GUT BUGS ARE CRITICAL FOR OVERALL HEALTH & AUTOIMMUNITY PREVENTION
(BUT DON’T FORGET THE VITAMIN D!)
As long as there is balance in the microbiome, the immune system idles softly, ready for immediate response if called upon. However, when there is a disruption in gross numbers or ratios of these organisms (DYSBIOSIS), the end result is sickness and disease of numerous kinds — diseases that are linked in more ways than the average doctor realizes or typically cares to understand (HERE). When AUTOIMMUNE DISEASES RESULT (click for a list of some of the more common ones), it’s critical to realize that most of these have nothing overtly to do with the gut. In other words, the self-immune system attack and subsequent symptoms can occur anywhere, which is why, regardless of symptoms, natural healers have been preaching “heal the gut, heal the body” since well before THE ADVENT OF MODERN MEDICINE. Today we will look at a few brand new studies that spell this out.
Next month’s issue of Current Opinions in Rheumatology (The Microbiome in Systemic Autoimmune Disease: Mechanistic Insights From Recent Studies) tells us exactly why this is happening. “Recent changes in modern societies have disrupted homeostasis and contributed to a rise in immune-mediated conditions.” First, to call what’s going on a ‘rise‘ is like me calling the Grand Canyon a ditch (HERE). The truth is, thanks to modern, Westernized lifestyles, we have been facing an EXPLODING INCIDENCE OF AUTOIMMUNITY for decades. Secondly, we see today’s first mention of compromised epithelial barriers (‘THE LEAKIES‘). “Recent studies highlight that a breach of the gut barrier and translocation of commensal bacteria to non-gut organs can trigger several autoimmune pathways that can be prevented by commensal vaccination or dietary interventions.“
While it’s quite true that vaccinations can cause autoimmunity via the dysbiosis pathway (HERE), this is not the sort of “vaccination” these authors are speaking of. They are talking about “vaccinating” (their word, not mine) using entities such as PROBIOTICS, FECAL MICROBIOTA TRANSPLANTS, VAGINAL SWABBING (SEEDING) for babies born via C-section, or maybe even plain old GARDENING OR HAVING AN INDOOR / OUTDOOR PET. It could be as simple as feeding your microbiota with plenty of NON-DIGESTIBLE FIBER. The object is to get people exposed to diverse microorganisms, and lots of them, while feeding them what they need to colonize the Gut. As the authors reveal, this diminishes inflammation and helps shore up the “leaks” that allow these organisms into the general circulation. Let’s move on to another concept that is starting to gain traction in the current research on GUT HEALTH — molecular mimicry as a cause of autoimmunity (as seen in the same study).
“Recent findings suggest that autoimmune manifestations in genetically susceptible individuals can arise through cross-reactivity with commensal orthologs of autoantigens or commensal-mediated posttranslational modification of autoantigens. Physiologic responses to gut, oral, or skin commensal bacteria can thus be misdirected toward such autoantigens in susceptible hosts.”
Two things to talk about here. First is that in most cases, the majority of those who are “genetically susceptible” do not get sick. Why not? Because as I’ve shown you HERE and HERE, epigenetic factors (bad habits and exposure to bad things like THIRD-HAND SMOKE, TOXIC CHEMICALS, SUGAR, or XENOESTROGENS) are, at least in the vast majority of cases, much more important than raw genetics and whether or not you carry a particular gene. This is why I have said repeatedly that you are not controlled by your genes nearly as much as you have been led to believe (HERE). Secondly, in many ways this phenomenon is similar to GLUTEN CROSS-REACTIVITY.
Because there are many foods with proteins that have a similar molecular structure to GLUTEN (wheat protein), in certain individuals, these proteins can trigger serious gluten sensitivity-like reactions (EVEN IN NON-CELIACS). The highlighted paragraphs simply show that some “commensal organisms” (bacteria, fungi, etc that we live with every day) are “orthologs of autoantigens“. This is a fancy way of saying that some of these microorganisms contain or secrete compounds with a similar enough molecular architecture to a tissue, enzyme, or protein in your own body that given the right conditions, your immune system may actually start attacking said tissue, enzyme or protein in the case of autoimmunity.
We just saw an example of this in a study on a common autoimmune issue, ECZEMA, that was published earlier this week in Science Translational Medicine (The Nonlesional Skin Surface Distinguishes Atopic Dermatitis with Food Allergy as a Unique Endotype). Bottom line, while it’s always possible for the immune system to go haywire without any outside help, these sorts of dysfunctions are mostly related to epigenetic issues — issues that if understood, can be somewhat controlled or at least managed.
Now, back to the leakies. Last month’s issue of the International Journal of Molecular Sciences (Recent Advances on Microbiota Involvement in the Pathogenesis of Autoimmunity) had this to say about LEAKY GUT SYNDROME (which in the scientific medical community is known as increased intestinal permeability or similar)…..
“The impact of an imbalanced gut microbiome in the pathogenesis of autoimmunity has been suggested by an increasing amount of experimental evidence, both in animal models and humans. Several physiological mechanisms, including the establishment of immune homeostasis, are influenced by commensal microbiota in the gut. An altered microbiota composition produces effects in the gut immune system, including defective tolerance to food antigens, intestinal inflammation, and enhanced gut permeability. In particular, early findings reported differences in the intestinal microbiome of subjects affected by several autoimmune conditions, including prediabetes or overt disease compared to healthy individuals.”
Not only do we see “enhanced gut permeability” here, which allows an array of particles to get into places they shouldn’t, we see the authors talking about both “food antigens and intestinal inflammation“. Let’s see how these work in concert with a leaky Gut to cause autoimmunity. If you are consuming foods that your body is sensitive to, whatever those might be and for any number of reasons (GRAINS, DAIRY, NIGHTSHADES, LECTINS, etc, etc) your body will react by creating INFLAMMATION. This inflammation causes the cellular ‘tight junctions’ that separate the contents of your intestines from your blood stream to actually get bigger (looser). The end result is that particles of undigested food, PARASITES, toxins and other “stuff” are allowed to leak through, winding up in systemic circulation, where the body mounts increasingly intense immune system responses against them. What’s interesting is that for nearly a century, science has shown that once the immune system starts attacking gluten, it’s much more prone to start attacking self — it’s own cells, tissues, enzymes, proteins, etc (HERE) via autoimmune reactions.
Just so you are aware, the importance of GUT HEALTH encompasses both autoimmunity and a wide array of inflammatory diseases (see earlier link on inflammation) as seen in this three month old issue of Clinical Science (Impact of the Gut Microbiome in Cardiovascular and Autoimmune Diseases).
“The gut microbiome functions like an endocrine organ, generating enzymes and bioactive metabolites, which affect host physiology. Alterations in intestinal microbial and metabolic composition play an important role in human health and disease, including cardiovascular and autoimmune diseases. Changes in the composition of gut microbiota (dysbiosis) are linked to chronic inflammation, thrombosis, atherogenesis, chronic kidney disease, obesity, and type 2 diabetes. Moreover, significant evidence exists to implicate the role of microbiota in blood pressure regulation and heart failure. Microbiota interacts with the host through multiple pathways…..”
The GUT BACTERIA AS AN ENDOCRINE ORGAN? Of course! It’s why none of this should be shocking if you understand some of the larger “pathways” indicated in the last sentence. For instance, we’ve known for a long time (HERE) that cardiovascular disease is not so much caused by consuming fat (HERE) as it is caused by consuming sugar and high glycemic processed carbs. I would take that a step further, saying that virtually every modern health problem has roots in BLOOD SUGAR DYSREGULATION. And the cherry on the sundae is that sugar feeds infection, dysbiosis included (HERE). This is why I have written so many articles on doing whatever it takes to BREAK YOUR SUGAR ADDICTION.
Now that we’ve established that your microbiome is critical for your health, the most important question to ascertain is what you might be doing to foul it. Although most drugs have anti-microbial properties (HERE), the one class of drug that will absolutely throw your microbiome into dissaray is ANTIBIOTICS. Nothing, and I mean nothing screws people up faster, longer, and often times earlier in life than antibiotics (the most dangerous offender of being the family of antibiotics known as FLUOROQUINOLONES such as cipro). THIS ARTICLE shows the numerous ways in which antibiotics are screwing up people’s health. A brand new study, takes it a step further, showing that prescribing babies antibiotics messes up their brains. From last month’s issue of Science Reports (Oral Neonatal Antibiotic Treatment Perturbs Gut Microbiota and Aggravates Central Nervous System Autoimmunity)…..
“Gut microbiota dysbiosis has been considered the essential element in the pathogenesis of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). Antibiotics were administered orally to Dark Agouti (DA) rats early in their life with the aim of perturbing gut microbiota and investigating the effects of such intervention on the course of EAE. As a result, the diversity of the gut microbiota was reduced under the influence of antibiotics. Consequently, aggravation of EAE, paralleled with stronger immune response in lymph nodes draining the site of immunization, and increased inflammation within the CNS, were observed in antibiotic-treated DA rats. Thus, the alteration of gut microbiota leads to an escalation of CNS-directed autoimmunity in DA rats. The results of this study indicate that antibiotic use in early life may have subsequent unfavourable effects on the regulation of the immune system.”
The last link above proves that while this might be scary, it cannot in any ways be considered new information. How scared should you be as a parent or grandparent of young children if you are taking them to the doctor for antibiotics for anything less than life-threatening situations?
“There is an increasing awareness of serious consequences of antibiotic use on gut microbiota. Indeed, a rising number of observational, clinical, and epidemiologic studies focused on children and antibiotics use show that antibiotic exposure-related dysbiosis of intestinal microbiota increases the risks for various diseases such as obesity, diabetes, inflammatory bowel diseases, celiac disease, allergies and asthma. Antibiotics are the most commonly prescribed pediatric drugs, taking a share of more than 30% of all drugs prescribed to children younger than two years.”
If this doesn’t wake you up, this next study might. Thanks in part to antibiotics, “rare” diseases are becoming increasingly less rare. January’s issue of the Journal of Autoimmunity (The Microbiome and Immunodeficiencies: Lessons From Rare Diseases) described a few of the pathways whereby this increase in previously rare disease is occurring. The study started by describing PID’s (Primary Immune Deficiencies) as “inherited disorders,” leaving those individuals more prone to “malignancy, inflammation and autoimmunity“.
Next, the authors suggested that a DIMINISHED HOMEOSTASIS of the gut bacteria (dysbiosis) leads to “altered intestinal permeability and bacterial translocation“. In other words, bacteria and their metabolites gain access to the systemic circulation, where the immune system either attacks these bugs outright or via the ‘molecular mimicry’ pathways we spoke of earlier. This leads to “immune system dysregulation,” which results in “enhanced pathobionts colonization” (can anyone say BIOFILMS?), “increased disease susceptibility and secondary infections in these patients“.
Here’s where things really start to get dicey. Not only do the factors discussed by the authors (increased inflammation, increased autoimmunity, increased malignancy) occur directly, they can occur indirectly as well. We are seeing this in the numbers of studies relating chronic latent infections to these sorts of problems. Although I spoke of this relationship recently in a post linking still another infection to Alzheimer’s (HERE), in my post titled SECOND THOUGHTS ON THE GERM THEORY, I wrote……
“Despite our best efforts to “cure” infectious disease, why are rapidly growing numbers of people plagued with illnesses that are increasingly believed to be the result of what Dubos referred to as “latent infections” (ALZHEIMER’S DISEASE, DISC HERNIATIONS, EBV, PANDAS/PANS, IBS, FLACCID PARALYSIS, DISEASES FROM ROOT CANALS OR OTHER ORAL INFECTIONS, and on and on and on)?“
More importantly, how do these authors — MD / Ph.D research types from prestigious institutions and universities in both Italy and the United States — propose we solve this issue? Pay close attention. “Finally, we provide evidence, in preclinical models of PIDs, for the efficacy of microbiota manipulation to ameliorate disease complications, and suggest that the potential use of dietary intervention to correct dysbiotic flora in PID patients may hold promise.” There are essentially four ways to deal with underlying dysbiosis, with doctors (especially doctors with a ‘natural’ bent) trying them in various combinations.
- You can try to kill the dysbiosis off with either natural or chemical antibiotics (which often means you kill everything and have to start completely over or almost so from scratch).
- You can do FMT, which is quite amazing and effective if YOU CAN FIND THE RIGHT DONOR (it’s all about your donor).
- You can take prebiotics, probiotics, and various bacterial metabolites marketed as nutritional supplements (the problem is, at least with probiotics, they don’t do a very good job of matching your gut’s natural microbiome — HERE).
- You can change your diet, because there is abundant evidence that what you feed your “Gut Bugs” is either driving or squelching your health (i.e., antibiotics usually precipitate dybiosis, but sugar and high glycemic carbs feed it). See earlier link on fiber.
How can information like this help you solve your chronic health issues? For starters, simply by better understand and deciphering the current scientific literature. For instance, the issue of Autoimmune Reviews that came out about six weeks ago published a study titled Autoimmunity in Celiac Disease: Extra-Intestinal Manifestations that dealt with all the “extra-intestinal” (non-gut) ways that CD can affect people (something I’ve shown you previously in my posts on gluten’s association to neurological disease — HERE, HERE or HERE). Here are the mechanisms, exactly as we have previously discussed today….
“Nutrients, dysbiosis, dysbiotic components and their mobilome, post-translational modification of naive proteins, inter-enterocyte’s tight junction dysfunction resulting in a leaky gut, microbial lateral genetic transfer of virulent genes, the sensing network of the enteric nervous systems and the ensuing pro-inflammatory messengers are mutually orchestrating the autoimmune interplay. Genetic-environmental-luminal events-mucosal changes are driving centrifugally the remote organs autoimmunity, establishing extra-intestinal multi organ injury.”
Super technical sounding, but what is this really saying? That certain nutrients (gluten, for instance, is a protein) can team up with dysbiosis and the molecular byproducts created by these ‘bad’ organisms, causing the tight junctions to become loose or leaky, which can lead to bacteria transferring “virulent genes” to their buddies. The result is an “interplay” (a vicious cycle that can feed itself while spinning either direction) between inflammation and autoimmunity. Once the necessary factors are in play to actually turn these ‘bad’ genes on (the very definition of epigenetics), the problems they cause are not constrained to the Gut, but can travel to the farthest (remotest) reaches of the body, leading to even more “autoimmunity and multi-organ injury“.
Although we could play “pick a disease, any disease” and watch this phenomenon in action, let’s take a look at arthritis. In December’s issue of Arthritis and Rheumatology (Microbiome Analytics of the Gut Microbiota in Juvenile Idiopathic Arthritis Patients...) we see something that we already knew or at least suspected; that the guts of children with inflammatory autoimmune arthritis are different than the guts of children without. “We found evidence for dysbiosis in JIA patients.” Why is this important to both know and understand? The same month’s issue of Cell Immunology revealed via its title (Modulation of Autoimmune Arthritis by Environmental ‘Hygiene’ and Commensal Microbiota) that there are steps that people can be taking to help themselves, without relying on DANGEROUS DRUGS for everything.
“Specific commensal organisms are associated with enhanced severity of arthritis in susceptible individuals, while exposure to certain microbes or helminths can afford protection against this disease. In addition, the role of metabolites (e.g., short-chain fatty acids, tryptophan catabolites), produced either by the microbes themselves or from their action on dietary products, in modulation of arthritis is increasingly being realized. In this context, re-setting of the microbial dysbiosis in RA using prebiotics, probiotics, or fecal microbial transplant is emerging as a promising approach for the prevention and treatment of arthritis.”
Interesting because this is exactly what I was talking about in my earlier bullet points (although I fialed to mention the part about purposefully creating HELMINTH INFESTATIONS). It’s all about the HYGIENE HYPOTHESIS folks. And although VITAMIN D is mentioned in my GENERIC AUTOIMMUNE PROTOCOL (not to mention several of these studies), let’s take a bit deeper look at why it’s doubly critical to understand for those of you with AUTOIMMUNITY. Just remember as you read this next (short) section that the reason that Vitamin D gets so much publicity in relation to other vitamins is because it’s not really a vitamin at all, but an immuno-modulating hormone precursor.
GUT HEALTH, AUTOIMMUNITY AND
THE CONNECTION TO VITAMIN D
Under a header titled Vitamin D and the Innate Immune System: Antimicrobial Activity, we start to learn how necessary Vitamin D really is if you want to stay healthy. We’ll get there, but first let’s talk about the innate immune response (as opposed to acquired immunity). The innate response pertains to the aspects of immunity that you are born with, namely white blood cell function (except for lymphocytes) and inflammation as well as the cellular barriers that I already showed can become “leaky”. Also under innate immunity you’ll find numerous types of enzymes and other proteins that have varying degrees of antimicrobial properties. Acquired immunity pertains mostly to the antigen / antibody reactions, which we will cover momentarily.
Citing studies from the 1940’s, the authors wrote that “Vitamin D is a well-known regulator of innate immunity…. D3 increases chemotaxis, autophagy, and phagolysosomal fusion of innate immune cells…. and up-regulates CAMP in cells participating in the innate immune system as first-barrier defenses” In essence this means that with Vitamin D the body can get the proper cells or metabolites to where they need to go quicker (chemotaxis), that the body is better adapted to a form of detoxification that involves deconstructing and recycling old and worn out cells in an orderly fashion (autophagy), that the cells that engulf and dissolve harmful invaders in “BLOB-LIKE” fashion are working at full capacity (phagocytosis / phagolysosomal fusion), as well as aiding in cellular signaling / messaging (up-regulating cyclic AMP). What did the authors conclude after looking at these factors in detail?
“Taken together these data point to a role of vitamin D in defending the organism against pathogens, suggesting that vitamin D sufficiency has to be granted in patients affected by acute or chronic infection.”
In other words, if a person is dealing with an infection (overt, occult as we spoke of above, or some form of dysbiosis), decades worth of studies mean it’s a given that Vitamin D levels will be compromised / depleted. What this really means is that if you have an infection (dysbiosis included), there is an entire cascade of harmful effects to the immune system that will follow. The authors discussed why “THE LEAKIES” (hyperpermeable epithelial barrier membranes) are a factor in Vitamin D deficiency as well.
“Vitamin D is responsible for the barrier function of the intestinal epithelium and for the modulation of the bowel immune system, hence, low levels may be associated with greater gut permeability and, consequently, with Gut-induced metabolic endotoxemia that induces a low-grade inflammation. Moreover, vitamin D administration may influence Gut composition. In animals with vitamin D depletion and the knockout of the Vitamin D Receptors, Gut dysbiosis favors metabolic disorders. Other studies in mice demonstrated that Vitamin D Receptor [dysfunction] reduces the response to infection of the intestinal epithelium.”
Metabolic endotoxemia implies that lipopolysaccharides (LPS) is present in the blood stream or organ that these epithelial barriers are trying to protect (lungs, brain, spinal cord, nerves, etc). LPS are byproducts of certain kinds of bacteria and are not only heavily associated with low grade inflammation, but with the sort of immune system hyper-reactivity that can lead the body to start attacking itself (although they are also associated with T2D, LOW T (or HIGH T), high levels of IL-6 and TNFA, DEPRESSION, FATTY LIVER, PARKINSON’S, OBESITY, and for those who regularly follow my site, CHRONIC PAIN).
The authors went on to mention Vitamin D’s relationship to something I’ve already touched on, cellular apoptosis. “Over-expression of VDR in the intestinal epithelium induces resistance to colitis and decreases mucosal inflammation suppressing epithelial cell apoptosis, boosting tight junction function.” In other words, having lots of (an “over-expression of“) receptors for Vitamin D suppresses epithelial apoptosis. Activated by the TH-17 part of the immune system mentioned earlier, apoptosis is cellular death that is programed to occur when one of several things happen. Of course AGE can be a factor, and so can STRESS (metabolic stress, physical stress, psychological stress, etc).
Another factor, kind of like falling dominoes, is the fact that if I’m a cell and the cell next me undergoes apoptosis, I’m very likely to undergo apoptosis as well. Not to freak you out, but the average adult loses 50 to 70 billion cells a day to apoptosis, while children lose about half that many. Thus, it’s easy to see why slowing this process down by addressing the factors that speed it up (vitamin D deficiency being one of many) could have some very beneficial results. Furthermore, research that was published just last week shows that making the correct changes to the cellular environment can slow down and in some cases, actually REVERSE cellular apoptosis.
Adaptive / acquired immunity is the opposite of innate immunity and deals with a type of white blood cell (lymphocytes) that will differentiate into either T-cells or B-cells (to see the difference, you can read THIS POST on the relationship between overactive immune systems and autoimmunity) or Natural Killer cells.
“D3 suppresses adaptive immunity. In experimental models it down-regulates the immune responses mediated by T helper (Th) 1 cells, thus inhibiting the production of pro-inflammatory cytokines, such as Interferon-y, IFN-y, IL-6, IL-2, and TNFA……. It has been suggested that Vitamin D3 acts as an immunomodulatory not only by suppressing Th1 cells activation, but also modulating Th2 cells, T regulatory (Tregs) cells activity, and Th17 cells.”
We just discussed the TH-17 system, but TREGS are interesting because you want them activated in cases of autoimmunity. Why? They slow down or “regulate” an immune system that’s galloping out of control.
After suggesting that there is strong data for the role of Vitamin D’s ability to act as a modulator of the immune system to better fight pathogens, the authors revealed that there are no medical recommendations for Vitamin D supplementation in those specifically coping with autoimmune issues — issues that by official counts affect almost 25 million Americans. Once, however, you start factoring in the dozens (maybe hundreds) of diseases that are believed to be autoimmune but not proven because the specific auto-antigen —- the entity that’s being attacked — has yet to be discovered), many experts put this number at at least double or even triple this. Not surprisingly and for many reasons that are no fault of their own, the author’s Vitamin D “recommendations” fall short.
“Thanks to the evidences of immunomodulatory effect of vitamin D the role of vitamin D deficiency and supplementation in autoimmune diseases has long been studied. Animal studies showed an important role of D3 supplementation in the control of autoimmune diseases….” [However], “There is no current indication for vitamin D3 supplementation in patients with infections and/or autoimmune diseases.”
What we can do is read between the lines a bit. Even though, depending on one’s age (older people are supposed to take a higher dose), the RDA for Vitamin D ranges from 400 to 800 international units (IU) per day, every FUNCTIONAL MEDICINE expert I know (including many who are MD’s) laughs at this. While I am not going to make any recommendations of my own, suffice it to say that the authors of this study talked about certain conditions and studies where the participants received as much as 50,000 IU a week, or (gulp) 300,000 IU in a one-time “bolus“. One of the more brilliant functional medicine MD’s I know has told me that for certain patients in certain situations, he sometimes recommends as much as 80,000 IU’s a day, short term (do not do any of this without first consulting your physician).
If you are interested in seeing some more information on Vitamin D as it pertains to natural light (HERE and HERE) or how it plays a part in my generic health protocol (HERE), as well as what the profile of the average autoimmune sufferer tends to look like (HERE), just follow the links. And as always, if you like what you are seeing, be sure and like, share, or follow on FACEBOOK as it’s still a great way to reach the people you love and care about most.