A Probiotic to Reduce Physiological Effects of Stress and Anxiety: Clinical Trial Results

Today’s good news is brought to you by researchers in Finland and Germany who are looking for natural means of alleviating the development of mood and stress-related disorders.[i]  I don’t know about the rest of you, but I sure as hell could use some improvement in my current stress levels!

The opening paragraph of the paper points out that while short-term stress is a “beneficial adaptation” to normal stressors, chronic stress is a whole different story:  it is a “…major risk factor for the development of a wide range of physical and mental disorders.”  How about this for a staggering statistic?  According to the American Psychological Association, as of 2018, nearly 75% of adults in the country experience at least 1 physical or emotional stress in the last month, and about 50% of people report stress levels higher than what is regarded as acceptable.  And that was before COVID!

The authors assert that the evidence supporting the connection between the gut  microbiota and health is “overwhelming.”  Lacticaseibacillus paracasei, formerly known as Lactobacillus paracasei, has shown promise in previous studies in preventing chronic stress-associated behaviors from developing.

This double-blind, placebo-controlled clinical trial was conducted on 117  healthy adults, aged 18 through 45, who were broken up into groups, one control, one treatment.  The experimental group received 1.75 billion (low potency – I am not sure why as there’s no explanation given) units of a very specific strain of the probiotic Lacticaseibacillus paracasei  (Lpc-37) one time per day for 5 weeks.  The primary goal was to see if the probiotic affected heart rate in response to a stress test but they also looked at different biomarkers and self-reported symptoms.

The results are interesting.  LPC-37 reduced heart rate in those with low levels of chronic stress but strangely, it was significantly higher in those with high levels of chronic stress.  In the discussion section, they authors state that they cannot as yet explain the phenomenon. The probiotic also had no effect on salivary cortisol level, which is a marker for stress and actually, the probiotic had little effect in many of the parameters being tested but in looking at certain subgroups, clinically significant differences were noted.  For example,  during the stress testing, blood pressure in the women in the experimental group increased markedly less than those in the placebo arm.  Why?  No one knows yet.   Two more notes of interest on the results:  the probiotic did significantly reduce the “perceived exhaustion/fatigue” in response to the stress test in those with low levels of chronic stress.  This may be related to the reduced heart rate also seen in this group.  Also, the Lpc-37 significantly decreased blood pressure (both diastolic and systolic) in those with high levels of stress and in women.  In previous research, which I have covered (see here), this probiotic has been shown to decrease blood pressure after 4 weeks of treatment.

So even more good news on the targeted probiotic front.  It really does feel like some progress is being made.

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[i] Patterson, E, Griffin, SM, Ibarra, A, Ellsiepen, E, Hellhammer, J. Lacticaseibacillus paracasei Lpc-37 improves psychological and physiological markers of stress and anxiety in healthy adults: a randomized, double-blind, placebo-controlled and parallel clinical trial (the Sisu study). Neurobiology of Stress. 2020:13.   https://doi.org/10.1016/j.ynstr.2020.100277

Progress In Finding Targeted Bacteria to Potentially Treat a Variety of Issues

Again, trying to stay positive this month, for the sake of all our mental health:  the results of a recent large, international dietary study including Harvard physicians confirm yet again that a diet rich in plant-based foods is linked with a lower risk of developing obesity, type 2 diabetes and cardiovascular disease.[i]  The researchers looked at the composition of individuals’ microbiota as well as long-term dietary information and metabolic and cardiovascular blood markers.  They found “strong evidence” that the make-up of the microbiota is linked with these disorders and in fact, are much more important to the risk of their development than are genetics!

The study included 1098 participants from both the UK and the US who were a part of the PREDICT trial (Personalised Responses to Dietary composition Trial).  They found  “…many significant associations between microbes and specific nutrients, foods, food groups and general dietary indices, which were driven especially by the presence and diversity of healthy and plant-based foods.”  They also found microbiome-based biomarkers for obesity, cardiovascular disease and issues with glucose tolerance.  A microbiome rich in Prevotella copri and Blastocystis species was associated with keeping blood sugar low after eating.  (I have written about P. copri many times on this blog.  If you’re interested in learning more about it, look here first.  In general, it is a probiotic species but like so many other bacterial species, it has its bad side too.)

What’s particularly amazing is that their results were so consistent throughout this incredibly varied population that they believe that microbiome data can be used to determine the risk of cardiovascular disease in people, even before they have symptoms!  A personalized diet can then be created to reduce the risk of developing disease.  Says one of the senior researchers, from Harvard:  “”This study demonstrates a clear association between specific microbial species in the gut, certain foods, and risk of some common diseases…We hope to be able to use this information to help people avoid serious health problems by changing their diet to personalize their gut microbiome.”[ii]

And more good news:  other researchers, at MIT and Harvard, are working on isolating what gut bacteria influence cholesterol levels.[iii]  They found bacteria that produces a substance called ismA, which breaks cholesterol down and people with it have lower blood and fecal cholesterol levels:  “By introducing cholesterol-metabolizing gut bacteria into human gut microbiotas, or by increasing their abundance with prebiotics, it may be possible to achieve targeted effects on host serum cholesterol, a strategy that has already shown promise in influencing other areas of human metabolism.”  The bacteria involved were previously uncharacterized and have yet to actually be cultured in a lab, which is why it’s taken so long to find them and track down this particular pathway.  So, while it will be awhile before these bacteria hit the market in a probiotic product, at least we now know what bacteria are needed…which is a huge step forward.

So all in all, some good news on the “targeted” probiotic front!

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[i] Microbiome connections with host metabolism and habitual diet from 1,098 deeply phenotyped individuals, Nature Medicine (2021). DOI: 10.1038/s41591-020-01183-8 , www.nature.com/articles/s41591-020-01183-8

[ii] https://medicalxpress.com/news/2021-01-landmark-human-reveal-strong-links.html

[iii] Kenny, DJ, et. al. Cholesterol metabolism by uncultured human gut bacteria influences host cholesterol levels.  Cell Host & Microbe. 2020. 28(2):245-257. https://doi.org/10.1016/j.chom.2020.05.013

Type 2 Diabetes and Obesity: Specific Probiotic Species to Treat????!!!

In my efforts to start off this New Year on a positive note, I am trying to only share good news this week on the Biome Buzz’ Facebook page, and to write only upbeat posts.  I refuse to let 2021 be a repeat of last year!  On that note, I thought this new research out of Oregon State University was absolutely amazing and potentially a huge step forward in finding a natural way to treat obesity and type 2 diabetes.  (Can you believe that metabolic diseases now affect about 23% of adults (18 and over) in the USA?![i]

These researchers theorized that individual members of the gut microbiota, altered by diet, may have a profound effect upon insulin sensitivity and thus, blood glucose levels.[ii]  They used a new data-driven approach called transkingdom network analysis to look at host-microbe interactions while the host consumes a traditional Western diet (high in sugar, unhealthy fats, etc.)  This allowed them the ability to see what individual species might be responsible for metabolic changes in the way a person’s body handles glucose.

They found 4 specific species had major effect:  Lactobacillus johnsonii and Lactobacillus gasseri were “improvers” of glucose metabolism and Romboutsia ilealis and Ruminococcus gnavus were “worseners.”  One of the lead researchers points out that, “The overall indication is that individual types of microbes and/or their interactions, and not community-level dysbiosis, are key players in type 2 diabetes.”[iii]

To test this analysis, the scientists fed mice a Western diet and then gave them either improver probiotics or the worsener species.  Sure enough, the former led to improvements in how the animals metabolized glucose and lipids, and had lower BMIs (body mass index) than the control mice, who did not receive any supplemental bacterial species.  The researchers found correlations in the medical literature from earlier studies done on humans:  more of the improvers meant lower BMIs in people, while more of the worseners meant a higher BMI.  In fact, Romboutsia ilealis was found in more than 80% of people with obesity, which suggests that it may be a pathobiont in those who are overweight. You may remember, from my previous post on this subject, that a pathobiont is a species which is ordinarily a normal commensal but under certain circumstances, it may become a pathogen and cause disease.

To sum up, their work “…provides further support for the hypothesis that variations in abundance of a few key (but not keystone) microbes rather than overall changes of the microbial community might explain microbiota-related damage caused by western diet in T2D [type 2 diabetes].”  Both :  Lactobacillus johnsonii and Lactobacillus gasseri are decreased by consumption of a Western-type diet, and both improve system glucose control.  Thus, they conclude, that it looks promising that type 2 diabetes may be treated by simple supplementation of a targeted probiotic therapy, as opposed to needing to restore the entire gut microbiota.

I have no idea if these brands are any good, but just FYI, it appears you can buy Lactobacillus gasseri  here L. johnsonii  is available here but it is very low potency.  If anyone gives this a shot, I know I would love to hear about your experience!

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[i] https://www.heart.org/en/health-topics/metabolic-syndrome/about-metabolic-syndrome

[ii] Rodrigues, R.R., et al. (2021) Transkingdom interactions between Lactobacilli and hepatic mitochondria attenuate western diet-induced diabetes. Nature Communications. doi.org/10.1038/s41467-020-20313-x.

[iii] https://www.news-medical.net/news/20210104/Few-organisms-in-the-gut-microbiome-found-to-play-a-key-role-in-type-2-diabetes.aspx

FMT and Psychiatric Issues: What We Know Now

My long-time readers may remember my tirade from almost 4 years ago re:  the FDA denying patients the right to use natural treatments like helminths and fecal microbiota transplant (FMT) as they see fit.  I had been (and still am) incensed after reading a 2014 article in a legal journal, “Of Poops and Parasites: Unethical FDA Overregulation.”[i] From that article:  “Thousands of Americans suffer from illnesses untreatable by presently available therapies. And while unapproved treatments may exist and even be known to be efficacious, the FDA persists in making them unavailable (ex. clinical trials are not finished), leaving no choice for the doctor, and no choice for the patient.”  Currently, FMT is only permitted by the FDA for the treatment of Clostridium difficile infection, even if a doctor wants it as an option for treating patients.

That post came to mind this weekend when I read a new review article in BMC Psychiatry on the use of FMT to treat psychiatric disorders. [ii]   It especially hit home because my own son, Alex, who if you’ll remember, is diagnosed with autism, has been suffering horribly with debilitating anxiety the last year.  And in my work teaching nonspeaking individuals with autism how to communicate via spelling, I see daily their suffering from OCD and anxiety.  It breaks my heart.  (You can read more about autism and anxiety here.)

These researchers culled through the medical literature and found 21 clinical studies that met their inclusion criteria.  Spoiler alert – I’m giving you the conclusion first:  there is “strong evidence” that psychiatric illnesses like anxiety and depressive disorders can be treated through this non-invasive method, with negligible side effects.

Here are some highlights from the article:

  1. In the background section, the authors point out that the gut bacteria are “…critical in the normal development of the immune system, central nervous system(CNS) circuitry, GI functioning, and autonomic nervous system (ANS) functioning.” (See the second paragraph of this post, re:  Alex and my other students with autism.)  Studies in rodents has clearly demonstrated many times that lack of exposure to normal commensal organisms leads to abnormalities in stress response in adulthood.  That I’ve written about innumerable times on this blog!
  2. If you can believe it (and I don’t recall ever reading this before myself), FMT was first ever used in fourth century China to treat food poisoning and diarrhea! So we have essentially 1700 years of empirical data showing efficacy.
  3. FMT (which may be delivered via endoscopy, enema or oral feeding of freeze-dried material) has been explored for not only the treatment of gastrointestinal disorders and psychiatric issues, but also for autism (you can read about that here), Parkinson’s disease and multiple sclerosis. The data are still accumulating.
  4. The paper breaks down the included studies into three groups: preclinical – animals only, preclinical – human microbiota transferred into animals, and human clinical trials.
  5. There were 11 preclinical studies on animals included in this paper. It has been demonstrated that transferring the microbiota of anxious mice to  healthy mice transfers the anxiety issues.  In another study, the microbiota of mice forced into “alcoholism” were transferred to healthy controls, thereby transferring depressive behavior.  Conversely, transferring healthy microbiota into mice with anxiety and other disorders results in the reduction of anxiety and depressive symptoms in the affected animals.
  6. 9 studies of human-to-rodents were included. A couple of examples include FMT from people with depression into germ-free mice results in depression-like behaviors in the animals.  As in the animal-to-animal studies, transferring the microbiota from human alcoholics into rodents results in the development of anxiety and depressive behaviors in the mice.  Interestingly, giving “alcoholic” mice transplants from healthy humans had a protective effect on the mice’ behaviors:  they did not develop the normal depression seen in alcohol-dependent mice.  One more interesting one:  FMT from people with anorexia to mice results in the animals developing obsessive and compulsive behaviors.  Amazing, right?
  7. 8 human clinical trials made it into the paper, all of which assessed for psychiatric symptoms, some depression, some anxiety, one for neuroticism, and 2 or quality of life related in irritable bowel syndrome, one for fatigue. In the short-term, ALL the papers found improvement in depression symptoms.  The long-term results were more inconsistent though, some finding the effects wore off after 3 months, some found they lasted up to 6 months.  All 4 studies which assessed anxiety found efficacy, although one did not reach statistical significance.  Like anxiety and depression, the other psychiatric issues assessed (i.e. fatigue, neuroticism, etc.) all improved – the only variable being, for how long the effects lasted.

This then seems to be the only issue:  the treatment likely will need to be repeated every 3-6 months.

The exact mechanisms of action are as yet unknown.  Some of the prevailing theories have to do with serotonin production, immune response, short-chain fatty acid production, and bacterial metabolites affecting vagus nerve signaling to the brain.  I won’t be surprised if all these play a role:  time will tell.  What we do know is that it works, it works well, side effects are negligible.  As these authors point out, antidepressant medications are also highly effective but, “…a large proportion of individuals with psychiatric illnesses do not respond to these first-line treatments, and thus need to try alternatives]. Further, many antidepressant users also experience side effects such as restlessness, nausea, vomiting, anxiety, insomnia, sexual dysfunction, gastrointestinal cramps and diarrhea, and headaches that can make the arduous process of searching for effective treatments even harder.”

Thus, they conclude, FMT is a “promising candidate” for treating psychiatric illness.  (Ya think?)  We can only hope that those of us with such issues, or with a loved one suffering, these treatments will soon become available.  If I could treat Alex today, the door would not be hitting me on the way out.

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[i] Young, KA. Of poops and parasites: unethical FDA overregulation. Food and Drug Law Journal. 2014;69(4):555-574.

[ii]  Chinna Meyyappan A, Forth E, Wallace CJK, Milev R. Effect of fecal microbiota transplant on symptoms of psychiatric disorders: a systematic review. BMC Psychiatry. 2020 Jun 15;20(1):299. doi: 10.1186/s12888-020-02654-5. PMID: 32539741; PMCID: PMC7294648.

My Annual End-of-the-Year Wrap-Up: Your Top 5 Picks!

For my annual year-end post, I’ve decided to once again review YOUR top 5 choices of the year.  I guess I shouldn’t be shocked by what you were most interested, in what has been quite the remarkable year for the world.  Here’s to hoping that 2021 is a banner year for all of us, across the world, and that this time next year, COVID is but a memory.

  1. At number 5, is my post from August 20th: New Info on COVID, the Immune System and the Microbiome.  In this post, I reported on research examining the connection of body fat to COVID risks.  The statistics are frightening:  those with a BMI of over 25, which includes those who are fairly mildly overweight, have a 40% greater chance of hospitalization from COVID, and those who are obese with a BMI over 30, have a 70% chance of hospitalization.  Those with excess weight also tend to have altered gut bacteria and high levels of inflammation – a HUGE area of study worldwide at the moment – and it tuned out that dysbiosis is also a huge risk factor in terms of disease severity.

 

  1. In March, I wrote an update on research into the gut/Parkinson’s disease (PD) connection. I have to say, PD is one area where I feel like there has been considerable progress the last couple of years.  Did you know that there are 44 blog posts on the topic on The Biome Buzz?!  Anyway, this post is kind of a summary of the current model for the development and progression of PD.  The first sign of the impending disease tends to be constipation:  it starts with abnormal peristaltic movement of the gut.  It appears that a currently “unknown pathogen” invades the gut, which causes alterations (folding) in the formation of α-synuclein which some believe to be an immune molecule.  (In the paper I covered that day, they postulate that α-synuclein plays a role in modulating the supply and release of dopamine.) It’s believed this mis-folded protein can make its way to the brain via the vagus nerve, causing a detrimental immune effect in the brain.  Stay tuned on this rapidly-developing story!

 

  1. June 27:  I wrote about a clinical trial for constipation in the autism population.  I am still amazed by this statistic:  in one study (with 124 chlildren) it was found that 34% of them suffered from constipation.  Anyway, this post was about a small clinical trial using a prebiotic derived from guar gum (a carbohydrate derived from the guar plant’s bean).  As a pilot study, it was small – only 13 children – all of whom suffered from severe constipation  The results were kind of extraordinary though: constipation improved, blood inflammatory markers decreased significantly, and irritability also significantly improved.  The prebiotic seems to be available depending upon where you live – I’m disappointed no one has tried it and let me know the results!  If anyone does, please do let me know!

 

  1. In July I wrote one of my best-read posts of all time:  Glyphosate, Gut Bugs and Autism.  Like all of you, I am particularly interested in this topic.  I maintain my scientific objectivity at this point and continue to follow the research as it is published.  For those unfamiliar, glyphosate is the herbicide found in products like Roundup, the most used herbicide in the world.  I mention, in my post, that as of October, 2019, a summary article that I wrote about then concluded that we still don’t know enough to conclude anything.  The article I covered in this blog post actually predated that:  it was published in 2018 and looked specifically at whether or not glyphosate can lead to higher levels of Clostridia.  If you read my blog regularly, you know that there is a huge amount of evidence pointing to the short-chain fatty acid, propionic acid, produced by Clostridia as a leading cause of autism.

This paper pointed out that glyphosate can alter gut bacteria, and that pathogenic bacteria are particularly resistant to it, whereas as probiotic species (like Lactobacillus) are much more susceptible.  However, the fact remains that the relationship of glyphosate to the development of autism, via alterations in the gut bacteria, is still hypothetical.  And a new paper, published just this past September, actually concludes that many of the studies in the literature have methodological weaknesses and that it is still impossible to “…draw any definitive conclusions regarding glyphosate’s influence on health through alterations in the gut microbiome.”[i]  They specifically look at whether or not there is evidence that the glyphosate used on wheat is responsible for wheat sensitivities.  Double-blind, randomized clinical trials do not support the supposition that gluten is responsible for symptoms in healthy people.  However, research does support glyphosate’s effects on the microbiome:  “Exposure to glyphosate alone or through the administration of herbicide appears to promote gut dysbiosis through a reduction in commensal bacteria species, including Lactobacillus spp., and butyrate-producing bacteria and an increase in opportunistic pathogens.”  They go on to say, “Glyphosate may also have ramifications for early microbiome development when exposed both pre and postnatally,”  so theory that there may be a link to autism is not impossible.  It is not, however, proven so we do need to wait for better designed studies to be conducted.  From the concluding paragraph:

“Glyphosate may be a critical environmental trigger in the etiology of several disease states associated with dysbiosis, including celiac disease, inflammatory bowel disease and irritable bowel syndrome. Glyphosate exposure may also have consequences for mental health, including anxiety and depression, through alterations in the gut microbiome. However, the research surrounding glyphosate’s effects on the gut microbiome also suffers from numerous methodological weaknesses including artificially high-doses, insufficient duration, proprietary ingredients and an over reliance on animal models.”

I will absolutely stay on top of this critically important story so stay tuned.

 

  1. And finally, the number one most-read blog post ever on The Biome BuzzCovid-19 and Probiotics: A (Successful) Clinical Study, which I posted in August.   Anyone surprised?!  (NOT!) In this post, I describe work done in Italy on 70 hospitalized patients with COVID severe enough to require hospitalization but not a ventilaor.  28 of these subjects received a probiotic, 42 did not.  All those who received the probiotic improved much faster than those who did not, in terms of both respiratory and digestive symptoms: as opposed to those who did not get the probiotic, no one treated ended up requiring a ventilator, a stay in the ICU, or died.

Just bear in mind that to get this effect, high doses of probiotics were used.

Everyone, stay safe.  And as I said at the start, I hope with all my heart that 2021 brings all of us good health, happiness, many more human clinical trials for me to report to you – and an end to this awful pandemic.

Judy

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[i] Barnett, JA, Gibson, DL.  Separating the empirical wheat from the pseudoscientific chaff: a critical review of the literature surrounding glyphosate, dysbiosis and wheat-sensitivity.  Frontiers in Microbiology. 2020. https://doi.org/10.3389/fmicb.2020.556729

Top Biome News Stories of the Year, Part 1

It’s the last week of the year, so it’s time for the inevitable yearly round-up posts!  There’s a good article on Gut Microbiota for Health summarizing some of the major microbiota scientific breakthroughs this year.[i]  Of course, you read it first here on The Biome Buzz!  I did a good job of covering the stories they regarded as “top news items,” if I don’t say so myself! The author points out that COVID has had major effects on the scientific community as a whole:  he suggests that it has made science “nimbler,” which I can believe.  Researchers world-wide needed to rapidly pirouette, moving into new fields and new ways of thinking.  Perhaps some of you may remember that when the virus first made an appearance, no one realized that gastrointestinal symptoms were a common symptom.  In that first month or two, that observation led to rapid deployment of scientists and physicians, looking for the meaning behind those symptoms.  I’ve covered that news for you on this blog.  For example, here’s a post on COVID, immunity and the microbiome and here’s an summary of COVID/microbiome research from this past September.

According to the author of today’s article, here are some other major breakthroughs of the year:

  1. As noted above, the rapid recognition that the GI tract is a target for treating COVID.  As I read the article, I thought about  how rapidly that Italian clinical study using probiotics was thrown together.  It was done by the end of March/ early April, and published in August.  Read about the details here.
  2. More work was done this year on the effects of diet on the microbiota and health. There is an increasing body of evidence that shows that peppermint oil, certain probiotics, psyllium supplementation and a low-FODMAPS diet can help with irritable bowel syndrome. An inflammatory diet has been further linked to the risk for developing Crohn’s disease (see here for more information ), hypertension (see here for more on this topic from this year), and diabetes.  (There are a bunch of articles on The Biome Buzz about diabetes research this year, like here for example.
  3. More evidence has accumulated this year implicating the herbicide, glyphosate, in human disease. I have covered that on the blog too.  Here is a post about recent research on glyphosate and autism, and here is one  from November on new research associating it with alterations to the gut bacteria.
  4. Here’s a really interesting one: “The microbiomes of fermented foods are extremely diverse and their potential health-promoting attributes are superior when compared to non-fermented equivalents.”  2021:  make time for the kimchi and yogurt!
  5. On that note, the mechanism of action of fermented foods has been clarified this year: thus far, it appears most likely that they improve health by improving gut barrier function.  I wrote about this topic (i.e. fermented foods and the gut barrier) in September.

Later this week, I’ll touch on a few of my personal favorite biome stories of the year.

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[i] https://www.gutmicrobiotaforhealth.com/what-major-scientific-breakthroughs-have-been-made-in-gut-microbiome-science-in-2020/

Promising Research: A Probiotic to Battle Obesity and Glucose Metabolism Issues

I think this is a very timely post, considering that we are in the midst of holiday season when we all over-indulge and then, come New Year’s, swear we’ll lose all the pounds we’ve pack on!  Research out of Ireland, University College Cork, first tested their hypothesis in animals.[i]  Prior research had shown that the probiotic bacterium, Bifidobacterium longum APC1472, seems to help modulate the levels of ghrelin, which is a hormone that regulates appetite and fat metabolism.

Using mice with diet-induced obesity, they confirmed that the strain does lead to weight loss, reduces fat deposits, improves glucose tolerance and reduces fasting cortisol levels.  They found too that the probiotic reduced levels of the hormone, leptin, which is made by adipose (fat) cells and which helps to regulate energy by balance by inhibiting hunger, thus reducing food consumption and fat storage.  They then tested this in humans.  Over 100 obese (but otherwise healthy) humans were included in their translational study.  The people were divided into controls and treatment groups, and the latter received daily doses of the probiotic for 12 weeks.  The results were somewhat promising.  In people, the probiotic reduced fasting blood glucose levels, decreased cortisol levels, and improved ghrelin levels.  However, the people did not lose weight or fat:  “…we show the promising potential of B. longum APC1472 to be developed as a valuable supplement in reducing specific markers of obesity…Most notably, the decrease in fasting plasma glucose induced by B. longum APC1472 may have clinically significant health implications for prediabetic and type 2 diabetes mellitus populations in particular.”

Why did the probiotic not have the same fat/weight reducing effect in people as in mice?  The researchers don’t as yet know but they suggest that as opposed to the mice, the humans in the treatment group were not prediabetic, meaning that the weight loss component was due to the normalization of glucose metabolism.  If glucose metabolism is already generally normal well – the probiotic may not help much for weight loss.  Also, the mouse study was longer than the human study which the researchers suggest may also be a factor.  I also note that the humans were given only 10 billion units

The good news is that the research is certainly supporting a role for the probiotic in helping to control prediabetes and diabetes.  They also note that the reduction in cortisol levels is really important as there is a well-confirmed relationship between stress and weight gain.  (Tell me about it!)  Cortisol is your main stress hormone, and when under stressful conditions, the body has a survival mechanism of packing on weight. (Makes sense if you think about it:  from an evolutionary standpoint, having the ability to retain weight while under negative circumstances like famine would greatly enhance the chances of survival.)   The ability of this species of probiotic to modulate that cortisol stress response is promising in terms of improving mental health as well as physical health:  “The translational findings are solid and the modulation of cortisol awakening response, warrant further investigation of this B. longum APC1472 and its potential use as a psychobiotic to improve mental health,” says one of the scientists involved in this work.[ii]

I took a look around to see if this particular strain is yet available for purchase.  Here’s what I found, dated December 18th:  “The APC Microbiome Ireland SFI Research Centre, which identified and patented Bifidobacterium longum APC1472, is now talking to “interested parties” about the commercialization of the strain.”[iii]  So sounds like it will be available someday, but is not as yet.

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[i] Schellekens, H, et. al.  Bifidobacterium longum counters the effects of obesity: Partial successful translation from rodent to human.  EBiom Medicine. 2020. DOI:https://doi.org/10.1016/j.ebiom.2020.103176

[ii] https://newatlas.com/health-wellbeing/anti-obesity-stress-metabolism-microbiome-gut-bacteria-strain/

[iii] https://www.nutritioninsight.com/news/fighting-obesity-apc-to-commercialize-new-bacterial-strain-for-metabolic-and-mental-health.html

Stress, Depression, the Microbiome: A Possible Mechanism of Action Revealed!

For years, I’ve covered the developing story about the relationship between the gut biome and depression and mood disorders.  With a son diagnosed with autism, who has severe anxiety issues (like so many of my students with autism diagnoses), research into this is one of my primary interests.  For several years now, we’ve known that you can actually transfer anxiety and depression to a rodent by using fecal microbiota transplant from another animal, or a human, with a mood disorder.  However, the exact mechanism has not as yet been elucidated…which brings me to today’s paper.[i]

French researchers at the Pasteur Institute and several universities wanted to figure out how the gut bacteria actually influence mood and behavior.  Their findings stunned me:  at least part of the answer is that it changes the animals’ endocannabinoid system!  This system was not even discovered in humans until 1992 (you can read more about that here):  it involves cannabis-like molecules that are naturally made by our bodies that are critical in regulating behavioral, neurological and immune processes.  (For those interested in this topic in particular, you may want to check out this post from 2018 where I wrote about how helminths manipulate this system for both their benefit (i.e. ensuring their survival) and ours.  See here.  Changes to the endocannabinoid system, particularly in the hippocampus, have already been linked to depression and mood disorders.  In this case, the researchers found that the microbiome alterations led to a reduction in endocannabinoid signaling in the hippocampus.  Interestingly, disruptions to the hippocampal endocannabinoid system has already been connected to other neurological disorders.[ii]

To summarize: stress induced changes to the gut bacteria, which resulted in a reduction in production of fatty acid metabolites  that are precursors to endocannabinoids.  They found that in depressed animals, a particular strain of Lactobacillus, plantarum, was dramatically reduced.  This has also been found in humans.  In some good news, supplementing the rodents with the probiotic increased endocannabinoids in the brain of the rodents and alleviated their depression.  The animals were supplemented for 5 weeks and the researchers found this restored normal levels of hippocampal fatty acids, reversed the depressive behaviors, partially restored the production and survival of new neurons:   “Lactobacilli are more prominent in the small intestine, the primary site of lipid absorption. Studies in rodents have shown that Lactobacilli species modulate lipid metabolism. In addition, Lactobacilli may indirectly influence lipid absorption by modulating intestinal transit.”  L. plantarum is believed to regulate fatty acid metabolism; other Lactobaccilus strains may do so as well.  Further research is needed.

In the introductory paragraph of this paper, the authors point out – as I have many times on this blog – that depression is the leading cause of disability in the world and currently affects more than 300 million people.   Their conclusion most certainly inspires some hope that help is not far off:  “In sum, our data show that microbiota dysbiosis induced by chronic stress affects lipid metabolism and the generation of  eCBs [endocannabinoids], leading to decreased signaling in the eCB system and reduced adult neurogenesis in the hippocampus. This might be the pathway, at least in part, that links microbiota dysbiosis to mood disorders, which in turn, may affect the composition of the gut microbiota through physiological adjustments and modulation of the immune system…our study supports the concept that dietary or probiotic interventions might be effective levers in the therapeutic arsenal to fight stress-associated depressive syndromes.”

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[i] Chevalier, G., Siopi, E., Guenin-Macé, L. et al. Effect of gut microbiota on depressive-like behaviors in mice is mediated by the endocannabinoid system. Nat Commun 11, 6363 (2020). https://doi.org/10.1038/s41467-020-19931-2

[ii] https://newatlas.com/science/gut-microbiome-brain-depression-endocannabinoid/

The Gut’s Own Disinfectant

The human body is remarkable.  Some days it hits me right between the eyes!

Before I explain recent findings out of the University of California, Davis[i], some background first.  As you may remember from previous posts, the mucus lining of the intestines protects the gut lining from the microbes that inhabit the gut.  If that mucus layer is compromised in any way, microbes can activate the immune system of the gut, leading to inflammation of the epithelial lining.  And if that lining is in any way compromised, leaky gut can occur, leading to systemic inflammation.  The lining of your gut is crucial to good health and normal immune functioning, meaning that bacteria need to be kept away.  As most gut microbes are anaerobic (i.e. need a low-oxygen environment to live), until now, scientists believed that the separation between the gut lining and the microbiota was maintained by oxygen being released by cells to prevent microbes from getting too close.

These new findings show that in actuality, to protect itself, the colon lining secretes an enzyme that creates hydrogen peroxide (H202) which is a known disinfectant.  The enzyme, NOX1, is a “significant source” of hydrogen peroxide and regulates the location of gut microbes.  It essentially acts as a filter to regulate the location of the microbiota:  pathogens that use H202 for fuel can only do so when attached directly to the lining of the colon, suggesting that “the body uses the disinfectant to protect the mucosal surface.”[ii]  The commensal organisms of the gut remain safely at a distance from the colonic surface.

What does this mean for humans?  Says one of the lead researchers, “We need to shift the focus of gut inflammation treatments from targeting bacteria to fixing habitat filters of the host and restoring their functionality.”  That is, we have within ourselves the means of controlling infection, dysbiosis and inflammation – we just need to figure out how to get it to work when it becomes dysfunctional.   And of course, figure out why it may become dysfunctional in the first place.

As I read about this research, I got to thinking about my post of  a couple of weeks ago where I described research from a Swedish University in which the scientists isolated a potential gut bacteria that may be the cause of irritable bowel syndrome in many cases, which they found in the mucus of the gut lining.  In that case, scientists were able to treat the infection with antibiotics which, as you know, bring their own set of problems.  Imagine if we could treat gut bacterial infections by just boosting the body’s natural defense system?!  That’s a pretty cheerful thought!  I’ll definitely keep an eye out on further research on this subject.

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[i] Miller, B.M., et al. (2020) Anaerobic Respiration of NOX1-Derived Hydrogen Peroxide Licenses Bacterial Growth at the Colonic Surface. Cell Host & Microbe. doi.org/10.1016/j.chom.2020.10.009.

[ii] https://www.news-medical.net/news/20201209/Colon-lining-releases-hydrogen-peroxide-to-protect-the-body-from-gut-microbes.aspx

Isolating Which Bacterial Species Boost Immune Functioning

As you all know, I like to report on studies done in humans whenever possible, so here goes!  Scientists at Memorial Sloan Kettering Cancer Center, In New York City, conducted really interesting research on patients who had received bone marrow transplants as part of their treatment for cancers like leukemia and lymphoma.[i]  During treatment for these illnesses, chemotherapy and radiation are used to destroy the cancerous bone marrow – where many of our immune cells are produced – and then this is replaced with stem cells.  Over time, the donated stem cells restore the bone marrow but while it is recovering, these patients need to take antibiotics to prevent infection, as they are hugely immunologically compromised and vulnerable.  Once the bone marrow is restored, they can stop taking antibiotics, allowing their bacterial microbiomes to also recover.  This set of unavoidable circumstances gave researchers the opportunity to watch, in incredible detail, how the microbiota affect the immune system.

On a daily basis, they tracked (via blood and stool samples) the changes in the microbiota and the number of immune cells in the blood of more than 2000 patients.   They also collected information about the patients’ medications as well as side effects.  This resulted in, as you can imagine,  thousands of data points, allowing them to spot patterns in the data.  Said one of the senior researchers, “The parallel recoveries of the immune system and the microbiota, both of which are damaged and then restored, gives us a unique opportunity to analyze the associations between these two systems…”[ii]

The results may end up being incredibly useful  in helping patients recover more quickly.  They found that Faecalibacterium, Ruminococcus, and Akkermansia were associated with increased levels of neutrophils, a kind of immune cell, in the blood.   Other bacteria (Rothia and Clostridium sensu stricto) were associated with reduced neutrophil levels.  Thus, the hope is that further research provides a means of more rapidly recolonizing, via a customized probiotic, the damaged guts of these patients:  “Simulations predict that microbiota enriched in these genera accelerate immune reconstitution, and reduce the time until neutrophils reach a [normal] level…”

Of course this research is not only relevant to those who’ve had bone marrow transplants.  The fact that they were able to clearly isolate species that specifically boost immune levels and normalize functioning may well be highly significant in countless diseases.  Their concluding sentence:  “Our demonstration that the microbiota influences systemic immunity in humans opens the door towards an exploration of potential microbiota-targeted interventions to improve immunotherapy and treatments for immune-mediated and inflammatory diseases.”

Amen to that, right?!

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[i] Schluter, J., Peled, J.U., Taylor, B.P. et al. The gut microbiota is associated with immune cell dynamics in humans. Nature (2020). https://doi.org/10.1038/s41586-020-2971-8

[ii] https://www.medicalnewstoday.com/articles/gut-bacteria-can-help-rebuild-the-immune-system#Thousands-of-data-points