Lupus and Helminths: Preventive Promise?

I continue to monitor the macrobiome space, watching as the evidence (very) slowly but surely continues to mount in support of helminths’ ability to alleviate, or even prevent, the development of autoimmune diseases.  The latest news is that, in an animal model, Japanese researchers have found that a species of helminth (intestinal worms native to all mammals), Hymenolepis microstoma (HM), a species of tapeworm, native to rodents,  can stop lupus in its tracks.[i]

First, a little about lupus, in case you’re not familiar.  According to the Mayo Clinic, it is a systemic autoimmune disease that can affect many systems including your joints, skin, kidneys, blood cells, brain, heart and lungs.[ii]  The National Center on Lupus states on their website that at least 1.5 million Americans have the disease, 90% of whom are women.  It is potentially an extremely serious disease:  it is among the top 20 leading causes of death in females, aged 5-64.[iii]

As is the case with all autoimmune diseases, no one knows either the cause or the cure for lupus, and like many others, is treated with an array of immune-suppressants and biological agents.

I have described the known immune-modulatory effect of helminths many times on this blog (2 quick examples of many here and here), so won’t go into details in this post.  For those unfamiliar, a very brief explanation:  in order to survive, helminths have evolved to modulate the inflammatory response of their hosts to keep from being killed off.  They are potent activators of the regulatory system (the off switch to the inflammatory one).  Improved sanitation (toilets, shoes, purified drinking water, etc.) has led to the eradication of  our native macrobiomes in the industrialized world, leaving us with lower levels of regulatory cytokines and thus, the tendency to have excessive and perpetual inflammation.

While many studies now exist in animal models, and some in humans, showing helminths’ benefits in treating diseases like allergy, multiple sclerosis,  and even autism, etc., prior to this paper, none really existed looking at their efficacy in treating lupus.  Apparently, this is because of a lack of a good animal model of the disease.  In this experiment, the researchers used mice that have been bred to spontaneously develop a lupus-like syndrome.

Three different helminths were tested in germ-free mice: Trichuris muris (a roundworm native to rodents); Heligmosomoides polygyrous (another roundworm native to rodents); and Hymenolepis microstoma, which, as I mentioned above, is a different kind of helminth  –  a flatworm (tapeworm).  Only the tapeworm was able to successfully colonize the lupus-prone mice, and thus, it was the only one which ended up being used for this experiment.

The lupus-prone mice, after colonization, were monitored via blood draws, looking for the production of autoantibodies.  Uninfected mice gradually began to produce the autoantibodies, peaking at 8-9 months of age.  However, the mice with the helminths on board never produced autoantibodies.

The kidneys are primary targets for lupus autoantibodies, and the degree of damage can be measured by protein in the urine (proteninuria).  The uninfected mice developed proteninuria around 9 months of age; the  mice with the helminths never developed it.  The mice were autopsied and indeed, in the mice with the helminths, the kidneys were completely normal as opposed to those of the uninfected mice, which showed major pathology.

An interesting note:  if the mice were given an anti-helminth agent after only a month of infection, these protective effects were not seen.  It is the long-term presence of the helminths which provided protection from the development of lupus.

The authors conclude, “Helminthic infections are known to induce immune regulatory cells to modulate immunity.  We found that perivascular inflammatory responses…were suppressed, suggesting that the immune suppression induced in Hm-infected mice attenuates inflammation through activation of regulatory T cells (Tregs).”  This is exactly what so many other studies have found.

This study is significant in that,  “…the suppressive effects of Hm on inflammatory diseases have never been reported. Thus, our report includes two novel findings: the suppression of the natural onset of SLE in a helminthic infection, and the protective ability of Hm against inflammatory diseases.”  The Hymenolepis family of tapeworms are not well-studied in terms of their inflammation suppressing effects in diseases. (It is not completely unstudied though.  I talked about a couple of new papers looking at Hymenolepis dimimuta about a year ago, here.   This paper is a big step forward in providing among the first such studies on these helminths. And lupus is, as I mentioned above, way understudied in terms of helminths.

To end on a really interesting final note:

“Infection with Hm improved all symptoms and signs of SLE and prevented death.”

That is, 70% of the mice with helminths lived until the end of the experimental period, far longer than those uninfected:  “Hm prevents natural development of SLE and prolonged survival of NZBWF1 mice.”

So there you have it.  Yet another feather in the cap for our macrobiotic old friends.


[i] Olia, A, Shimokawa, C, Imai, T, Kazutomo, S, Hisaeda, H. Suppresion of systemic lupus erythematosus in NZBWFI mice infected with Hymenolepis microstoma.  Parasitology International.  2020.



Bile Acids and Your Microbiome (It May Not Sound Sexy but…They are a Huge Factor in Health)

Ok, it’s time for me to tackle a topic that is totally new to me. Today’s subject:  bile acids.  It may not sound exciting but it turns out, bile acids have a huge part to play in your health, and that effect is based upon the contents of your microbiome.

Several months ago, I first stumbled across the topic when I came upon a 2014 article out of the University of California, Davis, relating bile acid dysregulation to gut dysbiosis and gastrointestinal (GI) cancer.[i]  Before I describe this, and then some new research, let’s start with a definition.  Bile acids (BA) are made by your liver to break down fat that you eat.  They are derived from cholesterol.  Primary bile acids, secreted by the liver into your GI tract, are then converted into secondary bile acids by enzymes secreted by your gut bacteria.

According to that 2014 article, our modern diet, which is high in (unhealthy) fat and sugar (along with other factors, including lack of physical exercise, etc.) has led to the current epidemic of obesity and diabetes, both of which are linked to an increased risk for cancer.  Both diabetes and obesity have also been linked to dysregulation of bile acids and also, dysbiosis of the microbiome.  Subsequent elevated levels of secondary bile acids, along with a pro-inflammatory shift in the bacterial microbiome, have been linked to cancer:  “…recent findings have implicated a detrimental interplay between BA dysregulation and intestinal dysbiosis that promotes carcinogenesis along the gut-liver axis.”

The exact mechanisms are, of course, not as yet understood…which brings me to two new pieces of research out of Harvard.[ii]  Just as too much is not good, neither is too little.  To boot, BA have a direct major effect upon the immune system.

It turns out that bile acids “…promote the differentiation and activity of several types of T cells involved in regulating inflammation and linked inflammatory conditions.”  And as the bacteria of the gut are critical in converting bile acids into secondary bile acids, and immune-signaling molecules, they are also critical in this immunological process.

The first study showed, in an animal model, that bile acids, once converted into these immune-regulatory molecules by gut bacteria, activate two kinds of immune cells:  Treg (T regulatory cells, which are the off-switch to the inflammatory system) and T helper (effector) cells, Th17, which are proinflammatory.  Of course, to remain healthy, you need an inflammatory response to fight pathogens, and you equally need a regulatory system to turn that inflammation off when it’s no longer needed.  There is a crucial balance between the two.  These researchers found that two particular bile acid molecules affected Treg and Th17, and these two molecules are indeed found in human stool, which suggests that this research also applies to us.  Says the lead researcher on this study, “Our findings identify an important regulatory mechanism in gut immunity, showing that microbes in our intestines can modify bile acids and turn them into regulators of inflammation.”

If these findings are confirmed in humans, these natural molecules can be used to modulate inflammation in diseases affecting the gut, like inflammatory bowel diseases (IBD).

The second  Harvard study showed that gut microbes and diet “…work in concert to modify bile acids, which in turn affect the levels of colonic Tregs in mice.”  Low levels of Treg cells, from low levels of bile acids, make the mice prone to developing inflammatory conditions, like IBD.  This study is a bit more complicated, and involved populating mice with gut bacteria in which genes which are responsible for BA conversion (into these immune-signaling molecules) are silenced.  They then put these bacteria, or normal bacteria, back into germ-free mice.  Those animals who were given the modified bacteria had markedly lower levels of Treg cells (and therefore, higher inflammation).  In other words, gut microbes which convert BA are critical for gut health.

They then tested the effects of diet.  Animals fed minimal diets had low levels of BA and thus, low levels of Treg, which of course makes senses.  Fat in the diet is what stimulates the body to produce BA after all.  However, animals with germ-free guts who received rich diets also had low levels of Treg, proving that gut microbes are crucial in producing those immune-signaling molecules from BA.

In a second part of their experiment, the scientists broke up the mice into 3 groups.  The first was fed a minimal diet.  The second was fed a nutrient-free diet and the third group was fed minimal food, but was also supplemented with bile acid signaling molecules.  All three groups were then given a substance that induces colitis.  Not surprisingly, only the animals fed a minimal diet who were not supplemented with the BA molecules actually went on to develop the disease.

Back then to that first 2014 article:  it concludes with a section which suggests that there are potential treatments for BA dysregulation, which include probiotics and prebiotics (to improve the quality of the microbiome), as well as dietary changes.  For example, vitamin B6 has been shown to improve colon health.  Other natural substances include burdock root (from a plant in the daisy family) powder and genistein (an isoflavone derived from plants like soy), which have shown, “…moderate efficacy in normalizing BA homeostasis and the gut microbiome in animal models.”

If you think about it, diet is crucial in more ways than one.  That is, a healthy diet, rich in nutrients, is crucial for the stimulation of BA, as shown by the above studies.  Diet is crucial for maintaining a healthy weight and thus, avoiding the inflammation discussed in the 2014 article.  And diet also modulates the health of the microbiome, thereby indirectly affecting inflammation by affecting the bacteria responsible for converting BA into the immune-signaling molecules necessary to maintain health.

So your take home message is, yet again, eat a health diet!


[i] Tsuei, J, Chau, T, Mills, D, Wan, YJY. Bile acid dysregulation, gut dysbiosis, and gastrointestinal cancer.  Experimental Biology and Medicine. 2014; 239(11): 1489–1504.   doi:10.1177/1535370214538743.


More On Propionic Acid and Autism (or…I’m sorry, but I Can’t Help Myself…)

I know that everyone (including me) wants answers to the question “how do you fix a broken biome.”  I am always happy when I come across any information that may actually help people, especially since, at this point, there’s precious little known about how to actually make things better.

On Tuesday, I wrote about new papers on the adverse effects of excess levels of the short-chain fatty acid, propionic acid (PPA), on the developing brain.[i]  At one point, in the paper on how PPA affects the amygdala (the emotion center of the brain), I was struck by the following sentence:  “…recently it was established that the patients who are unable to metabolize PPA are more common than previously thought; many of such patients have cognitive impairments, movement disorders, and seizures.”  The reference given was for a paper written by Dr. MacFabe back in 2013.[ii]  I was curious – what did that sentence mean?  So, I went and read that older paper.

Firstly, I have to say that it was a wonderful read – more “user friendly” than ordinary scientific papers.  Dr. MacFabe talks about how he came up with the PPA theory of autism, and this story-like quality that makes it really enjoyable.  To boot, there were some extraordinary bits of information in it that I absolutely need to share with you.  In fact, there are so many that I’ll need to narrow things down to make sure this doesn’t turn into a Biome Buzz version of War and Peace.

1. To start, I learned a new term:  “gap junctions.”  These are defined as, “An organized collections of protein channels in cell membranes that allows ions and small molecules to pass between adjacent cells.”[iii]  In other words, these junctions allow cells to communicate with each other.

2.  Why is this important? Because it turns out that PPA closes gap junctions:  “…closed glial gap junctions may render neuron hyperexcitable…In turn, this decrease in gap junction coupling may lead to inhibited cortical pruning in development, consistent with the larger brain sized found in ASD.  Gap junction communication is involved in neurotransmission in the basal ganglia, prefrontal cortex, nucleus accumbens, and hippocampus: all areas that are implicated in seizure and movement disorders.  Given these findings, it seemed possible that propionic acid-induced alterations to gap junction function and in neural development, as well as systemic effects (ie. GI motility), may play a role in ASD.”  Thus, PPA has the potential to cause the pattern of brain issues seen in the autism population.

3.  Back to the fact that difficulty metabolizing PPA is more common than once thought. There are apparently people with various inherited metabolic disorders, including one called propionic acid academia, who cannot metabolize this SCFA.   There are much higher rates of these disorders than was recognized in the past.  Dr. MacFabe references 2 papers from which he derived this information, one of which was published back in 2002:  a study of 130,000 infants born in Japan found that, there was “…a frequency of patients with propionic academia more than ten times higher than reported.”  There are mild forms of this illness which are much harder to detect.  Why is this significant for the ASD population?  Firstly, the overlap in symptoms between those with ASD and those with this inheritable disorder are remarkable:  “…regressive cognitive impairment, seizure, and movement disorder, often in the context of GI symptoms.”  Secondly, the difficulty of diagnosing PPA toxicity applies to both populations: “Propionic acid’s habit of ‘hiding’ inside cells makes it difficult to detect, even in patients with a metabolic crisis.”  It does make you wonder if PPA toxicity in the autism population (or even in the non-autism population!) is not WAY under-diagnosed.

4.  Back in May 2018, I wrote a post about Desulfovibrio bacteria in autism.  In today’s paper, Dr. MacFabe mentions this and it’s worth bringing up here again to remind everyone that we are talking about a very complex dysbiosis:  “Ongoing work by Dr. Finegold has identified further novel bacterial populations (ie. Desulfovibrio), which in addition to making propionic acid also produce hydrogen sulphide to damage mitochondrial function, thus potentiating propionic acid’s effects.”  Science has barely scraped the surface of how these citizens of the human biome interact and affect each other.

5.  We know that those on the autism spectrum have issues with mitochondria, the powerhouse of the cell.  The cells are consistently “underpowered,” meaning that they work in a suboptimal way.  As you can imagine, this has a major effect on the functioning of the body.  PPA “…puts a ‘wrench’ in mitochondria…” by affecting the metabolism of carnitine, a substance that is critical in energy production in the mitochondria.

6.  On the bright side (if there is a bright side in all this), there are some things that may help. Firstly, since PPA is produced in large part by certain members of the Clostridia family of bacteria, diets that reduce carbohydrate consumption may work as well as they do by reducing substrate for these bacteria.  This may well explain the incredible efficacy of the Specific Carbohydrate Diet in autism.[iv]  Giving carnitine and  vitamin B12 to “…improve fatty acid metabolism or, in the future, eradicating/reducing ASD-associated propionic acid-producing GI-tract bacteria” may make a difference as well. (Don’t forget too, that back in September 2019, during the first Biome Buzz Propionic Acid Week, I described research showing that the old diabetes medication, pioglitazone (Actos), may treat the negative effects of excess PPA.  I’m waiting for follow up studies on that.

I want to conclude with a wonderful sentiment expressed by Dr. MacFabe.  In my personal opinion, the fact that he adheres to this belief is what makes him such an extraordinary researcher:

“The people who have taught me the most are the parents who refuse to believe what they were told –  that their child’s regression and associated symptoms were all in their imagination….I must stress that we absolutely need the scientific rigor of asking the proper questions and designing the proper experiments and controls, but we also need the art of medicine and the ability to actually observe and listen to patients.  The spark for understanding autism and the GI tract could come only from seeing the patients as an individual, not as a collection of symptoms, and seeing some of the assets as well as the disabilities in this condition.  Deducing whether clinical expertise or science is more important in addressing enormous problems like ASD is like asking which half of a pair of scissors are more important.  We need both.”

Truer words have never been spoken.


[i] Lobzhanidze, G, Lordkipanidze, T, Zhvania, M, Japaridze, N, MacFabe, DF, Pochkidze, N, Gasimov, E, Rzaev, F. Effect of propionic acid on the morphology of the amygdala in adolescent male rats and their behavior. Micron. 2019.  doi: 10.1016/j.micron

[ii] MacFabe, D. Autism: Metabolism, Mitochondria, and the Microbiome.  Global Advances in Health and Medicine. 2013;2(6):52-66.



New Research into the Negative Side of Short-Chain Fatty Acids: Too Much of a Good Thing

I have spent a fair bit of virtual ink over the years talking about both the positives and the negatives of short chain fatty acids (SCFAs), mentioning that indeed, you really can have too much of a good thing.  For example, as healthy as it is to stay well hydrated, you can actually kill yourself by drinking too much water.  (This is called water intoxication, and by diluting the blood too much, you can dilute the levels of electrolytes (like sodium), which leads to swelling of cells and disruption of brain function.)  When it comes to health, just-the-right-amount is key.

Gut bacteria produce SCFAs upon their consumption of polysaccharides (fibers) and in turn, SCFAs feed other good bacteria, on top of having many direct positive effects upon the human body.  Science has shown  that some diseases (Parkinson’s, for example), are associated with low levels of SCFAs.

SCFAs are really complicated:  it turns out that not only do you need just the right amount, but you also need just the right amount at just the right time, especially when it comes to brain development. I’ll come back to this in a moment.

As I mentioned above, I have actually talked on this blog about the dangers of excessive levels of SCFAs, especially propionic acid (PPA or propionate), excess levels of which are now generally accepted as one of the likely causes of autism in our current epidemic. (Read about that here. )  I first mentioned this concept several years ago, not long after I started this blog, in a post about Dr. Derrick MacFabe, a Canadian neuroscientist, whom I first saw speak at a conference many years ago – and whose research I believed from that first moment to be among the most critical ever done in the field of autism.    Dr. MacFabe has spent nearly 2 decades now looking at the neurotoxic effects of excess levels of propionic and his findings have been continually ground-breaking.

In that first post, I described a paper he published back in 2012:  “According to Dr. MacFabe, PPA can readily enter the blood stream from the gut.  In his rat models, in the short term, small amounts immediately produce hyperactivity, repetitive behaviors and social impairment.  Repeated administration of PPA over time, increases the severity and effects, which suggests ‘…that PPA can exert permanent effects on brain and behavior.’”[i]

My regular readers may remember that Dr. MacFabe actually contacted me not long after that, and I had a conversation with him just this past week about some of his more recent research.  Over the next few months, I am going to delve in depth into both his work and other research into PPA as it is a topic of major concern for all of us, in regards to our health and the health of our children.

While excess PPA is now implicated in the development of autism (so all you prospective parents, new parents, and parents of children already on the spectrum should pay particular attention to these posts), PPA also looks like a likely suspect in many other chronic illnesses of our modern era, including potentially obesity.  This past September (during what I dubbed the Buzz’s first official Propionic Acid Week), I discussed research out of Harvard which showed that PPA  adversely affects metabolism by raising blood sugar levels.[ii]  From that post:  “The scientists looked at both animal and humans, and the latter were involved in a double-blind trial with 14 healthy volunteers. The researchers discovered that PPA stimulates the liver to produce more glucose by increasing levels of the hormones, glucagon and fatty acid-binding protein 4, which signal the liver to release sugar into the blood…In the humans in the study, this continued release of unneeded blood sugar led to insulin resistance:  their bodies no longer responded optimally to insulin, which lowers blood sugar levels.”

Remember:  PPA is not just produced by gut bacteria but is ubiquitous in foods commonly eaten in industrialized societies, including cheeses, baked goods and artificial flavors. So between those exogenous sources and what is produced in the gut from potentially altered bacterial composition, raised levels of PPA may be becoming one of the big health dangers of modern times. Fetuses, who are exposed to maternally derived PPA through the placenta are especially at risk during this critical period of brain development.  PPA easily passes through the placenta and the blood-brain barrier.

A very recent paper of Dr. MacFabe and colleagues demonstrates that even physiological levels (normal amounts found in humans) of SCFAs, including PPA, may affect brain development.[iii]  In vitro experimentation done on human neural progenitor cells (hNPCs, which are stem cells that develop into either neuron cells or glial cells (support cells for the neurons)) shows that exposure to normal, physiologic doses of SCFAs (acetate, propionate, butyrate), “…increased the growth rate of hNPCs significantly…,” while “…high levels…of SCFAs had toxic effects on hNPCs.”  As the authors write, “The SCFAs present in the human body fluid derive mainly from bacterial carbohydrate fermentation in the gut.  However, they are also present naturally in dairy, fermented foods, maternal milk and are added as antifungal agents in refined carbohydrates and dairy.  The amounts and composition of gut short-chain fatty acids are dependent not only on bacterial species but also on type of substrate (increased propionate with wheat and dairy, increased butyrate with inulin-containing diets).  Their effects are remarkably tissue and dose dependent.”  And timing dependent, too.  If babies are exposed to high levels in utero, brain development is potentially affected.

On the topic of altering the brain: Dr. MacFabe and other scientists published another 2019 study that showed that in rats, “…the data indicate that even low dose of propionic acid produces in adolescent rodents immediate changes in social behavior, and structural/ultrastructural alterations in amygdala.”[iv]  The amygdala is the area of the brain responsible for the perception of emotion (anger, fear, pleasure, etc.) and for controlling aggression.

The take-away message:  in the right amounts at the right times, SCFAs, including propionic acid, are crucially important for good health.  On the other hand, excessive amounts, from altered gut flora and dietary intake (and in fetuses, maternal exposure) appear to have profoundly negative effects on brain development and human health.

In one of those coincidences you all know I love, I happen to notice a market research report just released over this past weekend:  Sodium Propionate Market Will Generate Massive Revenue in Coming  Years.[v]  I’ll end this post then on an extremely disturbing note: “Rising demand for food preservatives in the food industry is the major driving factor for the global sodium propionate market. Sodium propionate prevents the growth of mold and some bacteria, thereby prolonging the shelf life of packaged baked goods. According to the Code of Federal Regulations, sodium propionate is generally recognized as safe when used as a food additive. It is also used to prevent mold growth in packaged and processed cheese products.”

(For more information on Dr. MacFabe’s work, check out his website, The Kilee Patchell-Evans Autism Research Group (KPEARG))


[i] MACFABE, Derrick F.. Short-chain fatty acid fermentation products of the gut microbiome: implications in autism spectrum disorders. Microbial Ecology in Health and Disease, [S.l.], v. 23, aug. 2012. ISSN 1651-2235.

[ii] Tirosh, A, et. al.  The short-chain fatty acid propionate increases glucagon and FABP4 production, impairing insulin action in mice and humans.  Science Translational Medicine. 2019:11(489).  DOI: 10.1126/scitranslmed.aav0120

[iii] Yang, LL, Millischer, V, Rodin, S, MacFabe, D, Villaescusa, JC, Lavebratt, C. Enteric short-chain fatty acids promote proliferation of human neural progenitor cells.  Journal of Neurochemistry. 2019.  doi: 10.1111/jnc.14928

[iv] Lobzhanidze, G, Lordkipanidze, T, Zhvania, M, Japaridze, N, MacFabe, DF, Pochkidze, N, Gasimov, E, Rzaev, F. Effect of propionic acid on the morphology of the amygdala in adolescent male rats and their behavior. Micron. 2019.  doi: 10.1016/j.micron


2019: A Top Post Roundup

As promised, I am writing my annual review of top stories from the previous year but this time, I’m not picking my favorites, I’m picking yours. I thought it would be fun to see which of my posts got the top views for the year.

So, for your enjoyment, here are the top 5:

At number 5:  February 14th:  Your Blood Type and Your Microbiome

This was one of my personal favorite posts of the year as the information in was entirely new to me:  the antigens in your blood that designate it type A, B, AB, or O (which are carbohydrates that evokes an immune response), are also expressed on platelets, immune cells, bodily excretions, tissues, etc.  These antigens, as it turns out, have a major effect on the composition of the gut flora.  One of the studies  I describe in this post  states: “Our novel finding indicates that the ABO blood group is one of the genetically determined host factors modulating he composition of the human intestinal microbiota, thus enabling new applications in the field of personalized nutrition and medicine.”  This may go a long way toward explaining the individual variations in gut flora composition found even among health individuals.

At number 4:   April 18: Evolutionary Mismatch, The Human Biome…and a Bit More on Obesity

This post provides strong support for the biome depletion paradigm (formerly known as the hygiene hypothesis).  It’s about how our  modern lifestyles have led to massive and abrupt changes to our biomes, leading to our current epidemic of inflammatory diseases and obesity.  For example, our western diets – high in unhealthy fats and sugar – have led to a global disturbance of the gut flora.  The main paper I focus on in this post concludes, “Public health efforts to counter negative effects of the Western diet, support breastfeeding, and assure access to high-fiber, low-sugar, and low-fat foods may have an outsized effect on seemingly unrelated widespread diseases such as diabetes, autism, and childhood obesity.”

At number 3:  April 11:  Spondylitis and Microbiome Dysbiosis: Both Bacterial and Fungal

I referred to this old post just this past Tuesday.  I was really surprised at the enormous viewership this April post received.  It describes a small study on 22 people with Spondylitis and the significant differences found between their microbiomes and those of healthy controls.  The biggest surprise to me was that it was the degree of mycobiome (yeast) dysbiosis that correlated to disease severity and the level of inflammation in the body, more than the dysbiotic bacteria.  I’m not sure that finding has yet been replicated, but certainly – as I talked about on Tuesday – the altered bacterial microbiome found in those with the disease now has been.

At number 2:  August 29: The Bacterial Microbiome and Immune Response to Vaccines

If you remember, I was really nervous about writing this one, but it turned out to be a non-issue. Reader response was very balanced and you all seemed to find this as scientifically interesting as me.  As I wrote last August, “When you consider that at least 70% of your immune system is in your gut, and the crucial role we now know the gut flora plays in immunity, it makes perfectly logical sense that there may be a connection, especially considering the variability in immune responses to vaccines. Some people require only 1 to achieve a lifetime of immunity while other people need to be re-inoculated multiple times, while still others never gain immunity at all.  Why that is, no one knows, but scientists are starting to suspect that gut bacterial variability is a key factor.”

You all know how much I love coincidences!  Well, what was crazy about this post was that a week later, big news came out of Stamford University that was all over the press:  “People’s response to flu vaccine influenced by gut microbes:  Decimating levels of intestinal bacteria with antibiotics reduced the immune system’s responsiveness to a seasonal influenza vaccination, a Stanford-led study found.”[i]

I am particularly glad that this is a growing area of research as its importance cannot be overstated.

At number 1, most read post this past year:  June 13:  Zeoring in on an Inflammatory Bowel Disease Culprit

Researchers at Harvard University have narrowed down the bacterial culprits in IBD and one of the prime suspects is a little-known species that ordinarily comprises less than 1% of our flora:  Ruminococcus gnavus. During IBD flare-ups though, this little devil can jump to 50% of the bacteria in the gut and it produces a polysaccharide that causes huge increases in inflammation in the body.  No one yet knows why or how this bacteria suddenly blooms, but as their findings were so significant, research is ongoing.  Hopefully I’ll be able to report more on this story in 2020.



Alterations in the Bacterial Microbiome Associated with Ankylosing Spondylitis: A Larger and Confirming Study

My long time readers know that at this time of year, I typically review my favorite stories from the prior year but I was so darn busy this holiday season, I simply did not have the time this past week.  I will try to do so as a throw-back Thursday present this week.

In the meantime, I know that one of the most read posts of 2019 was the one I wrote on April 11th about a small study that showed that those with Ankylosing spondylitis (AS) have distinct bacterial and fungal microbiome differences from healthy controls:  “The study included 22 patients with  AS and 16 healthy controls (HC).  They found major differences in the bacterial microbiomes between the two groups, including a ‘significant increase’ in diversity in the AS group that included a nearly 3-fold increase in Proteobacteria and a decrease in Bacteroidetes species, including Prevotella.” The researchers also noted that the fungal microbiome was depleted in those with AS, in relation to the bacterial:  that is, the ratio of bacteria to fungi is off.  And the severity of disease completely coincided with the degree of alteration to the bacterial microbiome.

That study though was on only 22 patients.  Obviously, the results needed to be replicated with a larger cohort, and I am happy to announce that a new study has done just that.  Researchers at a Swedish University evaluated the fecal microbiota in 150 patients with AS, and compared them to patients with ulcerative colitis and healthy controls over a 5 year period of time.  Like the earlier, smaller study, they also assessed inflammation levels.[i]

Sure enough, “…the fecal microbiota in AS was characterized by a higher abundance of Proteobacteria, Enterobacteriaceae, Bacilli and Streptococcus species, as well as Actinobacteria, but lower abundance of Bacteroides and Lachnospiraceae.”[ii]  Notice that these results somewhat parallel the earlier smaller study:  a higher level of Proteobacteria, a decrease in Bacteroidetes.

One other interesting finding in this study:  the scientists also measured calprotectin, a marker for intestinal inflammation.  Those individuals with dysbiosis, including lower levels of anti-inflammatory bacteria and higher levels of Streptococcus, had higher levels of calprotectin in their feces.  As 87% of those with AS in the study suffered from dysbiosis, the researchers conclude that intestinal inflammation is common in the disease.

Which leads me to a few points that I never knew about AS.  Yes, I knew that gut issues are commonly found alongside AS, but here are a few facts I did NOT know:

  1. “AS is characterized by microscopic intestinal inflammation, which has been demonstrated in 40–60% of the patients.”
  2. “AS patients also have an increased risk of developing IBD, especially CD.”
  3. “Interleukin (IL) 23 and IL17, which are key cytokines in AS, are produced in the inflamed gut, both in AS and in IBD.”

What to do about it, no one yet knows, just as is the case with all these inflammatory illnesses that seem to originate in the gut.  I did point out, in my first ever post about AS, that in one 2007 study, patients with AS were given Moxifloxacin, an antibiotic and that this “…resulted in a significant and sustained improvement…”  on top of reducing inflammation.  I haven’t found any kind of follow up on that though.

Spondyloartropathies are incredibly common, as I’ve pointed out before – way more common than Parkison’s, MS, and other much better known diseases.  As so many of you seem interested in this topic, I most certainly I will continue to watch out for any new information.


[i] Klingberg, E, et. al. A distinct gut microbiota composition in patients with ankylosing spondylitis is associated with increased fecal calprotectin.  Arthritis Research & Therapy. 2019.  doi:10.1186/s13075-019-2018-4.


Migraines and the Bacterial Microbiome: Are Probiotics a Solution?

For those of you who suffer migraines (or know someone who does): I don’t know about you, but I’ve been waiting for an article relating those damn headaches to the gut biome.  (You knew it had to be coming…)  Considering that migraine is the 3rd most common illness in the world[i], I reckon many of you will be really interested in this. .

In 2016, research was published which showed that migraine sufferers have more bacteria (especially in the mouth) which produced the gas, nitric oxide, a known migraine trigger.  This was an association only – not proof – but it was a great first step in that it potentially explained why some people are more susceptible to the headaches and also, why certain foods (like chocolate and wine) may be problematic.[ii]

It turns out that when bacteria in the GI tract break down nitrates (such as those found in many foods, including some kinds of hotdogs), the nitrates are converted to nitric oxide which dilates blood vessels.  (It is already known that medications which contain nitrates (which are given for angina or heart failure) trigger migraines.)

This most recent study involved examining the bacteria from oral (172) and fecal (1996) samples from migraine sufferers.  In both types of samples, the bacteria that break down nitrates were at slightly higher levels than in the normal controls.  The researchers next step is to look at how foods affect blood levels of nitric oxide.

Some good news:  another 2019 study[iii] was conducted on 100 people with migraines (50 with episodic, 50 with chronic); half received a placebo, half received a probiotic.  The results were incredibly significant, and showed that those with episodic migraine, who received the 14 strain probiotic (which contained Bifidobacterium, Lactobacillus and Bacillus subtilis) for 10 weeks had dramatic improvement:  “After a 10-week intervention, among episodic migraineurs the mean frequency of migraine attacks significantly reduced in the probiotic group compare to the placebo group…A significant reduction was also evident in the migraine severity…Episodic migraineurs who received the probiotic also showed significant reduction in abortive drug usage per…while there was no significant changes within the placebo group.”

Those with chronic migraines, who took the probiotic for 8 weeks, had equally dramatic improvement compared to controls:

“The frequency of attack fell by 45% among those with chronic migraine and by 40% among those with episodic migraine. For a reduction in migraine intensity, the corresponding figures were 31% and 29%.”[ii]

For those interested, the probiotic the experimental group was given was 2 capsules daily of Bio-Kult.

Now that I know a relationship between the gut biome and migraines is likely, I will be sure to watch out for ongoing research to share with you all.




[iii] Jahromi, SR, et al. The effects of a multispecies probiotic supplement on inflammatory markers and episodic and chronic migraine characteristics: A randomized double-blind controlled trial.Cephalalgia 2019;39(7)

High-Fat Meals, the Gut’s Endocrine System and Bacteria

As you know, there are certain topics that are of particular interest to me including autism; Parkinson’s; -omes, other than just the bacterial microbiome; neglected illnesses like chronic fatigue and fibromyalgia; obesity; etc.; and of course, diet and its relationship to the organisms of the biome and health.  A short post today about a research out of Duke University, looking at how a high fat diet affects the gut and its contents.[i]

One thing I haven’t had much opportunity to write about is the endocrine (hormone) system of digestive system, simply because I really haven’t seen much about it and its interaction with the gut bacteria.  The scientists noticed, in zebrafish, that these endocrine cells (in the gut, they are referred to as entereoendocrine cells and they are found in the mucosal lining), which normally send signals to brain and body by releasing hormones, shut down for a number of hours after a high fat meal.  Ordinarily, the hormones they produce tell the body about gut movement, fullness, digestion, nutrient absorption, insulin sensitivity and energy shortage.  However, after encountering high fat food, they shut down for several hours – and no one has a clue why.

There are several possibilities.  A possible negative view: one of the authors states, “Since enteroendocrine cells are key players in digestion, the feeling of being full and subsequent feeding behavior, this silencing may be a mechanism that somehow causes people eating a high-fat diet to eat even more….If this happens every time we eat an unhealthy, high-fat meal, it might cause a change in insulin signaling, which could, in turn contribute to the development of insulin resistance and Type 2 diabetes.”

Inside cells are multiple organelles (their version of organs), including one called the endoplasmic reticulum, in which new proteins (like neurotransmitters and hormones) are synthesized.  This organelle appears to undergo stress when the cells are confronted with a high-fat meal, and become overstimulated and then exhausted.  For a time then, the cells are silenced – they cannot communicate with the rest of the body at all.

What’s even more interesting is that in germ-free fish, this does not happen.  In fact, the researchers were able to narrow down and isolate the specific bacteria that causes this effect:  Acinetobacter.  This is a really rare (les than .1% of the gut bacteria), but after a high-fat meal, they increase 100-fold.

At this point, the scientists don’t even know yet if it’s a good or a bad thing.  It’s possible that it’s a “maladaptive response to high-fat foods” ultimately leading to metabolic disorders.  On the other hand, it is “…also possible that the silencing is a beneficial adaptation to protect the animal from over-stimulation of the gut cells.”

Considering the incredibly dramatic increase in metabolic disorders and obesity in the last 3 decades, figuring out this kind of thing is incredibly important.  I’ll watch for updates.



Using Yeasts to Fight Yeasts

I like it when I can report on -omes other than the bacterial microbiome, especially when the research is about using a natural and benign substance to treat a serious pathogen in fighting disease.  In this case, researchers in the USA and India have found a way of treating the life threatening, often fatal, infection, Candida auris, a yeast which is resistant to treatment by antifungal medications.[i]  C. auris infections, which are rife in hospitals and a major threat to people with weakened immune systems, was recently listed as an urgent threat by the USA’s Center for Disease Control.

A relation of the much more commonly known Candida albicans – which is the leading cause of fungal infections acquired in the hospital – C. auris, is virtually impossible to treat.  It typically affects people who are immune-compromised or who have had implanted medical devices.  Candida yeasts can penetrate the tissue of the gastrointestinal tract and make their way into other internal organs, causing systemic infection, including the deadly blood infections seen with C. auris.  One of the reasons it is so resistant to treatment is that it can form biofilms – complex matrices which protect the species inside.  I’ve written about the threat of biofilms before here and here.  (Think of the film on your teeth before brushing.)

It turns out that two food derived yeasts, Issatchenkia occidentalis, which grows on foods like fruit, and common Baker’s yeast, Saccharomyces cerevisiae, can actually inhibit adhesion of these pathogenic yeasts to epithelial tissue (the lining of the gut) and prevent the formation of biofilms.  When applied to non-biological surfaces, such as you’d find in medically implanted devices, these yeasts were able to reduce C. auris’ ability to adhere to these surfaces by 53% and to form biofilms by 70%. They also inhibited the pathogenic yeasts’ ability to evade the immune system.

More than that, the scientists found that these yeasts were effective against adhesion to human epithelial cells and, when given to C.elegans (the worm I’ve mentioned many times before that is frequently used in experiments to mimic the human intestinal tract – for example, here) infected with C. auris, the worms lived longer.  The pathogenic yeasts were less active when treated with the two beneficial ones.  Interestingly, extracts from the food-derived yeasts also worked, which suggests that it is, at least in part, metabolites of the yeast which have this beneficial effect.

The fact that these probiotic yeasts successfully treat infections with pathogenic ones did not surprise me.  It’s long been known that Sacchromyces boulardii is a probiotic yeast which does so.  It is considered a safe treatment for many ailments, even in children.  According to WebMD:  “Saccharomyces boulardii is most commonly used for treating and preventing diarrhea, including infectious types such as rotaviral diarrhea in children, diarrhea caused by gastrointestinal (GI) take-over (overgrowth) by ‘bad’ bacteria in adults, traveler’s diarrhea, and diarrhea associated with tube feedings. It is also used to prevent and treat diarrhea caused by the use of antibiotics.”[ii]  I myself have used it very successfully for years with both my family and nutrition clients.  The study I am writing about today, however, had results which did shock me:  “The probiotic properties of these novel yeasts are better than or comparable to those of the commercially available probiotic yeast Saccharomyces boulardii, which was used as a reference strain throughout this study. These results indicate that yeasts derived from food sources could serve as an effective alternative to antifungal therapy against emerging pathogenic Candida species.”

I will not be surprised if a commercial supplement with one or both of these species hits the market very soon.  Baker’s yeast is obviously already commercially available, although there’s no standardized amount for treatment as yet.  And of course, we don’t know for sure if it will treat these pathogenic yeast infections in humans.  But without any good alternatives, we can only hope those studies are carried out quickly:  “To meet the growing need for treatment options for biofilm-associated clinical complications, these food-derived yeasts represent a safe and attractive alternative to conventional treatment for Candida infections.”


[i] Kunyeit, L, Kurrey, NK, Anu-Appaiah, KA, Rao, RP. Probiotic yeasts inhibit virulence of non-albicans Candida species. MBio. 2019.  10:e02307-19.


Another Promising Treatment for Leaky Gut?

Researchers at Wake Forest School of Medicine (in North Carolina), have discovered that using inactivated (dead via the application of heat) Lactobacillus paracasei (derived from humans) appears to have a remarkably beneficial effect in an animal model of leaky gut, thereby reducing inflammation.[i]  In doing so, they significantly extended the lives of C. elegans, a roundworm frequently used in laboratory experiments. They then tested the inactivated bacteria on elderly mice, finding that it “…helped prevent the development of metabolic dysfunctions that a high fat diet causes.  It also improved gut permeability, making leakages less likely, reducing inflammation, and boosting cognitive function…”[ii]

If you a regular reader of this blog, you will remember that leaky gut is a major factor in inflammatory diseases.  For those unfamiliar, this is a condition in which inflammation leads to the mucus lining of the intestines becoming permeable, allowing bacteria, toxin metabolites of bacteria and yeast, undigested food, etc. to make their way into the blood stream.  Leaky gut is also a natural result of the aging process: the gut becomes increasingly permeable and while a result of inflammation, it is also a major cause, increasing the risks of developing illnesses like obesity, diabetes, cardiovascular illness, Alzheimer’s and other cognitive problems, and many more.

 The scientists discovered that it is a component of this bacteria’s cell wall (lipoteichoic acid) which led to the health improvements in the animals. This is not the first time an inactivated bacterial strain has been shown to have major health benefits.  Many of you may remember that back in July of this year for one, I wrote about using inactivated Akkermansia to treat the development of fat (i.e. obesity) and insulin resistance. In that case, a 3 month long, double-blind, randomized trial in human showed that heat-killed Akkermansia “…helps to limit the increase of different cardiovascular risk factors in subjects who are overweight and obese.”  Again, the researchers believe that it is a component of the cell wall which has the beneficial effect.

This story gets even more interesting.  The Wake Forest scientists discovered that this inactivated species “…significantly increases mucin production, and proportionately, the abundance of mucin-degrading bacteria Akkermansia muciniphila also increases.”  (Mucin is a component of mucus.  Thus, increasing the food supply leads to an increase on probiotic species that thrive on that substance.) Likely then, the L. paracasei is exerting its beneficial effects both directly (i.e. it’s cell wall) and indirectly, by boosting levels of other beneficial probiotic species.

Considering the importance of finding effective treatments for leaky gut, this is very promising.  This has obviously not as yet been tested in humans but the lead researcher has applied for a patent for the product.  I’ll keep an eye out for any further news.


[i] Wang, et. al. Lipoteichoic acid from the cell wall of a heat killed Lactobacillus paracasei D3-5 ameliorates aging-related leaky gut, inflammation and improves physical and cognitive functions: from C. elegans to mice. GeroScience. 2019.