About 20 miles southeast of South Bend, Indiana, straddling US highway 6, lies the farming village of Nappanee, population 6,692. The town has the distinction of being the only municipality in the United States with a name in which each letter is repeated once.

Nappanee is also known as the “southern gateway to Indiana Amish country.”

Derek Jensen CC2
Source: Derek Jensen CC2

A few miles north of the city, a family we’ll call Stoltzfus (a common Amish name) runs a small dairy farm that has been in the family for many generations. A traditional Amish farm, the Stoltzfus operation is decidedly low tech: Horses, not tractors, do the heavy work, and the family feeds and milks its cows by hand. The distinctive red barn sheltering the farm animals sits right next to the farmhouse. The Stoltzfus family uses manure instead of fertilizer and never employs pesticides on its 80 acre plot.

The Stoltzfuses are typical of Amish farmers in the region in most respects, including the happy circumstance that none of the Stoltzfus children suffer from asthma.  

According to research from the University of Arizona cited recently in the prestigious New England Journal of Medicine (NEJM), about 5 percent of Indiana Amish children suffer from asthma, compared with 10 percent in the general population.

That’s a whopping difference in prevalence of the allergic disorder. What accounts for the astonishingly low asthma rates: Diet? Exercise? Lifestyle? Genetics? Low pollen count? Clean and tidy homes?

None of the above.
 
The August 2016 NEJM article, "Innate Immunity and Asthma Risk in Amish and Hutterite Farm Children," asserts that the cause of the low asthma rates is most likely… dust.
 
Owing to the close proximity to farm animals and frequent contact with bacteria-rich dirt, house and barnyard dust on Amish farms is chock full of microbes and bacterial toxins called endotoxins. This rich cocktail of seemingly harmful microscopic particles is unique, even among farming communities.  For example, the Arizona researchers discovered that dust in homes of Hutterites of South Dakota,  a religious group similar to the Amish, lacked many of the unhygienic constituents of Amish dust.
 
The reason? Hutterites make extensive use of new technology, operating “industrial” farms in which animals are kept far from farmhouses. So bugs and toxins from the farm animals don’t make their way into household dust.
 
Coincidentally, Hutterite children suffer from Asthma at rates comparable to or even greater than the national average.
 
So why does “toxic dust” paradoxically protect against asthma, and what does asthma have to do with mental health?
 
A fast-growing body of research suggests that immune disorders such as asthma (in which the body attacks harmless particles such as pollen, triggering damaging inflammation) may be acquired in childhood when the immune system fails to get proper “exercise” by being exposed to “old friend” microbes (bacteria, viruses and parasites that have co-evolved with humans over thousands of years) that seldom cause disease, but stimulate and educate the immune system to differentiate between harmless and harmful antigen proteins.
 
Thus through early exposure, the “old friends” build healthy immune systems that neither overreact—with allergies and autoimmune disease (e.g. arthritis, colitis, eczema)—nor underreact, lowering resistance to infection or cancer.
 
As a consequence, individuals with healthy immune systems will generally have less inflammation due to allergy, autoimmune reaction, or infection.
 
Which brings us to mental health. Chronic inflammation has been recently implicated in a broad range of mental disorders, including depression, anxiety, bipolar disorder, OCD, and schizophrenia.
 
Elevated inflammatory compounds such as cytokines have been shown to trigger depression, social avoidance, and inactivity, which probably evolved as a protection against further injury or infection when our distant ancestors were sick or injured.
 
Research also suggests that inflammation in the central nervous can disrupt neuronal function and trigger or exacerbate mental disorders such as schizophrenia.
 
New hope for preventing and treating mental illness?
 
The links between “old friend” microbe exposure and low inflammation on the one hand and high inflammation and mental illness on the other hand raise a question: Could exposure to “old friend” microbes help prevent or treat some mental illness by developing healthier immune systems that don’t promote inflammation from allergy or autoimmune response?
 
Epidemiological data suggest that the answer is a firm… maybe. Here are the numbers:

  • Mental illness is less common among the Amish than the general population, according to psychiatrist Abram Hostetter, who has extensively researched mental health of the religious group.  Although bipolar disorder is somewhat higher than average (probably due to genetic factors, according to Hostetter), rates of other mental diseases such as major depression, anxiety disorder and schizophrenia are markedly lower.  Suicide rates among the Amish of Lancaster Pennsylvania are less than half the national average (5.5 per 100,000 vs. 13 per 100,000). 
  • Factors other than exposure to “old friend” microbes, such as religious faith, strong community support, and healthy lifestyle could also protect against mental illness among the Amish. Autism rates among the Amish (who typically do vaccinate their children) are 369 per 100,000 of population vs. 1,639 per 100,000 in the general population.
  • The World Health Organization reports that overall prevalence of mental illness is 27 percent lower in low-to-middle income countries (11,000 per 100,000 of population), such as those in sub-saharan Africa, than in high-income countries (14,000 per 100,000). Children in low-income countries typically are exposed to more bacteria, viruses, and parasites than children in wealthy countries.
  • In high-income countries, prevalence of depression in urban settings, which feature markedly less “old friend” exposure, are 39 percent higher than in rural settings. Anxiety disorders are 21 percent more common in urban than in rural environments. Peen et al of the Arkin Mental Health Institute in the Netherlands, pooling data from 20 separate studies, found that the overall rate of mental illness is 38 percent higher in cities than in the countryside.

None of these statistics prove conclusively that exposure to bugs prevents mental illness or that lack of such exposure promotes it. However, the numbers do suggest promising new avenues of research for prevention and treatment of a wide range mental health problems.
 
Near-term implications for preventing and treating mental disorders

It’s unlikely that you’ll see certified Amish dust inhalers or sprays in the supplement section of your local supermarket or pharmacy anytime soon, although physicians researching the apparent protective properties of “old friend” dust have seriously suggested nasal sprays containing the potent dust as a prophylactic measure against asthma during infancy.

But recent studies of child health in different environments hint at some relatively simple ways that infants' immune systems and future mental health might be boosted.

Exposure to dogs, cats, and mice in the first year of life seems to lower asthma risk. But there is evidence of a “critical period” for training children’s immune system, where exposure after the first year is much less effective than in infancy. Although very little research has been done on early exposure to animals and eventual development of mental disorders, the inflammation theory of psychiatric disorders suggests that there could well be some benefits of pet ownership for families with infants. Also, incidence of depression is lower in people who do not have chronic inflammatory diseases such as hay fever, asthma or eczema.

The likelihood of developing childhood asthma decreases as the number of older siblings increases, hinting that microbes brought into the home by other children could be protective for infants. Thus, only-child infants might benefit from more frequent proximity to other children, for example, in day care centers.

What about older children and adults with allergies and/or mental disorders aggravated by chronic systemic inflammation?

First, anti-inflammatory medications, such as aspirin, ibuprofen, and especially celecoxib (Celebrex) have recently been shown to reduce anxiety and depression in some patients. Coincidentally, traditional antidepressants, such as SSRI inhibitors, have also been shown to have anti-inflammatory properties. Of course any mental health benefits of taking anti-inflammatory medications must be weighed against the risks (bleeding with aspirin, gastrointestinal side effects with both aspirin and other NSAIDs).

Second, although evidence for any benefit of exposure to “old friends” after infancy is scant, fast-accumulating research in the field of biomics (on harmless microbes in the gut and on the skin) suggests alternate ways to reduce some forms of chronic inflammation and mental illness.

Imbalance of gut microbes, as with Crohn’s disease and Irritable Bowel Syndrome, is associated with higher rates of depression and anxiety, possibly due to inflammation and direct influence of “bad bugs” in the gut on mood centers in the brain. Aware of such correlations, UCLA scientists found that the brains of women who regularly consumed yogurt containing “good bugs” exhibited less stress and anxiety responses on an fMRI than brains of women who did not eat the culture-rich yogurt, suggesting that “good” bugs in the gut can be beneficial to mental health. This finding correlates with other research showing protective effects of yoghurt consumption for post partum depression in women. Another study showed that men who took probiotic pills had lower anxiety than men who did not. 

Irish researchers at the University College Cork studying link between gut microbes and mental health found that fecal matter transplants from depressed and anxious humans into rats produced signs of depression and anxiety in the rodents. The researchers speculate that fecal transplants from “non-depressed” humans into depressed and anxious humans could have beneficial effects.

Summing up, our journey began with the mystery of unusually low asthma rates among the Amish, but ended, as often happens in science, in an unexpected place—with new possibilities for reducing mental illness, such as early pet exposure and day care centers for infants and consumption of microbe-laced concoctions for older children and adults.
 
Yes, some of these new strategies may be hard to swallow—literally and figuratively—but my gut tells me they are worth exploring further.
 
  www.drhaseltine.com

  www.braincandyfun.com
 

References

Peen J1, Schoevers RA, Beekman AT, Dekker J., The current status of urban-rural differences in psychiatric disorders. Acta Psychiatr Scand. 2010 Feb;121(2):84-93. doi: 10.1111/j.1600-0447.2009.01438.x. Epub 2009 Jul 13.

Graham A. W. Rook,*, Christopher A. Lowry, and Charles L. Raison, Microbial ‘Old Friends’, immunoregulation and stress resilience, Evol Med Public Health. 2013; 2013(1): 46–64.

Souhel Najjar,1,5 Daniel M Pearlman,2,5 Kenneth Alper,4 Amanda Najjar,3 and Orrin Devinsky1,4,5Neuroinflammation and psychiatric illness, J Neuroinflammation. 2013; 10: 43.

Strachan DP. Hay fever, hygiene, and household size. BMJ. 1989;299:1259-1260. Abstract

Bloomfield SF, Stanwell-Smith R, Crevel RW, Pickup J. Too clean, or not too clean: the hygiene hypothesis and home hygiene. Clin Exp Allergy. 2006;36:402-425. Abstract

Webb EL, Nampijja M, Kaweesa J, et al; LaVIISWA trial team. Helminths are positively associated with atopy and wheeze in Ugandan fishing communities: results from a cross-sectional survey. Allergy. 2016;71:1156-1169. Abstract

Motika CA, Papachristou C, Abney M, Lester LA, Ober C. Rising prevalence of asthma is sex-specific in a US farming population. J Allergy Clin Immunol. 2011;128:774-779. Abstract

Holbreich M, Genuneit J, Weber J, Braun-Fahrländer C, Waser M, von Mutius E. Amish children living in northern Indiana have a very low prevalence of allergic sensitization. J Allergy Clin Immunol 2012;129:1671-1673.

Bach, J.F. (2002) The effect of infections on susceptibility to autoimmune and allergic diseases. N. Engl. J. Med. 347, 911–920 Sawczenko, A. et al. (2001) Prospective survey of childhood inflammatory bowel disease in the British Isles. Lancet 357, 1093–1094

Rook, G.A. et al. (2004) Mycobacteria and other environmental organisms as immunomodulators for immunoregulatory disorders. Springer Semin. Immunopathol. 25, 237–255

Wildin, R.S. et al. (2002) Clinical and molecular features of the immunodysregulation, polyendocrinopathy, enteropathy, X linked (IPEX) syndrome. J. Med. Genet. 39, 537–545

Akdis, M. et al. (2004) Immune responses in healthy and allergic individuals are characterized by a fine balance between allergen-specific T regulatory 1 and T helper 2 cells. J. Exp. Med. 199, 1567–1575

Viglietta, V. et al. (2004) Loss of functional suppression by CD4+CD25+ regulatory T cells in patients with multiple sclerosis.J. Exp. Med. 199, 971–979

Kriegel, M.A. et al. (2004) Defective suppressor function of human CD4+ CD25+ regulatory T cells in autoimmune polyglandular syndrome type II. J. Exp. Med. 199, 1285–1291

Powrie, F. et al. (2003) Control of immune pathology by regulatory T cells. Novartis Found. Symp. 252, 92–98

Kraus, T.A. et al. (2004) Failure to induce oral tolerance to a soluble protein in patients with inflammatory bowel disease. Gastroenterology 126, 1771–1778

Babu, S. et al. (2006) Regulatory networks induced by live parasites impair both Th1 and Th2 pathways in patent lymphatic filariasis: implications for parasite persistence. J. Immunol. 176, 3248–3256

van der Kleij, D. et al. (2002) A novel host-parasite lipid crosstalk. Schistosomal lyso-phosphatidylserine activates Toll-like receptor 2 and affects immune polarization. J. Biol. Chem. 277, 48122–48129

Smits, H.H. et al. (2005) Selective probiotic bacteria induce IL-10- producing regulatory T cells in vitro by modulating dendritic cell function through dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin. J. Allergy Clin. Immunol. 115, 1260–1267

van den Biggelaar, A.H. et al. (2000) Decreased atopy in children infected with Schistosoma haematobium: a role for parasite-induced interleukin-10. Lancet 356, 1723–1727

King, C.L. et al. (1993) Cytokine control of parasite-specific anergy in human lymphatic filariasis. Preferential induction of a regulatory T helper type 2 lymphocyte subset. J. Clin. Invest. 92, 1667–1673

Fan X, et al. "Inflammation and Schizophrenia," Expert Reviews of Neurotherapies (July 2007): Vol. 7, No. 7, pp. 789–96.

The International Schizophrenia Consortium. "Common Polygenic Variation Contributes to Risk of Schizophrenia and Bipolar Disorder," Nature (July 1, 2009): Electronic publication ahead of print.

Miller AH, et al. "Inflammation and Its Discontents: The Role of Cytokines in the Pathophysiology of Major Depression," Biological Psychiatry (May 1, 2009): Vol. 65, No. 9, pp. 732–41.

Yolken RH, et al. "Are Some Cases of Psychosis Caused by Microbial Agents? A Review of the Evidence," Molecular Psychiatry (May 2008): Vol. 13, No. 5, pp. 470–79.

Musselman, D.L. et al. (2001) Higher than normal plasma interleukin-6 concentrations in cancer patients with depression: preliminary findings. Am. J. Psychiatry 158, 1252–1257

Raison, C.L. and Miller, A.H. (2003) Depression in cancer: new developments regarding diagnosis and treatment. Biol. Psychiatry 54, 283–294

Ferketich, A.K. et al. (2005) Depressive symptoms and inflammation among heart failure patients. Am. Heart J. 150, 132–136

Chapman, D.P. et al. (2005) The vital link between chronic disease and depressive disorders. Prev. Chronic Dis. 2, A14

Beuther, D.A. et al. (2006) Obesity and asthma. Am. J. Respir. Crit. Care Med. 174, 112–119

Maes, M. et al. (1999) Lower serum zinc in major depression in relation to changes in serum acute phase proteins. J. Affect. Disord. 56, 189–194

Lynch SV, Wood RA, Boushey H, et al. Effects of early-life exposure to allergens and bacteria on recurrent wheeze and atopy in urban children. J Allergy Clin 

Ownby, D., Johnson, C., & Peterson, E. L. (2002). Exposure to dogs and cats in the first year of life and risk of allergic sensitization at 6 to 7 years of age. JAMA, 288 (8), 963e972.

Ronald C. Kessler, Sergio Aguilar-Gaxiola, Jordi Alonso, Somnath Chatterji, Sing Lee, Johan Ormel, T. Bedirhan Üstün, and Philip S. Wang, The global burden of mental disorders: An update from the WHO World Mental Health (WMH) Surveys, Epidemiol Psichiatr Soc. 2009 Jan–Mar; 18(1): 23–33.

Ronald C. Kessler and Evelyn J. Bromet, The epidemiology of depression across cultures, Annu Rev Public Health. 2013; 34: 119–138.  

You are reading

Long Fuse, Big Bang

The "Deep State" Warns Us About Shallow Thinking

Why yesterday's psychology has wrecked today's politics.

Brain Imaging Shows We Can Unlearn Chronic Pain

Neuroanatomical changes observed with learning and unlearning of chronic pain.

Let’s Put the Focus on Bullying Where It Belongs

Shifting the spotlight from the stage to the audience.