Autoimme diseases are

[ThinkGutBacteria]

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.

[911RN]

This is my excuse for a dusty house:) I am helping my children's immune system by not having an overly clean, hygienic atmosphere

Works for me!

[pr40]

if I did not grow up under poor conditions in a third world country, I could bring myself to believe the hypothesis. I had pets, drunk row milk, ate "young" cheese, raw eggs, and whatnot, and still had autoimmune problems. There were kids round me who had asthma and all sorts of autoimmune issues.

Back to the drawing board, I guess.

Edited February 7, 2013 by pr40

[nicklemama]

I grew up in small town Oklahoma. That might seem like third world to some, lol. Had pets. Drank raw milk. Lived in an old house. No a/c, windows open all summer. We didn't do all the hand washing done today. My mom worked and she was not June Cleaver with the house cleaning. I have an autoimmune disorder.

[cobbiemommy]

I grew up in MO with no air conditioning and a Mother who liked to clean. Her mother (my Grandmother) was a nurse and they lived on a farm in the 1930's before they had electricity and modern cleaning products and had allergies and health issues. My mother had horrible allergies her whole life from the time she was little. She almost died after being stung by a bee when she was nine.

 

I was the youngest of seven children and had horrible allergies; my eyes used to swell shut in ragweed season when I was a kid in the 70s. I used to play in the dirt and slept with open windows every night in the spring, summer and fall. I will have an anaphylactic reaction if I have even a bite of melon.

 

My brother spent a month at the University of Missouri hospital in 1967 after he almost died from nephritis caused by an infection. It was an autoimmune reaction. You will never meet a rowdier guy who loved to be outside with the dogs, the cats, and dirt.

 

My husband and I live on a farm on a gravel road and my son played in the mud, had a cow that they maintained, and he has autoimmune disease. I think the hygene hypothesis is just another way of blaming moms for being "too clean", kind of like blaming Refrigerator Moms who were "too cold".

 

I think a genetic component is a more accurate basis for investigation with regards to our children having autoimmune disease!

Edited February 8, 2013 by cobbiemommy

[ThinkGutBacteria]

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.

[ThinkGutBacteria]

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

[cobbiemommy]

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 didnt exist in poorer farm families, who had a much greater exposure to pollen.12 More than a century later, soon after Strachans 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 cityfour 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 15 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

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.

Edited February 8, 2013 by cobbiemommy

[ThinkGutBacteria]

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

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.

[ThinkGutBacteria]

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

[ThinkGutBacteria]

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

[ThinkGutBacteria]

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.

[ChrissyD]

I was going to ask your opinion on that. Talked with Dr Hollander's assistant late last summer about possibly evaluating my son for PANDAS, and based on my son's history they felt he was a good candidate for their whipworm study. Didn't even consider it at the time because my son was in crisis. But now that I'm learning more I'm intrigued by the concept.

[ThinkGutBacteria]

I was going to ask your opinion on that. Talked with Dr Hollander's assistant late last summer about possibly evaluating my son for PANDAS, and based on my son's history they felt he was a good candidate for their whipworm study. Didn't even consider it at the time because my son was in crisis. But now that I'm learning more I'm intrigued by the concept.

 

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.

[ChrissyD]

Thanks for the link. That goes back awhile. My son is doing IVIG next week so if I'd ever consider pursuing it, it wouldn't be anytime soon. But I'm open minded to anything that would help my son. I'm enjoying your posts ThinkGut. Thx.