Yesterday morning, I posted a story on my Biome Buzz’ Facebook page about 2 new studies that independently showed that there is a distinctive microbiome composition associated with colorectal cancer.[i] One study “…identified a set of 29 species indicative of colorectal cancer across 7 countries,” while the other showed “…higher gut microbiome richness” than controls, which ordinarily sounds like it should be a good thing but in this case, that richness came from bacteria that are native to the mouth that had moved to the colon, where they are not meant to be. This led to altered glucose metabolism in the large intestine, as well as the “putrification” of amino acids, etc.
I read that article with great interest as I was intending to start writing this post about a recent summary of what we currently know about using probiotics in treating and preventing cancer – and you all know I love coincidences![ii]
Upon reading this new article, the first thing that struck me was how long ago research into the connection of cancer to the gut bacteria began. Back in 1980, two researchers (Goldin and Gorbach[iii]) first demonstrated an, “…association between a diet enriched with Lactobacillus and a reduced incidence of colon cancer (40% vs. 77% in controls)”! That’s almost 30 years ago! And so very little progress, really, has been made since then. Of course though, thankfully, there has been at least some.
So a few highlights:
Unfortunately, as I said earlier, all this research – as promising as it is – is still pretty early stage, as most studies have been done in animals. On the bright side, I hope with all my heart (considering how many people I already know who have had to fight (and all-too-often succumbed to) cancer: “…evidence from the latest studies points towards the idea of possible implementation of probiotics in cutting-edge cancer therapy.”
[ii] Gorska, A, Przystupski, D, Niemczura, MJ, Kulbacka, J. Probiotic bacteria: a promising tool in cancer prevention and therapy. Current Microbiology. https://doi.org/10.1007/s00284-019-01679-8
[iii] Goldin BR, Gorbach SL (1980) Effect of Lactobacillus acidophilus dietary supplements on 1,2-dimethylhydrazine dihydrochloride-induced intestinal cancer in rats. J Natl Cancer Inst64:263–265.
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.
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:
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.