Our 'Army' in Turmoil
The immune system can be considered as a large army able to recognize and defend our body from possible aggressors, whose cells (soldiers) perform their work in an organized and coordinated manner. In certain situations, our immune system can start to react excessively to small non-threatening stimuli, and our army, instead of protecting, starts to attack ourselves, thus generating an allergic reaction process.

When the immune system detects an allergen (a substance which causes an allergic reaction in certain subjects), it starts an output of immunoglobulin in an attempt to protect the body. This immunoglobulin (the most famous is the IgE, but IgG, IgM, and IgA are also important) binds to the allergen and, in connection with the immune cells - called mast cells - triggers a type of reaction known as degranulation, which releases histamine and other substances that call the whole "army" to fight this allergen. These substances, in turn, generate a process of inflammation resulting in the typically known allergy symptoms, such as itching, redness, swelling ... and in some cases can cause anaphylactic shock (rapid closing of the airways that can lead to death).

Genetic predisposition is the most frequent cause of cases of allergic reactions. About 50-80% of diagnosed patients have a family history of allergies. The probability of a child being allergic if her or his parents have some sensitivity is about 75%. But genetic factors cannot be blamed in isolation, they indicate the probability, but the environment must activate this mechanism. It is believed that the incidence of childhood allergy is caused by a combination of genetic and ambient factors.(1)

Data available from the Brazilian Association of Allergy and Immunopathology (ASBAI, 2015) shows that about 30% of the general population suffers from some allergy, and of these, 20% are children.(2) The prevalence has increased over the years and concerns health professionals. Several hypotheses try to explain this effect. This article will present some of them proven to explain this phenomenon.(3-5)

How Does The Gut Influence The Allergic Processes?

In recent years, the gut has been the focus of many studies. Increasingly it is clear that the gut is much more than a simple organ that metabolizes and excretes waste. It is involved in many pathological processes, including allergy. The gut is able to house up to 100 trillion bacteria, a quantity that exceeds the number of cells present in an individual; 60 to 70% of the immune cells are located in this area, and it is believed that the individual’s routine and food habits dramatically change this microscopic population.(6-8)

The gut flora has important functions such as synthesis and the body's defense. Once deregulated, a process called dysbiosis (also called dysbacteriosis) occurs in which the body can not properly absorb vitamins or break peptides, therefore it reabsorbs the toxins and this causes numerous pathological processes such as autoimmune deregulation and, consequently, allergic processes.(6) A process of dysbiosis, the imbalance between the microorganisms in the intestinal flora, means a predominance of pathogenic bacteria, as well as fungi, over the beneficial bacteria. It causes a production of highly toxic chemical by-products that are absorbed from the intestinal tract to the bloodstream. Such harmful organisms, along with its by-products, are able to destroy the lining of the gastrointestinal tract (GI tract) opening holes in the intestinal epithelium. Thus, undigested food molecules are able to pass through these holes, and thus, the immune system recognizes them as invaders, generating antibodies and causing food allergy.(9)

The transfer of bacteria from the mother to the fetus begins during pregnancy. The infant microbiota and their genes undergo several changes during its development that can occur until 3 years of age. This entire process is under direct influence of genetics, environmental factors, use of medicines (antibiotics), and nutrition.(8)

The type of delivery is already the first major influence on the constitution of the future child’s flora: children born vaginally are more colonized by beneficial bacteria than children born via C-section. Children born by C-section have a larger amount of Clostridium difficile bacteria type, e.g., and may have more abdominal cramps than the ones born by vaginal birth.(10,11)

Afterwards, breastfeeding directly influences the formation of the microbiota of a child, because human milk contains some natural probiotic bacteria, besides being rich in oligosaccharides (prebiotics) that assist in the development of child’s flora.7 A study published in the Journal of Pediatric Gastroenterology and Nutrition evaluated newborn infants’ fecal samples during the first 20 days of life, formula-fed and breast-fed, and concluded that the species Bifidobacterium (one of the most beneficial GI tract bacteria) is dominant in breast-fed infants.(6)

A study published in Clinical Exp. Allergy showed that the nursling (study objects) who had food allergies also had an imbalance in its microbiota, with less beneficial bacteria and prevalence of malefic ones, such as Staphylococcus aureus. Additionally, an intestinal microbiota imbalance was found in children with atopic eczema.(12,13)

Too much hygiene can work against us

Modern life has made us often exaggeratedly concerned about hygiene. Cleaning products and constant asepsis with alcohol or other disinfectants seek to keep the child in an almost sterile environment, preventing their contact with microorganisms and, conse-quently, the development of their immune system. We could make an analogy with physical activity: the immune system is becoming increasingly sedentary. An article published in Pediatrics (2014), conducted with 1,000 Swedish children, shows, e.g., that the act of washing dishes by hand reduces the risk of allergy in half when compared to families who use a washing machine. This is because the washing machine washes at high temperatures and eliminates much of the microorganisms.(20) It is reported that children living in large cities are more likely to develop allergies than those living in rural areas, precisely because children living in rural areas have direct contact with soil, animals, and most of the food is not highly processed. Their immune systems are constantly active and exercised.

Food as Allergens

It is difficult to estimate accurately the number of allergic children as well as the exact prevalence of allergy to certain food. It is believed that about 4% to 8% of children suffer from food allergy. Milk, egg, peanuts, tree nuts, soy, wheat, fish, and crustaceans are described as having the highest potential to cause allergic sensitization.(14,15)

To assess the incidence of food allergy reactions, a United Kingdom study of 13 million children (1998-2000) showed a rate of 0.89 hospital admissions per 100,000 children per year. Main allergens were peanut (21%), tree nuts (16%), cow’s milk (10%), and eggs (7%). Current studies have shown that the incidence has increased and that milk allergy, which often was solved by its own up to 5 years of age, has been maintained throughout life.(15,16) Data released by the Center for Disease Control and Prevention, USA, in 2013, revealed that children’s food allergies increased by 50% since 1997.(17)

With increased alterations in intestinal permeability (holes in the gut that allow food to come into contact with the immune system, or leaky gut), we are facing a new situation in addition to acute IgE-mediated allergy. There is a chronic IgG production by the body exposed to certain foods, and this "excess" leads to formation of immune complexes that can be deposited in any part of the body. This reaction is called type III hypersensitivity (immune or antigen-antibody complexes), and explains why some people do not have acute reactions to certain foods, and when they exclude these foods from the diet, they improve their allergy. Improvement of allergic rhinitis or asthma by removal of milk or wheat often occurs by this mechanism (non-celiac gluten sensitivity). This means that you can be oversensitive to gluten without having celiac disease. Any food used continuously and repetitively can cause this phenomenon of sensitivity.(18,19)

Diagnostic Tests

The diagnosis of food allergy is still mainly based on a detailed clinical history and physical examination. Clinical or laboratory tests only serve as a tool for confirming the diagnosis. Conventional techniques include skin tests and in vitro tests for specific IgE antibody and food challenges (elimination diet). When done correctly, oral food challenges remain the gold standard in diagnosis. Recently, non-conventional diagnostic methods are increasingly used. These include food specific IgG, antigen leukocyte antibody and intradermal/sublingual provocation tests, as well as cytotoxic food, applied kinesiology, and electrodermal screening. But these methods lack scientific rationale, standardization, and reproducibility. To date, there are no well-designed studies to support them, with several authors who refute their usefulness.

Prevention for Allergies

As described throughout this article, allergic processes (whether induced by food, respiratory or topically) are due to an immune system imbalance. Asthma, rhinitis, hives… no matter which form an allergy takes, the altered immune system reacts excessively, and it is known to be closely related to the GI tract. Thus, food and an imbalance of intestinal microbiota may be feeding this process. Ideally, a change in diet by the intake of unpasteurized fermented products, rich in lactobacillus, rich in fiber, and organic, as well as the removal of food containing agrochemicals, antibiotics, and processed products filled with sugar, colorant, preservative, and soy.(21)

Prevention of allergies in children begins with good eating habits of the mother during intrauterine life and continues with the encouragement of breastfeeding for as long as possible. Beneficial microorganisms and nutrients are passed to the baby. Good nutrition, with balanced intestinal flora, is critical during this period. The introduction of solid foods should also be carefully selected with organic fruits, vegetables, and meats, avoiding processed foods. This habit should be maintained until the infant is age 3, minimum.(22)

Fibers (called “prebiotics” as they feed good bacteria) are great allies in the regulation of intestinal microbiota. An interesting scientific work, developed by researchers at the University of Lausanne, Switzerland, and published in the renowned journal Nature Medicine, showed that a high-fiber diet was able to change the microbiota of the gut and lung, protecting against allergic inflammation in the lung, when compared to the control group (no fiber intake).(23)

As for probiotics, numerous studies also associate their use with reduced episodes of allergy.(21,24) Children may have less abdominal cramps if given probiotics in the first months of life. Mothers who use probiotics during pregnancy have children with less allergic eczema.(25,26)

The use of some supplements and ingredients, such as beta-glucans, thymomodulin and EpiCor, vitamin C, magnesium, and omega-3, can be used to stimulate the immune system as well as prevent the release of histamine. Vitamin D also shows powerful immune modulator activity. Studies even suggest that people with lower dosage of vitamin D are more susceptible to allergic processes.(27)

army
Like in a battle, the “army” (i.e. the immune system) needs to be well led to recognize its real enemies. To achieve this, you need to provide sustenance and training, which can be done with good eating habits and a better quality of life. Small decisions, but with big results are able to rearrange a weakened army.

References:
1. HONG, X.; TSAI, H.; WANG, X. Genetics of food allergy. Curr Opin Pediatr., v. 21, n. 6, p. 770-776, 2009.
2. ASBAI – Associação Brasileira de alergia e Imunologia. Disponível em: http://www.sbai.org. br/secao.asp?id=633&s=51. Acesso em: 09/12/15.
3. DANA V. W.; MARK S. D. The diagnosis and management of rhinitis: an update practice parameter. Journal Allergy Clin Immunol., v. 122, n. 2, p. S01 – S83, 2008.
4. CORSINI, E.; SOKOOTI, M.; GALLI, C.L.; MORETTO, A. COLOSIO, C. Pesticide induced immunotoxicity in humans: A comprehensive review of the existing evidence. Toxicology, v. 307, p. 123-135, 2013.
5. WEISS, S. T. Eat dirt - the hygiene hypothesis and allergic diseases. The New EnglandJournal of Medicine, v.. 347, n. 12, 2002.
6. HARMSEN H. J. M, WILDEBOER-VELOO, A. C. M., RAANGS, G. C. Analysis of Intestinal Flora Development in Breast-Fed and Formula-Fed Infants by Using Molecular Identi cation and Detection Methods. J Pediatr Gastroenterol Nutr, v.30, p. 61-67, 2000.
7. VANDENPLAS, Y.; VEEREMAN-WAUTERS,G.; DEGREEF, E. Probiotcs and prebiotics in prevention and treatment of diseases in infants and children. J Pediatr, v. 87, n. 4, p. 292-300, 2011.
8. WEST, C. E.; JENMALM, M. C., PRESCOTT, S. L. The gut microbiota and its role in the development of allergic disease: a wider perspective. Clinical Experimental Allergy, v. 45, p. 43–53, 2014.
9. SHAW, W. BIOLOGICAL TREATMENTS FOR AUTISM AND PDD - LEARN 618.92 SHA.
10. NEU, J; RUSHING, J.Cesarean versus Vaginal Delivery: Long term infant outcomes and the Hygiene Hypothesis. Clinical Perinatology, v. 38, n. 2, p. 321-331, 2011.
11. PANDEY P. K.; VERMA, P. Comparative analysis of fecal micro ora of healthy full-term Indian infants born with different methods of delivery (vaginal vs cesarean): Acinetobacter sp. prevalence in vaginally born infants. Journal of Biosciences, v.37, n.6, p.zZz 9-998, 2012.
12. BJORKSTEN, B.; NAABER, P.; SEPP, E.; MIKELSAAR, M. The intestinal micro ora in allergic Estonian and Swedish 2-year-old children. Clin. Exp. Allergy, v. 29, p. 342-346, 1999.
13. KIRJAVAINEN, P.V.; APOSTOLOU, E.; ARVOLA, T. Characterizing the compositionof intestinal micro ora as a prospective treatment target in infant allergic disease. FEMS Immunol. Med. Microbiol. v. 32, p. 1-7, 2001.
14. LONGO, G.; BERTI, I.; BURKS, A. W.; KRAUSS, B.; BARBI, E. IgE-mediated foos allergy in children. The lancet, v. 382, p. 1656 – 1664, 2013.
15. JOSHUA, A. B.; AMAL, A.; WESLEY, B.; STACIE, M. J.; HUGH, A. S.; ROBERT, A. W.; MARSHALL,P.; SUSAN, F. C.; Matthew J. F. Guidelinesfor the Diagnosis and Management of Food Allergy in the United States: Summary of the NIAIDSponsored Expert Panel Report. J ALLERGY CLIN IMMUNOL, v. 126, n. 6, p. 1105-1118, 2010.
16. COLVER, A.F.; NEVANTAUS, H.; MACDOUGALL, C.F,; CANT, A.J. Severe food allergic reactions in children across the UK and Ireland, 1998–2000. Acta Paediatr, v. 94, p. 689–695, 2005.
17. JACKSON, K. D.; HOWIE, L. D.; AKINBAMI, L. J. Trends in Allergic Conditions Among Children: United States, 1997-2011. National Center for helth statistics, n. 121, 2013.
18. ZAR, S.; MINCHER, M.J. Food-speci c IgG4 antibody-guided exclusion diet improves symptoms and rectal compliance in irritable bowel syndrome. Scand J Gastroenterol. v. 40, n.7, p. 800-807, 2005.
19. MANSUETO, P.; SEIDITA, A. Non-celiac gluten sensitivity: literature review. Jam Coll Nutr. v. 33, n.1, p. 39-54, 2014.
20. HESSELMAR, B.; HICKE-ROBERTS, A.; WENNERGREN, G. Allergy in children in hand Versus machine dishwashing. Pediatrics, v. 135, n.3, 2015.
21. VERNOCCHI, P.; CHIERICOA, F. D.; FIOCCHI, A. G.; HACHEM, M.; DALLAPICCOLA, B.; ROSSI, P.; PUTIGNANI, L. Understanding probiotics’ role in allergic children: the clue of gut microbiota pro ling. Curr Opin Allergy Clin Immunol, v. 15, n. 5, p. 495-503, 2015.
22. Nancy Elazab, Angelico Mendy, Janvier Gasana, Edgar R. Vieira, Annabelle Quizon, Erick Forno. Probiotic Administration in Early Life, Atopy, and Asthma: A Meta-analysis of Clinical Trials. Pediatrics, v. 132, n. 3, 2013.
23. TROMPETTE, A.; GOLLWITZER, E. S.;YADAVA, K.; SICHELSTIEL, A. K.; SPRENGER,N.; NGOM-BRU, C.; BLANCHARD, C.; JUNT,T.; NICOD, L. P.; HARRIS, N. L.; MARSLAND,B. J. Gut microbiota metabolism of dietaryber in uences allergic airway disease and hematopoiesis. Nature medicine, v. 20, n. 2, 2014.
24. Fats and fatty acids in human nutrition Report of an expert consultation, FAO Food and Nutrition Paper 91, FAO, Rome, 2010.
25. INDRIO, F; DI MAURO, A. Prophylactic Use of a Probiotic in the Prevention of Colic, Regurgitation, and Functional Constipation - A Randomized Clinical Trial. JAMA Pediatr. v. 168, n. 3, p. 228-233, 2014.
26. KALLIOMÄKI, M; SALMINEN, S. Probiotics in primary prevention of atopic disease: a randomised placebo-controlled trial. Lancet. v. 357, p.1076-1079, 2001.
27. OSBORNE, N. J.; UKOUMUNNE, O. C.; WAKE, M., ALLEN, K.J. Prevalence of eczema and food allergy is associated with latitude in Australia. J Allergy Clin Immunol. v. 129, n.3, p.865-867, 2012.