Organophosphates: Yet Another Environmental Toxin that Adversely Affects the Gut Biome and Health

Another popular request, courtesy of the survey I ran a couple of weeks ago, was for more information on how environmental toxins may affect the human biome.  I wrote about the herbicide, glyphosate (that’s found in Roundup), several months ago, and while the role that plays in human health and disease is still controversial (although less so every day), that is not the case of organophosphates (OPs), which are a family of insecticides, still commonly used in agriculture. They were also used in household products in the USA (including flea and tick collars for animals!), until the Environmental Protection Agency (EPA) banned them in 2001.  However, these chemicals are also still permitted to be used in the USA to combat mosquitoes in public areas. I am not sure about the laws concerning these chemicals in other countries.

So while the EPA recognized that the chronic exposure of these chemicals was extraordinarily toxic, especially to children, even today, “With the emergence of West Nile virus in the northeastern Unites States, programs of spraying have been implemented in large urban areas, in particular New York’s Central Park.”[i]

(Apparently, because no children play there. (Yes, I usually do try to refrain from editorializing but sometimes I can’t help it.  I am only human.))

The health effects and mechanism of action of heavy exposure to these chemicals is pretty well understood, and has to do with the alteration of the acetylcholine system in the body.  However, the health effects, and mechanism of action, of chronic low–level exposure is not.  The belief is growing that the detrimental effects of OP exposure are via the bacterial microbiome.[ii]

Because these chemicals are still in widespread use in agriculture, they easily make their way into our food and water supply at low levels:  “Consumption of these compounds affects several central nervous system functions,” as well as causing “… neonatal developmental abnormalities, endocrine disruption, neurodegeneration, neuroinflammation and cancer.  In addition, neurobehavioral and emotional deficits following OP exposure have been reported.”   That these chemicals are extraordinarily toxic is not actually controversial.  In fact, included in this family is the nerve gas, sarin. Heavy exposure can cause death.

As mentioned above, high-level, acute exposure causes an increase of the chemical messenger, acetylcholine, at the nerve synapses and neuromuscular junctions, leading to an overstimulation of the nerves and muscles.  This, in turn, leads to autonomic dysfunction (sweating, hyper salivation, diarrhea, etc.) and weakness, twitching, respiratory failure, convulsions, and possibly coma and death.

Chronic low level exposure is currently the subject of much research.  Various symptoms have been documented in both adults and children:  a more extensive list includes neurobehavioral problems (including executive functioning issues, working and visual memory, etc.), developmental neurotoxicity, cognitive changes, attention issues, anxiety, and learning problems.  Also seen are respiratory problems, metabolic issues (like obesity and diabetes), and neurodegenerative diseases like Alzheimer’s and Parkinson’s.  Animal studies indicate that exposure at levels too low to cause acetylcholine issues also appear toxic.  And this has led to great interest and investigation by the scientific community.

As I said earlier, the current thinking is that this effect is the result of OPs altering the gut bacteria, and evidence for this hypothesis is rapidly mounting:  “Emerging scientific evidence links gut microbiota dysbiosis with exposure to environmental agents such as OPs.”  One OP, chlorpyrifos (CPF), is the best studied.  Researchers find (in animal studies) that 99% of CPF is absorbed by the small intestine, and also, that it significantly alters the bacteria of the gut, lowering levels of Proteobacteria and increasing the proportions of Firmicutes and Lactobacillales.  Scientists have also found that, “…chronic CPF-exposure during critical pre- and postnatal periods causes morphological changes in the intestinal epithelium and increases intestinal permeability…”  That is, it causes leaky gut. In rats, it’s been shown to alter the pups’ microbiota, including increasing the abundance of Clostridium…and you’ve read many times on this blog (here’s just one example) about the detrimental effects of excessive propionic acid, the short-chain fatty acid produced by Clostridium.  “Collectively, these data suggest that prenatal and lactational exposure to CPF have both short-term and long-lasting impacts on the microbiota, indicating that exposure in infancy should be avoided.”

While studies into the microbiome effects of other OPs are scarce, what we do have indicates that they too have adverse effects.  For example, in mice, the OP, malathion, greatly altered the gut biome, including increasing Clostridum.

These authors conclude that, “The research above shows that several Ops, such as CPF, caused dysbiosis both in childhood and adulthood…Therefore, gut  microbiota dysbiosis should be taken into consideration when evaluating the neurotoxicity of these compounds.”

There is limited evidence to date of ways to manipulate the gut bacteria to alleviate the effects of exposure to OPs. However, the prebiotic, inulin, has shown some promise. In one rat study, in which the animals were exposed to CPF, those who also received inulin showed less loss of biome diversity and less loss of SCFA production.  In an in vitro model, “…the dysbiosis and metabolic imbalance in the intestinal environment observed after CPF exposure could be prevented by co-treatment with inulin.”

Probiotics have also shown some good initial results.  Lactobacillus bacteria bind to OPs and reduce intestinal absorption, in vitro.  In an animal model (Drosophila, which are fruit flies commonly used in scientific studies), pre-treating with Lactobacillus rhamnosus reduced mortality and growth deficits.

So to summarize, it appears that avoiding exposure to these chemicals is key…but since it appears we may not be able to fully do so, once again, protecting our gut bacteria via the intake of pre- and possibly probiotics may be helpful.  As I always say to you at the conclusions of these kinds of post – I’ll keep an eye out for any new developments!



[ii] Roman, P, Cardona, D, Sempere, L, Carvajal, F. Microbiota and organophasphates. NeuroToxicology. 2019;75:200-208.   doi: 10.1016/j.neuro.2019.09.013.

Parkinson’s, Fecal Transplant, Probiotics, Prebiotics…No Answers Yet

Yesterday morning, I got a comment on the Biome Buzz’ Facebook page, in response to last week’s post on the microbiome and the basal ganglia, that said, “Could you put it more simply and tell us what to do about it?  This is Facebook remember not a scientific magazine.”  (And there you have it…yet another example of no good deed going unpunished.  I spend time I don’t have writing these posts for free…and, well…I guess you can’t make all of the people happy all of the time!)

Those of you who regularly read this blog know that I am neither a scientist nor a physician.  I am simply an interested individual with a great personal stake in the progress of research into the gut biome.  I am a mother of a son profoundly affected by autism.  I have an autoimmune disease and fibromyalgia.  I have friends and family who are already suffering, some for years, with illnesses ranging from Parkinson’s disease to cancer.  I have already had to watch my grandmother die of dementia.  Yes…I have a very, VERY big personal stake in this research.

What I do not have are the answers.  Then again, neither do the hundreds, if not thousands, of brilliant doctors and scientists around the world who are in the process of trying to figure this all out.

I won’t even bother to comment on the snark in her comment.  Sheesh.

Anyway, on that note – i.e. more questions than answers – I read a little article[i] over the weekend on fecal microbiota transplant and Parkinson’s disease (PD), which you all know, is of particular interest to me, seeing as how I already have 3 friends with it.  This is a great follow up article to that last post on the basal ganglia, which contains the part of the brain wherein PD is centered. According to this article,  all studies done on PD show alterations in the bacterial microbiome, and while there is some variance, there is also a great deal of overlap:  all agree on an increase in Lactobacillacea, Akkermansia, Enterobacteriaceae and Bifidobacterium, and a decrease in Prevotellaceae, Faecalibacterium and Lachnospiraceae.  There are several hypotheses about how these alterations may play a part in the development of the disease.  One example:  because some of these species found at lower levels in the PD gut are producers of short chain fatty acids (SCFAs), there is a belief that the subsequent decreased levels of SFCAs lead to an increase in inflammation in the PD gut:  “The fact that faeces from PD patients contain lower amounts of SCFA and have increased levels of intestinal inflammation, supports this hypothesis.”

However, as yet, there is no fully cohesive picture:  “The studies do not converge on a specific signature or metabolic pathway for PD…”  What makes this an even more confusing picture is that other neurological and neurodevelopmental disorders, like Alzheimer’s and autism, also show microbiome variability.  What specific microbial profile leads to each specific disease though, since there are many overlaps, is unknown.  (That is, what exact changes lead to Alzheimer’s versus PD?)  More than that, correlation does not prove causality.  We simply do not as yet know definitively if these bacterial differences cause PD.  For example, it is possible that PD causes constipation which, in turn, leads to microbiome alterations.  We also do not, as yet, know if the changes found in those with PD are simply the result of the dopamine medications those affected need to take.  And of course, there is also the bee-in-my-bonnet issue:  none of the current studies looked at any other gut resident other than bacteria.  As yet, there’s no real research into possible alterations in the other members of the microbiota:  fungi, archaea, viruses, let alone the macrobiotic organisms.

I’ve written before, many times, about fecal microbiota transplant and the promise it holds for the treatment of a huge variety of illnesses.  In spite of the ever-growing evidence of a relationship between bacterial microbiome alterations and PD, there are zero clinical studies looking to see if FMT might help.  Apparently, as of today, there is 1 case study in the medical literature:  “…a recent Chinese case study on a PD patient with severe constipation. The constipation as well as his PD symptoms greatly improved after FMT.”  (It just makes you want to scream sometimes, doesn’t it?)  The only good news I can offer is that right now, finally, a human study IS being conducted at a Belgian university, and is scheduled to be completed by the end of this year.  It includes 40 PD patients who will be followed for a year, with checkups every 3 months.

There are animal studies, however:  “These studies mimic the FMT procedure with arguably successful results for the model PD mice, indicating that FMT might work in humans in spite of our incomplete insight in its specific mechanisms.”  It is also significant that giving patients with PD probiotics (Lactobacillus and Bifidobacterium) over 4-12 weeks has “..repeatedly proven to be effective in treating constipation,” and one of these studies assessed motor issues as well:  “…Patients being treated with probiotics showed an improved motor score compared to placebo-treated patients, as well as a reduction of clinical signs of inflammation and oxidative stress compared to placebo-treated patients.”  Unfortunately, this study was hugely flawed in that patients were only assessed after treatment, not before, so there’s no real way of knowing what kind of improvements were actually made, if any.  There have been no trials of prebiotics in PD.  One animal study showed that giving the short-chain fatty acid, butyrate, did lead to an improvement in PD symptoms.  Apparently, though, another paper showed that, again in a rodent model, the introduction of SCFA worsened neuroinflammation in PD.  So the picture is murky, at best.

The authors of this paper discuss in detail why people with PD should not rush to try FMT and why their medical practitioners should exercise great caution at this time:  we don’t know which patients may respond, we don’t know at what stage of PD it may be too late to respond, we don’t know the optimal procedures for making FMT a success due to lack of clinical trials, we don’t even yet know if dysbiosis is directly related to the development of PD.  They conclude that while FMT does hold promise for the eventual treatment of PD, “We think that it would be better to wait for the results of the ongoing trials, in order to shape future protocols, instead of performing new trials without good evidence how to design  these. FMT at this moment is a black box with too many unanswered questions.”  And there is not yet any definitive data on using pro- or prebiotics to help treat the illness.

So back to my disgruntled Facebook reader:  I am sorry that I don’t provide you with non-existent answers.  I can only report the science, and hope, over time, that it provides us with those answers for which we are all anxiously waiting.


[i] Van Laar, T, Boertien, JM, Herranz, AH. Faecal transplantation, pro- and prebiotics in Parkinson’s Disease; Hope or Hype?  Journal of Parkinson’s Disease.

The Microbiome and the Basal Ganglia in …The Case of the Leaky Gut?

I recently read an article looking at the effects of bacterial microbiome alterations on particular circuits in the brain (the thalamo-cortico-basal ganglia)  that are associated with compulsive behavior, addiction, altered sensations and motor output.[i]  What struck me is how closely related seemingly unrelated disorders actually are, from a biological point of view.  That is: while autism, Parkinson’s disease (PD), addiction/substance abuse and compulsive behaviors on the surface have nothing to do with each other, it turns out that on a brain level, they actually have a whole lot in common.

This review paper focused on the basal ganglia, a group of structures found deep in the central brain,  near the base (brain stem) that include the substantia nigra, the part of the brain affected in Parkinson’s disease:  “The contributions of the basal ganglia to movement are complex and still not completely understood. In fact, the basal ganglia probably have multiple movement-related functions, ranging from choosing actions that are likely to lead to positive consequences to avoiding things that might be aversive. But the basal ganglia are most often linked to the initiation and execution of movements. One popular hypothesis suggests that the basal ganglia act to facilitate desired movements and inhibit unwanted and/or competing movements.”[ii]

The key to all this is that the basal ganglia are located near the blood-brain barrier, which becomes permeable in conditions of systemic inflammation:  “…toxins produced by the microbiota have differential access to different brain regions depending on the permeability of the blood-brain barrier.”  For example, “Regions of the basal ganglia are situated near the blood-brain barrier that are particularly leaky in PD patients.”

Remember that the same tight cell junctions found in the epithelial lining of the gut (which should prevent undigested food, bacteria and their metabolites, etc. from making their way directly into the blood stream) are also found in the blood-brain barrier.  If this becomes “leaky,” these substances can make their way into the brain causing an inflammatory response.  You can read more about this phenomenon in this post.

I’ve written about the connection of PD to the gut bacteria pretty extensively on this blog (here and here, as just two examples) so I won’t go into much detail on this today.  I’ll just mention one particularly interesting study this paper describes.  Mice that are genetically prone to developing PD are protected from the disease if raised in a germ-free environment.  If colonized though with the fecal microbiome from normal control mice or healthy humans, the mice developed a movement disorder.  If these mice are colonized with the microbiome of humans with PD, that movement disorder is markedly worse.  To date though, there is no definitive description of the PD microbiome.  Studies have had conflicting results.

In terms of autism, the basal ganglia have long been looked at as the potential area responsible for repetitive behaviors and tics.  Research has shown that increasing the intestinal load of lipopolysaccharides (toxic metabolites from a type of gut bacteria) increases repetitive behaviors.  Again, I have written before about the autism-Clostridia connection (for example, here).

Repetitive and compulsive behaviors are not only a hallmark of autism, but of other “compulsive” disorders as well, including some cases of obesity, i.e. compulsive eating:  “Obese individuals exhibit significant comorbidity with obsessive-compulsive disorder along with several neurobiological markers of addiction…”  The gut microbiota also appear to be heavily involved in the development of compulsive substance abuse:  “Recent work has found that the gut microbiota both influences and is influenced by the effects of psychostimulant drugs and may contribute to compulsive substance use.”  For example, in an animal model, depleting the normal microbiome using antibiotics led to an increased sensitivity to the behavioral effects of cocaine.”  The animals treated with antibiotics reacted to the drug at doses that had no effect on control animals.  The current theory is that alterations to the gut microbiome alter neurotransmitter receptor expression, including to dopamine, which is very much responsible for  reward and goal-directed behaviors (motivation).

We know that the microbiota, “…actively maintain normal basal ganglia physiology” and “…may affect basal ganglia function and behavioral output.”  Accumulating evidence points to “…wholesale depletion and modification of gut microbiota either ameliorating or worsening disease state in animal models of PD, obesity, and cocaine addiction.”  Certainly, the recent successful clinical trial on fecal microbiota transplant and autism suggest that the gut microbiome play an enormous role in the development of this condition.   This article suggests that, “One potential core mechanism may be increases in gut permeability, which may be mediated by several dysbiotic changes in gut microbiota.”  One suspect bacterial type is Prevotella, which maintains gut barrier integrity (i.e. protects against leaky gut).  It is sometimes found at lower levels in people with PD and autism, but there are conflicting data.  An overgrowth of Proteobacteria, which increases intestinal permeability, is also on the short suspect list, as this is seen in PD, autism, obesity and cocaine addiction.  Again though, definitive proof is lacking.

That said, the current, prevailing hypothesis is that, “…changes in bacterial composition, likely interacts with several environmental and genetic risk factors to precipitate specific disease outcomes…Increases in gut barrier dysfunction may alter other gut microbial communication pathways to the brain…”  Remember this post from earlier this year, re:  a potential treatment for leaky gut?  As time goes on, the crucial importance of a treatment becomes more and more evident.

p.s.  As I was about to post this, I noticed a new article on Parkinson’s News Today entitled, “Review Addresses Problems in Studies of the Gut Microbiome in Parkinson’s.”[iii]  To sum it up, as mentioned in the article I discussed today, differing methodologies have led to inconsistent results and as of now, there is no confirmed “PD microbiome” that has been established that could be used to diagnose or guide future treatment options.  This paragraph struck me as particular noteworthy, in light of what I’ve written above:  “While the researchers noted that, ‘several findings, such as an increase of Verrucomicrobiaceae and Akkermansia, and a decrease of  Prevotellaceae were robustly replicated,’ other findings were inconsistent or even directly contradictory. For example, some studies reported increased numbers of the bacterial groups Lactobacillaceae and Bacteroidetes in people with Parkinson’s, while others found the opposite.”  So low levels of Prevotella in those with PD, which maintain gut barrier function, actually does appear to be pretty accepted at this point.  Interesting, huh?


[i] Fields, CT, Sampson, TR, Bruce-Keller, AJ, Kiraly, DD, Hsiao, EY, de Vries, GJ. Defining dysbiosis in disorders of movement and motivation. The Journal of Neuorscience. 2018;38(44):9414-9422.



Fibromyalgia and the Bacterial Microbiome

A couple of weeks ago, I asked all of you to let me know if there are topics of particular interest to them.  I’ll be covering a number of these suggestions in the next few weeks.  Thanks for all your feedback and keep it coming!

The number one request was for more information on the relationship of the gut biome to fibromyalgia (FM) and chronic fatigue syndrome (CFS).  For once, I was not surprised. For decades, these two overlapping, yet distinct, illnesses were ignored by the medical community and now, so many years later no one has yet figured out how to properly diagnose them, let alone effectively treat either of them.  (Here is a post I wrote about CFS and microbiome, for those interested.)

In one of those coincidences that I love so much, last week, a paper was published in the major medical journal, Pain, entitled, “Altered microbiome composition in individuals with fibromyalgia.”[i]  Can you believe the timing?!

To sum up:  there are distinct differences in the composition of the gut bacteria in those with FM, so much so that it looks like a promising way of accurately and rapidly diagnosing the disease in the not-very-distant future. (I have written a bit about FM and the biome before, like here.) Previous research has shown that the rate of false positive diagnosis of FM (i.e. telling people they have FM when in fact, they are suffering from something else) is between 66-73%!  A reliable way of definitively diagnosing FM is desperately needed.

The justification for the present study:  in CFS, which is closely related to FM, a small amount of research has shown altered gut microbiota, and one small study of those with FM itself showed altered intestinal permeability, and a “…distinct urine metabolomics signature was demonstrated, which could be attributed to gut microbiome alterations.”  This study included 166 participants, 77 with FM and 79 healthy controls.

Highlights of their findings:

  1. As mentioned earlier, there were distinct differences in the gut bacterial composition of those with FM versus those without.  These alterations showed a very distinct pattern.  More than that, there was a quantitative association between certain kinds of bacteria and the severity of FM symptoms including pain intensity, pain distribution, fatigue, sleep disturbances and cognitive symptoms.
  2. Some of these changes include low levels of the following species: prausnitzii, B. uniformis, P. copri, and Blautia faecis. This latter species, “…is one of the most abundant and well-studied butyrate producing bacteria in the human gut. This species has been reported to be depleted in multiple intestinal diseases and was therefore suggested as a potential marker for gut disorders…. B. uniformis is one of several species that have recently been reported as having altered relative abundance in patients with inflammatory arthritis…” (That said, there are distinct differences in the composition of the microbiota in FM patients versus those with traditional rheumatic diseases.)
  3. FM patients had markedly higher levels of bacteria that are known to produce high levels of the short-chain fatty acid (SCFA), butyrate: butyriciproducens, F. plautii, B. desmolans, E. tayi, and E. massiliensis.
  4. Higher levels of the SCFAs butyrate and propionate are found in the blood of those with FM versus healthy controls.

The authors conclude that their study provides evidence of a unique bacterial signature for FM, which could, “…offer new insights into the pathogenesis and pathophysiology of FM, and possibly suggest leads to explore the possible effects of trigger events, personal susceptibility, and individual prognosis.”  Certainly this research may, at the very least, provide a way to properly diagnosis the illness.  And over time, I certainly hope it leads to new treatments because, as of now, there are none.  (In fact, I recently wrote about the fact that the science is simply not there yet regarding using probiotics to treat either CFS or FM.)


[i] Minerbi, A, et. al.  Altered microbiome composition in individuals with fibromyalgia. Pain. 2019:160(11).

Histamine Intolerance and the Altered Micobiome

A week or so ago, a reader wrote to me asking if I had ever heard of an intolerance to fermented foods.  Indeed I had:  histamine intolerance.  I have worked with a very few nutrition clients over the years who have suffered from this syndrome, and while it is still somewhat controversial (I’m not sure why, as the mechanism of action is actually at least partially known), there is no doubt in my mind that it exists.

Anyway, this inspired me to do some searching and I came across an article published last year which correlates histamine intolerance to alterations in the gut bacteria. [i]

Why are none of us surprised?

Histamine intolerance (HIT) is defined in this article as, “…an adverse reaction of ingested histamine that affects different organ systems and results in various intestinal and extra-intestinal symptoms.” Some common symptoms of HIT include flushing, pruritus (skin itching), nausea, vomiting, diarrhea and abdominal pain.  Every organ system can be affected, including the respiratory tract, skin, cardiovascular, nervous, and digestive systems.) Foods that contain histamine include shellfish, peanuts, chickpeas, vinegar, chocolate,  cheese, red wine, beer, like sauerkraut, pickles and more.  (Below see a link for a more complete list.)

As I mentioned above, the exact mechanism of action is not entirely understood, but we do know that many people with this issue have a reduced level of an enzyme called diamine oxidase (DAO) in their intestines.  This enzyme degrades histamine, and thus, if it’s level is low, more histamines from foods will make their way into the blood stream and cause symptoms.

Several species of gut bacteria are known to convert histidine (an amino acid) into histamine, including some of the lactic acid producing bacteria like Lactobacillus reuteri, Lactobacillus casei, etc:  “The presence of these bacteria in the human intestine might contribute to increased histamine levels and promote histamine sensitivity in some persons.”

In this study, 64 patients were broken up into 4 groups, for comparison: 25 were determined to have food hypersensitivities (FH), 21 had outright food allergy (FA), 8 had histamine intolerance (HIT) with decrease DAO activity, and 10 were healthy controls.  All contributed blood and stool samples for analysis.  To sum up the results:

  1. Surprisingly, there was no increase in histamine producing bacteria in those with HIT.  However, the authors do suggest that more research is needed in regards to this question.
  2. However…there were significant differences in gut bacteria in those with HIT, and FA and FH, in comparison to the healthy controls. Those with HIT had markedly higher levels of Proteobacteria, which are associated with dysbiosis.  Low grade inflammation is actually known to promote an increase in this species:  “An intestinal inflammation may cause an epithelial dysfunction and increase the oxygen levels in the colon.  This promotes the growth of facultative anaerobic bacteria, e.g. various species of Proteobacteria, that compete against obligate anaerobic bacteria comprising beneficial ones like Bifidobacteria.  There, an increase in Proteobacteria is also suggested as a marker for epithelial dysfunction [i.e. leaky gut].”  A leaky gut would, of course, permit the excess histamine to enter the blood stream more readily.
  3. Since DAO is synthesized in the enterocytes (cells that line the intestine) and stored in these mucosal cells, any disruption of these cells by inflammation will lead to reduced DAO production, which, in turn, leads to higher levels of histamine in an inflamed and leaky gut. This study did not look at the gut inflammation in depth, and the authors suggest that this is a prime area for future work.  (I will keep an eye out!)
  4. Zonulin is a protein that regulates the tight junctions between the cells in the gut. Patients with HIT were found to have increased zonulin in their stools, which “…suggests a mild alteration of gut permeability in patients with a high intestinal histamine exposure.”
  5. “In summary, our results suggest an alteration of the microbial composition in food intolerances, especially in patients with histamine intolerance. The increase abundance of Proteobacteria, the decreased abundance of Bifidobacteriaceae/Bifidobacterium and the lower bacterial diversity points to a dysbiosis and an impaired intestinal barrier in this patient group.  The positive correlation between intestinal histamine and stool zonulin levels indicates a negative effect of histamine on gut permeability.”

In other words, those with HIT are caught in a vicious cycle.  Raised levels of histamine in the gut (from improper breakdown of food derived histamine) leads to compromised gut wall integrity and inflammation…which in turn leads to lower levels of the enzyme necessary to break down histamine…which leads to higher levels of histamine…and so on.  Which is the chicken and which is the egg, no one yet knows.

How to break the vicious cycle?  Firstly avoid foods with histamine.  Here is a list of good and bad foods for you to consider.  Secondly, for those of you who suspect leaky gut issues:  prior research has shown that supplementation of Bifidobacterium bifidum enhances “…epithelial function by promoting the epithelial tight junction integrity…” in humans.  Supplementation with that probiotic may help over time.

Also, be aware that certain medicines can interfere with DAO activity, including antibiotics, antidepressants, aspirin, and many more.  Look at this page for more info.

While considered rare, you really do have to wonder if HIT is actually more common than believed, and just infrequently recognized by doctors unfamiliar with it.


[i] Schink, M, et. al. Microbial patterns in patients with histamine intolerance.  Journal of Physiology and Pharmacology. 2018;69(4):579-593.

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.


[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


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.


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



[ii] tps://

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?




[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.



[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. 


[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.


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?!


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


[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