely that exposure to UVB light somehow alters the immune system in the skin initially, then more systemically, which in turn affects how favorable the intestinal environment is for the different bacteria…”[ii]

3 thoughts went quickly through my head, as I read the article and various summations of it:

  1. Firstly, it’s been long known that inflammatory diseases are seen at much higher levels in colder places, where the populations’ vitamin D levels tend to be lower due to lack of sunlight exposure much of the year.  “Several chronic inflammatory diseases display seasonal patterns in the severity of disease.  Specifically, the relapsing and remitting nature of IBD and MS are strongly associated with vitamin D levels.”[iii] You do have to wonder just how much this vitamin D/microbiome alterations piece plays a role in the ever increasing rates of inflammatory disease.  There are other major differences that play a role:  diet, lifestyle, helminth exposure, and so forth.  Remember this blog post from this past June, which showed two contrasting world maps, one illustrating the rates of autoimmune disease, the other, in total contrast, the levels of helminth exposure? Well, it might as well apply to vitamin D too:  those of us living in North American, Europe, Asia also have far less sun exposure than our southern hemisphere neighbors. This is yet another example of just how incredibly complex this question is:  what factors are a significant part of the inflammatory epidemic and to what degree?!
  2. Seasonal affective disorder also immediately came to mind.  We know it’s associated with vitamin D levels.  We know depression is associated with microbiome alterations.  This all cannot be a coincidence!

To sum up: while this study certainly shows that sun exposure, via vitamin D production, has an effect on the microbiome – and probably a significant one too – it would be a mistake to blame this factor entirely for the inflammatory disease epidemic we currently face.  Still, considering that “Winter is Coming” for us in the north 🙂 , in yet another “things you can do now,” maybe a little vitamin D supplementation for the next few months?

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[i] https://www.medicalnewstoday.com/articles/326782.php#2

[ii] https://newatlas.com/health-wellbeing/uvb-sunlight-skin-gut-microbiome-vitamin-d-autoimmune/

[iii] Bosman, ES, Albert, AY, Lui, H, Dutz, JP, Vallance, BA.  Skin exposure to narrow band ultraviolet (UVB) light modulates human intestinal microbiome. Frontiers in Microbiology. 2019;10(2410).  doi: 10.3389/fmicb.2019.02410

Fermented Foods and Infant Health

Reading and writing about epidemiological research is not my favorite, but I spotted a study on Tuesday that captured my interest as it’s in the vein of “things you can do now,” which you all know IS my favorite.

Looking to ascertain the health benefits of fermented foods on infants, Japanese researchers culled data from a nationwide study on the effects of environmental influences on the health of children (the Japan Environment and Children’s Study).[i]  Moms-to-be filled in questionnaires early in their pregnancy, late in their pregnancy, and then at 1, 6 and 12 months after their babies were born.  Included in the questionnaire were questions on diet (including infant consumption of yogurt and cheese) and physician-diagnosed infectious disease related to the GI tract (diarrhea, vomiting, viral gastroenteritis, rotavirus, norovirus, etc.)  From a dataset of 103,062, these researchers selected 82,485 for this current study.

They found that by the time the children were a year, “…the incidence of gastroenteritis was significantly lower in infants who consumed yogurt ≥ 7 times/ week and 3-6 times/week than in infants who had yogurt <1 time/week.”[ii] Unfortunately, they did not collect data on how much yogurt was consumed per meal – just the frequency of consumption.

Eating cheese made no discernible difference in health.  However, again, there was no data on the type or amount of cheese consumed.  That is, it’s possible that cheese products containing no live cultures was eaten frequently, which would have no effect on the gut bacteria, or the amounts were minute.

There is, unfortunately, a lack of uniformity in so many of the studies currently in the medical literature on the benefits of probiotics or fermented foods.  The paper provides several examples:  one study of children aged 1-5, living in an urban slum in India, found that probiotics helped prevent acute diarrhea.  Another, conducted in South Korea, showed that Bifidobacterium longum and Lactobacillus acidophilus had “…strong anti-rotavirus activity and significantly shortened the duration of the symptoms without adverse events.”  Other studies, however, have found little to no effects of yogurt consumption on gastroenteritis.  Of course, the amounts and strains used varied widely so there’s really no way to know for sure at this point.  That is a weakness in this study as well:  brands, strains, the use of supplemental probiotics, etc. – none of it was assessed.  Still, as the authors write, this current study was very large, which lends it credence.

A meta-study was published in July, which reviewed the medical literature (no date restrictions) for studies on the health effects of yogurt and fermented milk products on infants.[iii]  Out of 1,624 abstracts, they ended up with 10 that fit their criteria.  (And they allowed in all randomized controlled trials, observational studies and and prospective cohort studies, which is a pretty broad array. The fact that they ended up with only 10 shows pretty dramatically how little work has been done in this field.)  Their results:  “5  of 6 studies showed a positive effect of yogurt consumption on infectious diarrhea.  Two studies reported a positive effect on gut microbiota composition.  Two cohort studies reported a positive effect on reducing the incidence of atopic dermatitis, one of which also reported a positive impact on food sensitivity.”

Of course you want to avoid fermented milk products that are high in sugar.  But for my part, knowing what we now know about the disastrous effects of biome depletion:  were I the parent of a young infant/child, I would certainly be sure that a high quality, no sugar product were a regular part of my baby’s diet.

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[i] Nakamura M, Hamazaki K, Matsumura K, et al. Infant dietary intake of yogurt and cheese and gastroenteritis at 1 year of age: The Japan Environment and Children’s Study. PLoS ONE 2019 14(10):e0223495. 

[ii] https://medicalnewsbulletin.com/could-probiotics-help-prevent-gastroenteritis-in-infants/

[iii] Donovan, SM, Rao, G. Health benefits of yogurt among infants and toddlers aged 4 to 24 months: a systemic review.  Nutrition Reviews. 2019:77(7);478-486.  doi: 10.1093/nutrit/nuz009.

The Miracle of Mucus?

When giving a talk, Elaine Gottschall, the author of Breaking the Vicious Cycle (the book that lays out the specifics, and science, of the Specific Carbohydrate Diet) used to show 3 slides, illustrating the incredible mucus production in intestines afflicted with inflammatory bowel disease.

 

This is the villi of a healthy intestine.

without

This is one with inflammatory bowel disease.  You can see that the villi are flattened and that goopy looking white stuff stretched across them is excess mucus.

with mucus.jpg

Many of us saw massive amounts of mucus coming out with our children’s stool a couple of months after starting the diet.  I remember that, at the time, we wondered if it weren’t a sign of healing…the body evacuating excess mucus? I still don’t know the answer.  Elaine hypothesized that the mucus production was the result of excess acids (i.e. short-chain fatty acids, for example) being produced by bacterial overgrowth, damaging the lining of the intestines:  “Bacterial growth in the small intestine appears to destroy the enzymes on the intestinal cell surface preventing carbohydrate digestion and absorption and making carbohydrates available for further fermentation.  it as at this point that production of excessive mucus may be triggered as a self-defense mechanism whereby the intestinal tract attempts to ‘lubricate’ itself against the mechanical and chemical injury caused by the microbial toxins, acids, and the presence of incompletely digested and unabsorbed carbohydrates.”[i]  (Think what would happen if, for example, you inhaled pepper into your nose.) But after reading the following article, over the weekend, you do have to wonder if there’s not even more to it.

“More than 200 square meters of our bodies — including the digestive tract, lungs, and urinary tract — are lined with mucus. In recent years, scientists have found some evidence that mucus is not just a physical barrier that traps bacteria and viruses, but it can also disarm pathogens and prevent them from causing infections.”[ii]

It turns out that mucus is “…a therapeutic gold mine…”  And apparently, humans produce liters of it every day.

Work just published out of MIT shows that glycans (of which there are hundreds of kinds), complex sugar molecules in mucus, appear to have a profound effect on the gut bacteria.  They appear to have the ability to neutralize the negative effects of pathogenic organisms, including halting bacterial communication and the formation of biofilms.  (You can read more about these in slimy hotbeds of bacteria and yeast here.)

“A slimy, hydrated mucus gel lines all wet epithelia in the human body, including the eyes, lungs, and gastrointestinal and urogenital tracts. Mucus forms the first line of defense while housing trillions of microorganisms that constitute the microbiota. Rarely do these microorganisms cause infections in healthy mucus, suggesting that mechanisms exist in the mucus layer that regulate virulence.”[iii]

Researchers exposed a pathogenic bacterium, Pseudomonas aeruginosa, to glycans and found that doing so made the bacteria harmless.  In fact, these scientists have also found that treating burn wounds infected with this pathogen with glycans reduced the infection.  Essentially, the glycans prevent the bacteria from establishing an infection.

Going forward, these scientists plan to look at the anti-bacterial properties of individual glycans, as well as looking at these sugars’ ability to negate the harmful effects of other pathogens, including Streptococcus and the yeast, Candida albicans.  Thus far, work on the former looks promising.  Someday, these may be used in lieu of antibiotics, which has tremendous advantages.  As one of these researchers says, “What we find here is that nature has evolved the ability to disarm difficult microbes, instead of killing them. This would not only help limit selective pressure for developing resistance, because they are not under pressure to find ways to survive, but it should also help create and maintain a diverse microbiome…”  It also looks likely that glycans play a major role in determining the composition of the bacterial (and possibly fungal) microbiome.  They may actually act as a source of nutrients for probiotic bacteria.  (After all, structurally, glycans are very similar to the oligosaccharides found in breast milk.)

Back to the excess mucus then found in Elaine’s diseased intestines:  I really do wonder if the body doesn’t produce extra mucus when faced with infection, at least in part, as an anti-pathogen mechanism?  That excess mucus may be protective in more ways than we currently understand.  I don’t know the answer.  But how exciting a proposition is the idea of harnessing the power of our own, natural antibiotics to treat infection and benefit the composition of the microbiome?!

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[i] Gottschall, E. Breaking the Vicious Cycle.  1994. Kirkton Press: Baltimore, Ontario.

[ii] https://www.sciencedaily.com/releases/2019/10/191014111737.htm

[iii] Kelsey M. Wheeler, Gerardo Cárcamo-Oyarce, Bradley S. Turner, Sheri Dellos-Nolan, Julia Y. Co, Sylvain Lehoux, Richard D. Cummings, Daniel J. Wozniak & Katharina Ribbeck. Mucin glycans attenuate the virulence of Pseudomonas aeruginosa in infection. Nature Microbiology, 2019 DOI: 10.1038/s41564-019-0581-8

The Deworming Question: A Good Idea? Pointless? Detrimental? The Evidence Mounts…

Last month, a meta-analysis paper came out searching the medical literature through the year 2018, looking for evidence of the benefits promised by the worldwide efforts at deworming school children, recommended by all global advocacy organizations including WHO.  The authors, from the Department of Public Health and Policy at the University of Liverpool, UK,  state their objective is, “To summarize the effects of public health programmes to regularly treat all children with deworming drugs on child growth, haemoglobin, cognition, school attendance, school performance, physical fitness, and mortality.”[i]  Their conclusion is not what you  might expect…at all:

“Public health programmes to regularly treat all children with deworming drugs do not appear to improve height, haemoglobin, cognition, school performance, or mortality… Studies conducted in two settings over 20 years ago showed large effects on weight gain, but this is not a finding in more recent, larger studies. We would caution against selecting only the evidence from these older studies as a rationale for contemporary mass treatment programmes as this ignores the recent studies that have not shown benefit.”

(This, by the way, was an update from their 2015 paper…which concluded the same.  There is no health or cognitive benefit to deworming programs.  They did not, of course, look at whether there are any detrimental health effects of such programs, as that was beyond the scope of the paper.)

I’ve been considering sharing that paper for the last few weeks and after reading another really interesting paper on the effects of deworming today, I decided that the time has come.

The paper I finished reading this morning dates back to this past February, and these scientists – most of whom are at the National Institute of Health – looked at the effects of deworming on the bacterial microbiome.[ii]  There were a few really interesting points that I want to convey.

In this study the researchers collected stool from 5 villages in Kenya prior to administering anti-helminth drugs, then again 3 weeks after the drugs were administered and then 3 months after the drugs were administered.  They considered the presence of only 2 kinds of helminths:  Ascaris lumbricoides and Necator americanus (hookworm). They found that neither “…significantly altered the overall diversity of the microbiota.”  (They point out that it is likely that all participants at some point were colonized by helminths, even if not at the exact time of testing.  This likely plays a role in the fact that significant variability was not found among the participants.  In other papers, like the one I discuss in this post, the biomes of native populations with helminths was compared to people in industrialized countries and the differences in microbiomes was vast.)

Following treatment with the anti-helminth drug, “…there were significant increases in the proportion of the microbiota made up by Clostridiales and reductions in the proportion made up by Enterobacteriales…” and even significant changes in those individuals who did not have helminths on board at the start of the trial.  (This is how mass deworming programs work:  everyone is treated, without first testing to see who is colonized.)  However, they do conclude that clearing helminths (in this case, the N.americanus more than the A.lumbroicodies) from the human body does lead to alterations in the microbiome…and that the health effects of this must be considered going forward.

As far as we know as of this moment, it appears that changes to the bacterial microbiome depend on the species of helminth.  (Since most studies are done in native populations where helminths are still endemic, the exact size of the colony inhabiting the individuals is unknown.  Do larger numbers of helminths induce more changes?  We don’t yet know.)  The authors acknowledge this:  “…there is still no clear consensus of the impact of STH [soil transmitted helminths] on microbiota diversity and composition.  This could be in part because of differences in the STH species, prevalence, and intensity of infection in these different locations…”

In a section the authors entitle “Importance,” they state:  “Intestinal worms may have an important impact on the composition of the gut microbiome.  Without a complete understanding of the impact of deworming programs on the microbiome, it is impossible to accurately calculate the cost-effectiveness of such public health interventions and to guard against any possible deleterious side effects.”  They agree that “…the presence of  helminth infections has been linked with increases in microbial diversity.”  In their discussion, they also mention a study in which pregnant women in Africa with helminth colonies were given anti-helminth drugs and their children showed an increase in allergy risk. They conclude that this deleterious effect was the result of the drug use during pregnancy but neglect to mention that those authors also state, “The detrimental effects of treatment suggest that exposure to maternal worm infections in utero may protect against eczema and wheeze in infancy.”[iii]

These scientists conclude their paper stating, “…the next step will be to understand the impact of the identified differences on human health…” of mass deworming.  Prior to posting this, I have 58 articles on this blog regarding the established health benefits of the human macrobiome. Anyone want to put money on what those future studies will find?

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[i] Taylor-Robinson, DC, Maayan, N, Donegan, S, Chaplin, M, Garner, P.  Public health deworming programmes for soil-transmitted helminths in children living in endemic areas.  Cochrane Database of Systemic Reviews. 2019.  doi: 10.1002/14651858.CD000371

[ii] Easton, AV, et. al. The impact of antihelminthic treatment on human gut microbiota based on cross-sectional and pre- and postworming comparisons in Western Kenya. mBio: American Society for Microbiology. 2019;10(2).   DOI: 10.1128/mBio.00519-19

[iii] Mpairwe H, Webb EL, Muhangi L, Ndibazza J, Akishule D, Nampijja M,Ngom-Wegi S, Tumusime J, Jones FM, Fitzsimmons C, Dunne DW,Muwanga M, Rodrigues LC, Elliott AM. 2011. Anthelminthic treatmentduring pregnancy is associated with increased risk of infantile eczema:randomised-controlled trial results. Pediatr Allergy Immunol 22:305–312.https://doi.org/10.1111/j.1399-3038.2010.01122.x

Probiotics for Breast Cancer? (or…Talking About Needing More Research…)

I was surprised, but not surprised, by an article I read last night on the potential use of probiotics in treating breast cancer (BC).[i]  As several friends have already battled BC, this is a topic of particular interest to me.  I knew there was a known inflammatory component to some forms, and a microbiome connection, and have actually written before about this  on this blog.

First, some statistics, for those of you who don’t know just how prevalent BC is:  breast cancer “…is the most frequent cancer in women, the second most common cancer worldwide, and the second primary cause of cancer-related deaths.”  So yes, I think research into anything that might help is more than merited!

A bit of education, in case you are unfamiliar with breast cancer:  the most common kind is hormone (estrogen and/or progesterone) receptor positive. Excess estrogen is a known risk factor for the development of BC:  “The increase in the amount of free estrogens for reabsorption contributes to the risk of development of hormone-driven malignancies such as BC.”  Gut bacteria play a major role in modulating this reabsorption and the circulation of estrogens.

As I mentioned in my last post on this subject, antibiotics and dysbiosis appear to be a major risk factor for the development of BC, and indeed, factors which affect the gut bacteria, such as diet, also affect BC development.  For example, “Strict vegetarians have increased fecal excretion of conjugated estrogens compared with non-vegetarians, leading to decreased plasma estrogen concentrations and protect against subsequent BC risk.”  High cholesterol levels are another known risk for the development of BC, so this may be the connection.  A vegan diet is typically much higher in fiber than other diets, and certainly affects the composition of the gut flora.  Alcohol consumption, which is another established risk factor, also alters gut bacterial composition in animal models and, at the very least, in humans who abuse alcohol (and/or have alcohol cirrhosis of the liver).   In humans, “…alcohol intake after BC diagnosis is associated with both increased risk of recurrence and deaths. There doesn’t seem to be a lot of research on the microbiome and occasional use of alcohol.

Basically all studies on the potential benefits of probiotics to treat this awful disease have been done in animals, and the results have been really very promising.  Here are 2 examples:

  1. Lactobacillus acidophilus was given to rodents starting 2 weeks before they had BC tumors transplanted into them, and the probiotic was continued for 30 days afterwards.  “The results showed a significant increase in the survival time among the L. acidophilus group compared to that of the controls, demonstrating that this treatment can promote the immune responses…Additional animal studies confirmed that oral administration of acidophilus displays anticancer activity to mice bearing breast tumors.”
  2. Another, particularly virulent form of breast cancer – not associated with hormones – is called triple negative. Mice with triple negative tumors were fed kefir, which led to greatly reduced tumor size.
  3. Other studies which have shown positive effect were done with Lactobacillus casei, yogurt and Lactobacillus plantarium.

Thus far, there has been very little clinical work done with humans.  One Japanese study asked 306 women with BC, and 662 women without, about their diets, lifestyles and other risk factors and found that regular and long-term consumption of L. casei Shirota (found in Yakult yogurt, and which I have written about before – for example,  here ) was “…significantly associated with decreased BC risk in Japanese women.”

The conclusion of the article:  the results of what in vivo and in vitro studies that we have is that, “…probiotics may have an anticancer systemic property, enhancing the systemic immune system, useful for interventions to prevent and control progression of BC.”  Sounds like it might be yet another, “can’t hurt and could help, so why not do it” scenario.

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[i] Mendoza, L. Potential effect of probiotics in the treatment of breast cancer.  Oncology Review. 2019;13(422).  doi: 10.4081/oncol.2019.422

Pancreatic Cancer and the Mycobiome

A brief post today as I find myself way behind on, well, everything!

I found this really interesting and I don’t often get to write about the mycobiome. New research has just come out which shows that a particular form of pancreatic cancer – which, as you may know, is one of the deadliest  that exist – may be the result of fungi moving into the pancreas from the gut.[i]  Scientists have k nown for some time that bacteria, viruses and parasites may play a role, but until now, fungi/yeasts were not suspect.

Pancreatic ductal adenocarcinoma is cancer of the tube of the pancreas, which allows its digestive juices to flow into the small intestine.  This appears to be the exchange site for the movement of fungi into the pancreas.

The scientists treated mice that already had pancreatic tumors with antifungals, and the tumor shrank 20-40% in 30 weeks.  They then looked at the species of fungi in the intestines of mice with and without pancreatic cancer in order to figure out which kind were moving into the pancreas of those affected.  They found that certain types of fungi moved at a much higher rate, including one called Malassezia, which is usually found on the skin and scalp and is responsible for dandruff and some kinds of eczema.  However, this species has also been linked to colon and skin cancers.  Incredibly, when Malassezia was allowed to grow unchecked, pancreatic cancers grew 20% faster in mice.  Candida, Saccharomyces, Aspergillus did not have this same effect.[ii]

They believe the mechanism of action is that the fungi stimulate the immune system in such a way as to lead to the growth of abnormal tissue.

As you know, abnormalities of the mycobiome are associated with other illnesses including autism and inflammatory bowel disease, and even perpetuating C.difficile infections.  You have to believe that with the explosion of research into the human biome, this list is going to get longer and longer.

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[i] https://www.webmd.com/cancer/pancreatic-cancer/news/20191004/fungal-invasion-may-drive-some-pancreatic-cancers#2

[ii] Aykut, B, et. al. The fungal mycobiome promotes pancreatic oncogenesis via activation of MBL.  Nature. 2019;574:264-267.

Glyphosate and Human Health: Is the Bacterial Microbiome the Connection?

In various posts, I’ve explored different potential mechanisms that may play a part in the epidemic of biome alterations we have experienced in the industrialized world, including diet, formula feeding, chronic stress, and so forth.  Another potential mechanism, environmental toxins, is another area of interest and something I have been keeping an eye on.

Over the weekend, I got an article[i] that looks at glyphosate (gly) as one possible culprit. This is, of course, a hugely controversial subject but as always, I work hard to maintain scientific objectivity.  It’s all too easy to get caught up in the hype.  But you know me – I want the facts.

I think it would be best to report on this article from conclusion and go backwards from there.  So the conclusion first:  we have no definitive proof at this time that glyphosate is harmful to human health.  There is a paucity of studies, and those that have been done have been useless, in some ways: for example, the amounts used on animals have been far beyond what humans might regularly be exposed to, invalidating their usefulness in truly determining gly’s toxicity to the ordinary person:  “…relating to most studies, the main limitation is the use of high doses of gly…which is difficult to obtain in mammalian tissues, calling into question clinical relevance.”  What we have at this time seems to be a growing body of evidence that there are indirect adverse effects via the chemical’s ability to alter the human bacterial microbiome:  “…the lack of information, contradictory data and independency of studies have generated controversy concerning the safety of Gly for humans….We have assessed the mechanism by which a Gly induced intestinal microbiome disturbance could be involved in emotional disorders and neurological diseases such as ASD [autism spectrum disorders].  However, more research is certainly required to expound the role of Gly on the gut’s bacterial community…”

It is important for you to understand that gly works on plants by disrupting a particular enzyme of the intestine that blocks the formation of certain amino acids.  However, this enzyme is absent in humans and we obtain these amino acids from our diet.  That said, many of the yeast and bacteria, such as exist in the human microbiome, do express this enzyme and thus, are affected directly by gly.

Here are a few of the points they made that really struck me as interesting:

  1. Glyphosate is used in the commercial product Roundup, and studies have shown that it can permeate the water supply and cause changes in animal’s (including mammalian) behavior.
  2. It is found in our food supply: “Traces of the herbicide have recently been found in formula milk, honey, cereal grains or soy…”  It’s also been found in beer and wine.
  3. Toxicity has been demonstrated in other mammals. For example, gly led to infertility and birth deformities in pigs.
  4. There is some correlative data associating the increased use of gly with human diseases including cancer, ADHD, autism, depression, anxiety, Alzheimer’s and Parkinson’s diseases.
  5. Gly is known to damage DNA in rodents as well as in vitro human cell lines.
  6. In mice, chronic ingestion of gly leads to a decrease in the overall number of intestinal bacteria; maternal exposure leads to biome alteration in the pups.
  7. I didn’t have time to get this article to find out who these crazy people are LOL: “…A striking case of voluntary ingestion of gly was reported and indicated a predisposition to the development of Clostridium tertium bacteraemia in humans together with an effect on intestinal mucosa.” People ingested this stuff voluntarily?!
  8. “Few studies have been performed on gly…on microbiota in mammals, but so far, all findings indicate an overgrowth of gly resistant microorganism such as Clostridum spp [species] and possibly several Salmonella Strains…”
  9. “…Gly severely depletes manganese (Mn) levels in plants. Glyphosate’s disruption of the Mn homeostasis selectively affects Lactobacillus and can lead to several disorders such as PD.”
  10. “Evidence of correlations between neurodevelopmental disorders and Gly perinatal exposure were reported in pregnant rodents treated with Gly….” Interestingly, these scientists saw an increase in the release of the neurotransmitter, glutamate, which is similar to what is seen in those with autism.

So to summarize:

  1. Animal studies such as I mention above, and others (including, for example, one which showed that oral exposure to Gly, “…reduces the abundance of Firmicutes, Corynebacerium, Baceroidetes and Lactobacillus…” while also altering mouse behavior) suggest that gly can be detrimental to humans via altering the composition of the bacterial microbiome.
  2. Considering the number of diseases now known to be associated with the depleted biome, and considering how ubiquitous in our diets are sources of exposure (including baby formula which is obviously used very early in life when the biome is developing), this is potentially a huge issue that needs to be actively and diligently researched.
  3. Gly, in the form of Roundup, is “…the most utilized herbicide in agriculture.”
  4. Gly adversely affects probiotic species of bacteria but pathogenic ones, like certain species of Clostridium and Salmonella, are resistant, potentially leading to dysbiosis.
  5. Many more studies must be conducted before conclusions can be drawn.

I’ll continue to monitor this research, of course!

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[i] Rueda-Ruzafa, L, Cruz, F, Roman, P, Cardona, D. Gut microbiota and neurological effects of glyphosate. Neurotoxicity. 2019;75:1-8.   doi: 10.1016/j.neuro.2019.08.006

Fecal Microbiota Transplant: the Answer for Alzheimer’s Disease?

Ok, yeah…more on fecal microbiota transplants (FMT).  This is my obsession for the week. But after reading my last post…can you blame me?!

In that post, in case you missed it, I talked about a new article reviewing the potential of FMT to treat a huge variety of illnesses, and included in that list was Alzheimer’s disease (AD).   Imagine my joy, then, when I spotted a brand new bit of research looking more in depth at FMT’s effects on AD.  Yes, this is a mouse model but still – it’s very promising.

This study[i], out of South Korea, used mice that have been genetically created to develop the same type of neurological issues (amyloid plaques, neurofibrillary tangles, and memory deficits) as those with AD. They refer to this group of mice as “ADLP mice.”  As controls, they used healthy wild-type (WT) mice, with normal bacterial microbiomes. In comparing the two, they found that early in life (by 2 months), the microbiome of the ADLP mice begins to shift from the norm.  The gut bacteria of ADLP mice did not so much differ from the WT mice in terms of specific types of bacteria, but rather, total composition of the flora, on a community-wide level.  However, these differences, from a functional point of view, are extremely significant:  “These gut-associated changes may mutually contribute to the increased gut barrier permeability and chronic inflammation seen in the intestine of ADLP mice; these problems are considered potential risk factors of AD.”

Which brings me to the next major difference between the two kinds of mice. ADLP mice display a “…loss of epithelial barrier integrity [leaky gut] and chronic intestinal and systemic inflammation.”  By looking at the blood of the ADLP mice, they determined that indeed, metabolites (including highly toxic lipopolysaccharides (LPS)) produced by gut bacteria were making their way into the  circulatory systems of the animals, causing a body-wide inflammatory response. High gut permeability “…can deteriorate the blood-brain barrier, and CNS [central nervous system] is easily exposed to the contents of the altered gut microbiota.  LPS has been found in the brain and participates in AD pathology.”

The crux of the experiments: the scientists orally gave the ADLP mice fresh feces from the WT mice nearly daily for 16 weeks.  Within 2 months, the gut bacteria of the mice was significantly altered, and after 4 months, the microbiota of the two groups of mice were indistinguishable.  They then tested the mice’ memory, both long and short term, and found significant improvement in cognitive function.  They also found that the amyloid plaques were “significantly decreased” as were the other neurological alterations in the ADLP mice.

Another interesting finding:  the researchers discovered altered gene expression in in tissue from the colons of the ADLP mice, which was normalized by FMT.  The genes that were altered “…are associated with ageing-related tissue degeneration and deterioration of mucosal immunity…Specifically, the genes unregulated in ADLP mice contribute to decreased cell proliferation, cellular senescence and cell growth arrest, which are well-characterized ageing-related phenotypes.  The downregulation of genes related to mitochondrial and ribosomal activities in ADLP mice…are considered key features of ageing and neurodegenerative diseases.”

The authors state, “These results indicate that microbiota-mediated intestinal and systemic immune aberrations contribute to the pathogenesis of AD in ADLP mice, providing new insights into the relationship between the gut (colonic gene expression, gut permeability), blood (blood immune cell population) and brain (pathology) axis and AD (memory deficits). Thus, restoring gut microbial homeostasis may have beneficial effects on AD treatment.”

In doing my usual snooping around, I found a 2nd article – also just published – looking at the effects of FMT on a different mouse model of AD.  And guess what?  “We also found that FMT treatment reversed the changes of gut microbiota and SCFAs. Thus, FMT may be a potential therapeutic strategy for AD.”[ii]

So the question I asked myself, in reading, and rereading the paper – and writing this blog post – is:  AD is currently an incurable terminal illness that brings heartbreak to the affected person and their families.  (You can read about my own devastating personal experiences with it here.) Where are the clinical trials in humans?!  And good news, for once, everyone:  the University of Wisconsin is conducting one right now, as I type this.  The study concludes in May 2022.  If this blog still exists in 3 or so years, I’ll let you know the results!

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[i] Kim, MS, et. al. Transfer of a healthy microbiota reduces amyloid and tau pathology in an Alzheimer’s disease animal model. Gut. 2019;0:1-12. doi: 10.1136/gutjnl-2018-317431.

[ii] Sun, J, et. al. Fecal microbiota transplantation alleviated Alzheimer’s disease-like pathogenesis in APP/PS1 transgeneic mice.  Nature. 2019;9(189).