Scientific hypotheses are essential for progress in rapidly developing academic disciplines. Proposing new ideas and hypotheses require thorough analyses of evidence-based data and predictions of the implications. One of the main concerns relates to the ethical implications of the generated hypotheses. The authors may need to outline potential benefits and limitations of their suggestions and target widely visible publication outlets to ignite discussion by experts and start testing the hypotheses. Not many publication outlets are currently welcoming hypotheses and unconventional ideas that may open gates to criticism and conservative remarks. A few scholarly journals guide the authors on how to structure hypotheses. Reflecting on general and specific issues around the subject matter is often recommended for drafting a well-structured hypothesis article. An analysis of influential hypotheses, presented in this article, particularly Strachan's hygiene hypothesis with global implications in the field of immunology and allergy, points to the need for properly interpreting and testing new suggestions. Envisaging the ethical implications of the hypotheses should be considered both by authors and journal editors during the writing and publishing process.
Allergy and Immunology ; Databases, Bibliographic ; Ethics, Research ; Hygiene Hypothesis ; Peer Review ; Publications ; Writing

The hygiene hypothesis (HH) proposed by Strachan in 1989 was expanded to explain the inverse association between the occurrence of allergy disorders and the risk of infectious diseases and parasite infestation. The microflora hypothesis (MH) suggests that gut microbial dysbiosis in early life might trigger hypersensitivity disorders. The sharing concept of both HH and MH is gene-environment interaction, which is also a key concept in epigenetics. The amalgamation of epidemiology and epigenetics has created a scientific discipline termed epigenetic epidemiology. To accomplish an era of gene-environment-wide interaction studies, it is necessary to launch a national human epigenome project.
Allergy and Immunology ; Communicable Diseases ; Dysbiosis ; Epidemiology ; Epigenomics ; Gastrointestinal Microbiome ; Gene-Environment Interaction ; Humans ; Hygiene Hypothesis ; Hygiene ; Hypersensitivity ; Parasites

The hygiene hypothesis (HH) proposed by Strachan in 1989 was expanded to explain the inverse association between the occurrence of allergy disorders and the risk of infectious diseases and parasite infestation. The microflora hypothesis (MH) suggests that gut microbial dysbiosis in early life might trigger hypersensitivity disorders. The sharing concept of both HH and MH is gene-environment interaction, which is also a key concept in epigenetics. The amalgamation of epidemiology and epigenetics has created a scientific discipline termed epigenetic epidemiology. To accomplish an era of gene-environment-wide interaction studies, it is necessary to launch a national human epigenome project.
Allergy and Immunology ; Communicable Diseases ; Dysbiosis ; Epidemiology* ; Epigenomics* ; Gastrointestinal Microbiome ; Gene-Environment Interaction ; Humans ; Hygiene Hypothesis ; Hygiene* ; Hypersensitivity ; Parasites

Relationships between gastrointestinal viscera and human emotions have been documented by virtually all medical traditions known to date. The focus on this relationship has waxed and waned through the centuries, with noted surges in interest driven by cultural forces. Here we explore some of this history and the emerging trends in experimental and clinical research. In particular, we pay specific attention to how the hygiene hypothesis and emerging research on traditional dietary patterns has helped re-ignite interest in the use of microbes to support mental health. At present, the application of microbes and their structural parts as a means to positively influence mental health is an area filled with promise. However, there are many limitations within this new paradigm shift in neuropsychiatry. Impediments that could block translation of encouraging experimental studies include environmental forces that work toward dysbiosis, perhaps none more important than westernized dietary patterns. On the other hand, it is likely that specific dietary choices may amplify the value of future microbial-based therapeutics. Pre-clinical and clinical research involving microbiota and allergic disorders has predated recent work in psychiatry, an early start that provides valuable lessons. The microbiome is intimately connected to diet, nutrition, and other lifestyle variables; microbial-based psychopharmacology will need to consider this contextual application, otherwise the ceiling of clinical expectations will likely need to be lowered.
Allergy and Immunology ; Anxiety ; Depression ; Diet ; Dysbiosis ; Hand ; Humans ; Hygiene Hypothesis ; Life Style ; Mental Health* ; Microbiota* ; Neuropsychiatry ; Psychopharmacology ; Viscera ; Child Health

PURPOSE: Allergic rhinitis (AR) is a multifactorial disease whose genetic and environmental risk factors have been studied for decades. Many pediatric studies have pointed out the familial history of allergy, hygiene hypothesis, breast-feeding, pet ownership, and diets as risk factors of AR. However, most of factors are still up for debate. This preliminary report aimed to confirm the known risk factors and find the novel risk factors for AR in the Korean pediatric population. METHODS: A bi-seasonal, winter and summer, study in 2 elementary schools included all students whose parents completed the questionnaire of medical and social histories, quality of life, infant and early-childhood history, and the living styles. Skin prick tests and endoscopic examinations were conducted on all participants. RESULTS: Among total 1,020 children, 338 participants had AR. The multivariate logistic regression analysis highlighted 6 factors: male gender (OR, 2.10; 95% CI, 1.32-3.33), older age (1.65; 1.03-2.65), previous history of allergic conjunctivitis (14.25; 4.99-40.74), asthma (2.73; 0.96-7.76) and pneumonia (0.39; 0.19-0.82), and an hour increase in daily playing time (0.90; 0.80-1.00). CONCLUSIONS: Lack of pneumonia in early childhood and short playing time are newly found risk factors for Korean pediatric AR in this study confirming male gender, older age and previous history of allergic conjunctivitis and asthma as the risk factors.
Asthma ; Child* ; Conjunctivitis, Allergic ; Diet ; Humans ; Hygiene Hypothesis ; Hypersensitivity ; Infant ; Logistic Models ; Male ; Ownership ; Parents ; Pneumonia ; Quality of Life ; Rhinitis* ; Risk Factors* ; Skin ; Surveys and Questionnaires

A complex interplay between genetic and environmental factors partially contributes to the development of allergic diseases by affecting development during prenatal and early life. To explain the dramatic increase in the prevalence of allergic diseases, the hygiene hypothesis proposed that early exposure to infection prevented allergic diseases. The hygiene hypothesis has changed to the microbial hypothesis, in which exposure to microbes is closely linked to the development of the early immune system and allergic diseases. The intestinal flora may contribute to allergic disease through its substantial effect on mucosal immunity. Based on findings that exposure to microbial flora early in life can change the Th1/Th2 balance, thus favoring a Th1 cell response, probiotics may be beneficial in preventing allergic diseases. However, evidence from clinical and basic research to prove the efficacy of probiotics in preventing allergy is lacking. To date, studies have yielded inconsistent findings on the usefulness of probiotics in allergic diseases. It is difficult to demonstrate an exact effect of probiotics on asthma, allergic rhinitis, and food allergy because of study limitations, such as different first supplementation period, duration, different strains, short follow-up period, and host factors. However, many studies have demonstrated a significant clinical improvement in atopic dermatitis with the use of probiotics. An accurate understanding of the development of human immunity, intestinal barrier function, intestinal microbiota, and systemic immunity is required to comprehend the effects of probiotics on allergic diseases.
Asthma ; Dermatitis, Atopic ; Follow-Up Studies ; Food Hypersensitivity ; Humans ; Hygiene Hypothesis ; Hypersensitivity ; Immune System ; Immunity, Mucosal ; Metagenome ; Prevalence ; Probiotics ; Rhinitis ; Rhinitis, Allergic, Perennial ; Th1 Cells

PURPOSE: The mast cell plays a pivotal role in the human immune response. Crosslinking of 2 IgE molecules bound to the high affinity IgE receptor (FcepsilonRI) on the surface of the mast cell results in mast cell degranulation and the release of several proinflammatory mediators. Patients with type-I allergy have increased levels of IgE in the blood compared to healthy individuals. METHODS: In a 6-week culture system of stem cells to human mast cells we investigated the effect of the concentration of IgE. The mast cells were cultured with different concentrations of IgE for the last 10 days of the maturation period. It was observed how the IgE concentration affects the histamine release, FcepsilonRI density on the mast cell surface and the concentration of other mediators. RESULTS: A clear correlation between IgE concentration in culture medium and the release of histamine upon activation was observed. It showed a bell-shaped dose response curve, with maximal response around an IgE-concentration of 250 ng/mL. Furthermore, the sensitivity of the mast cells and surface density of FcepsilonRI on mast cell surface was also influenced by the IgE concentration in the culture medium. CONCLUSIONS: IgE in the culture medium during the last 10 days of mast cell maturation influences the release of the preformed mediator histamine after mast cell activation and the density of FcepsilonRI on the mast cell surface. The release of the de novo synthetized mediator prostaglandin D2 and the expression of chymase and tryptase are not influenced by IgE in culture medium.
Chymases ; Histamine ; Histamine Release ; Humans ; Hygiene Hypothesis ; Hypersensitivity ; Immunoglobulin E ; Mast Cells ; Prostaglandin D2 ; Stem Cells ; Tryptases

PURPOSE: The mast cell plays a pivotal role in the human immune response. Crosslinking of 2 IgE molecules bound to the high affinity IgE receptor (FcepsilonRI) on the surface of the mast cell results in mast cell degranulation and the release of several proinflammatory mediators. Patients with type-I allergy have increased levels of IgE in the blood compared to healthy individuals. METHODS: In a 6-week culture system of stem cells to human mast cells we investigated the effect of the concentration of IgE. The mast cells were cultured with different concentrations of IgE for the last 10 days of the maturation period. It was observed how the IgE concentration affects the histamine release, FcepsilonRI density on the mast cell surface and the concentration of other mediators. RESULTS: A clear correlation between IgE concentration in culture medium and the release of histamine upon activation was observed. It showed a bell-shaped dose response curve, with maximal response around an IgE-concentration of 250 ng/mL. Furthermore, the sensitivity of the mast cells and surface density of FcepsilonRI on mast cell surface was also influenced by the IgE concentration in the culture medium. CONCLUSIONS: IgE in the culture medium during the last 10 days of mast cell maturation influences the release of the preformed mediator histamine after mast cell activation and the density of FcepsilonRI on the mast cell surface. The release of the de novo synthetized mediator prostaglandin D2 and the expression of chymase and tryptase are not influenced by IgE in culture medium.
Chymases ; Histamine ; Histamine Release ; Humans ; Hygiene Hypothesis ; Hypersensitivity ; Immunoglobulin E ; Mast Cells ; Prostaglandin D2 ; Stem Cells ; Tryptases

Allergic disorders such as atopic dermatitis and asthma are common hyper-immune disorders in industrialized countries. Along with genetic association, environmental factors and gut microbiota have been suggested as major triggering factors for the development of atopic dermatitis. Numerous studies support the association of hygiene hypothesis in allergic immune disorders that a lack of early childhood exposure to diverse microorganism increases susceptibility to allergic diseases. Among the symbiotic microorganisms (e.g. gut flora or probiotics), probiotics confer health benefits through multiple action mechanisms including modification of immune response in gut associated lymphoid tissue (GALT). Although many human clinical trials and mouse studies demonstrated the beneficial effects of probiotics in diverse immune disorders, this effect is strain specific and needs to apply specific probiotics for specific allergic diseases. Herein, we briefly review the diverse functions and regulation mechanisms of probiotics in diverse disorders.
Animals ; Asthma ; Dermatitis, Atopic ; Developed Countries ; Humans ; Hygiene Hypothesis ; Immune System Diseases ; Insurance Benefits ; Lymphoid Tissue ; Metagenome ; Mice ; Probiotics ; Sprains and Strains

Under the hygiene hypothesis, children born by cesarean section (CS) may consequently have an increased risk of asthma and other allergic diseases. CS has been shown to have a delayed and altered development in establishment of gut flora and altered cytokine production. Concerns about the relations between CS and the risk of children's asthma are rising due to the growing number of CS performed in many countries. However, finding the concrete evidence to correlate CS with higher risk of asthma is still controversial. There were significant covariate imbalance between groups of children born by CS vs. vaginal delivery that include the number of maternal age, gestational age, birth weight, complication during pregnancy, complication during labor, socioeconomic status, a parental history of atopy, and maternal smoking history. And there were considerable heterogeneity in methods and study subjects between the studies of delivery by CS and the offspring's risk of asthma and other allergic diseases. Therefore, as we proceed into the further study, researchers must refer to the literatures and look for the best way proving their hypothesis that are based on the methodological subject group. Of which should be accordance with the research purposes. Also, researchers have to search for identifying the core biological mechanism in order to know whether there is a causal relationship exists between the CS and asthma.
Asthma ; Birth Weight ; Cesarean Section ; Child ; Female ; Gestational Age ; Humans ; Hygiene Hypothesis ; Maternal Age ; Parents ; Population Characteristics ; Pregnancy ; Risk Factors ; Smoke ; Smoking ; Social Class