Remember last week when I told you all that I have a million great new pieces of research to write about? Well, things have only gotten worse(or is it better?!) since then. I found a bunch more stuff to keep us all very busy these next few weeks.
Which is good news, I guess!
Today I am turning back to the topic of helminths because I found a pretty incredible article on a topic that is of particular interest to me. As a nutritionist, one of my biggest concerns is the growing epidemic of obesity plaguing the industrialized world, as my regular readers know. A quick look at the latest statistics: according to the CDC, 39.8% of adults in the USA are obese (during 2015-2016)[i]. A 2017 article in Forbes points out that, “…nearly 4 in 10 U.S. adults have a body mass index classifying them as obese. Adult obesity rates have continued to increase steadily since the turn of the century, rising from 30.5 percent in 1999-2000 to 39.6 percent in 2015-2016, a record high. Young Americans have also been piling on the pounds and the obesity rate among the country’s youth (aged 2-19 years old) currently stands at 18.5 percent.” But that’s only a part of an increasingly-grim picture as, “…just over 70 percent of all Americans are either overweight or obese, meaning people with normal weight levels are now a minority.”
70%! Holy cow.
Over the years since starting this blog, I have looked at various pieces of research wherein scientists are trying to figure out the cause of this explosion of obesity. There is no simple answer: it’s most certainly not just “people are eating too much.” Yes, diet is a major piece (probably THE major piece – remember my post of a few weeks ago about increased consumption of fructose? ), but there are many other factors to take into consideration. For example, biome depletion also plays a major role.
In fact, back in April 2018, I wrote about research into bacterial microbiome alterations and obesity. In that experiment, scientists from the University of Chicago “…started with germ-free mice and found that even when fed high fat foods, they did not gain weight as the fats were excreted with their stool. However, mice who have a very high level of non-pathogenic gut bacteria, did gain weight. Very rapidly, the microbes in their small intestines changed, with increasing amounts of Clostridiaceae and Peptostreptococcaceae, the former of which in particular appears to be responsible for fat absorption. Levels of Bifidobacteriacaea and Bacteriodacaea, microbial families associated with leanness, rapidly decreased.”
So obviously diet is a key factor, and also, research into microbiome alterations associated with obesity continues to grow. But again, that is only one “ome” native to the human ecosystem. In March of 2018, I also wrote about research on the relationship of obesity to macrobiome depletion. Those researchers found that colonizing mice with the helminth, Heligmosomoides polygyrus (Hp), resulted in “…significantly attenuated obesity.” They noted that the colonized mice also had highly improved blood markers, like reduced glucose and triglyceride levels and higher levels of regulatory cytokines (which reduce inflammation), and they concluded, “The significant inhibitory effect of H. polygyrus infection on diet-induced obesity in our model supports the idea that helminth parasites, which infect millions of people worldwide, particularly in the developing world, may have beneficial metabolic effects. Our results also support the potential for helminths as a new class of biologics in treating inflammatory diseases and metabolic disorders….[R]esults from our study raise the intriguing possibility of using helminths as novel, safer and effective therapeutics in the treatment of obesity and other immune and metabolic disorders.”
So now, back to the pearl I discovered this past week.
Japanese researchers, expanding upon this helminth research, looked in detail at the mechanism by which helminths protect against obesity.[ii] As they point out, “Several lines of evidence indicate an inverse correlation between helminthic infections and obesity as well as inflammation-mediated disorders, suggesting that helminths may have suppressive effects on these diseases.” They go on to say though that the “…protective mechanism involved in how helminths suppress obesity are largely unknown.” So – they wanted to figure out how it all works.
There are several metabolic control systems in the body that are meant to protect us from obesity, including one that tells fat cells (adipocytes) to burn calories and convert them to heat, as opposed to storing them as more fat. There is a protein expressed in the mitochondria (the powerhouse of every cell in your body) of adipocytes called uncoupling protein 1 (UCP1). UCP1 tells the cell to convert fat and glucose (fuel) to heat as opposed to storing it as more fat. UCP1 is activated by the hormone norepinephrine (NE), which is a major chemical messenger in your body. NE is released from nerves, including those that are distributed through your body fat. So to summarize this: norepinephrine stimulates the production of UCP1, which, in turn, tells the fat cell to burn and not store fat.
Back then to our Japanese scientists…
They fed mice high fat diets which rapidly cause major weight gain. Again though, as in the previous study, those mice who were given helminths first (also Hp) were protected from gaining weight. In fact, the obese mice who were given helminths and who were still continually fed a high fat diet actually lost weight and had improved dyslipidemia (elevated bad cholesterol/low good cholesterol). These findings completely replicated those of the 2018 study.
As these scientists knew that the presence of helminths beneficially improves the bacteria of the gut (increasing beneficial, anti-inflammatory species and decreasing pathogenic, pro-inflammatory ones), they hypothesized that this protective effect was due to this modulation of the bacterial microbiome. And guess what? “We found that helminthic infection affected gut bacteria, resulting in increased NE production that upregulated UCP1 in adipose tissues.” Wow, right?!
To double check that they had correctly pinpointed the mechanism of action, they first gave some mice an agent to essentially block norepinephrine in the adipocytes. Sure enough, even mice with the helminths on board gained weight: “Thus, the protective role of Hp infection against obesity is dependent on NE, presumably by inducing UCP1 for energy expenditure in adipocytes.” They then wanted to make sure that the source of the increased norepinephrine was the gut bacteria and not the mice’ own nervous systems. They noted that giving a chemical to block NE production led to a “completely suppressed NE production in adipose tissue” BUT mice who had helminths “still contained substantial amounts of NE after treatment…suggesting the existence of other sources of NE besides sympathetic nerves.” They treated a group of mice with antibiotics to reduce the intestinal bacteria and found that doing so, “…decreased both the NE concentration and expression of UCP1 in Hp-infected obese mice, resulting in the attenuated suppression of weight gain.” So yup, the source of the protective norepinephrine in the helminth-colonized mice was the gut bacteria.
Much to my delight, they did then zero in on which bacteria were producing the NE. Mice that were given helminths had more Firmicutes and Proteobacteria compared to the mice without helminths and “…previous studies reported that two bacteria genera, Bacillus and Escherichia belonging to Firmicutes and Proteobacteria, respectively, produced NE in the intestines.” Levels of both were greatly increased in the mice with helminths and “…NE concentration in Hp-infected obese mice was closely correlated with the amount of those bacteria.” That is, the more Bacillus and Escherichia in the intestine, the higher the levels of norepinephrine.
Obviously, these findings have yet to be replicated in humans. We can only hope, as always, that such studies happen soon as we, in the industrialized world, only continue to get fatter and rates of obesity-associated illnesses continue to climb.
[ii] Shimokawa, C, Obi, S, Shibata, M, Olia, A, Imai, T, Suzue, K, Hisaeda, H. Suppression of obesity by an intestinal helminth through interactinos with intestinal microbiota. American Society for Microbiology: Infection and Immunity. 2019. Apr 2019, IAI.00042-19; DOI: 10.1128/IAI.00042-19
So many interesting things to write about…so little time!
Last October, I wrote a post about spondyloarthropothies, which is a family of autoimmune diseases that affect the spine. These include Ankylosing spondylitis, psoriatic arthritis, arthritis related to inflammatory bowel disease, reactive arthritis, and juvenile idiopathic arthritis. There has been a suspicion for some years now that the gut biome was related to the onset and progression of these diseases. As I emphasized in that post, while these diseases remain strangely unfamiliar to most people – as opposed to the well-recognized rheumatoid arthritis, multiple sclerosis, Parkinson’s disease, etc. – at least 2.7 MILLION people suffer from these diseases in the USA alone, which is almost 3X the number of people that suffer from the way better known Parkinson’s disease alone, for example!
I’ve thus kept an eye out for anything new, as you can imagine as I am quite sure I have readers who suffer from these illnesses, or know someone who does. I was happy to see a newly published paper which took an in-depth look at the biome differences between those with Ankylosing spondylitis (AS), the best studied in this family of illnesses, and healthy controls.[i] The results were fascinating.
The study included 22 patients with AS and 16 healthy controls (HC). They found major differences in the bacterial microbiomes between the two groups, including a “significant increase” in diversity in the AS group that included a nearly 3-fold increase in Proteobacteria and a decrease in Bacteroidetes species, including Prevotella. The bacteria of the AS group, “…showed that the gut bacteria in AS patients expressed more abundant genes involved in human diseases….” As I pointed out in that October post, “A 2007 study: patients with AS were given Moxifloxacin, an antibiotic that works against both Gram-positive and negative bacteria. The results ‘…have shown that AS patients treated with Moxifloxacin resulted in a significant and sustained improvement…Serum inflammatory markers were greatly reduced after 12 weeks.’” If these results hold up in further studies, i.e. the increased levels of disease-causing bacteria in the guts of those with AS, the improvements seen using an antibiotic actually make a whole lot of sense.
What really interested me even more though was this: “…a more pronounced fungal dysbiosis than bacterial dysbiosis in AS patients was detected in this study. We observed a significant decrease in the diversity of intestinal fungi in these patients….” The ratio of fungi to bacteria was also significantly decreased. That is, there are proportionally way too many bacteria and too few fungi, in comparison to the healthy controls. Seeing as these two kinds of organisms tend to keep each other balanced, it’s not surprising that this ratio is off, considering the high levels of bacteria found. This study was the first time anyone has looked at this aspect of the human biome in sponylitis.
The results were so striking that the researchers flat out state that their findings “…suggest an alteration of the entire ecosystem in the guts of AS patients.”
Also of note: the degree of mycobiome alterations coincided with disease severity: “…the patients with level III and IV [i.e. more severe] damage in their spines had different fungal microbiota structure than patients with level II damage or healthy controls.” They state, “These results suggested a possible role of the mycobiome in the development of AS.”
By the way, there was also a correlation between blood markers for inflammation (like C-reactive protein (CRP)) and fungal dysbiosis. In fact, the scientists compared those undergoing treatment for AS (using the biologic medication, Enbrel, or using NSAIDS (non-steroidal anti-inflammatory medications)) to those newly diagnosed who had not as yet started treatment. These anti-inflammatory treatments had “…profound effects on changing specific gut microbial and fungal groups, which may be associated with altered disease activities in AS patients…” That is, lowering inflammation levels via treatment seems to have a major effect on the composition of the gut biome.
Seems to me this is a pretty major step forward in spondyloarthritis research and almost more exciting to me, is to read a paper wherein more than just the bacterial content of the gut was taken into account. I hope this becomes a trend as I am quite sure, similar dysbiotic issues are factors in other inflammatory diseases as well.
[i] Li, M, et. al. Altered bacterial-fungal interkingdom networks in the guts of Ankylosing Spondylitis patients. mSystems. 2019;4(2). DOI: 10.1128/mSystems.00176-18
Well – I am feeling somewhat overwhelmed! A brief internet search yesterday morning, in which I was looking for new and interesting research, led me to 10 papers that I want to read and write about for you. Considering that it takes quite a while to make my way through scientific papers…I have my work cut out for me the next couple of weeks! On the bright side, lots of interesting stuff for you to read about.
So for today, I’ve settled on a general review of nutritional approaches to treating autism (ASD).[i] I’ve written many times before (here and here, for example) about biome alterations in the population and am, of course, always on the look out for “things you can do now” papers to treat this. While far from comprehensive, there were enough items of interest in it to warrant a mention in my blog.
The authors’ conclusion: “It is reported than in individuals with ASD, while the gluten-free casein-free and KDs [ketogenic diets], camel milk, curcumin, probiotics, and fermentable foods can play a role in alleviating ASD symptoms, the consumption of sugar, additives, pesticides, genetically modified organisms, inorganic processed foods, and difficult-to-digest starches may aggravate symptoms.”
Helpful information to know but as I mentioned above, as far as I’m concerned it’s incomplete. There are simply not enough studies done to really draw any conclusions, even about those treatments they mention, let alone therapies like the Specific Carbohydrate Diet, which anecdotally is unbelievably effective…but mostly untested in proper clinical trials.
[i] Cekici, H and Sanlier, N. Current nutritional approaches in managing autism spectrum disorder: a review. Nutritional Neuorscience. 2019;22(3):145-155.
A week ago or so, I got an email from a company that makes a really interesting prebiotic product. They offered to let me try it out on myself, and after looking through their website, I readily agreed. (I took my first dose this morning.) I also asked them for any literature they may have on the product and was sent 4 papers, including two small clinical studies. There were certainly enough items of interest in these to share with you, even though I have not had time to test the product first. After all, you know that I am always looking for “things we can do now” to improve our health!
The product is called Biome Bliss, and in the research papers, it is referred to it as a GIMM (gastrointestinal microbiome modulator). It has 3 components: the prebiotic fiber, inulin (isolated from agave); the prebiotic fiber, beta-glucan (isolated from oats); and polyphenols (anthocyanins, isolated from blueberries). If you remember, I have written about polyphenols multiple times before, as they are not only powerful antioxidants but also have prebiotic properties. In fact, I myself have been using grapeseed extract and Triphala for many months now. Polyphenols from blueberries also have profound effect on glucose/insulin metabolism. These 3 ingredients were specifically chosen to work in harmony, encouraging the growth of specific gut bacteria that help modulate glucose levels (I have also written several times about this subject), improve short-chain fatty acid production (which you all know are highly anti-inflammatory), reduce feelings of hunger, improve bowel regularity and other health benefits, including improved GI health: “B-glucans and inulin-type fructans are prebiotics that are not only preferentially fermented by specific types of bacteria, but also promote proliferation of the bacterial species such as Bifidobacteria. These bacteria are associated with a beneficial impact on the host through their potential involvement in diabetes-related inflammation and the development of obesity.”[i] B-glucan from oats also “…protects the intestine’s mucosal lining and supports the immune system.”[ii] By the way, I should mention that the product is fine for those on low- or controlled-carbohydrate diets as the sugars have been mostly removed.
One of their studies was double-blind and placebo controlled, which involved 28 (randomized to 2 groups) overweight/obese individuals with high fasting blood glucose levels. One group was put on the GIMM, the other a placebo, which they consumed twice daily for 4 weeks. The experimental group did notice an increase in flatulence (which is not surprising as fiber should really be increased slowly to give the GI bacteria time to adjust), but reported no meaningful adverse effects. The study found that, after eating, glucose levels rose less in the experimental group than in those taking the placebo and also, those taking the prebiotic showed a reduced desire to eat. There was an increase in their blood levels of the hormone PYY (release of this hormone is stimulated by SCFAs), which makes you feel full, and a decrease in another hormone, ghrelin, which makes you feel hungry. They did find an increase in the levels of fecal SCFAs, but this did not reach statistical significance. However, they also saw a decrease in fecal pH, which indicates improved gut fermentation of the prebiotic fibers.
The 2nd study, which was done on overweight people with type 2 diabetes who were also taking the diabetes medication, metformin, found too that “…fasting glucose decreased more during the period when metofmin was combined with GIMM compared to metformin combined with placebo.”[iii]
The other two papers are general discussions of the importance of prebiotics to health, and there were several interesting items to share.[iv]
Over the years, I have worked with innumerable people, both adults and children, with a wide variety of inflammatory disorders as well as issues with weight, metabolic syndrome, and so forth. There is a reason I write about prebiotics so often! Research done in the last 15 years or so has shown that the addition of prebiotics to the diet is as important – if not MORE important – than the use of probiotics. I am looking forward to giving this product a try and will report back to you all after a month or so of use. I hope some of you will try it along with me so we can compare notes! Email me and let me know!
[i] Rebello, CJ, Burton, J, Heiman, M, Greenway, F. Gastrointestinal microbiome modulator improves glucose tolerance in overweight and obese subjects: a randomized controlled pilot study. Journal of Diabetes and Its Complications. 2015;29(8):1272-6. doi: 10.1016/j.jdiacomp.2015.08.023
[ii] Cervantes, ER and Pfost, D. Prebiotics & Metabolic Regulation Benefits Beyond the Gut. Naturopathic Doctor News and Review. 2019. https://ndnr.com/gastrointestinal/prebiotics-metabolic-regulation-benefits-beyond-the-gut/
[iii] Burton, JH, Johnson, M, Johnson, J, Hsia, DS, Greenway, FL, Heiman, ML. Addition of a gastrointestinal microbiome modulator to metformin improves metformin tolerance and fasting glucose levels. Journal of Diabetes Science and Technology. 2015; 9(4):808-14. doi: 10.1177/1932296815577425
It’s not often that I get to write about the more esoteric members of our gut biomes. Our bacteria get the most hype in the scientific literature, but as you all know, there are many other kinds of residents of our inner ecosystems. I was excited, therefore, to spot an article late last week about Archaea.[i]
Let me start with a definition: “Archaea [which is pronounced ar-key-a] are organisms whose cells lack a defined nucleus. They are not bacteria (their cell walls are different) and they are not eukaryotes (which are complex, multi-celled organisms, including plants and animals, whose cells do have a defined nucleus). Many are found in anaerobic (without air) environments, including hot springs, marshes and the guts of animals and humans.[ii]
A study just published in the Journal of Allergy and Clinical Immunology[iii] looked at the relationship of gut Archaea to the development of childhood asthma. The researchers found that high levels of a species, Methanosphaera stadtmanae, were associated with a lower risk for asthma. They analyzed 472 samples in total, and concluded that, “…the presence of M. stadtmanae was associated with a lower risk for asthma at 6 to 10 years of age.” Higher levels of this organism are also somewhat associated with a lower risk for eczema, airborne allergies and food allergy, but not to the point of reaching statistical significance. They have not, as yet, figured out the mechanism of action, but believe their results were meaningful enough to indicate that a beneficial link very likely exists.
I myself know very little about Archaea, so thought I’d do some snooping around to see what other kinds of information I could glean to share with you. I did find some interesting papers. For example, just this past February, a paper was published looking at Archaea’s involvement in the development of abscesses. An interesting couple of sentences from the abstract: “They have been implicated in dysbiosis of the oral microbiota…They have also been associated with dysbiosis of the digestive tract microbiota linked to metabolic disorders (anorexia, malnutrition and obesity) and with lesions of the digestive tract (colon cancer).”[iv]
Perhaps the most interesting thing I found was a paper from last year which took an in-depth look at what we currently know about Archaea’s involvement in human health and disease.[v] They state that the role these organisms play has been vastly underrated: “It has been reported that the impact of methanogens [methane producing Archaea] of the gut microbiota on pathological conditions has been grossly underestimated. Methanobrevibacter smithii and Methanosphaera stadtmanae are specifically recognized by the human innate immune system, and it is considered that these species contribute to immune responses in the body, including inflammatory responses.” These organisms are found in the gut, on the skin, in the vagina, and in the mouth, including in dental plaque (with one species, Methanobrevibacter oralis, being significantly associated with periodontal disease). Whether or not though most are beneficial or pathogenic is currently unknown, but it seems likely that, like bacteria, helminths, etc, some species are good, some are bad, and perhaps, some can be both depending on circumstances.
An example of this (i.e. a species being beneficial or pathogenic, depending on circumstance): higher levels of certain Archaea are found in obese people. It is believed the organisms may improve the efficiency of energy (calorie) absorption from food. However, in those with anorexia, higher levels of the species, M. smithii, have been found, which would “lead to increased energy efficiency in severely low caloric diets.” The increased levels of the species may be the result of the body’s attempt to survive in the face of starvation.
There does seem to be a link between some Archaea and inflammatory bowel disease because they do seem to evoke an inflammatory response. That said, a 2012 study showed lower levels of Archaea in those with IBD as opposed to healthy individuals but there is some belief this is because diarrhea would lead to a reduction in numbers. No one is yet sure though.
There may also be associations between Archaea and irritable bowel syndrome, diverticulitis and periodontal disease. Their conclusion, “Several studies in the last decade directly or indirectly suggested a link between methanogens and a number of metabolic diseases. In addition…methanogens should be considered as an important target for the studies relating to modulation of the gut microbiota in humans for improving health or reducing risk of disease. Consequently, there is merit in proposing dietary intervention studies targeting the manipulation of archaeal components of the gut microbiome…This concept could even be extended to consider their use as a probiotic whereby live preparations of archaea could be used as dietary supplements (archaeobiotic).”
I reckon we are a long way from being able to buy Archaea probiotics. On the other hand, at least we know scientists are starting to take a meaningful look at these organisms which undoubtedly play a huge role in our biomes and thus, in our health. I will of course keep a close eye on developments!
[iii] Barnett D, Mommers M, Penders J, Arts ICW, Thijs C. Intestinal archaea inversely associated with childhood asthma [published online February 20, 2019]. J Allergy Clin Immunol. doi:10.1016/j.jaci.2019.02.009
[iv] Sogodogo, E, Drancourt, M, Grine, G. Methanogens as emerging pathogens in anaerobic abscesses. European Journal of Clinical Microbiology and Infectious Diseases. 2019. doi: 10.1007/s10096-019-03510-5
[v] Chaudhary, PP, Conway, PL, Schlundt, J. Methanogens in humans: potentially beneficial or harmful for health. Applied Microbiology and Biotechnology. 2018. DOI:
Today’s post is a little off topic but I can’t not share this research[i] with you, especially considering the post I wrote a few weeks back about “lysogenic” bacteria. If you remember, it was about those types of bacteria that carry dormant viral DNA in them, which, when subjected to the right environmental circumstances, produce bacteriophages (viruses that kill bacteria) that kill their own bacterial hosts. One of the factors that triggers this phage production is fructose. The exact metabolic purpose of this is still unknown, but certainly there exists the possibility that the huge increase in our fructose consumption in the last 30+ years or so (from the addition of high fructose corn syrup (HFCS) in so many foods) has adversely altered our bacterial microbiomes by excessively stimulating this production of bacteriophages.
In that post, I pointed out that, “…since the 1970s, and the ever-increasing inclusion of high-fructose corn syrup (HFCS) into our diets, our consumption of this sugar has increased fourfold.” According to the Food Research and Action Center, “Obesity rates have more than doubled in adults and children since the 1970’s…The latest data indicate that 39.6 percent of U.S. adults are obese. (Another 31.6 percent are overweight…)”[ii] A 2017 article[iii] on Medical News Today about research conducted by scientists from Imperial College London, in collaboration with the World Health Organization, points out that, “…obesity in children and teenagers is 10 times higher now than it was in 1975, and that 5 years from now, more will be obese than underweight.” The study was massive: 1000 researchers looked at the records of 130 million people living in 200 countries around the world, and found: “… in 1975, there were 5 million girls who were obese, and in 2016, this number rose to 50 million. The report counted 6 million boys with obesity in 1975, but this number spiked to 74 million in 2016. Last year, an additional 213 million children and teenagers were found to be overweight.”
There isn’t actually much controversy over whether or not all the added fructose is a part of the reason for this increase in obesity – and subsequent type 2 diabetes rates. How much it’s a factor though is of course still unknown.
Bearing all this in mind then: I found a recent article out of the Baylor College of Medicine and Weill Cornell particularly interesting. The study, which was published in the journal, Science, looked at the relationship between the consumption of even a “moderate” amount of HFCS (the equivalent of about 12 ounces of soda per day) and the growth of intestinal tumors. Says one of the authors, “”An increasing number of observational studies have raised awareness of the association between consuming sugary drinks, obesity and the risk of colorectal cancer…The current thought is that sugar is harmful to our health mainly because consuming too much can lead to obesity. We know that obesity increases the risk of many types of cancer including colorectal cancer; however, we were uncertain whether a direct and causal link existed between sugar consumption and cancer.”[iv]
To find out more about this potential link between fructose and colon cancer, the researchers created a mouse model wherein they delete a gene responsible for creating a protein called APC. Without APC, “…normal intestinal cells neither stop growing nor die, forming early stage tumors called polyps. More than 90 percent of colorectal cancer patients have this type of APC mutation.”
When given sugar water (with HFCS) to drink at will, the APC mice rapidly became obese. To prevent this, and to model humans drinking one can of soda, they limited the daily sugar water to a mouse equivalent. After 2 months of this limited amount, the mice did not become obese but they did develop tumors that were “larger and of higher-grade” than the mice given regular water to drink. The APC mice that were treated with the HFCS, “…showed a substantial increase in tumor size and tumor growth in the absence of obesity and metabolic syndrome. HFCS increased the concentrations of fructose and glucose in the intestinal lumen and serum [blood], respectively, and the tumors transported both sugars.” [i]
Summarizing their findings, the lead researcher states, “These results suggest that when the animals have early stage of tumors in the intestines — which can occur in many young adult humans by chance and without notice — consuming even modest amounts of high-fructose corn syrup in liquid form can boost tumor growth and progression independently of obesity….[O]ur findings in animal models suggest that chronic consumption of sugary drinks can shorten the time it takes cancer to develop. In humans, it usually takes 20 to 30 years for colorectal cancer to grow from early stage benign tumors to aggressive cancers.”
Another scientist involved in the work states, “This observation in animal models might explain why increased consumption of sweet drinks and other foods with high sugar content over the past 30 years is correlating with an increase in colorectal cancers in 25 to 50-year-olds in the United States…”
Remember though too how rapidly the mice which were allowed as much sugar water as they chose to drink became obese. And remember too that fat excretes huge amounts of pro-inflammatory chemicals. So while the accelerated tumor growth was independent of weight gain, obesity is only going to worsen the issue.
To find out how the fructose led to this increased tumor growth, the scientists investigated further and found high levels of fructose and glucose (both of which are found in sugary sodas) left in the colon – and in the blood. Cancerous tumors eat sugar. Further experimentation showed that, “…colorectal cancers utilize high-fructose corn syrup, the major ingredient in most sugary sodas and many other processed foods, as fuel to increase rates of tumor growth….While many studies have correlated increased rates of colorectal cancer with diet, this study shows a direct molecular mechanism for the correlation between consumption of sugar and colorectal cancer.”
So to sum up, it appears that our increasing consumption of HFCS may be in part not only responsible for microbiome alterations, but also the ever increasing rates of obesity and type 2 diabetes found around the globe…as well as the increasing rates of colorectal cancers. I obviously don’t know how all this is intertwined (after all, biome depletion also leads to increased inflammation, alterations in how food is digested, and so forth), but I’m sure it is somehow all connected. How much of the guilt HFCS bears is still unknown, but certainly, I think we know enough to absolutely avoid the stuff in our diets.
[i] Marcus D. Goncalves, Changyuan Lu, Jordan Tutnauer, Travis E. Hartman, Seo-Kyoung Hwang, Charles J Murphy, Chantal Pauli, Roxanne Morris, Sam Taylor, Kaitlyn Bosch, Sukjin Yang, Yumei Wang, Justin Van Riper, H Carl Lekaye, Jatin Roper, Young Kim, Qiuying Chen, Steven S. Gross, Kyu Y. Rhee, Lewis C. Cantley, Jihye Yun. High-fructose corn syrup enhances intestinal tumor growth in mice. Science, 2019; 363 (6433): 1345-1349 DOI: 10.1126/science.aat8515
A short article about helminths and inflammatory bowel disease [IBD] was just published, and is absolutely worth a read (and post).[i] I’d almost call it an op-ed piece. It reads like this researcher is berating a medical system that is ignoring an obvious solution to treating IBD.
The article starts by point out that “Inflammation plays a pivotal role in the pathogenesis of IBD that induces mucosal inflammation. Hence, treatment of IBD mainly targets on inhibition of pro-inflammatory mediators.” However, current treatments are pretty horrific. I wrote about the incredibly high side effect profile of the currently available medications almost 2 years ago, in April 2017. If you remember, I described an FDA report that concluded, “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…Drugs which suppress the immune system to fight inflammation can cause serious and sometimes lethal infections including tuberculosis, and have been linked with blood disorders, including lymphoma, a blood cancer.”
Back to this new little article: the author goes on to give a brief explanation of what we know about how helminths modulate the immune system, i.e. invoking a Th2 immune response that boosts levels of “…Treg cells to release immunoregulatory cytokines…” He goes on to further state that bacterial microbiome alterations are known to lead to the inflammatory response in IBD, but that helminths, “…can maintain microbiota of the GI in order to induce anti-inflammatory responses.” Thus, therapeutic helminths both raise levels of regulatory T-cells and cytokines (the off-switch to the pro-inflammatory system) while also improving and maintaining the quality of the bacterial microbiome, which also drastically reduces inflammation.
He then points out that benign helminths, like Trichuris suis ova (TSO) – which are whip worms native to pigs – have been shown in multiple human trials to have “no pathogenic potential for humans” and “has shown no side-effects.”
So his conclusion – which seems pretty obvious to everyone – except the world’s regulatory agencies: “Inasmuch as the resolution of inflammation is a therapeutic target of IBD and helminths have great immunomodulatory properties, helminth-based therapy may be efficacious for patients with IBD.”
As I have said before, I continue to live in hope that someday, someone with actual power AND common sense will listen.
[i] Abdoli, A. Therapeutic potential of helminths and helminth-derived antigens for resolution of inflammation in inflammatory bowel disesase. Aarchives of Medical Research. 2019. doi: 10.1016/j.arcmed.2019.03.001
Yesterday, I found a great complimentary article[i] to my Tuesday post regarding lack of exposure to commensal organisms and the development of asthma in children. This is another “it’s biome depletion not the darn ‘hygiene hypothesis’” kind of story!
Background information: babies are exposed to their first major onslaught of commensal organisms during the birth process. In an ideal world, the breast milk they are then fed for those first crucial few months leads to the development of a robust infant microbiome (consisting mainly of bifidobacteria and lacobacilli) with the oligosaccharides (prebiotics) in the milk being crucial for the developing biome.
Using a mouse model, researchers at the Institut Pasteur and Inserm looked at what happens in infants when solid food is first introduced and it’s pretty amazing.
Apparently, when solid food is introduced – typically between 3 and 6 months in humans (equivalent to two to four weeks for mice) – the number of bacteria increases 10- to 100-fold, and this rapid increase “…triggers an intense immune response,” which these scientists call a “weaning reaction.”[ii] This reaction occurs at a very critical time in immune development.
This rapid change in the microbiota (which of course also includes a major increase in bacterial metabolites) and the subsequent immune response (which consists of a huge increase in regulatory cytokines, which are the off-switch to the inflammatory system) is critical to normal immune development. When the scientists treated the infant mice with antibiotics during this crucial time window, disrupting this weaning reaction, they found that the mice were far more likely to develop inflammatory disorders, including allergies, colon cancer and inflammatory bowel disease. Thus, they conclude that if the microbiome is decimated by antibiotics very early in life, the weaning reaction will fail to occur…and since the production of regulatory cells during the weaning reaction requires bacterial metabolites, like short chain fatty acids, the infant is set up for low levels of Treg cells and an abnormal immune response throughout life.
Says Dr. Gerard Eberl, the lead author of the study, “This is what is known as pathogenic imprinting…that is to say, events occurring in early childhood determine future susceptibility to inflammatory disorders.”
During the many years I’ve worked as a nutritionist, I have noted that the single most common thread in the children I’ve seen – many of whom had autism and/or ADHD as well as gastrointestinal issues – was early introduction of antibiotics. (My own son, Alex, who is autistic and has a history of major immune issues and inflammatory bowel disease) was put on 5 days of IV antibiotics starting at 36 hours old, during which time he ceased to breast feed and I was forced by the hospital staff to start him on formula.) I’ve read many articles over the years exploring the connection of early antibiotics to later immune issues and finally, 25 years later, it looks like scientists have finally discovered the mechanism of action. As sometimes antibiotics cannot be avoided, with all my heart, I hope this rapidly leads to a therapeutic solution.
Dr. William Parker of Duke University Medical School, an eminent researcher into the effects of helminths on the immune system among other specialties, wrote a commentary in 2014 in the British Medical Journal entitled, The “hygiene hypothesis” for allergic disease is a misnomer.[i] His point is that it is not excessive hygiene that has led to our current epidemic of allergic, autoimmune and inflammatory disorders but biome depletion – the human body’s loss of commensal organisms with which we coevolved, and without whom our immune systems lack the necessary stimulation to function properly. As Dr. Parker states, “…a lack of handwashing often results in an increased incidence of flu and other acute infections, many of which exacerbate rather than mitigate allergy and autoimmunity. Furthermore, modern hygienic practices often alleviate, not increase, allergy—by reducing the levels of allergens produced by organisms such as dust mites, cockroaches, and mold. Thus, allergies and autoimmune diseases are not caused by ‘hygiene’ as people now think of it.”
That is, not washing your hands after using a shopping cart will set you up for a cold or the flu. But this will do nothing to modulate a chronic, excessive inflammatory response caused by a hyper-reactive immune system.
Thus, Dr. Parker has been very vocal about discontinuing the use of the phrase “hygiene hypothesis,” and instead, strongly promotes using the term biome depletion, which is not a hypothesis, but, as he states emphatically, a paradigm of modern medicine.
I am reminding you of this today for a very good reason. My regular readers already know that sensationalism in medical news makes me crazy. (You can read more of my rantings here, for example.) This past week, it was an article from Men’s Health that set me off: Why You Should Be Picking Your Nose and Eating Your Bogies to Boost Your Immune System? [ii] From the article: “According to Dr. Meg Lemon, a dermatologist treating people with allergies and autoimmune disorders, you should be picking your nose and eating the bogies and whatever else you scoop out of there in order to boost your immune system. Seriously. Dr. Lemon also says that people should be eating food they drop on the floor in order to expose the body to a range of germs that could help boost the body’s natural defenses and make people more resilient to infections and allergies.”
“Seriously”? This is what an issue with global health implications is reduced to? The cure is eating snot and dirty food?
This same story was also written up in Business Standard[iii] which (after giving the snot eating plenty of virtual ink), at least, went on to state, accurately: “Thanks to all the powerful learning we’ve done as a species, we have minimized the regular interaction not just with parasites but even with friendly bacteria and parasites that helped to teach and hone the immune system — that ‘trained’ it. It doesn’t encounter as many bugs when we are babies. This is not just because our homes are cleaner, but also because our families are smaller (fewer older children are bringing home the germs), our foods and water cleaner, our milk sterilized. Some refer to the lack of interaction with all kinds of microbes we used to meet in nature as the ‘old friends mechanism.’”
In this vein, I just read an interesting little article describing a study that came out in early January wherein researchers looked into the mechanism by which exposure to commensal bacteria alleviates asthma: Mechanism for impaired allergic inflammation in infants may explain hygiene hypothesis.[iv] They found, “…that infant mice need a higher exposure to a bacterial endotoxin [byproducts of many bacteria], compared to adult mice, to avoid developing asthma-like reactions to house dust mites.” That is, without higher levels of exposure to the byproducts of commensal bacteria (as compared to adult mice), the infant mice developed asthma after repeatedly being exposed to dust mites. And this phenomenon existed only during a certain window of development – the equivalent of human infants and toddlers. Interestingly, if the exposure to dust mites occurred simultaneously with a dose of bacterial endotoxins, the mice did not develop asthma. Bearing in mind that about 10% of school-age children in the USA now have asthma, this is a pretty key bit of research.
I won’t go into detail about their immune system findings which explain the mechanism of action, except to say that in infant mice, certain chemicals were not upregulated when the exposure to the bacterial endotoxin was too low, and this led to the production of certain proinflammatory immune cells. (In contrast, in adult mice, even a small amount of the bacterial endotoxin led to a much higher production of these chemicals, which prevented immune cells from differentiating into pathogenic, proinflammatory ones.)
They conclude, “Our data, therefore, provide a plausible mechanism underlying the higher susceptibility to allergic airway inflammation observed in children raised in uber-clean and sanitized environments.”
To sum up: that there is a huge difference between acute-disease causing “germs,” (like cold and flu viruses) and the commensal organisms that are native to our bodies and a natural part of our ecosystem’s biome. I’m all for biome enrichment but rest assured, I always wash my hands when I come home from the supermarket!
Here’s a topic I haven’t written about much: single-cell eukaryotes. A eukaryote is a living organism whose cells contain a nucleus (in which genetic material is contained) within a membrane. Thus, in the world of living things, only bacteria and archaea (which is sort of a kind of bacteria) are not eukaryotes. Protozoa, which I wrote about once before, are eukaryotes and as I pointed out, there are many single-celled organisms in the human biome that are not yet well studied.
One that is pretty well-known though – which many of you may have heard of – is Blastocystis, which up until now, was generally thought to be benign. Bearing that in mind, I thought it interesting that in my work as a nutritionist, I have come across many people who were thought to be experiencing GI issues from the organism. I have often wondered why it’s generally harmless – and yet, at times seems pathogenic. I took a wild guess that perhaps it had to do with the state of the biome, in general: perhaps, in people with inflammatory issues and dysbiosis, the organism caused a different reaction???… kind of like H.pylori which at times, is benign, at times, most certainly not.
As it turns out, the answer may be simpler. A group of researchers in Singapore have discovered a subtype of Blastocystis, ST7, that destroys probiotic bacteria in the gut.[i] Thus far, it’s only been found in Singapore, Japan and in one Danish study. But that’s simply because no one has been looking for it.
Blastocystis is, according to this paper, incredibly common, with at estimates claiming it is present in at least 1 billion people worldwide.
This strain of Blastocystis apparently induces oxidative stress in the gut. The molecules released (reactive oxygen species) kill Bifidobacterium. The Blastocystis also reduces Lactobacillus, although the mechanism of action for this is not yet known. Worse still, this type of Blastocystis also works with E.coli to kill even more probiotic bacteria. Remember a few weeks ago when I described gut bacteria carrying their own viral killers? It turns out that both E.coli and Bifidobacterium help Blastocystis to grow better.
“The results of this study indicated that Blastocystis can disrupt gut microbiota populations particularly decreasing the content of Bifidobacteria and Lactobacillus but increasing Escherichia coli. Possible explanations of these occurrences point to oxidative stress caused by Blastocystis as well as host factors induced by the parasite. Our data indicates that while Blastocystis spp. may be a member of healthy gut microbiota, specific isolates or rare ST may disrupt homeostasis leading to pathological states in the host.”
Blastocystis ST7 also injures the gut lining by triggering an inflammatory response, “…causing lesions (ulcers) and a disordered structure of the intestinal lining…Add to this the loss of the protective good bacteria, an infection with Blastocystis ST7 could be a recipe for long-term damage to the gut lining, possibly contributing to inflammatory bowel disease, irritable bowel syndrome, as well as gastrointestinal and colon cancers.”[ii]
Worst of all, it is resistant to metronidazole (Flagyl), which is the medicine most often used to treat Blastocystis. By the way, in case you are wondering, the organism is transmitted via food that has been contaminated with feces from infected animals (especially birds). Nice thought. (not)
Other subtypes of Blastocystis are strongly associated with a healthy gut. Several studies support this idea, one of which did look at subtypes of the organism and found ST1 and ST3 which “…are associated with asymptomatic infections.” Thus, the authors point out, the other studies – upon which the notion is based that Blastocystis is commensal – could have used subjects “…colonized with subtypes associated with lower pathogenic potential and may be associated with healthy gut microbiota.” One other epidemiological study though did find that the subtype ST4 (which has “moderate pathogenic potential”) was associated with irritable bowel syndrome and dysbiosis (and the populations infected had significantly lower levels of Bifidobacterium and Lactobacillus). Overall then, these scientists conclude that these findings, “…corroborate with the results of this study, both suggesting that virulent subtypes of Blastocystis are more likely to be associated with dysbiosis, and its pathological outcomes, including IBD and IBS.”
This could I imagine be a huge finding for those suffering from these illnesses. The question that is not addressed in the paper though is: as it’s resistant to the currently used medication, what do you do about it?!
[i] ohn Anthony Yason, Yi Ran Liang, Chin Wen Png, Yongliang Zhang, Kevin Shyong Wei Tan. Interactions between a pathogenic Blastocystis subtype and gut microbiota: in vitro and in vivo studies. Microbiome, 2019; 7 (1) doi: 10.1186/s40168-019-0644-3