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.
[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
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:
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.
[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.
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.
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.
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.
[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
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.”
[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
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.
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?!