In part 2 of this look at what we currently know about the benefits of probiotic and omega supplementation on chronic, low-grade inflammation, we’ll be looking at the most common and best studied probiotics, alone and in combination.[i]
As I mentioned in Tuesday’s Part I post , Lactobacilli and Bifidobacteria are very widely studied. They have been shown, for example, to improve the health of the intestinal barrier via a variety of mechanisms including the production of the short-chain fatty acid (SCFA), butyrate, which I have discussed in many prior posts (like here). Low butyrate is associated with intestinal barrier dysfunction, among other health issues.
A quick note: I have included in this summary the exact strains used in the studies listed. I’m not sure how completely relevant they are to efficacy, but for the sake of completeness, you’ll have them in front of you.
Let’s look at Lactobacillus first. This is a review of a few of the clinical studies we currently have:
Lactobacillus and Bifido Combinations: “Combining probiotic strains may produce synergistic effects, conferring additive benefits…” A couple of examples, for your reading pleasure:
We know that fatty acids have a highly beneficial effect on inflammation, and recent research shows that it may take markedly higher levels than previously recognized to make a physiological difference – as high as 2000 mg (or more) per day. On their own, omega 3s potentially can have a positive effect on inflammation-related conditions like Alzheimer’s and diabetes, and other diseases of aging. In combination though with probiotics, there may be a highly significant beneficial effect: omega 3s “…can act as prebiotics in the gut…” The mechanism is not yet fully understood, but it seems to increase the levels of LPS-suppressing bacteria (like Bifidobacteria) and decrease LPS-producing gram-negative bacteria (like Enterobacteria). Omega 3s’ interaction with probiotics also seems to promote the growth of bacteria which produce SCFAs, like butyrate, which improve the health of the epithelial barrier, while also promoting the growth of bacteria that are associated with leanness.
A randomized, controlled trial of 60 overweight adults, given a combination of omega 3s and the probiotic, VSL-3, resulted in “…greater improvement in insulin sensitivity than probiotic administration alone.” In fact, evidence is rapidly mounting that shows that “…combining probiotics and omega-3 fatty acid supplements may be a particularly beneficial strategy as they seem to promote health in various areas through synergistic effects.”
To conclude then this marathon discussion of some of the latest research findings: “Hypothetically, combining omega-3 fatty acids with probiotics offers a promising strategy to prevent the development of low-grade inflammation as well as offering non-pharmaceutical treatment modalities, which might be especially relevant in patient groups that suffer from increased systemic inflammation, such as aged and obese individuals. However, this research field is still in need of well-conducted and properly controlled clinical trials to further support this hypothesis.” While of course more research is desperately needed, seems to me that this is one of those “can’t hurt, could help” kind of scenarios!
[i] Hutchinson, A.N.; Tingö, L.; Brummer, R.J. The Potential Effects of Probiotics and ω-3 Fatty Acids on Chronic Low-Grade Inflammation. Nutrients 2020, 12, 2402.
A brand new topic today for The Biome Buzz, but after hearing the sports news earlier this week, this really struck me as interesting and odd, so here goes…
This past Sunday, September 20th, 7 players in the National Football League here in the USA tore their anterior cruciate ligaments (ACL). 7 in one day! What on earth is going on though that make this injury so unbelievably common these days?! As a big fan of sports, this has been a real bee in my bonnet these last few years.
Another anecdote, this one back in time: 10 years ago or so, one of my dogs tore his doggie version of an ACL just running outside to play. When I met with the surgeon who was to repair Apollo’s leg, he told me flat out that veterinarians have been talking for the past few years about how much more common the injury has become and they have no idea why. “He’ll likely tear the other hind leg at some point too,” he warned me, “Once one goes, so does the other.” Sure enough, 3 or 4 years later leg #2 popped, with my poor dog doing nothing but walking across the lawn.
Why these injuries are becoming more common is unknown but a new article really got me to thinking after reading this new research.[i] According to the paper, it’s important to know that 50% of patients who tear an ACL will develop osteoarthritis in the injured limb, called post-traumatic osteoarthritis (PTOA). The veterinarian surgeon warned me about this too, by the way. Anyway, I find it fascinating that in this newly published paper, researchers found that giving rodents oral antibiotics before such an injury reduces inflammation in the injured joint and slows down the progression of PTOA.
We already know that changes to the bacterial microbiome may reduce osteoarthritis inflammation, but next-to-nothing is known about changes to that biome prior to an injury.
The scientists gave antibiotics (an ampicillin/neomycin cocktail) to the animals for 6 weeks prior to the ACL rupture. A microscopic examination 6 weeks after the injury showed that the animals treated with antibiotics had less loss of cartilage at the injury site than did the untreated controls. There was less inflammation in the treated animals, and present at the wound site were more macrophages, which are immune cells associated with healing. What I think is actually the most interesting part of this research is that the antibiotics led to less inflammation in UNINJURED joints as well.
A summary of the research, which appears on Medical Express, points out that antibiotics are often prescribed for teens and young adults, who actively participate in sports, at the rate of 790 prescriptions per 1000 people. I admit to being shocked by this sentence: “…therefore, gut dysbiosis (a microbial imbalance) may be more common than expected in young athletes suffering an articular injury. In this scenario, the gut dysbiosis may provide a benefit to these young people, if they suffer a joint injury.”[ii] Wait…what?!
The overuse of antibiotics is already a major issue in this country and biome depletion is a known leading cause of many health issues, as you all know. Call me crazy but doesn’t this seem an odd way of assessing this new data! Bearing in mind, as I said above, that , “The results show that this particular antibiotic regime had a beneficial effect on the health of injured and uninjured joints…” – would that not imply that there is some component of the microbiome that is causing joint inflammation, which may LEAD to the increase in these severe injuries? We know these ligament tears are increasing in prevalence; in this study, giving antibiotics leads to better outcomes after surgically creating an injury, i.e. giving antibiotics reduces join inflammation. To me this implies that the next step to study (apart from the obvious question: will giving antibiotics after the injury help speed healing, which the scientists say they will look at in future work) is can antibiotics prevent the injuries in the first place? Or better still: what bacteria are being shifted in giving the antibiotic that cause improve joint health? But what do I know.
I’m really interested in these answers so stay tuned: I’m watching this space to see where this research leads.
[i] Melanie E. Mendez et al. Antibiotic Treatment Prior to Injury Improves Post-Traumatic Osteoarthritis Outcomes in Mice, International Journal of Molecular Sciences (2020). DOI: 10.3390/ijms21176424
When I was a kid, there was a commercial on TV that I’ve never forgotten, for Dannon Yogurt. It showed a bunch of people from Soviet held Georgia who were all around 100 years old, looking like they were in their 60s, actively running around doing farming, chopping wood, etc. The voice over pointed out that yogurt was a huge part of their diet. Take 30 seconds to watch it here – I just found it on You Tube!
Anyway, it made a huge impression on me, probably because we started eating yogurt around then, having NO idea what “active yogurt cultures” meant. (You’ll notice there is no mention of probiotics, bacteria, etc. in the commercial.) I loved yogurt as soon as I tasted it, and have been a big eater of it since. On that note, I came across an article definitely worth sharing with you on the health benefits of yogurt. Yogurt is “…a rich source of high-quality protein, calcium, phosphorus, and folate. Moreover, yogurt serves as an important source of probiotic bacteria that may also confer a benefit on gut barrier function by stimulating the diversity and function of the gastrointestinal microbiota, reducing intestinal transit time, and enhancing gastrointestinal innate and adaptive immune responses.”[i]
A cross-sectional study of 1076 men and women (from 2 different cohorts) was conducted at Harvard’s TH Chan School of Public Health looking at specific health outcomes from eating yogurt. The scientists wanted to see how yogurt affects a blood marker for gut barrier dysfunction (CD14), i.e. leaky gut. CD14 is a molecule released by certain immune cells as a response to lipopolysaccharides, which are toxic metabolites produced by some types of gut bacteria. An immune response to these toxins, seen in the blood, means that they are making their way out of the gut – thus, it is a marker for issues with the gut barrier.
The researchers found that the consumption of two cups of yogurt per week makes a statistically significant improvement in CD14 concentrations (especially in men) indicating that it makes a meaningful difference in improving epithelial barrier function: “Our findings suggest the strengthening of gut barrier function as a plausible mechanism for the observed inverse associations of yogurt consumption with gastrointestinal diseases and disorders involving other systems.”
By the way, we know from past research that diet is a major factor in gut health and barrier function, as you know. (Read this post, for example, from October 2018.) And we know from other studies that fermented milk products affect the immune system positively and protects against the risk factors for type 2 diabetes,[ii] as well as obesity, cardiovascular disease, certain cancers, and intestinal disorders.
So there you have it: high quality yogurt should certainly be a part of everyone’s diet!
[i] Luo, X., Sui, J., Birmann, B.M. et al. Association between yogurt consumption and plasma soluble CD14 in two prospective cohorts of US adults. Eur J Nutr (2020). https://doi.org/10.1007/s00394-020-02303-3
The results of a stage 1 clinical trial of a novel probiotic (created from purified human stool) in treating mild to moderate ulcerative colitis (UC) were just published in the journal, Gastroenterology.[i] I didn’t pay a huge amount of attention last week when I first spotted it, but decided to check it out this past weekend, in case there was anything useful for us. It turned out there is, so I’m glad I took the time.
It appears that this product will be, at least at first, considered a pharmaceutical. There’s good and bad to that, of course: the bad is that I’m afraid it will only be available via prescription and my guess is that, at least at first, it will only be covered by insurance for UC or perhaps, other inflammatory bowel diseases. Those of us without will likely be out of luck in obtaining it. The good is that for those who desperately need it, it will be covered by insurance and considering how expensive ordinary probiotics are, that’s not a bad thing. Still, this particular type of probiotic holds tremendous interest to, and promise, for all of us.
By the way, a quick aside: I did find a 2019 press release stating that an upcoming late stage 2B trial was in the works and that this trial is considered pivotal in that, the Company (Seres Therapeutics) who manufactures the product, “…recently obtained feedback from the FDA indicating that the results from this study, in conjunction with data from a second pivotal study, could enable a SER-287 Biologics License Application.”[ii]
Still, as probiotic capsules or liquids created from isolated, purified bacteria from human stool will someday be par for the course (remember that just such a product was used in the very successful studies on autism. Also, products, isolated from elite athletes, are also being created to improve athletic performance. So even if the products are not as yet available to us mere mortals, I think we should follow along with the research as it piles up.
Back to the now published phase 1 trial to establish safety and efficacy: this was a double blind trial on 58 adults with mild to moderate UC. They all received 6 days of either oral vancomycin (a gut antibiotic) or a placebo, and then 8 weeks of either the probiotic (SER-287) or a placebo. In total there were 4 groups: placebo/placebo; placebo/SER-287 once per week; vancomycin/SER-287 once a week; vancomycin/SER-287 daily.
The results: “A higher proportion of patients in the vancomycin/SER-287 daily group (40%) achieved clinical remission at week 8 than patients in the placebo/placebo group (0), placebo/SER-287 weekly group (13.3%), or vancomycin/SER-287 weekly group (17.7%)…” That’s a pretty outstanding result! By the way, there were no differences in adverse events reported among the various groups.
It’s also important to note that they found higher levels of the species in the probiotic in stool from those on the probiotic versus those on a placebo, but in the group that did not get vancomycin first, this was not maintained after a week. In those in the vanco groups, higher levels of SER-287 species were found in stool throughout the study compared to those who got the placebo (not vanco), and as you’d expect, the highest levels were found in those who got the probiotic daily. In other words, the treatment did exactly as planned: vancomycin wiped out much of the gut flora which was then successfully altered with the human-derived probiotic, which colonized the intestines leading to remission at a clinically significant rate.
Bear in mind that this was just a small, short phase 1 study too. For all we know, the rate of remission might be higher if it had lasted longer. Secondly, we also don’t know that optimal dosing was used yet. (We also, of course, don’t know what the participants were eating during the trial. Not relevant to this study. Still, wouldn’t it be interesting to know that when comparing those 40% who achieved remission versus those 60% who did not?!) They conclude, therefore, that, “SER-287 following vancomycin was significantly more effective than placebo for induction of remission in patients with active mild-to-moderate UC.”
In case you were wondering how the probiotic was produced: the FDA approved their process for screening, and 3 stool donors were selected. The stool was cleared of all impurities and 3 lots of SER-287 were produced, each lot from only 1 of the donors. They basically pulled out some of the bacteria that are not spore-forming, so that each product ended up with 10-20% spores by weight, and included species like Clostridium, Gemminger, Dorea, Roseburia, Blautia, and Faecalibacterium. After treatment, a decrease in non-spore-forming bacteria like 12 Veillonella, Streptococcus, and Bacteroides was noted. Spore-forming bacteria tend to be quite resilient because, when in an inhospitable environment, they retreat into hardy spores, and can reactivate when circumstances improve. (This is why C.difficile infections are so damn hard to eradicate.)
I am quite sure we are seeing the start of a trend: treatment of disease by eradication of “faulty” bacterial microbiomes followed by replacement with healthy bacteria. This is essentially non-invasive fecal microbiota transplant, but of course, with select species of bacteria.
I took a quick look at Seres Therapeutics website and found that they just released, in August, a press release announcing positive results from a phase 3 trial of another product, SER-109, to treat recurring C.difficile infection (CDI), in fact. “The study showed that SER-109 administration resulted in a highly statistically significant absolute decrease of 30.2% in the proportion of patients who experienced a recurrence in CDI within eight weeks of administration versus placebo, the study’s primary endpoint. 11.1% of patients administered SER-109 experienced a CDI recurrence, versus 41.3% of placebo patients.” They are now applying for final product approval from the FDA. Looks like this is a company we’ll have to keep an eye on!
[i] as: Henn MR, O’Brien EJ, Diao L, Feagan BG, Sandborn WJ, Huttenhower C,Wortman JR, McGovern BH, Wang-Weigand S, Lichter DI, Chafee M, Ford CB, Bernardo P, Zhao P,Simmons S, Tomlinson A, Cook D, Pomerantz R, Misra BK, Auninš JG, Trucksis M, A Phase 1b safetystudy of SER-287, a spore-based microbiome therapeutic, for active mild to moderate ulcerative colitis,Gastroenterology (2020), doi: https://doi.org/10.1053/j.gastro.2020.07.048.
It seems like new information is coming out daily about the relationship of COVID-19 to the gut, and I’m trying to stay on top of it as best as I can for us all. On Monday of this week, I spotted an article on Bloomberg about a new study out of a Hong Kong university, stating that the virus may linger in the gut long after it has cleared the respiratory system.[i] The actual study was conducted last February on 73 patients, more than half of whom tested positive for the virus in their stool. The scientists zeroed in on 15 of these positive cases to better understand what was happening, in terms of viral activity.
Interestingly, while active in the gut, the virus caused no GI symptoms in 7 of these people. And it remained active 7 days after respiratory samples were negative; in 1 patient, in fact, they found active virus in the gut 30 days after respiratory tests were negative. Whether or not stool is a means of transmission is being further tested. According to the lead researcher on this paper the gut bacteria of patients with GI COVID infection show a loss of protective bacteria and a proliferation of disease-causing ones, and this was worsened in those patients who were treated with antibiotics. He suggests that probiotics may be helpful in treating COVID. (Remember this blog post of mine from August 6th?)
On Wednesday, I found an article on News Medical about another paper just out that presents a host of new and interesting findings.[ii] Researchers at the Mount Sinai School of Medicine found that 60% of patients hospitalized with the virus have GI symptoms. They looked at 44 patients in their hospital during the peak of the pandemic here in New York, and collected stool samples during the acute and the convalescent phases of the infection.[iii] (Interestingly, re: my previous post on COVID, half the patients were characterized as obese and 70% had high blood pressure. There is no controversy over this: higher levels of systemic inflammation make you more prone to more severe COVID infection.) 70% of the patients studied had GI symptoms, mainly diarrhea. Some had nausea and vomiting. 41% of patients tested positive for the virus in their stools, and it was found more frequently in those with GI symptoms than without. That makes sense, and the numbers look similar to the Hong Kong study.
Here is where things get wonky. These scientists found that more patients without GI symptoms required admission to the ICU: 54% of them, versus only 19% of patients who did have GI symptoms. Weird, right?! It turned out that inflammatory markers were lower in those with GI symptoms, although this did not reach statistical significance. Unlike the study out of Hong King, they found that those with negative respiratory tests did not have detectable viral RNA in their feces. They DID find, however, that those who died of COVID had much higher viral loads in their feces than did the survivors, and that inflammatory cytokines were elevated in COVID patients – as is seen in other intestinal infections and inflammatory conditions – but that these did not associate with actual GI symptoms. Unlike the Hong Kong study, they found no specific microbiome alterations in the population. And finally, they found lower levels of regulatory cytokines (i.e. the off-switch to the inflammatory response) in the stool than of those severely infected.
So the biggest mystery, as far as I’m concerned, is why would it be that a “…significantly lower proportion of patients with GI symptoms were admitted to the ICU compared with those without GI symptoms”? There were no significant differences in blood markers for inflammation between the two groups. (What they did find, consistent with prior research, is that the more severe the disease presentation, the higher the levels of inflammatory cytokines found in the blood.)
Their conclusion is that while there is massive systemic inflammation in those with severe COVID, “…our data suggests that the gut can be an immunologically active organ during SARS-CoV-2 infection, as evidenced by virus-specific IgA, but there is little evidence for overt intestinal inflammation, even in patients with diarrhea or other GI symptoms.”
As soon as I finished writing this post for the first time, I found yet another article on COVID and the gut, this one on Gut Microbiota for Health[iv] , so just a couple more points. The authors of this article reiterate that some studies have shown bacterial alterations in those with COVID, and they point to two meta-analyses (here and here) showing the efficacy of probiotics in reducing the incidence, and the duration, of viral infections. (This, on top of the clinical trial I wrote about previously.)
The article points out that China’s National health commission and National Administration of Traditional Chinese Medicine both now recommend probiotics for the treatment of severe COVID. This is not, however, an accepted practice yet in the Western world. However, in light of the fact that we now know that what causes severe illness and death from COVID is actually a monster inflammatory response (cytokine storm), and at least 70% of the immune system is in the gut, the authors of this article state, “…one might argue that gut microbiome-immune system crosstalk could work as a team to normalize host immune response…”
I don’t know what to make of it all. Hopefully, we’ll get some more answers in the near future.
[iii] Britton, G. J. et al. (2020). SARS-CoV-2-Specific IgA And Limited Inflammatory Cytokines Are Present In The Stool Of Select Patients With Acute COVID-19. medRxiv preprint. doi: https://doi.org/10.1101/2020.09.03.20183947. https://www.medrxiv.org/content/10.1101/2020.09.03.20183947v1
A few days ago I received an email from a company (Dhow Nature Foods ) that is producing powdered baobab, asking if I’d consider writing a blog post about the product. I was pretty excited to hear from them. Baobab, you ask? What the hell is baobab and why was Judy excited?
Some of you may remember back in March, 2018, I wrote about research at Rutgers University which “…demonstrated that by adding a variety of fiber to the diet, a distinct group of gut bacteria are fed and produce highly anti-inflammatory short chain fatty acids which reduce inflammation and help control appetite.” In their study, two groups with type 2 diabetes ate the same healthy diets but one was given large amounts of dietary fiber, which, at the end of the 12 week study, resulted in a greater reduction of blood glucose and weight loss. At the end of the post, I mention the work of Dr. Jeff Leach and colleagues who studied the diet and biomes of the Hadza, one of the last true hunter-gatherer tribes left on earth. I was – and still am – astounded by one of the facts pointed out in the paper I referenced: the average American eats about 15 grams of fiber a day. The Hadza, whose microbiomes boast a diversity we cannot even imagine, eat about 100 grams.
According to a 2019 paper by Dr. Leach and colleagues, the Hadza live in Tanzania and subsist on 5 groups of foraged and hunted foods: honey, tubers, berries, meat and – you guessed it – baobab.[i] These foods do vary in quantity based upon the seasons, i.e. dry versus wet. Their gut bacteria do vary according to season. Baobab though is consumed year round. And their incredibly high-fiber diet has allowed them to preserve ancestral species of bacteria that we have at very low levels in the industrialized world – or have lost completely: “These bacterial taxa are candidates for future study toward a better understanding of the co-speciation of humans and gut microbes, and of what has been disrupted in recent times.”
Another article[ii] from 2018 states, “The study of traditional populations provides a view of human-associated microbes unperturbed by industrialization, as well as a window into the microbiota that co-evolved with humans. Here we discuss our recent work characterizing the microbiota from the Hadza hunter-gatherers of Tanzania. We found seasonal shifts in bacterial taxa, diversity, and carbohydrate utilization by the microbiota. When compared to the microbiota composition from other populations around the world, the Hadza microbiota shares bacterial families with other traditional societies that are rare or absent from microbiotas of industrialized nations.”[iii] One of the biggest differences is in the high level of microbes in the Hazda’s gut capable of degrading plant fiber; considering the amount they eat, this is not surprising. In comparison, the American gut is filled with microbes “…well adapted to forage on intestinal mucus,” as we tend to barely eat fiber at all. The authors actually name those species that have been lost or have become rare in industrialized societies the VANISH (volatile and/or associated negatively with industrialized societies of humans) taxa. Ugh.
Here’s an interesting fact: there was no decreasing levels of diversity in elderly people among the Hadza, such as we see in our elderly population in the industrialized world. The reason is likely due to the fact that the elderly continue to live with the rest of the camp, and are not isolated. This was found in a large study of healthy Chinese people as well, aged 30 to 100, again because traditionally, the elderly are revered and kept within the family.
So, a few facts about baobab: it grows in Australia, the Middle East, and parts of Africa. Really all of the tree is edible, including the bark, leaves, seeds, and fruit.. The fruit is rich in vitamin C (10x that of an orange), and is thought to have antimicrobial, antiviral, anti-oxidant and anti-inflammatory properties. In traditional societies, it is used to relieve everything from GI issues (i.e. diarrhea and constipation) to stimulating the immune system, to hydration and skin health. In one study at Oxford Brookes University, the baobab fruit extract, baked into bread, was found to lower glycemic response in humans. [iv]
In my eternal quest to find promising new products to try for gut health, I am very interested in this one. Dhow foods is now shipping outside of Africa to Australia and the UK, and will shortly be available in the USA. I will test it out once it’s available here in America. In the meantime, I checked out their recipe page which lead me to a different site, on which I found potentially wonderful recipes like this one: Ok…yum. If any of you in other countries where baobab is currently available do give it a try, please let us know how you fare!
[iii] Gabriela K. Fragiadakis, Samuel A. Smits, Erica D. Sonnenburg, William Van Treuren, Gregor Reid, Rob Knight, Alphaxard Manjurano, John Changalucha, Maria Gloria Dominguez-Bello, Jeff Leach & Justin L. Sonnenburg (2019) Links between environment, diet, and the hunter-gatherer microbiome, Gut Microbes, 10:2, 216-227, DOI: 10.1080/19490976.2018.1494103
A very recent paper, published just this past May, caught my eye because of its title: “Inflammatory bowel diseases, the hygiene hypothesis and the other side of the microbiota: Parasites and fungi.”[i] How often on this blog have I talked about the incredible complexity of the human biome? This paper was a very interesting read on this topic, so I definitely want to share some highlights.
It starts with one of the best explanations of “evolutionary mismatch” I have ever read: “According to this concept, an organism that evolved in a given environment might be maladapted to a novel, different environment. In other words, a mismatch in the conditions in which we live today, compared to the conditions in which our genes and bodies had been shaped by natural selection, might imply that several hereditary traits are maladapted; this, in turn could lead to overall perturbances in homeostatic equilibrium.” It goes on to point out that, until the industrial revolution – microseconds away in evolutionary terms – we lived in conditions essentially similar to those of wild animals.
To sum up: “Co-existence with parasites, and with a variety of other ‘almost-pathogenic’ microorganisms, is thus to be regarded as the normal condition for our ancestors…we humans evolved in a type of environment that no longer exits, and are now living in a radically different condition: we are experiencing an evolutionary mismatch.”
Here are a few super interesting facts from today’s paper:
A. Inflammatory bowel diseases were among the first pathologies to be associated with alterations in the microbiome. One of the papers referenced in this section dates back to 1991 in fact, even before more modern lab techniques were developed to look at the microbiota. Noted 30 years ago were the fact that bacteria like Desulfovibrio species (I have written about this too) were at increased levels in those with IBD.
B. There is now very strong evidence that the bacterial microbiota is heavily influenced by the presence (or lack of the presence) of other components of the biome, including protozoa, fungi and helminths. In turn, the bacterial components influence them right back. And of course, ALL these critters are influenced by diet and other lifestyle factors.
C. Some interesting facts about fungi in IBD:
D. Most of the info in the paper about the macrobiome (helminths) is stuff I have covered in past posts, but a quick refresher:
The authors point out, by the way, that other organisms, like protozoa, also undoubtedly play a critical role in the whole picture but were beyond the scope of this paper. (And don’t forget archaea too! And wait…how about the virome?! Seriously…the complexity is enough to boggle the mind.)
So, the conclusion? “There is now convincing evidence that a correct shaping of the immune balance requires some type of contact with parasites, and with a varied microcosm of gut-dwelling microorganisms, or perhaps even with just transient, but frequent, “gut-passengers. The so called dirty old friends.” They authors go on to state that obviously we are not going to go backwards and live in non-hygienic circumstances. They believe it would be difficult to “…imagine an extensive use of worm therapies,” and think the way to go is pharmaceutical products made from the excretions of helminths. I find that ironic in that, the whole paper talks about the incredible complexity of the interactions between all these native members of the human biome. Isolating one or two chemicals is hardly a replacement for the living interactions going on between all these organisms. It would be like saying that the droppings of birds in the woods is a replacement for their actual presence in the ecosystem of a forest, no? They suggest the same, by the way, for fungi: “We are still far from applications, but the prospects are encouraging, for a future in which molecules derived from parasites and fungi will vicariate the disappearance of our dirty old friends, helping us in the maintenance of a healthy gut.”
Maybe I’m wrong and “sterile” pharmaceuticals will work but…you can’t fool Mother Nature, can you?
[i] Panelli, S, et. al. Inflammatory bowel diseases, the hygiene hypothesis and the other side of the microbiota: Parasites and fungi. Pharmacological Research. 2020;159. https://doi.org/10.1016/j.phrs.2020.104962