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Human Gut Bacteria and the hygiene principle

Allergy, Eczema, Digestion, Asthma, Skin Conditions, General, Infant and Children | May 17, 2016 | Author: The Super Pharmacist

Children, allergy, infant, Asthma, Digestion

Human Gut Bacteria and the hygiene principle

Over the past three decades, there has been a dramatic increase in allergy-linked diseases such as asthma, atopic dermatitis and hay fever in developed (westernised) countries. Even factors such as improved diagnosis and hereditary influence fail to account for the marked rise in incidence of allergic disorders.

In contrast, the low baseline prevalence of allergic disease has not changed significantly over the same period in developing countries. The rapid pace of this epidemiologic shift tends to discount genetic causes, thus directing investigative efforts toward environmental factors instead. Interestingly, a similar trend has been observed for the incidence of autoimmune diseases as well.

While the incidence of many infectious diseases has declined in developed countries as a result of antibiotics, vaccines, improved hygiene and better socioeconomic conditions, there has been an almost parallel upward trend in the incidence of autoimmune diseases.

The ‘hygiene principle’ or more accurately, the ‘hygiene hypothesis,’ put forward to explain this phenomenon, has gained more acceptance in the scientific community.

What Is the Hygiene Principle?

The ‘hygiene hypothesis’ was first formulated in 1989 by epidemiologist, David Strachan who reported a relationship between family size and development of allergic disorders, and proposed that - a lack of early childhood exposure to infectious agents, symbiotic microorganisms and parasites increases susceptibility to allergic diseases by suppressing the natural development of the immune system.

It was believed that children must be kept in an environment that is as clean as possible, the hypothesis put forward suggests that being exposed to 'unclean' conditions is good for a child's immune system.

Research has indicated that those children who are kept in very clean environments have a higher rate of allergy type diseases.

According to the ‘hygiene hypothesis,’ the decreasing incidence of infections in western countries and more recently in developing countries is at the origin of the increasing incidence of both allergic and autoimmune diseases.

Allergic and Autoimmune Disorders in Australia?

Allergic disorders

Australia and New Zealand have among the highest prevalence of allergic disorders in the developed world.

According to a 2013 report issued by the Australasian Society of Clinical Immunology and Allergy (ASCIA), almost 20% of Australians have at least one allergic disease and this prevalence is increasing.

Hospital admissions for anaphylaxis (severe life threatening allergic reaction) have increased 4 fold in the last 20 years. Food-induced anaphylaxis has doubled in the last 10 years and 10% of infants now have an immediate food allergy.

It is predicted that from 2007 to 2050 the number of patients affected by allergic diseases in Australia will increase from 4.1 million (19.6% of the population) to 7.7 million (26.1% of the population).

Recent decades have seen increases in the prevalence of allergic rhinitis, asthma and atopic eczema (although the proportion of people with asthma has plateaued in the past few years). 

Evidence that food allergy is becoming more common, however, is limited to changes in prevalence of peanut allergy. Two separate studies of young children showed a doubling of clinical reactivity over 5 years. 

In a 2013 study, information on the global patterns and prevalence of food allergy was obtained by surveying all the member countries of the World Allergy Organisation, and some of their neighbouring nations. Australia ranked highest of the 16 countries where this data was available.

Autoimmune Disease

Autoimmune diseases affect 5% of Australians and are more common than cancer or heart disease. Immune diseases are among the fastest growing chronic conditions in Australia.
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Allergic and Autoimmune Disorders?

Over the last several decades, there has been a marked increase in the prevalence of autoimmune diseases such as type 1 diabetes, multiple sclerosis, inflammatory bowel diseases such as Crohn’s disease and ulcerative colitis, and celiac disease. 

Immune-mediated conditions are thought to result from a complex interplay between genetic predisposition, immune deregulation, and environmental factors. Since genetic basis has not undergone any major changes in such a short period of time, environmental factors are highly suspected to be responsible for this recent outbreak in both allergic and autoimmune disorders.

Increased attention is now being focused on critical environmental factors in the search for the origins of these diseases. Studies of immigrants, epigenetic studies and mapping of the gut microbiota have provided compelling evidence that the environment can fundamentally modulate immune function in humans. Poorly developed or broken immune tolerance plays a role in the pathogenesis of many diseases such as allergy, autoimmunity, and even cancer.

Intestinal microbiota 

The human body contains tenfold more microbial cells than human cells. These microorganisms colonise practically every surface of the human body that is exposed to the external environment, including the skin, oral cavity, respiratory, urogenital and gastrointestinal tract. Of these body sites, the gastrointestinal tract is by far the most densely colonised organ.

The complex community of microorganisms residing in or passing through the gastrointestinal tract is referred to as the intestinal microbiota.

Our gut flora comprises a critical component of our immune system.  When there is a lack of beneficial bacteria or overgrowth of harmful bacteria, yeast, or parasites this leads to a condition called leaky gut syndrome. This is simply loss of the normal barrier function of the intestine leading to increased intestinal permeability. As with food sensitivities, the resulting increased intestinal permeability may contribute to the pathogenesis of various autoimmune diseases. Therefore, the integrity of the intestinal barrier is a critically important factor in autoimmune disease.

The microbiota is variable and shows temporal fluctuation in early life. When a steady state is reached, the composition of the gut flora remains relatively stable over time, providing that no major changes in lifestyle or environment occur. Early environmental exposures are thus considered the key determinant of adult gut microbiota, as is the type of diet consumed.

Geographical influence

The geographical distribution of allergic and autoimmune diseases is a mirror image of the geographical distribution of various infectious diseases, including hepatitis A virus, gastrointestinal infections and parasitic infections. Further clues about the influence of environmental factors on the development of the gut microbiota have been obtained from studies of infants in Estonia and Sweden. 

Geographical influenceThese provide some of the first evidence that the composition of gut microflora between non-western and western children in early life differs and that these disparities could be associated with the manifestation of allergic diseases in later life. 

Using novel molecular-based methods, a Swedish study revealed that a more diverse gut microbiota early in life is associated with protection against allergy at the age of 5 years.

Immigrant studies

The immunomodulatory changes appear to occur within 10 years after arrival, and these changes are not restricted to young people only but also occur in adults as well. This immunomodulation by “cultural adaptation”, which leads to changes in disease susceptibility, appears to be universal and has been reported for various inflammatory diseases, including asthma and allergic diseases, autoimmune diseases, such as type 1 diabetes and multiple sclerosis,obesity and type 2 diabetes, depression and civilization cancers.
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Microbial deprivation

Previous studies reveal that microbe-rich environments confer protection against allergic and autoimmune diseases, but it is likely that declining biodiversity is more generally responsible for human immune dysfunction.

According to a recent study, atopic individuals had lower environmental biodiversity compared with healthy adolescents in the surroundings of their homes. The atopic adolescents also had significantly lower diversity of Gram-negative gamma proteobacteria on their skin.

The health effects of natural environments are obvious, but difficult to examine experimentally. According to one study, farm exposure during pregnancy increases the number and function of cord blood regulatory T cells (Treg cells).

Two of the multiple functions of Treg cells are:

  • Prevention of autoimmune diseases by establishing and maintaining immunologic self-tolerance
  • Suppression of allergy and asthma

There is mounting evidence for the hypothesis that low early life microbial exposure is associated with persisting methylation (silencing) of a specific gene in maternal regulatory T cells that ordinarily exerts a critical protective effect against allergic disease in maternal offspring. 

Natural microbial exposure has been identified as an important environmental condition that provides asthma protection in a prenatal window of opportunity. This protective effect is achieved via epigenetic regulation. Urbanization and general loss of biodiversity, combined with sedentary indoor lifestyles have been a principle driving factor leading to microbial deprivation.

Inflammatory diseases

Mounting evidence shows that alterations in the indigenous microbiota correlate with inflammatory disease states. Dysbiosis refers to a reduced diversity and disturbed composition of the gut microbial community. Not only does it influence the occurrence of asthma and allergies, but it also influences the development of other chronic and relapsing inflammatory conditions that include type 1 diabetes, inflammatory bowel disease, obesity and even psychiatric disorders, such as depression. 

Moreover, an imbalance of ‘pro-inflammatory’ and ‘anti-inflammatory’ microbes may also result in an increased susceptibility of the host to inflammatory diseases and could explain the increase in paediatric inflammatory bowel disease, one of the many inflammatory diseases being reported with increasing frequency in westernized countries.

Antibiotic use

Antibiotics modulate microbiota, and the effect may be long-term. One-week course affected the gut microbiota even for three years. 

To date, the findings from epidemiologic studies have supported and refuted an association between antibiotic use in early life and the development of asthma. 

A recent meta-analysis of antibiotic use in the first year of life has reported a twofold increased risk of childhood asthma following antibiotic use, but no association among studies conducted prospectively.

A longitudinal study (known as the Study of Asthma, Genes and the Environment) of a cohort of 13,980 children born in Manitoba in 1995 and continuously registered with the Manitoba Health Services Insurance Plan (MHSIP) until 2003.

The likelihood of asthma at age 7 years according to antibiotic prescription use during the first year of life was determined. Following adjustment for gender, maternal history of asthma, number of siblings, urban/rural location, and the number of health-care visits, antibiotic use in the first year of life (vs no use) was significantly associated with greater odds of the development of asthma at age 7. This likelihood increased with the number of antibiotic courses. In a model that adjusted for all risk factors for asthma, asthma was significantly more likely to develop in children receiving antibiotics in a dose-dependent manner.

Additional risk factors

Air pollution

Indoor and outdoor pollution is a major environmental risk factor for asthma and allergy not only increasing the prevalence of long-term symptoms but also acute attacks.The association studies indicate that ambient air pollution is connected to asthma, rhinitis, rhino-conjunctivitis, and acute respiratory infections.

Climate change

Climate change has direct impacts on aeroallergens, in particular pollens and mold spores and allergic diseases. Pre-Industrial CO2 levels in 1870 were 280 ppm, followed by a steady increase of 35% by 2005 to 379 ppm, with urban areas exhibiting the highest levels. Several studies have demonstrated direct correlations between rising CO2 and increases in both pollen and biomass levels, as well as increased allergenicity of the pollen.                                        

Epigenetic modulation

Epigenetics is the study, in the field of genetics, of how environmental factors can change how genes are expressed. For example, one epigenetic mechanism is the addition of a methyl group to the DNA of cells. This called ‘methylation.’ Another epigenetic mechanism is the removal or ‘demethylation' of DNA within cells. Epigenetics alters gene expression rather than altering the genetic code itself.

Cancer: While epigenetic changes are required for normal development and health, they can also be responsible for some disease states. 

The first human disease to be linked to epigenetics was cancer, in 1983. Researchers found that diseased tissue from patients with colorectal cancer had less DNA methylation than normal tissue from the same patients.

Preventing Allergy Disease

There are no clearly established guidelines for primary prevention of allergic disease or any established methods to non-specifically strengthen tolerance in established disease. However, data have accumulated to indicate that some simple behavioural activities can confer some protection against or alleviate allergic diseases, providing indirect evidence of their beneficial effects on tolerance. Not unexpectedly, such interventions include physical exercise, a healthy diet and connection with the natural world and countryside.

Physical activity

There is much evidence emphasizing the risks to health of a sedentary lifestyle. A lack of physical exercise increases the inflammatory burden, independently of obesity, and decrease systemic low level inflammation. The anti-inflammatory effects of physical exercise seem to be mediated by activating the regulatory circuits, including regulatory T cells. For example, in healthy adults, a 12-week program of moderate exercise 3 times per week significantly improved regulatory T cell numbers and function. Moderate exercise for 12 weeks in patients with type 2 diabetes, significantly decreased HbA1c levels. The anti-inflammatory effect of exercise has also been demonstrated in a murine model of asthma.

Healthy diet

In addition to micro-organisms, dietary factors have been extensively studied to uncover possible additional factors behind the asthma and allergy epidemics in modern urban environments, given the modulatory potential of nutrients on epigenetics, intestinal microbiota and immune function. While an inverse link between various nutrients or vitamins and occurrence of allergic diseases has been proposed in cross-sectional studies, the results are inconsistent and inconclusive.

However, a systematic review based on 62 reports and 11 databases concludes that although the epidemiologic evidence thus far is weak, it supports a beneficial role for increased consumption of more fruits and vegetables, associated with better asthma and allergy outcomes.

For example, a traditional Mediterranean diet confers protection against persistent wheeze and atopy. 

It must be also born in mind that at least a part of the beneficial effect of fresh fruit and vegetables may be mediated by microorganisms abundantly present on their surfaces. 

Vitamin D deficiency has been suspected to play a role in the ´asthma epidemic´ as it may influence genomic programming of foetal development and subsequent disease risk and is tightly linked to diet and exposure to sunlight. This hypothesis is in the process of being tested in a large controlled trial in pregnant women and their offspring for the primary prevention of asthma.

Probiotics

The benefits of probiotics to prevent or treat allergic diseases and asthma remain inconclusive. Bacteria-based products hold great promise for allergy prevention, but in the case of probiotics, the most beneficial bacterial strains, doses, duration and timing of supplementation are not determined.

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References

Eder W, Ege MJ, von Mutius E. The asthma epidemic. N Engl J Med. 2006; 23:2226–35.

Bieber T. Atopic dermatitis. N Engl J Med. 2008; 358:1483–94.

Asher MI, Montefort S, Björkstén B, et al. Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC Phases One and Three repeat multi-country cross-sectional surveys. 2006; 368:733–43.

Svanes C. What has the ECRHS told us about the childhood risks of asthma, allergy and lung function? Clin Respir J. 2008;2(Suppl 1):34–44.

SamoliƄski B, Raciborski F, Tomaszewska A, et al. Epidemiology of allergic diseases in Poland – ECAP study [Polish] 2008; 3940:26–8.

Bach JF. The effect of infections on susceptibility to autoimmune and allergic diseases. N Engl J Med.2002; 347:911–20.

Gale EA. The rise of childhood type 1 diabetes in the 20th century. Diabetes. 2002; 51:3353–61.

Joner G, Stene LC, Sovik O. Nationwide, prospective registration of type 1 diabetes in children aged < 15 years in Norway 1989–1998: no increase but significant regional variation in incidence. Diabetes Care. 2004; 27:1618–22.

Mayr WT, Pittock SJ, McClelland RL, et al. Incidence and prevalence of multiple sclerosis in Olmsted County, Minnesota, 1985–2000. 2003; 61:1373–7.

Strachan DP. Hay fever, hygiene, and household size. BMJ. 1989; 299:1259–60.

Allergy and Immune Diseases in Australia (AIDA) 2013. Australasian Society for Clinical Immunology and Allergy (ASCIA). Available at: https://www.allergy.org.au/images/stories/reports/ASCIA_AIDA_Report_2013.pdf Accessed 13 May 2016.

The International Study of Asthma and Allergies in Childhood (ISAAC) Steering Committee. Worldwide variation in prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema: ISAAC. Lancet 1998; 351: 1225-1232.

Robertson CF, Roberts MF, Kappers JH. Asthma prevalence in Melbourne schoolchildren: have we reached the peak? Med J Aust 2004; 180: 273-276.

Grundy J, Matthews S, Bateman B, et al. Rising prevalence of allergy to peanut in children: data from 2 sequential cohorts. J Allergy Clin Immunol 2002; 110: 784-789.

Sicherer SH, Munoz-Furlong A, Sampson HA. Prevalence of peanut and tree nut allergy in the United States determined by means of a random digit dial telephone survey: a 5-year follow-up study. J Allergy Clin Immunol 2003; 112: 1203-1207.

Mullins RJ. Paediatric food allergy trends in a community-based specialist allergy practice, 1995–2006. Med J Aust 2007; 186 (12): 618-621.

Prescott SL, Pawankar R, Allen KJ, et al. A global survey of changing patterns of food allergy burden in children. The World Allergy Organization Journal. 2013;6(1):21.

Lerner A, Jeremias P, Matthias T. The world incidence and prevalence of autoimmune diseases is increasing. Inter J of Celiac Dis. 2015;3(4): 151-155.

Gale EA. The rise of childhood type 1 diabetes in the 20th century. Diabetes 2002; 51:3353–61.

Joner G, Stene LC, Sovik O. Nationwide, prospective registration of type 1 diabetes in children aged < 15 years in Norway 1989–1998: no increase but significant regional variation in incidence. Diabetes Care 2004; 27:1618–22.

Mayr WT, Pittock SJ, McClelland RL, et al. Incidence and prevalence of multiple sclerosis in Olmsted County, Minnesota, 1985–2000. Neurology 2003; 61:1373–7.

Cosnes J, Gower-Rousseau C, Seksik P, Cortot A. Epidemiology and natural history of inflammatory bowel diseases. Gastroenterology. 2011; 140:1785–94.

Barak M, Rozenberg O, Froom P, et al. Challenging our serological algorithm for celiac disease (CD) diagnosis by the ESPGHAN guidelines. Clin Chem Lab Med. 2013;51; e257-259.

Haahtela T, Holgate S, Pawankar R, et al. The biodiversity hypothesis and allergic disease: world allergy organization position statement. World Allergy Organization Journal. 31 Jan 2013; 6:3.

Schwabe RF, Jobin C. The microbiome and cancer. Nature Reviews Cancer. 2013; 13:800-812.

Round JL, Mazmanian SK. The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol. 2009, 9: 313-324.

Garrett WS, Gordon JI, Glimcher LH: Homeostasis and inflammation in the intestine. 2010, 140: 859-870.

De Filippo C, Cavalieri D, Di Paola M, et al. Impact of diet in shaping gut microbiota revealed by a comparative study in children from Europe and rural Africa. Proc Natl Acad Sci USA. 2010, 107: 14691-14696.

Wu GD, Chen J, Hoffmann C, Bittinger K, et al. Linking long-term dietary patterns with gut microbial enterotypes. 2011, 334: 105-108.

Maslowski KM, Mackay CR: Diet, gut microbiota and immune responses. Nat 2011, 12: 5-9.

Kau AL, Ahern PP, Griffin NW, Goodman AL, Gordon JI. Human nutrition, the gut microbiome and the immune system. 2011, 474: 327-336.

Wallin MT, Page WF, Kurtzke JF. Multiple sclerosis in US veterans of the Vietnam era and later military service: race, sex, and geography. Ann Neurol. 2004; 55:65–71.

Yang Z, Wang K, Li T, et al. Childhood diabetes in China. Enormous variation by place and ethnic group. Diabetes Care. 1998; 21:525–9.

Green A, Patterson CC. Trends in the incidence of childhood-onset diabetes in Europe 1989–1998. Diabetologia. 2001;44(Suppl. 3): B3–8.

Sepp E, Naaber P, Voor T, Mikelsaar M, Björksten B. Development of intestinal microflora during the first month of life in Estonian and Swedish infants. Microbiol Ecol Health Dis. 2000; 6:22–26.

Sepp E, Julge K, Vasar M, Naaber P, Björksten B, Mikelsaar. Intestinal microflora of Estonian and Swedish infants. Acta Paediatr. 1997; 6:956–961.

Björksten B, Naaber P, Sepp E, Mikelsaar M. The intestinal microflora in allergic Estonian and Swedish 2-year-old children. Clin Exp Allergy. 1999; 6:342–346.

Sjögren YM, Jernmalm MC, Böttcher MF, Björksten B, Sverremark-Ekström E. Altered early infant gut microbiota in children developing allergy up to 5 years of age. Clin Exp Allergy. 2009; 6:518–526.

Newbold KB. Self-rated health within the Canadian immigrant population: risk and healthy immigrant effect. Soc Sci Med. 2005; 6:1359–1370.

Bodansky HJ, Staines A, Stephenson C, Haigh D, Cartwright R. Evidence for an environmental effect in the aetiology of insulin dependent diabetes in a transmigratory population. BMJ. 1992; 6:1020–1022.

Leung R. Asthma and migration. Respirology. 1996; 6:123–126.

Rosenberg R, Vinker S, Zakut H, Kizner F, Nakar S, Kitai E. An unusually high prevalence of asthma in Ethiopian immigrants to Israel. Fam Med. 1999; 6:276–279.

Hammond SR, English DR, McLeod JM. The age-range of risk of developing multiple sclerosis. Evidence from a migrant population in Australia. Brain. 2000; 6:967–974.

Kalyoncu AF, Stålenheim G. Serum IgE levels and allergic spectra in immigrants to Sweden. 1992; 6:277–280.

Grüber C, Illi S, Plieth A, Sommerfeld C, Wahn U. Cultural adaptation is associated with atopy and wheezing among children of Turkish origin living in Germany. Clin Exp Allergy. 2002; :526–531.

Creatore MI, Moineddin R, Booth G, Manuel DH, DesMeules M, McDermott S, Glazier RH. Age- and sex-related prevalence of diabetes mellitus among immigrants to Ontario Canada. CMAJ. 2010; 6:781–789.

Casimir GJ, Jean-Louis G, Butler S, Zizi F, Nunes J, Brady L. Perceived insomnia, anxiety, and depression among older Russian immigrants. Psychol Rep. 2010; 6:589–597.

Pinheiro P, Sherman R, Trapido E, et al. Cancer incidence in first generation U.S. Hispanics: Cubans, Mexicans, Puerto Ricans, and New Lationos. Cancer Epidemiol Biomarkers Prev. 2009; 6:2162–2169.

Hanski I, von Hertzen L, Fyhrquist N, et al. Environmental biodiversity, human microbiota, and allergy are interrelated. Proc Natl Acad Sci USA. 2012, 109: 8334-8339.

Schaub B, Liu J, Hoppler S, et al. Maternal farm exposure modulates neonatal immune mechanisms through regulatory T cells. J Allergy Clin Immunol.2009 Apr;123(4):774-82.e5.

Vuillermin PJ, Ponsonby A-L, Saffery R, et al. Microbial exposure, interferon gamma gene demethylation in naïve T-cells, and the risk of allergic disease. March 2009; 64(3): 348-353.

von Hertzen L, Hanski I, Haahtela T: Biodiversity loss and rising trends of inflammatory diseases: two global megatrends that may be related. EMBO Rep. 2011, 12: 1089-1093.

Golding J: Determinants of child health and development: the contribution of ALSPAC –a personal view of the birth cohort study. Arch Dis Child 2010, 95:319–322.

Wen L, Ley RE, Volchov PY, et al. Innate immunity and intestinal microbiota in the development of type 1 diabetes. Nature 2008, 455:1109–1113.

Frank DN, Feazel LM, Bessesen MT, et al. Molecular phylogenetic characterization of microbial community imbalance in human inflammatory bowel disease. Proc Natl Acad Sci USA 2007, 104:13780–13785.

Sokol H, Pigneur B, Watterlot L, et al. Faecalibacterium prausnitzii is an antiinflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc Natl Acad Sci USA. 2008, 105:16731–16736.

Turnbaugh PJ, Hamady M, Yatsunenko T, et al. A core gut microbiome in obese and lean twins. Nature 2009, 457:480–484.

Bienenstock J, Collins S: Psycho-neuroimmunology and the intestinal microbiota: clinical observations and basic mechanisms. Clin Exp Immunol 2010, 160:85–91.

Lee YK, Mazmanian S: Has the microbiota played a critical role in the evolution of the adaptive immune system? Science 2010, 330:1768–1773.

Lehtinen P, Ashorn M, Iltanen S, et al. Incidence trends of pediatric inflammatory bowel disease in Finland, 1987–2003, a nationwide study. Inflamm Bowel Dis 2011, 17:1778–1783.

Dethlefsen L, Huse S, Sogin ML, Relman DA. The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 165 rRNA sequencing. PLoS Biol. 2008, 6: 2383-2400.

Farooqi, IS, Hopkin, JM Early childhood infection and atopic disorder. Thorax 1998; 53,927-932.

Wickens, K, Pearce, N, Crane, J, et al Antibiotic use in early childhood and the development of asthma. Clin Exp Allergy 1999; 29,766-771.

von Mutius, E, Illi, S, Hirsch, T, et al Frequency of infections and risk of asthma, atopy and airway hyperresponsiveness in children. Eur Respir J 1999;14,4-11.

Droste, JH, Wieringa, MH, Weyler, JJ, et al Does the use of antibiotics in early childhood increase the risk of asthma and allergic disease? Clin Exp Allergy 2000;30,1547-1553.

Cohet, C, Cheng, S, MacDonald, C, et al Infections, medication use, and the prevalence of symptoms of asthma, rhinitis, and eczema in childhood. J Epidemiol Community Health 2004; 58,852-857.

McKeever, TM, Lewis, SA, Smith, C, et al Early exposure to infections and antibiotics and the incidence of allergic disease: a birth cohort study with the West Midlands General Practice Research Database. J Allergy Clin Immunol 2002;109,43-50.

Thomas, M, Custovic, A, Woodcock, A, et al Atopic wheezing and early life antibiotic exposure: a nested case-control study. Pediatr Allergy Immunol 2006; 17:184-188.

Illi S, von Mutius E, Lau S, et al Early childhood infectious diseases and the development of asthma up to school age: a birth cohort study. BMJ 2001; 322:390-395.

Celedon, JC, Litonjua, AA, Ryan, L, et al Lack of association between antibiotic use in the first year of life and asthma, allergic rhinitis, or eczema at age 5 years. Am J Respir Crit Care Med 2002;166,72-75.

Celedon, JC, Fuhlbrigge, A, Rifas-Shiman, S, et al Antibiotic use in the first year of life and asthma in early childhood. Clin Exp Allergy 2004;34,1011-1016.

Marra, F, Lynd, L, Coombes, M, et al Does antibiotic exposure during infancy lead to development of asthma? A systematic review and metaanalysis. Chest2006; 129,610-618.

Kozyrrskyj AL, Ernst P, Becker AB. Increased risk of childhood asthma from antibiotic use in early life. 2007;131(6):1753-1759.

Maio S, Cerrai S, Simoni M, et al. Environmental risk factors: indoor and outdoor pollution, p. 84–90. Edited by: Pawankar R, Canonica GW, Holgate ST, Lockey RF. 2011, World Allergy Organization (WAO) White Book on Allergy.

Beggs PJ, Bambrick HJ: Is the global rise of asthma an early impact of anthropogenic climate change? Environ Health Perspectives. 2005, 113: 915-919.

Beggs PJ: Impacts of climate change on aeroallergens: past and future. Clin Exp 2004, 34: 1507-1513.

Wolf J, O’Neill NR, Rogers CA, Muilenberg ML, Ziska LH: Elevated atmospheric CO2 concentrations amplify Alternaria alternata sporulation and total antigen production. Environ Health Perspectives. 2010, 118: 1223-1228.

D'Amato G, Rottem M, Dahl R, et al.WAO Special Committee on Climate Change and Allergy: Climate change, migration, and allergic respiratory diseases: an update for the allergist. World Allergy Organ J. 2011, 4: 120-125.

Wayne P, Foster S, Connolly J, Bazzaz F, Epstein P: Production of allergenic pollen by ragweed is increased in CO2-enriched atmospheres. Ann Allergy Asthma Immunol. 2002, 88: 279-282.

Ziska L, Caulfield FA: Rising CO2 and pollen production of common ragweed, Ambrosia artemisiifolia, a known allergy-inducing species: implications for public health. Aust J Plant Physiol. 2000, 27: 893-898.

Feinberg AP, Vogelstein B. Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature 1983; 301:89–92.

Bruunsgaard H: Physical activity and modulation of systemic low-level inflammation. J Leukoc Biol 2005, 78:819–35.

Yeh SH, Chuang H, Lin LW, Hsiao CY, Eng HL. Regular Tai Chi Chuan exercise enhances functional mobility and CD4CD25 regulatory T cells. Br J Sports Med 2006, 40:239–43.

Yeh SH, Chuang H, Lin LW, et al. Regulat Tai Chi Chuan exercise improves T cell helper function of patients with type 2 diabetes mellitus with an increase in T-bet transcription factor and IL-12 production. Br J Sports Med 2009, 43:845–50.

Lowder T, Dugger K, Deshane J, Estell K, Schwiebert L: Repeated bouts of aerobic exercise enhance regulatory T cell responses in a murine asthma model. Brain Behav Immun 2010, 24:153–59.

Kim JH, Ellwood PE, Asher MI: Diet and asthma: looking back, moving forward. Respir Res 2009, 10:49.

Nurmatov U, Devereux G, Sheikh A: Nutrients and foods for the primary prevention of asthma and allergy: Systematic review and meta-analysis. J Allergy Clin Immunol 2011, 127:724–33.

Jawetz F, Melnick JC, Adelberg EA. Review of Medical Microbiology. Los Altos, Calif: Lange Medical Publications; 1980.

Litonjua AA, Weiss ST: Is vitamin D deficiency to blame for the asthma epidemic? J Allergy Clin Immunol 2007, 120:1031–35.

Litonjua AA, Weiss ST: Vitamin D insufficiency. Correspondence. N Engl J Med 2011, 364:1378–80.

Johanssen H, Prescott SL: Practical prebiotics, probiotics and synbiotics for allergists: how useful are they? Clin Exp Allergy 2009, 39:1801–14.

Ozdemir O: Any benefits of probiotics in allergic disorders? Allergy Asthma Proc 2010, 31:103–11.

Fiocchi A, Burks W, Bahna SL, et al. On behalf of the WAO Special Committee on Food Allergy and Nutrition. Clinical use of probiotics in pediatric allergy (CUPPA): A World Allergy Organization Position Paper. World Allergy Organ J 2012, 5:148-167.

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