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
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.