Flash sale!!! Two for the price of one today at The Biome Buzz!
The first study that I want to share with you was performed in a collaboration between Japanese, Harvard and MIT scientists, and was published in the elite journal, Nature.[i] The researchers looked at the bacterial microbiomes of 160 centurions, average age of 107, and compared them to the younger peers, aged 85-89 and a second group, aged 21-55. Those who survived to extreme old age have higher levels of bacterial species which produce secondary bile acids. [ii] Remember back in January of 2020, I first started covering the bile acids story which has really taken off in terms of research. It turns out that bile acids, which are produced by the liver to digest fats, are HUGE players in health and inflammatory status. (If interested, you can read even more about them on The Biome Buzz. Here and here are just a couple more examples.)
These scientists believe that secondary bile acids protect the intestines from pathogens and also regulate the inflammatory response. To confirm this, the researchers took the bile acids from these remarkably old people and in vitro, treated common pathogenic bacteria with them. One molecule called isoalloLCA strongly inhibited the growth of Clostridium difficile. This proved to the be case in a rodent model as well: animals infected with C. diff but supplemented with isoalloLCA did not get sick. The molecule also protects against the growth of many other pathogens as well: “These findings suggest that specific bile acid metabolism may be involved in reducing the risk of pathobiont infection, thereby potentially contributing to the maintenance of intestinal homeostasis.” Further research will follow, looking at the link between longevity and bile acids.
The second bit of research I wanted to draw to your attention to was published in JAMA Network Open, and showed, in a cross-sectional study of over 2000 adults, that a more diverse microbiome is associated with a markedly lower risk of insulin resistance and type 2 diabetes. There were 12 specific species which appear to be tied to lower risk of diabetes: Clostridiaceae 1, Peptostreptococcaceae, C sensu stricto 1, Intestinibacter, Romboutsia, 2 types of Christensenellaceae, Marvinbryantia, and 4 types of Ruminococcaceae.[iii]
Several of these species have been previously found to be related to insulin resistance, but several are new findings. Interestingly, many of these are butyrate producers. How many times have I talked about the importance of this, in regards to health on this blog?! (Look here and here and here as just 3 examples of many more!) The researchers also point out that several of these have also been linked to obesity. They conclude, “In this cross-sectional study, higher microbiome α diversity, along with more butyrate-producing gut bacteria, was associated with less type 2 diabetes and with lower insulin resistance among individuals without diabetes. These findings could help provide insight into the etiology, pathogenesis, and treatment of type 2 diabetes.”
I know from past surveys that many of you, like me, are super interested in personalized nutrition. I just found another company that looks very promising: ZOE. The company has an impressive group of scientists at its helm. To name just a few: Tim Spector is a professor of genetic epidemiology at King’s College London; Sarah Berry is also a professor at the same institution, specializing ins Nutritional Sciences; and Andrew Chan is a Harvard professor who is Chief of Clinical and Translational Epidemiology at Mass General, one of Harvard’s teaching hospitals. Involved are also PhDs and professors from other illustrious institutions like Stanford, Tufts, Oxford and many more equally impressive scientists.
I love this quote from Dr. Spector – truer words were never spoken: “People are realizing the old mantras of ‘reduce your calories and exercise more’ simply aren’t working. Billions of dollars are being spent on diet plans that may work for five to six weeks but then fail.”[i] As though having 60% or more of Americans now overweight (and the rest of the industrialized world is in similar straights), we then were hit with COVID. According to the American Psychological Association, a recent study found that 42% of Americans report having gained significant amounts of weight during the lockdowns – an average of, believe it or not, 29 pounds![ii] We are in deep, deep trouble as a society. And as Dr. Spector points out, eating less just does not work: “Everyone following the same advice about eating identical foods and 2000 calories a day is nonsense. A calorie is not a calorie when it has a different effect on different people.”
The scientists involved in the creation of ZOE, in fact, are conducting the largest study of the relationship between food and COVID. Thus far, their results show that those people with the highest quality diet are 10% less likely to get the disease and a whopping 40% less likely to develop severe symptoms. This makes all the sense in the world, of course: COVID kills by inducing a massive inflammatory response. Eating an anti-inflammatory diet, keeping the immune system strong and modulated, logically would help prevent that. Without realizing it at that time that this study was associated with ZOE, I actually reported on it for you back in May.
25 years ago, Dr. Spector’s research led him to discover that identical twins, eating the exact same food, had an 8 to 10 fold difference in blood glucose levels, insulin release, fat and inflammatory responses. A study of 13, 000 twins showed the same. Everyone’s body is completely different, and we all have different metabolic responses to food. What works like a dream for one person may be the absolute worst diet on earth for another.
Like so many others in this field, Dr. Spector, who as a geneticist thought that genes would be the deciding factor, rapidly came to realize that the difference boiled down to the microbiome: after all, Identical twins, with the same genes, do not respond in the same way. Genes seem to ever so slightly affect how you respond to sugar and insulin (not enough to make a real difference), but not at all how you respond to eating fats. This is, ultimately, good news: you are not restricted by your genes. Over time, eating the right foods, you can modify the inhabitants of your microbiome, improving your health and ability to better metabolize food. Dr. Spector’s research shows that one of the most important factors is eating a wide variety of plants. There is research out there that shows that eating 30 different kinds of plants per week leads to the optimal gut bacterial diversity.
What have those who use ZOE found? Apparently, they do lose weight and also, find they have more energy and are not hungry all the time. ZOE’s business plan is clever: it’s a give and take. While users get personalized nutrition advice, there also contributing to what has become the world’s largest data set of microbiome/nutrition information. The focus of the company is not only on what you should eat – it’s also looking at how to eat for your body. Remember that gut bacteria have circadian rhythms. (I have talked about this several times on The Biome Buzz. Check here for just one example.) The timing of your meals may well be a crucial factor in achieving good health. In the next few years, ZOE will be conducting research into sleep and the timing of meals.
Having been one of the unfortunate people to put on a few pounds during COVID, I am currently trying a ketogenic diet for myself. I know so many people who have done amazingly well on it. I monitor my blood glucose and ketones almost daily, I log every bite of food I eat, I am following exactly what I need to do down to the last calorie – and yet, I have lost no weight. According to my blood tests, I am in state of fairly deep ketosis so how is this possible? (And for those of you who are keto fans, yes, I am checking my keto/glucose ratio as well.) I have read extensively about the diet, and as a nutritionist, yes, I know what I am doing. But as I have said over and over on this blog: there is no one right answer for all of us. How my body metabolizes fat may be radically different than how yours does. In fact, the scientists at ZOE predict that in the near future, we’ll also have fat monitors, to go with our glucose and ketone monitors. What my ideal diet is, I don’t know – I continue to grope in the dark.
Unfortunately, ZOE is not available in New York, New Jersey or Rhode Island due to the excessive regulatory environment of these states. I have signed up to be notified when I will be able to use it but if any of you make the decision to give it a try, I’d love to hear about it, as would your fellow readers I’m sure!
The biome buzz of last week surround newly published research out of the University of Utah.[i] You’ll remember from previous posts on this subject (see here and here as two examples) that the mycobiome appears to play a big role in the development of inflammatory bowel diseases. This research may be another big step ahead on this front.
We all have mycobiomes, fungi that inhabit our intestinal tract, and ordinarily, they appear to be either harmless or beneficial. However, we know that under certain circumstances, fungi can become extremely problematic, causing yeast infections that can actually be life-threatening. Fungi too, under adverse conditions, can cause damage to the intestines that leads to IBD. Ordinarily, a healthy immune system working with a healthy bacterial microbiome, can keep yeasts in check. However, when something goes off balance, yeast can become essentially pathogenic.
Researchers at the University of Utah noted that a common blood test for diagnosing Crohn’s disease involves looking for antibodies to fungi. They began to search for the source of those antibodies, and found that the most common yeast in the intestines, Candida albicans, elicited the strongest immune response (i.e. creation of the most antibodies). Further investigation of this phenomenon led them to realize that actually, the antibodies were meant to attack an elongated fungal cell called hyphae: specifically, the antibodies bound to a protein (adhesins) on the hyphae cells that help the yeast stick to surfaces and become invasive. Hyphae are long, fine filaments that fungi use to invade tissues.
Testing this out in mice, the scientists populated one group of animals with normal Candida and another with the abnormal, hyphae Candida. Sure enough, in the latter group, the yeast caused intestinal damage that looked just like Crohn’s. Thus, they were able to conclude that a normal antibody response would destroy the pathogenic form of Candida, thereby protecting the host.
Candida albicans also cause vaginal yeast infections, and the Utah scientists determined that a vaccine that is being developed to treat that issue actually induces an immune reaction against those same adhesin proteins on the hyphae Candida. When tested in mice that have been engineered to develop IBD, those that are given this vaccine are less likely to develop the disease. The question that obviously needs answering is whether or not this vaccine might cure, at least lessen the severity of, IBD. More than that, can this approach – manipulating the immune response – be used to treat other gut related ailments? In this case, the immune reaction essentially improves the quality of Candida albicans, creating a competitive disadvantage to members of its invasive state – thereby greatly benefiting the benign “…rounded, budding state, which improves their survival in the gut.” Essentially, the immune response is the primary factor in making our relationship with Candida a symbiotic one, where both parties benefit. Says the lead researcher, “We aim to exploit interactions with commensal microbes and the host immune system to harness microbial products for therapies…”
While the vaccine has not as yet been tested in humans with IBD, it’s a really interesting concept. I’ll definitively keep an eye out for updates in the future as they appear.
And just like last week, the Weizmann Institute in Israel strikes again. So much cutting edge research out of one place!
As many of you may know from previous posts on this blog (look here and here, as just two of many examples), over the last number of years, more and more research points to a connection between the gut biome and neurodegenerative diseases like Alzheimer’s, Parkinson’s, and ALS (Amyotrophic Lateral Sclerosis). The winner of the 2021 NOSTER & Science Microbiome Prize is Dr. Eran Blacher, whose research into the connection may have brought us one step closer to figuring out the mechanism of action. Talking about research that is desperately needed! – millions of people worldwide are suffering from these types of diseases which, “By gradually destroying motor abilities, communication skills, memory, and clear thinking, these devastating diseases rob patients of their independence and take a heavy toll on family members and caregivers.”[i]
Blacher and colleagues, working at the Weizmann Institute of Science, depleted the microbiomes of a specific type of genetically engineered mice using a broad spectrum antibiotic. Alterations to the microbiome led to subsequent changes in the metabolites normally produced by gut bacteria. In turn, this led to a progressive neurodegenerative disease that greatly resembles ALS. Remember that small molecules produced by gut bacteria can cross through the epithelial barrier and make their way into the blood stream, allowing the gut to communicate with the brain.
11 distinct microbial strains correlated to disease severity. Most exciting though is that probiotic treatment of the mice with either our old friend, Akkermansia muciniphila, or its associated metabolite (nicotinamide, which is a form of vitamin B3) improved these ALS-like symptoms by significantly improving motor function and restoring normal spinal cord gene expression patterns.
A preliminary study was also performed in humans, and the researchers found a similar pattern of changes in microbiome composition and function (i.e. metabolite production) in patients with ALS. Just like they found in the mice, they found reduced levels of nicotinamide in serum and cerebrospinal fluid: the “…study showed that the composition and function of the microbiome of ALS patients substantially differed from that of healthy family members. Moreover, we found a significant reduction in nicotinamide concentrations in both sera and cerebrospinal fluids of ALS patients.”
There was a very interesting note in the article concerning prior research which showed that inhibiting the glycoprotein, CD38, which is an efficient NAD+-consuming enzyme (i.e. it very efficiently metabolizes nicotinamide) is also a “…promising strategy to treat brain pathologies.” A quick search led me to a 2019 article which states, “In the central nervous system, vitamin B3 has long been recognized as a key mediator of neuronal development and survival.”[ii] This article concludes, “A growing body of evidence highlights the key role of vitamin B3 in neuronal health. What is emerging is that niacin bioavailability is crucial for neuronsurvival and functions: indeed, vitamin deficiency has been recognized as a pathogenic factor for neurological deficits and dementia, as well as for neuronal injury and psychiatric disorders.”
I will definitely be keeping a look out for more on this line of research. It really does look promising!
p.s. By the way, an aside for any of you who suffer – as I do – from migraines. From this 2nd article on nicotinamide: “When orally, intramuscularly or intravenously administrated, vitamin B3 (especially, nicotinic acid) has therapeutic effects in headache management.” Daily, I take a vitamin B complex, but I think I’ll be adding extra vitamin B3 going forward!
[ii] Gasperi V, Sibilano M, Savini I, Catani MV. Niacin in the Central Nervous System: An Update of Biological Aspects and Clinical Applications. Int J Mol Sci. 2019;20(4):974. Published 2019 Feb 23. doi:10.3390/ijms20040974
Back in 2018, I described research to you out of the Weizmann Institute in Israel, which involved creating an algorithm to figure out the optimal diet for someone based upon their microbiome analysis results.[i] That research led to the creation of the new company, DayTwo, which provides personalized nutrition for those with metabolic diseases. This idea of personalized nutrition absolutely fascinates me and I am sure it is the wave of the future.
These scientists continue to study individual responses to diet, based upon the microbiome.[ii],[iii],[iv] As I’ve talked about several years ago, they had a huge cohort of study participants, 800 people: the purpose of the study was to look at how these individuals’ bodies responded from a blood sugar point of view to various foods. The researchers created standardized meals that consisted of a known amount of calories and carbohydrates. Each participant logged their daily activities, meals, medications and other habits for 1 week. They also collected information from blood tests and microbiome samples. This vast amount of data permitted the researchers to create an algorithm to “…predict postprandial glycemic responses based on individual features.” Once the algorithm was created and verified, they used it to create a real-life menu plan for all the people in the study. For one week, the people ate a “bad” diet that would induce high blood sugar levels after eating, and a 2nd week, they followed their individualized menu. During the “good” week, those who followed their dietary plan maintained a normal glucose levels.
Says one of the researchers, “The major contribution of this study will be to those who struggle to maintain their blood glucose levels in a normal range. This is really good information for pre-diabetics, diabetics, or those suffering from a metabolic condition…” It’s also very important for maintaining a healthy weight. Amazing stuff, really.
So a few highlights from the most recent paper:
Apropos of my post from last week on artificial sweeteners: “One example of person-specific microbiome impact on dietary physiological responses to consumed food focused on artificial sweeteners, mainly saccharin, and demonstrated that glycemic responses to these seemingly inert food supplements were driven by variations in the human microbiome. Moreover, adverse glycemic responses to saccharin could be predicted using machine learning by utilizing microbiome data collected before sweetener exposure…” It’s incredible to think that even no-cal sweeteners can cause an adverse glycemic response! You really have to wonder then: how much of our (those of us who live in the industrialized world) issues with excess weight have to do with this interaction between our food and our microbiota. So many of us struggle to maintain a healthy weight in spite of eating what we believe to be a healthy, calorie-controlled diet. How exciting is it then that we can already predict how individuals will respond to sweeteners and carbohydrates based upon their microbiome compositions: “…a subject-specific response to nonnutritive sweeteners was exhibited in humans, with the microbiomes of responders and nonresponders clustering separately. Similarly, the glycemic response to different types of bread could be reliably predicted based on microbiome features…” (I wrote about the bread response back in 2018 also.)
Another interesting point: “The gut microbiome is strongly influenced by the composition, amount, and timing of its host’s diet. Mounting evidence suggests that the timing of feeding has a predominant effect on downstream metabolic and immune functions in microbiome-dependent and -independent manners. In a given person, substantial variability was noticed when identical meals were consumed at different times of the day…” I have written before (see here) about the circadian rhythms of the gut. Again, it’s easy to imagine how learning what to eat and when from a personalized nutrition standpoint could make a massive difference in health.
In the future, these scientists are looking to expand their algorithm to also optimize intake of lipids (fats) and protein, as well as micronutrients (vitamins and minerals). They’d also like to look beyond just glucose metabolism to explore other medical conditions like cancer and inflammation. But they recognize that they have their work cut out of them. After all, they haven’t even started to take in to account the other members of the biome: “Equally elusive are the potential roles of the viral, fungal, and parasitic microbiomes in contributing to personalized human responses to food, as well as roles played by niche-specific microbiomes along the oral and gastrointestinal regions.”
Still, on the bright side, progress continues to be made. I’ll continue to monitor the work coming out of the Weizmann Institute, which really is a leader in this field. The importance of this concept really cannot be overstated. As the 2020 paper states, “…as nutrition is estimated to impact a plethora of infectious, inflammatory, neoplastic, and even neurodegenerative processes, understanding of the causative food-induced and microbiome-modulated effects induced in the human host under these contexts may enable us to rationally harness precision nutrition as part of the therapeutic arsenal in these common and often devastating human diseases.”
I have so few guilty pleasures, what with calorie counts and nutrition information on everything. As much as I am pining to finally taste a mocha frappacino at Starbucks, as soon as I see that 400+ calorie count, I just can’t bring myself to buy one. I’ve reduced my “junk” food eating to the occasional piece of dark chocolate – which really doesn’t count because it’s chock full of antioxidants – ice cream, and the very occasional diet Coke. Well, after reading today’s paper[i], I think the latter will just have to go the way of donuts, sour gummy worms and milkshakes. Another one bites the dust.
I’ve written before about the evils of artificial sweeteners, and because of all the accumulating research, I’d reduced my diet soda drinking to maybe 4 times a month. (See two examples here and here.) After all, we know that these sweeteners can both change the microbiome as well as reduce diversity: “Recent studies have indicated considerable health risks which links the consumption of AS with metabolic derangements and gut microbiota perturbations.” This article lays out the results of many studies which show that, shockingly, artificial sweeteners do the exact opposite of what common sense would have you believe they do: they do not reduce glucose levels or help avoid metabolic diseases. Because they so disrupt the gut biome, studies have, for example, confirmed that in humans, after 4 days of aspartame in the diet, “…a significant difference in microbial diversity was observed.” Other researchers have shown that “…numerous pro-inflammatory mediators were potentially produced by gut bacteria following the consumption of sweeteners in the diet, which is associated with other metabolic disease conditions like diabetes and obesity.” The scary thing is that these sweeteners are not only consumed voluntarily: they have also been found in wastewater, surface water, groundwater, and drinking water systems.
Worse still: today’s paper, new research just published in the International Journal of Molecular Sciences, shows that saccharin, sucralose and aspartame actually make two kinds of bacteria, Escherichia coli (E.coli) and E.faecalis (Enterococcus faecalis) more pathogenic. Upon exposure to artificial sweeteners, these pathogenic bacteria can attach themselves to, invade and ultimately kill epithelial cells that line the walls of the intestines. At a concentration equivalent to only two cans of diet soda, all 3 sweeteners measurably increased the adhesion of these two species to epithelial cells, as well as increased the formation of biofilms. As you know from my previous posts on the topic (see here as one example), biofilms – like the plaque on teeth – can protect pathogenic bacteria (and yeasts, etc.) from antimicrobial treatments: “Findings show that sweeteners deferentially increase the ability of bacteria to form a biofilm. Co-culture with human intestinal epithelial cells shows an increase in the ability of model gut bacteria to adhere to, invade and kill the host epithelium.”
The inflammation caused by the artificial sweeteners causes increased permeability of the gut lining, leading to leaky gut. E. faecalis can actually cross the intestinal wall and get into the blood stream, causing infections in multiple organs (it can get into the lymph system including the spleen – and into the liver), and can cause septicaemia.
The senior author of the paper summed up the paper as follows:
“There is a lot of concern about the consumption of artificial sweeteners, with some studies showing that sweeteners can affect the layer of bacteria which support the gut, known as the gut microbiota. Our study is the first to show that some of the sweeteners most commonly found in food and drink—saccharin, sucralose and aspartame—can make normal and ‘healthy’ gut bacteria become pathogenic. These pathogenic changes include greater formation of biofilms and increased adhesion and invasion of bacteria into human gut cells. These changes could lead to our own gut bacteria invading and causing damage to our intestine, which can be linked to infection, sepsis and multiple-organ failure. We know that overconsumption of sugar is a major factor in the development of conditions such as obesity and diabetes. Therefore, it is important that we increase our knowledge of sweeteners versus sugars in the diet to better understand the impact on our health.”[ii]
Holy cow. How can I drink another diet soda after reading that?!
[i] Aparna Shil et al, Artificial Sweeteners Negatively Regulate Pathogenic Characteristics of Two Model Gut Bacteria, E. coli and E. faecalis, International Journal of Molecular Sciences (2021). DOI: 10.3390/ijms22105228
That the first few months of life are critical for the development of a healthy microbiome, which in turn, affects health life-long is now accepted as a self-evidient fact. For those of you who, like me, have been following biome research for the last 20+ years, it is still shocking though to see how cavalierly this fact is now referred to, when it wasn’t long ago that it was even discovered. I’m still taken aback when articles start with sentences like this one, “Many diseases caused by a dysregulated immune system, such as allergies, asthma and autoimmunity, can be traced back to events in the first few months after birth.”[i] This field really has come a long way in the last 2 decades, which may be the only bit of good news in an otherwise dark landscape: the incidence of diseases like asthma, type 1 diabetes, allergies, Crohn’s, obesity, autism, etc. are continuing to skyrocket in the industrialized world.
In fact, an article just appeared in the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition which shows that in the last 25 years, cases of pediatric celiac disease, another autoimmune disease, have doubled.[ii]
The article I cite above is about new research out of the Karolinska Institutet in Sweden, a real powerhouse in biome research. This particular paper is about the relationship between the early development of the gut bacteria and the immune system, and breast feeding. Prior research has shown that bifidobacterial are more common in babies that are breastfed in less developed nations where autoimmune diseases are at much lower levels.
We know that breast milk is rich in prebiotic sugars, including human milk oligosaccharides (HMOs), which babies cannot digest: from an evolutionary point of view, the sugars are meant to feed specific species of gut bacteria which, in turn, provide benefit to the infant’s developing immune system. Says the lead researchers, ““We found that babies whose intestinal flora can break down HMOs have less inflammation in the blood and gut…This is probably because of the uniquely good ability of the bifidobacteria to break down HMOs, to expand in nursing babies and to have a beneficial effect on the developing immune system early in life.”
Between 2014 and 2019, 208 breastfed babies had their immune systems analyzed through tiny blood samples. A second cohort of infants were followed by collaborating researchers at the University of California. These babies were also breastfed, but were supplemented with B. infantis as well.
It turns out that breastfed babies, who were given supplemental bifidobacteria, had higher levels of two molecules in their intestines. The first is called indole-3-lactic acid, which is needed to convert HMO molecules into nutrition for the baby. The second is called Galectin-1, a newly discovered molecule that is crucial for preserving beneficial, anti-inflammatory bacteria: “Galectin-1 is central to the activation of the immune response to threats and attacks.”
In future research, the researchers would like to follow such babies for longer periods of time to see which develop eczema, allergies and asthma, as well as comparing the immune systems of babies from Sweden with those from rural areas in Africa. The goal is, of course, the figure out a way of ensuring that all babies – breastfed or not – have an ideal biome/immune start in life. In case you missed it, a couple of weeks ago I posted, on my Facebook page, a story about research out of the University of Chicago that showed, in a mouse model, that “…restoring a single microbial species — Bacteroides sp. CL1-UC (Bc) — to the gut microbiome at a key developmental timepoint can prevent antibiotic-induced colitis in a mouse model of the condition.”[iii]
Repair to damaged or suboptimal microbiomes is possible early in life, and this should set babies up for better health as they age. It’s not a pipedream; it will happen. As the parent of a son with autism and a history of inflammatory bowel disease and severe immune dysregulation, I believe this line of research may be the most important being conducted in the world today.
Last week, I wrote about Akkermansia, which I have to believe will soon be available, perhaps as a medical food. Today, I am introducing you to a newly discovered “next generation” probiotic that I read about over the weekend – say hello to Dysomobacter welbionis.
Researchers in Brussels isolated this novel Ruminococcaceae species. It appears to be closely related to another species called Oscillospira guillermondii, which has been “consistently associated to leanness.”[i] As you know from reading this blog (look here for example), several specific species of bacteria have been found to have a direct effect on obesity and associated metabolic disorders. Enterobacter cloacae causes obesity and insulin resistance. Supplementing mice with Bilophila wadsworthia leads to glucose intolerance. On the flip side, giving mice Eubacterium hallii reduces obesity in mice genetically engineered to be obese. There are many more examples in the literature. In fact, these researchers showed in a 2013 study on mice that Akkermansia muciniphila, “…counteracts diet-induced obesity and related disorders, such as glucose intolerance, insulin resistance…” They also tested in humans and found the same. (You can read more about probiotics and obesity here and here.)
Using several large cohorts of people (including the American Gut Project, the Flemish Gut Flora Project, and several more), for a total of 11,984 subjects, the scientists cultured relative abundance of this species and found that it is highly prevalent in the general population, and that its abundance is negatively correlated with BMI and fasting glycaemia (high blood sugar even while fasting). They found that it is present in 62.7-69.8% of healthy subjects, and ranged in abundance (i.e. the percentage of the total species in the gut) from 0-9.2%. In those who were obese, levels of the bacterium was markedly lower.
They then supplemented this species in mice who were being fed a high fat diet, and found that it somewhat reduced body weight, as well as improving glucose and energy metabolisms. By the way, in this case, only the live bacteria worked – not the pasteurized (heat-killed) one, as has been shown effective with Akkermansia (see here for more on this).
While they do not as yet know the exact mechanisms of how this species exerts its beneficial effects, the scientists note that it is a producer of the short-chain fatty acid (SCFA), butyrate, which is known to increase energy production (meaning that you are using more calories). However, they did not find an increase in levels of butyrate in either blood or the gut. However, in spite of not knowing how it works, their data strongly suggests that D.welbionis helps regulate both the host’s energy metabolism and fat mass development: “Altogether, our data strongly support the beneficial effects of live D.welbionis J115T on diet-induced obesity and diabetes.”
Obviously, way more research is needed on this. This type of research always starts with animal models – will these results translate to humans? What will optimal dosing look like? Will combinations of these “fat busting” species work best and if so, what does that combination look like? Still, I for one find this kind of research very exciting and promising. Something is making us fatter, and we know that it’s not as simple as simply eating too much.
[i] Le Roy T, Moens de Hase E, Van Hul M, et al. Dysosmobacter welbionis is a newly isolated human commensal bacterium preventing diet-induced obesity and metabolic disorders in mice. Gut Published Online First: 08 June 2021. doi: 10.1136/gutjnl-2020-323778
For you fans of Akkermansia who’ve been waiting with baited breath for the next research paper on it, you’re in luck today!
Of course, because we’re talking the human biome, nothing is ever simple. Today’s research is a great example of just how immensely complex this all is. Prior research has shown a relationship between Akkermansia and obesity. For example, I talked about this last November in describing research using data from the American Gut Project which showed that decreased levels of Akkermansia are associated with increased risk for obesity. The previous year I wrote about how both live Akkermansia supplementation and heat-inactivated Akkermansia, given in supplement form, reduced the risk of obesity and insulin resistance in a small cohort of 32 people.
In today’s research, Chinese researchers wanted to explore the relationship between Akkermansia levels and the 5 main components of metabolic syndrome (MetS): hypertension, hyperglycemia, hypertriglyceridemia (high triglycerides), low levels of HDL (“good” cholesterol) and obesity. A diagnosis of MetS requires a person to have at least 3 of these risk components.[i]
Akkermansia, as you may remember, is a mucin-degrading bacteria (i.e. it lives in and on the mucus lining the gut) which is perhaps why this one study I wrote about in the past showed that high levels are associated with inflammatory bowel disease. But then in other research, like today’s paper, finds that a “…depletion of Akkermansia along with enrichment of other mucolytic bacteria…has been reported in both human and animal models of inflammatory bowel disease.” Confusing, right?
Now this might explain why differing studies find differing results: as these scientists state, “…its effect on host physiology depends on complex interactions with other intestinal microorganism.” And that right there is always the problem: looking at one species in isolation never makes a whole lot of sense when it comes to the human biome.
In this case, the scientists wanted to learn more about what bacteria affect Akkermansia’s ability to improve MetS as well as to figure out what is the threshold level of required to reduce the risk of MetS. They used a cross-sectional study of 6896 subjects and 97.7% of these subjects had detectible levels of Akkermansia. 20.4% of these individuals had MetS. Their findings: there is a significant association between Akkermansia and central obesity/waist circumference, hypertriglyceridemia, low levels of HDL and hypertension. There was a weaker association with hyperglycemia. Their findings, they point out, is in line with those of the American Gut Project, and the “…concordance of these results indicates that the protective effect of Akkermansia against obesity is independent of geography, ethnicity, sex, age, and dietary habits in Western and Eastern countries and may be generalizable to a large population.”
But again, since nothing in the gut is ever simple: they also found that “Ruminococcaceae and Lachnospiraceae were the 2 main families influencing Akkermansia abundance and the Akkermansia –MetS association.” That is, levels of other bacteria affected Akkermansia’s ability to improve the symptoms of MetS. And more than that, the level of the bacteria also mattered: Akkermansia was nonsignificant at low levels, which is in line with the findings of previous research which showed that in terms of supplementation, at least a billion units per day were necessary for efficacy. In this study, they found that Akkermansia must be at levels at the very least of .2% of the microbiome to have any effect on MetS risks. And its protective effects increased as the level of it goes up.
The paper points out that there have been very few human clinical trials with Akkermansia, but the few that have been done in overweight individuals showed that supplementation is tolerated, and another showed that even massive amounts of it in the gut caused no adverse effects. And the researchers conclude that “…These findings suggest that probiotic intervention with Akkermansia can prevent or alleviate MetS and related disorders such as heart disease or T2DM.”
Unfortunately, it is still not available to the general public (at least that I can find). And while Bofutsushosan, that Japanese herbal supplement I wrote about in April, 2020 which has been shown to significantly increase levels, is out there for sale, I don’t see any sources of it that make me comfortable. I guess this is all still a waiting game….
[i] Zhou Q, Pang G, Zhang Z, Yuan H, Chen C, Zhang N, Yang Z, Sun L. Association Between Gut Akkermansia and Metabolic Syndrome is Dose-Dependent and Affected by Microbial Interactions: A Cross-Sectional Study. Diabetes Metab Syndr Obes. 2021;14:2177-2188
Good morning, Biome Fans. Before I launch into today’s cool piece of research, I just wanted to let you all know that going forward, more often than not, I’ll only be blogging once per week, as opposed to the twice I’ve been doing for years now. As my regular readers know, this blog is my hobby, not my livelihood and I currently work two jobs to make a living. The good news is that my new business has really taken off: I am booked all day every day. Realistically, I just don’t have the time to read and research two posts every week. (I will, of course, post every weekday interesting tidbits on the Biome Buzz Facebook page!)
On to today’s science:
As many of you may remember, I’ve written before about the inadequacies and dangers inherent in the current treatments for inflammatory bowel diseases. (Look here too.) In that 2017 post I quote an article from the FDA: “FDA Reports Crohn’s Disease Side Effects Have Increased, Analysis Finds. The article explains that ‘Drugs used to treat Crohn’s disease and other autoimmune disorders are among those with the greatest number of reported side effects filed with the U.S. Food and Drug Administration…’”
So hooray for this week’s tidbit! Researchers at the University of North Carolina have found, in an animal study, that a mixture of bacteria, which have been found at low levels – or missing entirely – from the guts of those with inflammatory bowel diseases (IBD) can both prevent and treat colitis.[i] Such a treatment would, of course, negate the need to use immunosuppressive drugs in those suffering from IBD: a light-years advancement in medicine. As these researchers say, “We believe that this approach has the potential to maintain long term remission in a physiologic and safe manner…” Well, hallelujah to that!
The products tested were made by a company called Gusto Global. GUT-103 has 17 strains of bacteria that work symbiotically and feed each other. GUT-108 is a more refined version, containing 11 strains of native human species of bacteria. The combinations of bacterial species are designed to extend the lifespans of the bacteria once they reach the gut. Prior to treatment with these mixes, germ-free mice were given human bacterial microbiomes. Then these probiotic mixes were given the mice three times per week. The formulas successfully decreased pathobionts (pathogenic bacteria) and protected commensal bacteria, while also promoting healing of the mucosal lining and boosting immune-regulation Said the lead researcher: “Simply put – the treatment increased the good guys and decreased the bad guys.”[ii]
GUT-103 “…prevented and treated chronic immune-mediated colitis.” GUT 108 , “…reversed established colitis in a humanized chronic T cell-mediated mouse model.”
Next steps of course are testing the mixes – especially GUT-108 – in humans: “These integrated protective mechanisms make GUT-108 a promising novel therapy to treat a range of conditions whose pathogenesis is characterized by dysbiosis-mediated chronic intestinal inflammation and increased mucosal permeability. Besides IBD this could include graft versus host disease, hepatic encephalopathy, alcoholic liver disease, atherosclerosis, hypertension, obesity, metabolic syndrome, and type-2 diabetes mellitus.”
I’m watching this space carefully so stay tuned!
[i] Daniel van der Lelie, Akihiko Oka, Safiyh Taghavi, Junji Umeno, Ting-Jia Fan, Katherine E. Merrell, Sarah D. Watson, Lisa Ouellette, Bo Liu, Muyiwa Awoniyi, Yunjia Lai, Liang Chi, Kun Lu, Christopher S. Henry, R. Balfour Sartor. Rationally designed bacterial consortia to treat chronic immune-mediated colitis and restore intestinal homeostasis. Nature Communications, 2021; 12 (1) DOI: 10.1038/s41467-021-23460-x