ThinkGutBacteria

I know this is a popular topic nowadays, thanks to the autism debates. And it's true that health stats and definitions of diseases are tricky to nail down or often in flux (frustratingly so in the case of PANDAS/PANS/PITAND). However, there is a universal consensus that chronic inflammatory diseases are, on the whole, increasing in the developed world and now even in the undeveloped world as a direct result of modernization of sewers, water treatment facilities, and general living conditions in urban areas. Of course you can find exceptions to this trend--rheumatoid arthritis, for example, has slightly decreased in men since the 1990's. But overall, your hunch is correct that most diseases from chronic inflammation such as type 1 diabetes, multiple sclerosis, asthma, Crohn's disease, etc., are frankly too dire to have been dismissed or misdiagnosed. (Crohn's has a pretty interesting history. You should look it up sometime.) Also, medical records in industrialized nations have been fairly good throughout the 20th century, even in poor or rural areas. In fact, the penetration of health scouts into depressed areas was probably better than today in many cases. It's well documented that hay fever was never recorded before the mid-19th century in rural England not because of farmer stoicism or because no one knew what to call the sneezing and runny nose symptoms that occurred in country folk every summer, but because it simply didn't exist. The story of Charles Blackley and hay fever is pretty interesting and one I recommend reading up on if you're a history of medicine buff like me. Undoubtedly, awareness of these ailments is heightened for sure, but that's because they're more prevalent. No one talked about autism when I was a kid, but not because 1 in 54 "rainmen" were dismissed as being a little strange. (Here's a now famous graph from a 2002 article in the New England Journal of Medicine: http://www.cwr.uwa.edu.au/~jimberger/Life%20in%20a%20Changing%20Climate(New)/Resources_LCC/Visuals/4.02b_Immune%20Disorders%20Bach%20NEJM%202002.png) As for your doctor telling you that daycare is protective, it was but is becoming less so. As viruses like Hepatitis A and bacteria like H. pylori are eliminated from our society (like hookworm and polio decades ago), so too are the protections they offered. Things like rhinovirus and streptococcus pyogenes that are currently "shared" amongst children are not likely to confer any protection against allergies/autoimmunity and have indeed shown to make them worse. Same with animals. Being around them used to be very protective. But now the heavy use of antibiotics and herbacides in the pastures has changed the equation. Likewise having lots of siblings. It doesn't protect like it did 40 years ago. The right microbes just aren't around anymore and as more of us develop allergic/autoimmune conditions, more of us are passing on the effects of our screwed up immunity to subsequent generations, accelerating the problem. Fortunately, we're starting to make some research headway, curing autoimmune diseases in animal models with certain bits of bacteria (as in the case of Sarkis Mazmanian at Cal. Tech. or Denise Faustman at Harvard) or helminths (Joel Weinstock). Let's hope we're not too far gone micro-ecologically by the time treatments reach human patients.

In today's news we learn that Harvard scientists prevent and treat rheumatoid arthritis in mice by stimulating the growth of a certain kind of regulatory T cell (Treg) called CD8+ Treg. They do this in either of two ways: by directly injecting the cells into the mouse or by feeding it bits that stimulate the mouse to make its own CD8+ Treg. Either method worked especially well when Tregs were on the scene at the same time the disease was in flare, so to speak. As it turns out, two kinds of probiotic Lactobacilli induce the same CD8+ Treg growth in mice. L. paracasei BB5 and L. rhamnosus BB1. They worked best when taken together (not all probiotics do, some even work against each other). I'm going to do some more digging into which species have this function and see if I can uncover any commercially available. Most of the probiotics we buy are anyone's guess as to whether they dampen or promote autoimmune-based inflammation. The fact that once common now rare species of lactobacilli can dampen the immune response is yet more evidence for the hygiene hypothesis. http://www.dana-farber.org/Newsroom/News-Releases/New-strategy-prevents-rheumatoid-arthritis-in-mice.aspx http://www.sciencedirect.com/science/article/pii/S1567576912003177

See my note to cobble mommy. The hypothesis has nothing to do with how often you clean your house (thankfully). Also, I'm not really sure of the relevance of a/c and windows open. As far as anyone can tell so far, the important microbes tend to be orofecal and soil- and water-borne. Also, hookworms and other relevant organisms have been all but eradicated in the rural U.S. since 1914. Gotta take a global view of this issue.

About the blame thing, it's a pet peeve of mine too to blame the victim; however, this is precisely what the hypothesis does not do. According to the hypothesis, the rise in allergy, asthma, and autoimmunity does NOT come from personal or home cleanliness. It comes from a societal change. It comes from not being awash (so to speak) in microbes like Hepatitis A, toxoplasma gondii, lactobacilli, mycobacterium vaccae, and clostridia (the non-pathogenic species). The evidence is overwhelmingly in support of the hypothesis that some are calling it a theory (like gravity is a theory). And, like the theory of gravity, just because you see airplanes in the sky doesn't mean the theory of gravity is incorrect. It just means you have to step back and see the whole picture. An individual's immune system is affected by many, many things like one's mother's exposure to microbes when pregnant and vitamin D levels and how many helminths are in left in the soil you played in, how many antibiotics were given at a young age, whether your mom had a flu shot during pregnancy, whether or not your parents had allergies and on and on and on. Overall, looking at communities, the evidence in favor of the hypothesis is overwhelming. I can't possibly list it all here (just trying to give a few examples) but most experts accept the fact that our immune systems are educated by microbes and inflammation early in life (even before we're born) and autoimmune diseases are frequently the result of infections in people whose immune systems haven't been turned down by certain microbes. Chronic inflammatory diseases like type 1 diabetes and asthma are ancient, with reports of their occurrence throughout medical history, way before the advent of sewers and antibiotics. But their incidences have been rising steadily, in some cases alarmingly so, since the industrial revolution. There is currently no better explanation for this rise than the hygiene hypothesis. We'd be wise to research what it has to say and put it to use to help our kids.

Love propolis. It's a staple for cuts at our house. DD7 hates the smell, though. She'd never take it internally.

Here's an interesting article in Slate magazine showing the importance of the maternal vaginal microbial population What’s in Your Vagina? A healthy microbiome, hopefully. http://www.slate.com/articles/health_and_science/medical_examiner/2013/01/microbial_balance_in_vagina_miscarriage_infertility_pre_term_birth_linked.html Snippet: In 2008, scientists following a cohort of nearly 1,100 Boston mothers and their children announced that premature birth increased the risk of wheezing at 6 years of age by 70 percent. The real kicker emerged when they separated children of mothers who had suffered from chorioamnionitis during pregnancy. For those children, the risk of asthma was more than four times as high. A Finnish group has since replicated the finding among 15-to-17-year-olds, implying that the consequences of prenatal inflammation persist into adolescence and probably adulthood.

Here's something interesting...gluten-free diets may help people with autoimmune conditions regardless of whether they have celiac disease. "Gluten-free diet dramatically inhibits [type 1 diabetes] in animal models, and epidemiological data are supportive of such an effect in humans. The mechanisms include less subclinical intestinal inflammation and permeability, and changed composition of bacterial flora, which can also be obtained by intake of probiotics." http://www.ncbi.nlm.nih.gov/pubmed/21615797

No celiac in our family but glutens (gliadin in particular) are known binders of zonulin, which increases gut permeability (leaky gut). Prebiotics like fructooligosaccharides (FOS) and probably galactooligosaccharides (GOS) seem to improve leaky gut by inhibiting zonulin. (http://www.ncbi.nlm.nih.gov/pubmed/?term=prebiotics+AND+zonulin) See http://www.ncbi.nlm.nih.gov/pubmed/16635908

Still more evidence... Recently, researchers in Finland found the incidence of type 1 diabetes to be six times higher and the prevalence of celiac disease five times higher among Finnish children than among Russian children living just across the Finnish border in a region known as Karelia. [seiskari, 2007] The children were genetically similar (with the same distribution of MHC alleles implicated in atopic and autoimmune disorders) and were exposed to roughly the same level of vitamin D-inducing ultraviolet sunlight. The major difference emerged from their respective public hygiene facilities, being fully modernized in Finland but lacking considerably in Russian Karelia, especially in water treatment. Studies by the same researchers further showed that Russian Karelian school children were 15 times more likely to test positive for antibodies to Helicobacter pylori than Finnish children, five times more likely for Toxoplasma antibodies, and 12 times more likely for antibodies to hepatitis A virus. Karelian children also had considerably more antibodies against the enterovirus Coxsackie B4. [seiskari, 2007] --------- Keep in mind that in the US we vaccinate against HepA, pregnant women are kept far away from Toxoplasma (as they should, but it has consequences), and H. pylori infections are around 30% or less compared with over 90% just 30 years ago. Also remember the most critical period for exposure is in utero or in the first year of life. It's hard to understand that infections and microbes are not created equally in terms of risk for autoimmunity PLUS you have to consider the environmental impacts of dioxins, vitamin D, antibiotics, some vaccines, etc. on the early immune system.

It may take a while to see some benefit (interestingly, this can be the case for IVIg and tonsillectomy too.) Anyway, did you see this post from 2011? It's on that very topic! http://www.latitudes.org/forums/index.php?showtopic=14398 If you go through with it, please let me (us) know what happens.

Regarding helminths, a 2006 meta-analysis of 33 studies testing the effect of specific parasites on asthma risk found infection by the giant roundworm nematode (Ascaris lumbricoides) associated with a 34% increased risk of asthma, whereas hookworm infection was associated with a reduced risk of 66% among the most severely infected and of 50% among the moderately infected.28 This study highlights the importance of species specificity when addressing whether “infections” protect against disease and may confound studies assessing the effect of broad deworming campaigns on allergic disease. Similarly, University of Iowa gastroenterologist Joel Weinstock and colleagues showed disease abatement, even temporarily remission, after intentionally feeding eggs of a parasitic whipworm Trichuris suis to patients with Crohn’s disease and ulcerative colitis.29 Patients ingested 2,500 T. suis ova every 3 weeks. At week 24, 72% of patients were in remission. No adverse events were noted. Whipworms live in warm moist soil or food that has been contaminated by fecal matter. In animal studies, helminthic therapy has protected genetically predisposed mice against colitis, encephalitis, type I diabetes, and asthma.30 Clinical trials are underway testing helminths in humans with various autoimmune diseases. The following figure starkly illustrates the relationship between incidence of autoimmune disorders and helminth infestation worldwide.

We saw a big improvement too. Not a cure, sadly but we haven't slid back to baseline since either.

More evidence... Findings have not been replicated in all types of agricultural work, however. For example, no protection was found in children living on farms that exclusively produced wheat or cotton.22 Nor have findings been consistently reported in all regions of the world23, which suggests the importance of specific factors of the European farms studied, which were traditional, less-modernized family farms with livestock. Livestock involvement appears necessary for reduced risk of CID by farm life or consumption of farm products. Non-Farm Microbes Of course, Old Friend microbes needn’t solely come from farms. In a case-control study in Italy, Paolo Matricardi tested nearly 1,700 air force cadets for serum antibodies to selected foodborne and orofecal microbes and airborne viruses: Toxoplasma gondii, Helicobacter pylori, hepatitis A virus (HAV), measles, mumps, rubella, chickenpox, cytomegalovirus, and herpes simplex virus type 1. In support of the Old Friends hypothesis, he found that atopy was inversely related to foodborne or orofecal microbes (T. gondii, H. pylori, HAV) but not to the respiratory pathogens (measles, mumps, rubella).2 Suggestive of a synergistic effect, participants seropositive for at least two orofecal or foodborne infections had a ten-fold reduction in allergic asthma (0.4% versus 4.8%) and a nearly three-fold reduction in allergic rhinitis (6.5% versus 15.5%) compared with seronegative participants. Working at Stanford University, Jennifer J. McIntire, Dale T. Umetsu, and colleagues showed that infection by HAV strongly protected individuals from allergy and asthma if they carry a particular variant of the gene that encodes the cell-surface receptor used by the virus to infect human cells. No such protection was seen when the receptor was a less functional mutant.24 Studies by Chen and Blaser at New York University showed that children seropositive for H. pylori were 60% less likely to currently have asthma than children who weren't infected.25

It continues...(a little science jargon for those who like it) Debarry et al., isolated two species from cow sheds with strong allergy-protective properties—Acinetobacter lwoffi and Lactococcus lactis. These strains were able to protect mice against allergic airway inflammation, activate pattern recognition receptors, and induce maturation of dendritic cells to a more toleragenic state.19 A figure appearing below taken from this study clearly shows the reduction of eosinophils, a marker for atopy, following treatment with these bacteria. The authors’ in vitro results further demonstrated the ability of both strains to strongly downregulate mRNA levels of Jagged-1, a ligand of Notch on dendritic cells known to induce allergenic Th2 response. Maturation of dendritic cells via Jagged-1 results in an entirely different cellular program from that induced through toll-like receptor (via bacterial lipopolysaccharide) signaling. It promotes high-level production of IL 2 and IL 10, both of which promote Treg development and survival.20

I don't think you can include an Amish population when comparing modern day research groups because they do not immunize their children. Immunizations alert the immune system and for children like my kiddo who has an overactive immune system, it is a part of his overall problem. I also don't claim my child is part of an epidemic; I think each child is unique and has their own immunologic stressors. That's kind of the point. They don't immunize nor do they use antibiotics in the first years of life, precisely when immune systems learn from our Old Friend microbes.

Let's look at some evidence...Notice the incidence is never zero (even if you lived on a farm). Farm Life and Its Organisms of Immunoregulation An agrarian lifestyle was known to confer protection from allergic disease since 1873, when English physician Charles Blackley puzzled that hay fever was a growing problem among the upper socioeconomic classes yet simply didn’t exist in poorer farm families, who had a much greater exposure to pollen.12 More than a century later, soon after Strachan’s analysis, Bavarian pediatrician Erika von Mutius and colleagues published reports of surprisingly lower asthma and allergy rates in kids frequently exposed to farm stables compared with those from the city—four times lower, in fact.13 In one such study, the risk reduction was especially pronounced if the exposure to cow sheds and consumption of farm milk (i.e., fresh, unpasteurized milk) occurred in children younger than one year compared with those aged 1–5 years (1% vs. 11% for asthma, and 3% vs. 13% for hay fever). Continual long-term exposure to cow sheds until age five was associated with the lowest frequencies of asthma (0.8%), and hay fever (0.8%).14 Waser et al., who surveyed nearly 15,000 children from five European countries, later confirmed these studies in 2007.15 More recently, Holbreich et al., showed similar findings in a population of Amish children living on farms in Indiana compared with non-farm dwelling populations. Again, children who lived with cows and/or drank farm milk were less likely to have reported asthma (5% vs. 11%), dust mite allergy (6% vs. 16%), grass pollen allergy (3% vs. 40%), or test positive for general allergic sensitization (7% vs. 54%).16

Yes, you can still get autoimmune diseases in unhygienic places, but nowhere close to the level seen when certain organisms are eliminated. (And remember, genetics can't explain epidemics.) Glad you're reading! Here's the second post: To reconcile these findings, a revised hypothesis was put forth by one of the original reviewers of Strachan’s seminal paper, Graham Rook, now Emeritus Professor of Medical Microbiology at the Centre for Clinical Microbiology, University College London. The key as he saw it was to consider human evolutionary history. In so doing, Rook and colleagues were able to identify specific protective microbial agents, offer a viable mechanism of action underlying the protection, and account for not merely the rise in allergy and asthma but also the parallel rise in autoimmune and inflammatory bowel diseases, which somehow had escaped earlier notice of many in the field. Rook calls his revision, the “Old Friends” hypothesis, which he described for the first time in an article to Seminars in Immunology in 2003:11 In the rich, developed parts of the world there has been a steady and simultaneous increase in at least three groups of disease: (1) allergies, (2) inflammatory bowel diseases (IBD; e.g. Crohn’s disease and ulcerative colitis) and (3) autoimmunity (e.g. type 1 diabetes and multiple sclerosis). Because the medical world is so compartmentalised it was some time before the connection between these increases was noticed and understood. There is now evidence that the simultaneous increase in these diseases of immunodysregulation is at least partly attributable to malfunction of regulatory T cells (Treg)…the increasing failure of Treg is a consequence of diminished exposure to certain micro-organisms that are “old friends”, because of their continuous presence throughout mammalian evolution. These organisms…are recognised by the innate immune system as harmless, and as adjuvants for Treg induction. In other words, the microorganisms and worms from soil, water, and animal feces that were copious and inescapable in daily life for thousands of years evolved to induce broad immunological tolerance in their hosts. In their absence, the aggressive cells of innate immunity proceed unchecked, eventually resulting in a chronic inflammatory state. If the Old Friends hypothesis is true, which organisms are responsible? The obvious place to start looking for the answer was the farm.

All "body odor" comes from the action of microbes. Bad breath, underarm odor, foul smelling stools, etc. all signal an infection of some kind, a very common side effect of steroids. Maybe overgrowth of antibiotic-resistant bacteria, maybe thrush (yeast). Is she old enough to gargle? Also, when she sleeps, does she snore or stop breathing for a few seconds? Or did she when she was younger? It's true that many tonsils/adenoids swell (peaking around age 7) before returning to a more normal size, but if she's got sleep-disordered breathing, I strongly recommend researching tonsillectomy/adenoidectomy. Some of the risks include post-op bleeding and weight gain (if she's already overweight or vitamin D deficient) Some of the benefits include lowered anxiety, depression, and aggression.

Since some of you may be new to the hygiene hypothesis (also called the Old Friends hypothesis in some circles), which broadly explains why our children have PANS, I've decided to post an old term paper I wrote on the subject as an introduction. It's too long to fit into one post so I'll do it in parts. Feel free to disregard them doesn't fit with your understanding of the world. The little numbers are reference citations (just ask). Introduction In his original proposal of what was to become the hygiene hypothesis, epidemiologist David Strachan mused over the inverse correlation he discovered between family size and allergic disease—the fewer siblings a child had the greater his risk. He postulated the cause to lay in a paucity of childhood infections from improved hygiene. In a brief report to the British Medical Journal (now BMJ) in 1989, he writes:1 These observations…could be explained if allergic diseases were prevented by infection in early childhood, transmitted by unhygienic contact with older siblings, or acquired prenatally…Over the past century declining family size, improved household amenities and higher standards of personal cleanliness have reduced opportunities for cross-infection in young families. This may have resulted in more widespread clinical expression of atopic disease. Intense investigation during the years that followed, however, yielded minimal or no such protective effect for the classic infections associated with childhood such as measles, mumps, or chicken pox,2,3 not even in studies conducted by Strachan himself.4 Yet during this same period, a growing literature was reporting markedly reduced risks of asthma and allergy from decidedly unhygienic activities such as living with farm animals;5 drinking raw milk;6 keeping pets (especially dogs);7 drinking water contaminated by microorganisms;8 as well as an increased risk from Cesarean birth9 or antibiotic use before one year of age.10 By the close of the twentieth century, the hygiene hypothesis became less about cross-infection in families, and more about the changes humans have made to their environment and to their lifestyle. Catching the usual infections from an older sibling may not prevent allergy or asthma, but microbe exposure, especially in early life, appeared somehow related to developing chronic inflammatory disease.

Probiotics like L. reuteri break up bile salts, which pathogens use to produce their biofilms. So even if probiotics enter your gut, they can affect growth of bacteria elsewhere. They also lower LDL cholesterol by the same mechanism. (Cholesterol is also a kind of "door" through which invading pathogens use to enter host cells.) Good bacteria can also disrupt co-infecting species that S. pyogenes need to wreak havoc (like influenza virus). When applied topically, honey can break up biofilms too via two distinct mechanisms. I wrote a paper on it for one of my bio classes but it's on my other laptop. Garlic is another, albeit weaker, biofilm buster.

Generally avoid, but probably not a crisis if it happens. Melatonin levels have to reach extraordinarily high levels (even higher than 17-fold) before anything more than big-time sleepiness occurs. But it's a good idea to ALWAYS watch out for drug interactions. Grapefruit, for example, is a huge contributor to unintentional overdose (it inhibits the same liver enzymes mentioned above). Oranges and lemons are fine, but grapefruit and seville oranges (the source of the flavoring called "bergamot" in earl grey tea) are a big no-no with any medication. I imagine grapefruit and an SSRI like Luvox would be an issue. Don't mess around with serotonin syndrome. Thanks for posting!

In one study, PANS kids were more than 3 times more likely to have a mother with an autoimmune disease...Which means it's going to become more prevalent with the rising tide of autoimmunity. "Autoimmune disorders were reported in 17.8% of study mothers, which is significantly greater than the general prevalence among women in the United States (approximately 5%). Further, study mothers were more likely to report having an autoimmune disease if their children were considered “likely PANDAS” cases versus “unlikely PANDAS” cases." Source Maternal History of Autoimmune Disease in Children Presenting with Tics and/or Obsessive-Compulsive Disorder http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2991439/

Sleep is the key. Deep sleep too, (not merely a measure of how long her eyes are closed) which requires clear breathing. Do whatever you can--Vicks Vapor rub on the soles of the feet, a humidifier, Benadryl, ALL of the above. (I probably wouldn't mix melatonin with an antihistamine, though.) Unfortunately sleep is not something we take seriously as a society, but it's probably a little more important to good health than eating well and exercising. It has HUGE effects on autoimmunity too. I like the glutathione idea someone raised, that'll help fix her sleep too. Do you know about the work of Dr. Karen Bonuck? “We found that children with sleep-disordered breathing were from 40 to 100 percent more likely to develop neurobehavioral problems by age 7, compared with children without breathing problems.” -Dr. Bonuck Source: http://www.einstein.yu.edu/news/releases/771/kids-abnormal-breathing-during-sleep-linked-to-increased-risk-for-behavioral-difficulties/

Please let us know what happened. I was considering seeing him for DD7 PANS. Thanks.

Yeah, one dose won't work for most people. Faustman even says so in her most recent PLoS paper. I think she's on a very exciting track however. As for BCG not working well for TB, it depends on where geographically you live. See the fascinating work of John Stanford and Graham Rook in Good Germs, Bad Germs by Jessica Snyder Sachs, a must read for us types!