We have a big dividing line – metaphorically – running through my kitchen: on the one side is me with my beloved heaping salads; acorn squash stuffed with wild rice, cranberries and walnuts; mushroom risottos; cashew korma with basmati rice, etc. On the other, looking at me with horror-stricken expressions, are my sons, who walk around the house wearing t-shirts that read, “100% meatatarian” or simply, “meat.” For us, it’s a matter of taste although, interestingly, if you consider the “eat right for your blood type” way of thinking, my A blood would predispose me to a plant based diet, while their O bloods would sway them toward more meat. As you know from my previous posts on the subjects, that blood type/diet connection is not as yet fully substantiated though – but be that as it may, I still ponder it as, in case you hadn’t yet noticed, I am a brooder by nature!
With all the current research looking now at the connections dietary meat, the microbiome and heart disease, I was interested in learning more about this relationship that now has also been spotted in multiple sclerosis (MS), an overtly autoimmune disease. An article came out last week in eBioMedicine, which is a part of The Lancet system, describing a 6 month long research study performed on 49 participants, 24 of whom had untreated relapsing-remitting MS; and 25 of whom were age matched, healthy controls.[i] Their microbiomes were sequenced; their immune systems were analzyed in depth; and this was all then examined in light of food diaries, to see if correlations were to be found.
Indeed, there were rather extraordinary findings. There was distinct differences in the gut microbiome of healthy controls versus those with MS, and the degree of difference correlated to the severity of the disease. Immune markers also showed great differences, including fatty acid pathways, and many metabolites produced by gut bacteria were off. Remarkably, the one factor that stood out in terms of a distinct alteration in the microbiome was the consumption of meat, which was highly associated with a decrease in the gut bacteria B. thetaiotaomicron – which, in turn was associated with a marked increase in inflammatory Th17 helper cells, as well as a greater abundance of meat-associated blood metabolites. That is, the scientists found that meat eating is associated with “…increased meat-associated blood metabolite, decreased polysaccharides digesting bacteria, and increased circulating proinflammatory marker.”
The study was the joint effort of researchers at UConn Health School of Medicine and Washington University. Says one of the researchers, “This is the first study using an integrated approach to analyze the interplay between diet, gut microbiome, the immune system and metabolism and their contribution to disease pathogenesis and progression in people with MS. It opens a new modality to address future scientific questions by not looking at one individual factor but at their complex interplay.”[ii] This is exactly what is needed, when you consider the overwhelming complexity of the human biome, let alone the immune system, their interactions, and how this all relates to the most important factor in health and disease – our diets.
I have recently been doing some serious thinking about diet. I myself suffer from two autoimmune diseases, and have been flaring horribly since last summer. A week ago, fed up with how I have been feeling, how medicines make me feel (and how they so don’t seem to help), I decided to give a fully vegan diet a shot, with the specter of The China Study (any of you remember that book from about 15 years ago?!) hanging over me. For those unfamiliar, the book was one of the biggest best sellers on nutrition and health ever published in the USA, and it described research done in a collaborative effort between Cornell University, Oxford University and the Chinese Academy of Preventative Medicine. It showed that there is pretty much nothing more anti-inflammatory than a vegan diet. It made big headlines again when, a few years later, former President Bill Clinton – having suffered from massive heart disease – put himself onto the diet.
All this of course, to simply say: we need exactly this kind of research, and we need it soon. I have written many times on this blog about our need for personalized nutrition. I will, of course, continue to monitor this space and bring you the latest.
[i] Richardson TG, Fang S, Mitchell RE, Holmes MV, Davey Smith G. Evaluating the effects of cardiometabolic exposures on circulating proteins which may contribute to severe SARS-CoV-2. EBioMedicine. 2021 Feb;64:103228. doi: 10.1016/j.ebiom.2021.103228. Epub 2021 Feb 3. PMID: 33548839; PMCID: PMC7857697.
How many of you have heard of triclosan [TCS]? I had not, until I spotted a paper out of the University of North Carolina, Chapel Hill, the University of Massachusetts, Amherst and Hong Kong Baptist University, on its potential toxicity, re: our gut bacteria. Apparently, triclosan is an ingredient added to many over-the-counter consumer products because it has antibiotic properties. Thus, you can find it in many toothpastes and, in the past, antibacterial soaps. On the FDA website, it is clear that there are some concerns over its use: “Some short-term animal studies have shown that exposure to high doses of triclosan is associated with a decrease in the levels of some thyroid hormones. But we don’t know the significance of those findings to human health. Other studies have raised the possibility that exposure to triclosan contributes to making bacteria resistant to antibiotics. At this time, we don’t have enough information available to assess the level of risk that triclosan poses for the development of antibiotic resistance.” However, according to a summary article about today’s paper, the FDA did demand it be removed from hand soaps sold to both homes and hospitals, because enough evidence had emerged by 2016 that its presence contributed to the growing issue of antibiotic resistance. That said, it is still ubiquitous in our environment, as it’s used in exercise clothing, yoga mats (to reduce bacterial growth), and toothpaste, where it is positively linked with a reduction in gingivitis.
It turns out that triclosan has also been targeted as a potential suspect in the growing epidemic of inflammatory bowel disease (IBD). The study I am describing today was done in an animal model, so again, this may or may not apply to us humans. However, these researchers have identified the specific bacterial enzymes that trigger triclosan’s harmful effects. And, they also have managed to block the enzyme’s action, which causes the intestinal damage see in those with IBD. According to the paper, “The incidence and prevalence of inflammatory bowel disease (IBD), the chronic inflammation of intestinal tissues, have risen dramatically in recent decades. In 2015, an estimated ~1.3% of U.S. adults (~3 million) were diagnosed with IBD, representing a 50% increase from 1999 (~2 million).” A 50% increase in incidence in only 16 years?! How scary is that!
Enzymes, microbial beta-glucuronidase (GUS) proteins, released by bacteria drive triclosan to damage the gut lining. The researchers used an inhibitor to stop the enzyme’s activity, and by doing so, stopped triclosan from exerting its negative effects. And while these experiments were conducted in rodent models, the scientists found that, “…TCS exposure in humans, the human stool samples also exhibited the same TCS metabolic profile as we observed in the animal experiments and contained a high abundance of free TCS.” They go on to point out that TCS is readily absorbed by the intestinal tract in humans, and they call for a reconsideration of its safety by officials, after their extremely significant findings: “…the safety of TCS and related compounds should be reconsidered given their potential for intestinal damage. Beyond TCS, it seems likely that gut microbial enzymes could contribute to the metabolism and toxicology of other chemicals, highlighting the critical importance of incorporating the microbiota in our understanding of environmental toxicology and mechanisms of disease.”
A 2017 paper, by the way, found that TCS actually alters the gut bacteria composition adversely, in a rodent model – likely also leading to adverse health effects: “Triclosan exposure has a profound impact on the mouse gut microbiome by inducing perturbations at both compositional and functional levels,” which may lead to “…novel mechanistic insights into triclosan exposure and associated diseases.” As noted above, IBD is already strongly linked to it.
So, if you, like me, are now determined to not use a toothpaste containing this ingredient, consider Jason’s, Tom’s, Nature’s Gate, Desert Essence, and believe it or not, Crest – a brand that actually brags about not using TCS in its products.
 Zhang, J., Walker, M.E., Sanidad, K.Z. et al. Microbial enzymes induce colitis by reactivating triclosan in the mouse gastrointestinal tract. Nat Commun 13, 136 (2022). https://doi.org/10.1038/s41467-021-27762-y
 Gao, B., Tu, P., Bian, X. et al. Profound perturbation induced by triclosan exposure in mouse gut microbiome: a less resilient microbial community with elevated antibiotic and metal resistomes. BMC Pharmacol Toxicol 18, 46 (2017). https://doi.org/10.1186/s40360-017-0150-9
Almost exactly 3 years ago, I wrote a post about your blood type affecting your microbiome. From that post: “Like me, I’m sure most of you know that the best known way of categorizing blood type is the ABO system. That is, each of us has A, B, AB or O type blood…These actually refer to the antigens (carbohydrates, also referred to as glycans) on the outside of the red blood cells. (The word antigen means any substance that evokes an immune response by the body (like the production of antibodies, for example).) Which antigen you express (or in the case of O blood, no antigen) is genetically determined.”
If you remember, those antigens are presented not just on blood cells, but also on many kinds of immune cells as well as many bodily excretions (saliva, tears, breast milk, mucus, etc.) as well as in the mucus that coats the lining of the gut. About 80% of the human population are known as “secretors,” meaning that they are genetically prone to secreting these antigens in their bodily fluids. The two papers I described to you in that previous post demonstrate that secretors tend to have more stable microbiomes as compared to non-secretors because the mucus of the intestines serves as a food source for specific kinds of bacteria, including many probiotic species. What wasn’t known yet is exactly how this works: why are certain bacteria more likely to colonize a person with, let’s say, A type blood versus B?
Today’s paper answers that question.[i] Researchers at the Quadram Institute in the UK have been studying the gut’s mucus lining, trying to sort out how it encourages certain bacteria to colonize – and to colonize the correct part of the intestine. Remember that mucus is made of proteins called mucins, which are covered in sugars (carbohydrates). Mucin proteins, which present those blood group antigens, are “capped” with different molecules that prevent bacteria from getting to those sugars…unless, it turns out, the bacteria produce a specific enzyme that can break down that particular antigen-presenting cap. It is this specificity of the cap and the matching bacterial enzyme that promotes the growth of specific bacteria in certain intestinal sites.
These scientists focused on Ruminococcus gnavus bacteria because it is so common, found in about 90% of humans; and it is also one of the first bacteria to colonize infants. R. gnavus is also positively and negatively associated with certain diseases, including neurological disorders and inflammatory bowel diseases. They found that these bacteria produce a specific enzyme for breaking down the “caps” on the proteins that present only blood group A antigens.[ii] This means, of course, that we now know the mechanism by which certain blood types would lead to the colonization of certain bacteria – a really important step forward. That said, there are many unanswered questions still: what is the actual significance of this finding in humans? Does this mean that people with certain blood types have similar microbiome profiles? (So far, the results on that are mixed and provide no concrete evidence either way.) Can we use this to manipulate the gut bacteria to improve health?
The hope is that the study of these enzymes may eventually lead to a means of combating infections, since we know now that the blood antigens encourage the growth of specific bacteria: “Blood group antigens can play a direct role in infection by serving as receptors and/or coreceptors for microorganisms, parasites, and viruses.” For example, we know with certainty that people with blood types O and A are more susceptible to norovirus, while those with B or non-secretors are far less susceptible. Some studies done over the last couple of years suggest that those with O-negative blood type are less at risk of getting severe COVID, while A type blood is more susceptible. (These findings are still being researched and debated, however.)
I find this subject particularly interesting so stay tuned for further developments! Nice to see progress being made!
[i] Wu, H., et al. (2021) The human gut symbiont Ruminococcus gnavus shows specificity to blood group A antigen during mucin glycan foraging: Implication for niche colonisation in the gastrointestinal tract. PLOS Biology. doi.org/10.1371/journal.pbio.3001498.
There have been two papers recently on the growing understanding of the relationship between autism and inflammation. Both, ultimately, point to maternal immune activation (inflammation present in the mother leading to inflammation in her baby) as being the key factor. I’ve covered this topic multiple times on this blog: the fact that infections like flu, and maternal fevers, are associated with an increased risk of autism should not come as a surprise to my regular readers. (See here and here.)
The first paper is out of Columbia University, and on the list of authors are some names familiar to those of us long-time autism parents, like Mady Hornig.[i] The scientists analyzed 60 different immune markers: “Blood samples were collected during pregnancy (maternal mid-gestational blood sample) and at birth (cord blood) from 957 children, roughly half of whom were later diagnosed with ASD.”[ii] Yes, I also read that sentence several time: HALF of the children later developed autism?! I have no idea what to make of it either. They found that there is a link to ASD risk in groupings of inflammation-related molecules, with different groupings seen in boys versus girls. Two interleuins (IL1RA and IL4) were particularly predictive, and four molecules thought to be involved in fetal brain development were also linked to ASD risk in both sexes: TNFα, Serpin E1, VCAM1, and IL1β.
By the way, when collected at birth, these biomarkers collected at birth were only slightly less predictive than when collected during pregnancy.
So, why is Judy writing about this, this week? What does all this have to do with the biome? The second paper, on the same topic, explains the connection. This study – actually a compilation of 4 studies – was done on mice, and is out of Harvard and MIT.[iii] It pinpoints the missing link in our knowledge. While the link between autism and MIA has been recognized, the exact mechanism was not known, nor why children with autism have dysrgulated immune systems. The reason: “Infections during pregnancy can lead to high levels of the inflammatory signaling molecule interleukin-17a (IL-17a), which can not only affect brain development in the fetus, but also alter the maternal microbiome in a way that primes the newborn’s immune system for future inflammatory attacks.” Thus, we now see the reason so many with autism also have intestinal inflammation.
In the course of research, the scientists looked at the stool of MIA mice as compared to that of the controls. Differences were found so as their next step, they transplanted either MIA or control stool into germ-free mice who were then impregnated: “Unlike with the controls, pups born to mice that received stool from mice with MIA exhibited intestinal inflammation. These results indicate that the altered microbiome of mice with MIA leads to the postnatal immune priming of offspring during rearing.”
Says one of the lead authors, “Thus, increase in IL-17a in moms during pregnancy leads to susceptibility to produce more IL-17a in offspring upon an immune challenge…”
There are so very many unanswered questions: why are the mothers’ microbiomes altered in the first place? Many mothers have an infection of one sort or another during pregnancy, yet not all babies born to them develop autism. What differentiates one case from another? Since humans first stood upright, mothers have developed illnesses during pregnancy. Why is MIA now more and more of a factor? What is it about the current maternal immune system that wasn’t present in the past, when autism was rare – if it even existed at all? You have to suspect that alterations to the biome – from the many factors I have often discussed on this blog (changes in diet, biome depletion, etc.) plays a huge factor in all this but the jury is still out until science gives us answers.
[i] Che, X., Hornig, M., Bresnahan, M. et al. Maternal mid-gestational and child cord blood immune signatures are strongly associated with offspring risk of ASD. Mol Psychiatry (2022). https://doi.org/10.1038/s41380-021-01415-4
A very happy New Year to you all. I hope your holidays were wonderful.
First, an update on me. You may have noticed that I have been writing posts less regularly. My new business has really taken off, and I am working insane hours. I have a lot less free time to indulge my hobbies, which includes this blog. I had thought about closing the site down, in fact, but for the moment, I’ll keep it up. I really do enjoy staying on top of the literature and sharing the biome buzz with you all.
My resolution for the year: to feel a hell of a lot better than I currently do. My son, Alex, has been suffering from horrific OCD these past two years and it’s taken a toll on me, in terms of my autoimmune issues. We Buzzers are only too well aware of how stress affecting our biomes! And, how many times over the years have I written about the concept of biome depletion and its effects on human health? So, like we all didn’t have enough to worry about these days, there is now worry among many experts that the excessive “sterilization” caused by COVID fears is only making a bad situation worse. Probiotic species, like Lacotbacillus reuteri, which is well known to be highly beneficial, is found more and more frequently at reduced levels, and this is highly linked to inflammatory diseases. In fact, L. reuteri holds great promise at reducing autoimmunity.
On that note: a few weeks ago I spotted an interesting piece in Discover Magazine that I have been wanting to share with you.[i] According to this article, a specific strain called L. reuteri NCIMB 30242 has undergone multiple human trials. It has been shown to be beneficial for gut dysbiosis and poor microbiome diversity as well as poor bile acid metabolism. It also appears to help balance the ratio of Firmicutes versus Bacteroidetes species, which together comprise about 80-90% of all gut bacteria. A decreased ratio, as well as gut dysbiosis, are strongly linked now with: inflammatory bowel disease, obesity, type 1 diabetes, lupus, chronic fatigue, aging and depression. However, a excessively high ratio is also bad, and is associated too with obesity, irritable bowel syndrome (especially the diarrhea- and bloating- predominant types), fatty liver disease and heart disease.
While L. reuteri NCIMB 30242 is in the Firmicutes phylum, there is no evidence that high levels of any Lactobacilli contribute to any disease: “On the contrary, research associates their unhealthy [i.e. low] levels with various conditions and diseases.”
There are several conditions which L. reuteri NCIMB 30242 has been definitively proven to remediate: it lowers LDL and improves cholesterol status. In those with something called cholesterol hyperabsorbtion, who respond poorly to statin drugs, it normalizes total cholesterol level. L. reuteri NCIMB 30242 also has been proven to lower inflammatory markers in the blood like CRP (C-reactive protein) and other markers of heart disease.
Over the last 5+ years, I have written about L. reuteri many times. Just a few examples for you: providing immune protection for babies, improving immune tolerance (i.e. calming down allergies and autoimmunity) , several times about it potentially proving beneficial in autism (here’s just one example) and also, potentially helping with PTSD. I was, therefore, especially pleased that at the end of the article, Discover provided a link to a high quality source of this particular strain of L. reuteri. I have ordered it and am keeping my fingers crossed that it helps!
Today’s news is on a topic very near and dear to my heart, especially right now: stress. And the news isn’t good.
Researchers at McMaster University have isolated a mechanism by which stress causes a flare up of Crohn’s disease.[i] And surprise, surprise – NOT – the mechanism is via the bacterial microbiome. Using a rodent model for obvious reasons, the researchers induced stress in the animals by restraining them overnight; a 2nd group of mice (controls) were deprived of food and water for 16 hours. The mice in the first group showed a distinct increase in an invasive E. coli bacteria (which they call adherent-invasive E.coli (AIEC), which has already been linked to inflammatory bowel diseases (IBD).
The scientists then gave the mice AIEC, and again, either restrained them overnight or deprived them of food and water. In the restraint group, they found that AIEC dramatically increased overnight but in the water/food deprived group, the amount of bacteria remained unchanged. They continued their experiment for a month, weekly applying psychological stress to the animals. The chronic stress led to a continued increase in the levels of AIEC throughout the gut. They also found that increased levels of stress hormones (the result of chronic stress), killed off certain immune cells that make Interleukin 22 (IL-22), which is a cytokine (chemical messenger) that helps ensure that the cells of the gut wall are healthy and function normally. Without the presence of IL-22, bacteria like E.coli can flourish in the gut and cause inflammatory flare ups, such as are seen in Crohn’s.
There is good news: supplementing the animals with IL-22, did help correct the damage that stress hormones cause the gut tissue, as well as helping the AIEC from increasing.
The lead researchers absolutely believe this work may lead to new and improved treatments for Crohn’s disease. Giving IL-22 to humans is currently being tested in multiple clinical trials, and using a narrow-spectrum antibiotic to kill off the AIEC might also help these patients: “…there are numerous clinical-stage investigational therapies already under development targeting the factors studied here, including IL-22 and AIEC colonization, which could be particularly beneficial in patients at high risk of stress-related disease exacerbation.”
I will follow this line of research and try to keep an eye out for the results of these trials. Stay tuned.
And in the meantime: a very happy and healthy 2022 to all of you.
A couple of weeks ago, I found an interesting article in The Scientist that does a great job of summarizing the current status of helminth research.[i] I have been too busy in my “real” life to read it though, until this past weekend. So, for your reading pleasure…here goes.
The author of the article interviewed many of the main figures involved in the field. He starts with researcher, Alex Loukas, at James Cook University in Australia – where some of the best helminth studies are going on – who has inoculated himself with Necator americanus (hookworm). Why you ask? Because, “…work by his group and others indicates that there could be some unique benefits to controlled, low-level infection with certain worm species, particularly for combating so-called Western diseases, including allergies, autoimmune disorders, and various other inflammation-related conditions.”
Here are my top 10 highlights for you:
1. Rick Maizels, another renowned helminth research, points out that we co-evolved with helminths, and that until 100 or so years ago, all people had them. He is studying the mechanisms by which helminths reduce inflammation: “Maizels and others have also reported that helminth infection is associated with increased production of immunoglobulin G4 (IgG4), an antibody released by B cells that is associated with anti-inflammatory pathways. Levels of IgG4 typically fall in people whose helminth infections are eliminated with deworming drugs.”
2. The article covers P’ng Loke’s well-known case study of a man who ingested Trichuris trichuria (human whip worm) eggs to treat his ulcerative colitis. Loke, formerly of New York University, now at the National Institute of Allergy and Infectious disease, found that the helminths induced the production of IL-22, which led to reparation of the mucosal barrier in the man’s intestines.
3. Last year, a randomized trial of hookworm in the UK, for those with relapsing remitting multiple sclerosis (RRMS) found that those infected had higher levels anti-inflammatory Treg cells, and therefore, had few relapses than those in the placebo group. This is not the first time that helminths have been shown to help modulated MS.
4. This same London group is doing animal studies, looking at whether or not helminths can protect against diabetes: “had higher levels of anti-inflammatory cytokines such as IL-4 than uninfected controls and were protected from diabetes-like pathology. Loukas and colleagues are now running a randomized controlled trial to assess safety and tolerability of hookworm infection in people who are obese and show insulin resistance or other symptoms of metabolic syndrome.”
5. There has been wide-variety in the success of clinical trials using helminths. Why? Loke points out that firstly, the placebo effect tends to be strong in the trials and secondly, there is tremendous variability in how individuals respond. Our immune systems and our individual biomes are so radically different that giving the same dose or same helminth to everyone and looking for a consistent response is a recipe for failure: “One way to resolve this puzzle could be to learn more about variation in immune system responses to helminths, something that Loke is working on now.”
6. The article discusses in some detail how scientists are attempting to use secretions from helminths to make pharmaceutical options available. Since these medications are far in the future, I won’t bother to describe them here. I suggest though that those of you following helminth researchers take a look at the article: it is very interesting. One note though: in 2019, a helminth-derived “medicinal” product was shown to, in mice, lower the risk of developing Crohn’s disease in animals genetically prone. How? It seems that it “…promoted growth of certain Clostridiales bacteria that produce butyrate, a metabolite previously shown to promote bone formation and prevent bone loss in mice.” Which brings me to my next topic…
7. Some researchers are focusing their work on the interactions between helminths and the bacterial microbiome. This is an unbelievably complex topic. On really interesting example: “In one study, for example, Harris, Maizels, and colleagues reported that mice that were inoculated with polygyrus before being infected with a respiratory virus typically showed less lung inflammation than helminth-negative mice given the same virus, but this protective effect disappeared when the experiments were repeated with germ-free mice.”
8. We know already that the presence of helminths changes the composition of the gut bacteria. I discussed this in this post from X: Loke “…found that infection with Trichuris species was linked to greater phylogenetic diversity of bacteria in the gut.”
9. Worms appear to manipulate the gut bacteria by fostering the growth of particular species: “for example, Loke and colleagues reported that mice that were genetically susceptible to developing Crohn’s disease had a lower risk of developing intestinal inflammation if they were infected with Trichuris muris, and that this protective effect occurred via the microbiota: helminth infection favored growth of bacteria in the Clostridiales order, which in turn kept a check on the inflammatory bacterial species Bacteroides vulgatus.” There are multiple other interesting pieces of information in this article, if this topic interests you.
10. One other interesting point: Loukas points out that helminths affect brain chemistry. For example, scientists have found, in rodent studies, that helminths affect serotonin levels which would possibly explain, I would imagine, what helminth users call “the helminth high” when first starting self-inoculation. Says Dr. Loukas: “It could well be that worms manipulate brain chemistry to make people . . . have a greater sense of well-being than an uninfected person…”
There are WAY more questions than answers still, when it comes to helminths, their effects on the human immune system and the other residents of our biomes. I find it incredibly uplifting though to read articles like this one because honestly, I do believe that someday helminths will be a major source of relief for so many of us who currently suffer inflammatory illnesses.
As my regular readers are more than aware, one of my biggest interests is personalized nutrition. In 2003, I started my son, Alex, on the Specific Carbohydrate Diet when his inflammatory bowel disease proved recalcitrant to the array of pharmaceuticals his gastroenterologist prescribed for him. Within a year, his colonoscopy was clear. Thus,I follow the research on this topic as best as I can. And thus, I found a new paper in Gut particularly interesting. Why is it that some people with irritable bowel syndrome (which affects about 15% of the human population) respond beautifully to the FODMAPS (fermentable oligo-, di-, mono-saccharides and polyols) diet while many do not? What differentiates the responders from the non-responders?
To delve into this question, researchers analyzed stool samples from 56 people with IBS and 56 people who lived with those afflicted (but who did not have IBS), all of whom ate their usual diets.[i] Those with IBS were found to have two distinct microbial signatures which the researchers dubbed either “pathogen-like” (IBSP) or “health-like” (IBSH). The IBSH patients had microbiota that were similar to the other member of their household. However, the IBSP subjects had abundant levels of harmful Firmicutes species, including C.difficile, C.sordelli and C. perfringens, and to boot, was very low in beneficial species like Bacteroidetes. Two other interesting findings in the IBSP group: lactic acid bacterial species Streptococcus parasanguinis and Streptococcus timonensis, which are usually found in the mouth, were also abundant. And, the “…bacterial genes for amino acid and carbohydrate metabolism were overexpressed, which may explain the excess of some metabolites that are linked to IBS symptoms…”
In the next part of the study, 41 of these pairs had their stools analyzed after 4 weeks of the low FODMAPS diet. The microbiomes of the household members and those with the IBSH profile remained the same. However, those with the IBSP profile showed marked changes: their microbiota became healthier, with an increase in Bacteroidetes and a drop in Firmicutes species. Plus, the bacterial genes involved in the metabolism of amino acids and carbohydrates were no longer overexpressed.
Interestingly, 3 out of 4 patients with IBS showed symptom improvement on FODMAPS but the clinical response was greater in this with the IBSP profile.
The conclusion then? “…as shown elsewhere, the structure of faecal microbiota might predict the degree of response to restriction of FODMAPs. Second, restricting FODMAPs can correct IBS-associated dysbiosis in the community structure and also in the metabolic pathways, and this correction appears to be maintained even when FODMAPs are reintroduced into the diet with concomitant symptom control.”[ii]
Many questions remain, obviously, including a biggie: what do people with the IBSH profile have IBS symptoms if their microbiota resemble that of healthy individuals?! And what can be done to help them, since they are unlikely to respond dramatically to FODMAPS? Still, I thought this was really very interesting in that, it suggests that there may be a relatively simple and inexpensive way someday of reducing the guess work in picking what treatments, including diet, may be successful for a particular individual: “Reasons behind such heterogeneity of outcomes need to be defined so that the diet can be directed to the candidates more likely to respond or, more importantly, away from those highly likely not to respond.”
[i] Two microbiota subtypes identified in irritable bowel syndrome with distinct responses to the low FODMAP diet, Gut (2021). DOI: 10.1136/gutjnl-2021-326284
[ii] Two microbiota subtypes identified in irritable bowel syndrome with distinct responses to the low FODMAP diet, Gut (2021). DOI: 10.1136/gutjnl-2021-326284
This is an awesome piece of research out of Harvard Medical School, along with Brigham and Women’s Hospital, Seoul National University, and Monash University in Australia. They have essentially found a key piece of evidence that what you eat directly affects your immune system.[i]
In mice, the scientists followed the digestion, and subsequent breakdown, of dietary amino acids (branched-chain amino acids). For those unfamiliar, amino acids are the building blocks of proteins. When you eat protein, your body breaks it down into amino acids, which it then uses to create the proteins necessary for your body to function.
The researchers saw that our old friend, Bacteroides fragilis (remember this post on the good and bad of this particular bacterium?!) takes up these branched-chain amino acids and, using a specific enzyme, converts them into a sugar-lipid (fat) which are also branch-chained. These molecules are released by the bacteria, and then picked up by special immune cells, called antigen-presenting cells. These immune cells induce natural NK T cells to “…exercise their immunoregulatory response through upregulating inflammation-controlling genes and immune-regulatory chemicals.”[ii] That is, these molecules released by branch-chain-amino- acid- eating B. fragilis have a downstream anti-inflammatory effect. (It turns out that NK T cells “…line the human gastrointestinal tract and the lungs and are also found in the liver and spleen, they likely play a significant role in immune regulation.”)
Interestingly, each of the 3 different branch-chained amino acids consumed by the mice led to different structures of the bacterial sugar-lipid molecule, which led to a different pattern of binding to the immune cells. Said one of the researchers involved, “Our findings yield fascinating insights about the microbiome, diet, and immune function and provide interesting clues about how molecules made by our inner neighbors can be used to design therapies…”
Mice with ulcerative colitis were treated with these B.fragilis sugar-lipid molecules and compared to untreated controls (with UC). The intestinal cells of these treated animals showed minimal signs of colonic inflammation. This work follows previous research by the same team published in 2014. At that time, they realized that the anti-inflammatory effects of B.fragilis were due to it releasing some kind of molecule that spoke directly to the immune system but now, they have figured out the source (i.e. branch-chained amino acids) and the structure of that molecule (also a branch-chain structure), and it is the latter that causes the molecule to induce an anti-inflammatory effect, as opposed to a pro-inflammatory effect.
By the way, non-branched amino acids did not induce the anti-inflammatory effects. So, what foods contain branched-chain amino acids, you ask? Dairy products, beef, poultry, fish, eggs, beans, legumes, whole wheat and brown rice, for starters.
These anti-inflammatory molecules can be made in the lab so in the future, the scientists hope that this can be turned into a medication for those with IBD and other inflammatory illnesses: “We can never isolate enough of these immune-modulatory molecules from bacteria for therapeutic use, but the beauty of this is now we can synthesize them in the lab…The idea would be that we’d have a drug that can modulate inflammation in the colon and beyond.”
[i] Oh, S.F., Praveena, T., Song, H. et al. Host immunomodulatory lipids created by symbionts from dietary amino acids. Nature (2021). https://doi.org/10.1038/s41586-021-04083-0
Today a quick note about a novel and seriously interesting bit of research. As many of you likely know, your gut bacteria are responsible for synthesizing much of your neurotransmitters. For example, 95% of the serotonin in your body is produced in your digestive system. Too much or too little of certain bacteria means too much or too little of these chemicals that are responsible for the normal functioning of the brain. Dysbiosis can, therefore, lead to mental health issues.
Dr. Tae Seok Moon, a professor at Washington University in St. Louis, is working on a fix by genetically engineering bacteria that can – amazingly – monitor chemical production from inside a person and correct any imbalances.[i] What, you exclaimt?! That’s not possible! That’s the stuff of science fiction! But, believe it or not, Dr. Moon has already had a success: he has engineered bacteria that can sense temperature, pH, oxygen levels, light, pollutants and other toxic chemicals. “Specific and accurate quantification of chemical concentrations allows for adaptive regulation of enzymatic pathways and temporally precise expression of diagnostic reporters.”[ii]
The upshot of this new paper: Dr. Moon has created Escherichia coli Nissle 1917 (EcN) bacterium, which can discriminate between phenylalanine (Phe) and tyrosine (Tyr), which are two structurally similar molecules that are associated with the disorders (PKU) and type 2 tyrosinemia, respectively. He is now working on an “actuator” which is a protein that will act based upon what the bacteria senses. For example, in the case of PKU (a genetic disorder that causes babies to accumulate phenylalanine, as they lack the enzyme necessary to break it down), a sensor bacteria might be able to detect the levels of the amino acid, triggering the actuatory which will break the amino acid down.
This kind of bacteria, by the way, could also be used in the food industry, protecting us against poisons or toxins; in the pharmaceutical industry; or even in fields like the fuel industry. But for now, Dr. Moon is concentrating on humans: “When this and other neurotransmitters are out of whack, a person can suffer greatly, Moon said. He wants to put an end to this suffering. ‘This is the beginning of our engineering solution.’’”
Well, amen to that.
Anyway, I find this a fascinating concept. I’ll watch this space for more progress. Stay tuned.
[ii] Austin G. Rottinghaus, Chenggang Xi, Matthew B. Amrofell, Hyojeong Yi, Tae Seok Moon. Engineering ligand-specific biosensors for aromatic amino acids and neurochemicals. Cell Systems, 2021; DOI: 10.1016/j.cels.2021.10.006