Background. The hygiene hypothesis suggests that high hygiene standards have led to an immune dysfunction and an increase in allergic diseases. Farming-related exposures are associated with a decreased risk of asthma. Since the gut microbiota may be a pivotal component in the hygiene hypothesis, we studied whether perinatal exposure to pets, doctor's diagnosed wheezy bronchitis (WB), and compositional changes in the gut microbiota are interrelated among urban infants. Methods. Data were collected prospectively from a mother-infant nutrition study. Data on perinatal pet ownership, WB, and the microbiota composition of faecal samples of the infants assessed by quantitative PCR at 1 month were compared. Results. None of the 30 infants exposed to pets had suffered from WB by 24 months, whereas 15 of the 99 (15%) nonexposed infants had had WB (P = 0.03). The counts of Bifidobacterium longum were higher in samples (n = 17) from nonwheezing infants with pet exposure compared to those (n = 10) in wheezing infants without pet exposure (8.59/10.44 versus 5.94/9.86, resp. (median/upper limit of range, bacteria(log)/g of stool); P = 0.02). B. breve was more abundant in the wheezing infants (P = 0.02).
Multiple studies have demonstrated that early-life exposure to pets or siblings affords protection against allergic disease; these associations are commonly attributed to the “hygiene hypothesis”. Recently, low diversity of the infant gut microbiota has also been linked to allergic disease. In this study, we characterize the infant gut microbiota in relation to pets and siblings.
The study population comprised a small sub-sample of 24 healthy, full term infants from the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort. Mothers reported on household pets and siblings. Fecal samples were collected at 4 months of age, and microbiota composition was characterized by high-throughput signature gene sequencing.
Microbiota richness and diversity tended to be increased in infants living with pets, whereas these measures were decreased in infants with older siblings. Infants living with pets exhibited under-representation of Bifidobacteriaceae and over-representation of Peptostreptococcaceae; infants with older siblings exhibited under-representation of Peptostreptococcaceae.
This study provides new evidence that exposure to pets and siblings may influence the early development of the gut microbiota, with potential implications for allergic disease. These two traditionally protective “hygiene hypothesis” factors appear to differentially impact gut microbiota composition and diversity, calling into question the clinical significance of these measures. Further research is required to confirm and expand these findings.
Infants; Gut microbiota; Gut microbiome; Hygiene hypothesis; Microflora hypothesis; Pets; Siblings; Atopy; Allergic disease; Environmental exposures
The extended 'hygiene hypothesis' suggests that the initial composition of the infant gut microbiota is a key determinant in the development of atopic disease. Several studies have demonstrated that the microbiota of allergic and non-allergic infants are different even before the development of symptoms, with a critical time window during the first 6 months of life. The aim of the study was to investigate the association between early intestinal colonisation and the development of asthma in the first 3 years of life using DGGE (denaturing gradient gel electrophoresis).
In a prospective birth cohort, 110 children were classified according to the API (Asthma Predictive Index). A positive index included wheezing during the first three years of life combined with eczema in the child in the first years of life or with a parental history of asthma. A fecal sample was taken at the age of 3 weeks and analysed with DGGE using universal and genus specific primers.
The Asthma Predictive Index was positive in 24/110 (22%) of the children. Using universal V3 primers a band corresponding to a Clostridum coccoides XIVa species was significantly associated with a positive API. A Bacteroides fragilis subgroup band was also significantly associated with a positive API. A final DGGE model, including both bands, allowed correct classification of 73% (80/110) of the cases.
Fecal colonisation at age 3 weeks with either a Bacteroides fragilis subgroup or a Clostridium coccoides subcluster XIVa species is an early indicator of possible asthma later in life. These findings need to be confirmed in a new longitudinal follow-up study.
DGGE; infant; intestinal microbiota; asthma
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.
Hygiene hypothesis; Intestinal microflora; Gut-Associated lymphoid tissue; Probiotics; Atopic dermatitis
The “hygiene hypothesis” proposes that the increase in allergic diseases in developing countries reflects a decrease in infections during childhood. Cohort studies suggest, however, that the risks of asthma are increased in children who suffer severe illness from a viral respiratory infection in infancy. This apparent inconsistency can be reconciled through consideration of epidemiologic, clinical, and animal studies. The elements of this line of reasoning are that viral infections can predispose to organ-specific expression of allergic sensitization, and that the severity of illness is shaped by the maturity of immune function, which in turn is influenced by previous contact with bacteria and viruses, whether pathogenic or not. Clinical studies of children and interventional studies of animals indeed suggest that the exposure to microbes through the gastrointestinal tract powerfully shapes immune function. Intestinal microbiota differ in infants who later develop allergic diseases, and feeding Lactobacillus casei to infants at risk has been shown to reduce their rate of developing eczema. This has prompted studies of feeding probiotics as a primary prevention strategy for asthma. We propose that the efficacy of this approach depends on its success in inducing maturation of immune function important in defense against viral infection, rather than on its effectiveness in preventing allergic sensitization. It follows that the endpoints of studies of feeding probiotics to infants at risk for asthma should include not simply tests of responsiveness to allergens, but also assessment of intestinal flora, immune function, and the clinical response to respiratory viral infection.
asthma; gastrointestinal; lactobacilli; microbes; prevention
Hygiene hypothesis demonstrates that the lack of microbial exposure would promote the development of allergic airway disease (AAD). Therefore, the gut microbiota, including Escherichia coli (E. coli), would probably offer a potential strategy for AAD.
To investigate whether E. coli infection is able to suppress the induction of AAD and to elucidate the underlying mechanisms.
Nonpathogenic E. coli ATCC 25922 was infected by gavage before AAD phase in three patterns: 108 or 106 CFU in neonates or 108 CFU in adults. Then mice were sensitized and challenged with ovalbumin (OVA) to induce allergic inflammation in both the upper and lower airways. Hallmarks of AAD, in terms of eosinophil infiltration and goblet cell metaplasia in subepithelial mucosa, Th2 skewing of the immune response, and levels of T regulate cells (Tregs), were examined by histological analysis, ELISA, and flow cytometry, respectively.
E. coli, especially neonatally infected with an optimal dose, attenuated allergic responses, including a decrease in nasal rubbing and sneezing, a reduction in eosinophil inflammation and goblet cell metaplasia in subepithelial mucosa, decreased serum levels of OVA-specific IgE, and reduced Th2 (IL-4) cytokines. In contrast, this effect came with an increase of Th1 (IFN-r and IL-2) cytokines, and an enhancement of IL-10-secreting Tregs in paratracheal lymph nodes (PTLN).
E. coli suppresses allergic responses in mice, probably via a shift from Th1 to Th2 and/or induction of Tregs. Moreover, this infection is age- and dose-dependent, which may open up novel possibilities for new therapeutic interventions.
Lending support to the hygiene hypothesis, epidemiological studies have demonstrated that allergic disease correlates with widespread use of antibiotics and alterations in fecal microbiota (“microflora”). Antibiotics also lead to overgrowth of the yeast Candida albicans, which can secrete potent prostaglandin-like immune response modulators, from the microbiota. We have recently developed a mouse model of antibiotic-induced gastrointestinal microbiota disruption that is characterized by stable increases in levels of gastrointestinal enteric bacteria and Candida. Using this model, we have previously demonstrated that microbiota disruption can drive the development of a CD4 T-cell-mediated airway allergic response to mold spore challenge in immunocompetent C57BL/6 mice without previous systemic antigen priming. The studies presented here address important questions concerning the universality of the model. To investigate the role of host genetics, we tested BALB/c mice. As with C57BL/6 mice, microbiota disruption promoted the development of an allergic response in the lungs of BALB/c mice upon subsequent challenge with mold spores. In addition, this allergic response required interleukin-13 (IL-13) (the response was absent in IL-13−/− mice). To investigate the role of antigen, we subjected mice with disrupted microbiota to intranasal challenge with ovalbumin (OVA). In the absence of systemic priming, only mice with altered microbiota developed airway allergic responses to OVA. The studies presented here demonstrate that the effects of microbiota disruption are largely independent of host genetics and the nature of the antigen and that IL-13 is required for the airway allergic response that follows microbiota disruption.
Microbial deprivation early in life can potentially influence immune mediated disease development such as allergy. The aims of this study were to investigate the influence of parental allergy on the infant gut colonization and associations between infant gut microbiota and allergic disease at five years of age.
Methods and Findings
Fecal samples were collected from 58 infants, with allergic or non-allergic parents respectively, at one and two weeks as well as at one, two and twelve months of life. DNA was extracted from the fecal samples and Real time PCR, using species-specific primers, was used for detection of Bifidobacterium (B.) adolescentis, B. breve, B. bifidum, Clostridium (C.) difficile, a group of Lactobacilli (Lactobacillus (L.) casei, L. paracasei and L. rhamnosus) as well as Staphylococcus (S.) aureus. Infants with non-allergic parents were more frequently colonized by Lactobacilli compared to infants with allergic parents (p = 0.014). However, non-allergic five-year olds acquired Lactobacilli more frequently during their first weeks of life, than their allergic counterparts, irrespectively of parental allergy (p = 0.009, p = 0.028). Further the non-allergic children were colonized with Lactobacilli on more occasions during the first two months of life (p = 0.038). Also, significantly more non-allergic children were colonized with B. bifidum at one week of age than the children allergic at five years (p = 0.048).
In this study we show that heredity for allergy has an impact on the gut microbiota in infants but also that early Lactobacilli (L. casei, L. paracasei, L. rhamnosus) colonization seems to decrease the risk for allergy at five years of age despite allergic heredity.
The prevalence of allergic disease has increased dramatically in Western countries over the past few decades. The hygiene hypothesis, whereby reduced exposure to microbial stimuli in early life programs the immune system toward a Th2-type allergic response, is suggested to be a major mechanism to explain this phenomenon in developed populations. Such microbial exposures are recognized to be critical regulators of intestinal microbiota development. Furthermore, intestinal microbiota has an important role in signaling to the developing mucosal immune system. Intestinal dysbiosis has been shown to precede the onset of clinical allergy, possibly through altered immune regulation. Existing treatments for allergic diseases such as eczema, asthma, and food allergy are limited and so the focus has been to identify alternative treatment or preventive strategies. Over the past 10 years, a number of clinical studies have investigated the potential of probiotic bacteria to ameliorate the pathological features of allergic disease. This novel approach has stemmed from numerous data reporting the pleiotropic effects of probiotics that include immunomodulation, restoration of intestinal dysbiosis as well as maintaining epithelial barrier integrity. In this mini-review, the emerging role of probiotics in the prevention and/or treatment of allergic disease are discussed with a focus on the evidence from animal and human studies.
allergy; asthma; clinical; eczema; immunomodulation; probiotic
The human microbiota presents a highly active metabolic that influences the state of health of our gastrointestinal tracts as well as our susceptibility to disease. Although much of our initial microbiota is adopted from our mothers, its final composition and diversity is determined by environmental factors. Westernization has significantly altered our microbial function. Extensive experimental and clinical evidence indicates that the westernized diet, rich in animal products and low in complex carbohydrates, plus the overuse of antibiotics and underuse of breastfeeding, leads to a heightened inflammatory potential of the microbiota. Chronic inflammation leads to the expression of certain diseases in genetically predisposed individuals. Antibiotics and a “clean” environment, termed the “hygiene hypothesis,” has been linked to the rise in allergy and inflammatory bowel disease, due to impaired beneficial bacterial exposure and education of the gut immune system, which comprises the largest immune organ within the body. The elevated risk of colon cancer is associated with the suppression of microbial fermentation and butyrate production, as butyrate provides fuel for the mucosa and is anti-inflammatory and anti-proliferative. This article will summarize the work to date highlighting the complicated and dynamic relationship between the gut microbiota and immunity, inflammation and carcinogenesis.
microbiota; colon cancer; allergy; inflammatory bowel disease; diet
Diseases like asthma have dramatically increased in the last decades. The reasons for the rising prevalence are still controversially discussed. Besides the genetic predisposition a number of different causes are thought to affect the increase of allergies. These include the hygiene hypothesis as well as changes in intestinal microbiota. Allergic airway inflammation is driven by T cells but it has become clear that tolerance and also suppression of allergic inflammation are mediated by so called regulatory T cells (Tregs). Indeed, naturally occurring Treg as well as induced Tregs have been shown to suppress allergic airway disease. In addition, the effectiveness of different therapeutic strategies (e.g. allergen immunotherapy) are mediated via Tregs. In addition, several Treg based approaches have been shown to effectively suppress allergic airway disease in different models. However, more research is needed to explore these potentially interesting approaches for the treatment of human disease.
Allergy; asthma; inflammation; regulatory T cell; suppression
Perinatal programming, a dominant theory for the origins of cardiovascular disease, proposes that environmental stimuli influence developmental pathways during critical periods of prenatal and postnatal development, inducing permanent changes in metabolism. In this paper, we present evidence for the perinatal programming of asthma via the intestinal microbiome. While epigenetic mechanisms continue to provide new explanations for the programming hypothesis of asthma development, it is increasingly apparent that the intestinal microbiota plays an independent and potentially interactive role. Commensal gut bacteria are essential to immune system development, and exposures disrupting the infant gut microbiota have been linked to asthma. This paper summarizes the recent findings that implicate caesarean delivery, breastfeeding, perinatal stress, probiotics, and antibiotics as modifiers of infant gut microbiota in the development of asthma.
The gut microbiota is a remarkable asset for human health. As a key element in the development and prevention of specific diseases, its study has yielded a new field of promising biotherapeutics. This review provides comprehensive and updated knowledge of the human gut microbiota, its implications in health and disease, and the potentials and limitations of its modification by currently available biotherapeutics to treat, prevent and/or restore human health, and future directions. Homeostasis of the gut microbiota maintains various functions which are vital to the maintenance of human health. Disruption of the intestinal ecosystem equilibrium (gut dysbiosis) is associated with a plethora of human diseases, including autoimmune and allergic diseases, colorectal cancer, metabolic diseases, and bacterial infections. Relevant underlying mechanisms by which specific intestinal bacteria populations might trigger the development of disease in susceptible hosts are being explored across the globe. Beneficial modulation of the gut microbiota using biotherapeutics, such as prebiotics, probiotics, and antibiotics, may favor health-promoting populations of bacteria and can be exploited in development of biotherapeutics. Other technologies, such as development of human gut models, bacterial screening, and delivery formulations eg, microencapsulated probiotics, may contribute significantly in the near future. Therefore, the human gut microbiota is a legitimate therapeutic target to treat and/or prevent various diseases. Development of a clear understanding of the technologies needed to exploit the gut microbiota is urgently required.
gut microbiota; human health; dysbiosis; biotherapeutics; probiotics; microencapsulation
Gut microbiota have recently been implicated in the pathogenesis of the obesity and its related metabolic diseases. Avariety of factors including diet, genetic background, environment and host innate and adaptive immune responses define an individual’s gut microbiota. In this review we outline potential mechanisms by which gut microbiota can contribute to the development of obesity focusing on specific processes such as microbial energy extraction, microbiota induced-inflammation and regulation of appetite. We review the current understanding of each of these processes on regulating metabolism and examine potential therapeutic strategies for the treatment or prevention of the metabolic syndrome. We explore the hypothesis that alteration in gut microbiota may be an initial event leading to altered feeding behavior and/or systemic inflammation, ultimately leading to weight gain and the metabolic syndrome.
The exact prevalence of food allergy in the general population is unknown, but almost 12% of pediatric population refers a suspicion of food allergy. IgE mediated reactions to food are actually the best-characterized types of allergy, and they might be particularly harmful especially in children. According to the “hygiene hypothesis” low or no exposure to exogenous antigens in early life may increase the risk of allergic diseases by both delaying the development of the immune tolerance and limiting the Th2/Th1 switch. The critical role of intestinal microbiota in the development of immune tolerance improved recently the interest on probiotics, prebiotics, antioxidants, polyunsaturated fatty acid, folate and vitamins, which seem to have positive effects on the immune functions.
Probiotics consist in bacteria or yeast, able to re-colonize and restore microflora symbiosis in intestinal tract. One of the most important characteristics of probiotics is their safety for human health. Thanks to their ability to adhere to intestinal epithelial cells and to modulate and stabilize the composition of gut microflora, probiotics bacteria may play an important role in the regulation of intestinal and systemic immunity. They actually seem capable of restoring the intestinal microbic equilibrium and modulating the activation of immune cells.
Several studies have been recently conducted on the role of probiotics in preventing and/or treating allergic disorders, but the results are often quite contradictory, probably because of the heterogeneity of strains, the duration of therapy and the doses administered to patients. Therefore, new studies are needed in order to clarify the functions and the utility of probiotics in food allergies and ion other types of allergic disorders.
Food allergy; Probiotics; Allergic disease; Intestinal microbiota; Children
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.
Allergy; Hygiene hypothesis; Immunity; Microbiota; Probiotics
Over the past four decades, there has been a significant increase in allergy and asthma in westernized countries, which correlates with alterations in fecal microbiota (microflora) and widespread use of antibiotics (the “hygiene hypothesis”). Antibiotics also lead to overgrowth of the yeast Candida albicans, which can secrete potent prostaglandin-like immune response modulators. We have developed a mouse model of antibiotic-induced microbiota disruption that includes stable increases in gastrointestinal (GI) enteric bacteria and GI Candida levels with no introduction of microbes into the lungs. Mice are treated for 5 days with cefoperazone in the drinking water, followed by a single oral gavage of C. albicans. This results in alterations of GI bacterial populations and increased yeast numbers in the GI microbiota for at least 2 to 3 weeks and can drive the development of a CD4 T-cell-mediated allergic airway response to subsequent mold spore (Aspergillus fumigatus) exposure in immunocompetent mice without previous systemic antigen priming. The allergic response in the lungs is characterized by increased levels of eosinophils, mast cells, interleukin-5 (IL-5), IL-13, gamma interferon, immunoglobulin E, and mucus-secreting cells. In the absence of antibiotics, mice exposed to Aspergillus spores do not develop an allergic response in the airways. This study provides the first experimental evidence to support a role for antibiotics and fungal microbiota in promoting the development of allergic airway disease. In addition, these studies also highlight the concept that events in distal mucosal sites such as the GI tract can play an important role in regulating immune responses in the lungs.
Current evidence supports a role for gut colonization in promoting and maintaining a balanced immune response in early life. An altered or less diverse gut microbiota composition has been associated with atopic diseases and/or obesity. Moreover, certain gut microbial strain or strains have been shown to inhibit or attenuate immune responses associated with chronic inflammation in experimental models. However, there has been no fully adequate longitudinal study of the relation between the neonatal gut microbiota and the development of allergic diseases (e.g., atopic asthma) and obesity. The emergence of promising experimental studies has led to several clinical trials of probiotics (live bacteria given orally that allow for intestinal colonization) in humans. Probiotic trials thus far have failed to show a consistent preventive or therapeutic effect on asthma or obesity. Previous trials of probiotics have been limited by small sample size, short duration of follow-up, or lack state-of-the art analyses of the gut microbiota. Finally, there is emerging evidence that the vitamin D pathway may be important in gut homeostasis and in the signaling between the microbiota and the host. Given the complexity of the gut micriobiota, additional research is needed before we can confidently establish whether its manipulation in early life can prevent or treat asthma and/or obesity.
microbiota; asthma; obesity; allergic; eczema; vitamin D; probiotics; cytokines
Background: The hygiene hypothesis states that insufficient exposure to certain infectious agents during childhood increases the risk of developing asthma and atopic diseases. Improvements in hygiene levels may be partly responsible for this decline in exposure.
Aims: To assess whether hygiene levels in infancy are associated with wheeze and/or atopic eczema, independent of a number of possible confounding factors.
Methods: Data were gathered from the Avon Longitudinal Study of Parents and Children (ALSPAC). Parental self completion questionnaires provided symptom data on infant wheeze and atopic eczema at 0–6 months and 30–42 months, respectively. A simple hygiene score was derived using questionnaire responses at 15 months, which ranged from least hygienic to most hygienic. Multivariable logistic regression models analysed the effect of hygiene scores on health outcomes, while adjusting for a number of important confounding variables.
Results: Increasing hygiene scores were independently associated with wheezing (OR = 1.04; 95% CI: 1.00 to 1.08) and atopic eczema (OR = 1.04; 95% CI: 1.01 to 1.07) between 30 and 42 months, but not in the first six months. The odds ratio was higher for atopic eczema if the rash was reported to have become sore and oozy (OR = 1.09; 95% CI: 1.02 to 1.16).
Conclusions: High levels of hygiene at 15 months of age were independently associated with wheeze and atopic eczema reported between 30 and 42 months, and there was an increased risk for children with more severe eczema during this period. The importance of hygiene in public health should not be dismissed; however, the creation of a sterile environment through excessive cleanliness may potentially be harmful to the immune system.
Clostridium difficile is the leading cause of infectious diarrhea in hospitalized patients. Its epidemiology has shifted in recent years from almost exclusively infecting elderly patients in whom the gut microbiota has been disturbed by antimicrobials, to now also infecting individuals of all age groups with no recent antimicrobial use.
A stochastic mathematical model was constructed to simulate the modern epidemiology of C. difficile in a healthcare setting, and, to compare the efficacies of interventions.
Both the rate of colonization and the incidence of symptomatic disease in hospital inpatients were insensitive to antimicrobial stewardship and to the prescription of probiotics to expedite healthy gut microbiota recovery, suggesting these to be ineffective interventions to limit transmission. Comparatively, improving hygiene and sanitation and reducing average length of stay more effectively reduced infection rates. Although the majority of new colonization events are a result of within-hospital ward exposure, simulations demonstrate the importance of imported cases with new admissions.
By analyzing a wide range of screening sensitivities, we identify a previously ignored source of pathogen importation: although capturing all asymptomatic as well as symptomatic introductions, individuals who are exposed but not yet colonized will be missed by even a perfectly sensitive screen on admission. Empirical studies to measure the duration of this latent period of infection will be critical to assessing C. difficile control strategies. Moreover, identifying the extent to which the exposed category of individual contributes to pathogen importation should be explicitly considered for all infections relevant to healthcare settings.
Biodiversity loss and climate change secondary to human activities are now being associated with various adverse health effects. However, less attention is being paid to the effects of biodiversity loss on environmental and commensal (indigenous) microbiotas. Metagenomic and other studies of healthy and diseased individuals reveal that reduced biodiversity and alterations in the composition of the gut and skin microbiota are associated with various inflammatory conditions, including asthma, allergic and inflammatory bowel diseases (IBD), type1 diabetes, and obesity. Altered indigenous microbiota and the general microbial deprivation characterizing the lifestyle of urban people in affluent countries appear to be risk factors for immune dysregulation and impaired tolerance. The risk is further enhanced by physical inactivity and a western diet poor in fresh fruit and vegetables, which may act in synergy with dysbiosis of the gut flora. Studies of immigrants moving from non-affluent to affluent regions indicate that tolerance mechanisms can rapidly become impaired in microbe-poor environments. The data on microbial deprivation and immune dysfunction as they relate to biodiversity loss are evaluated in this Statement of World Allergy Organization (WAO). We propose that biodiversity, the variability among living organisms from all sources are closely related, at both the macro- and micro-levels. Loss of the macrodiversity is associated with shrinking of the microdiversity, which is associated with alterations of the indigenous microbiota. Data on behavioural means to induce tolerance are outlined and a proposal made for a Global Allergy Plan to prevent and reduce the global allergy burden for affected individuals and the societies in which they live.
Allergy plan; Biodiversity; Civilization disease; Epigenetics; Immune dysfunction; Microbiota; Microbiome; Urbanization
Colonization of the gastrointestinal tract (GIT) of human infants with a suitable
microbial community is essential for numerous aspects of health, but the
progression of events by which this microbiota becomes established is poorly
understood. Here, we investigate two previously unexplored areas of microbiota
development in infants: the deployment of functional capabilities at the
community level and the population genetics of its most abundant genera. To
assess the progression of the infant microbiota toward an adult-like state and
to evaluate the contribution of maternal GIT bacteria to the infant gut, we
compare the infant’s microbiota with that of the mother at 1 and 11
months after delivery. These comparisons reveal that the infant’s
microbiota rapidly acquires and maintains the range of gene functions present in
the mother, without replicating the phylogenetic composition of her microbiota.
Microdiversity analyses for Bacteroides and
Bifidobacterium, two of the main microbiota constituents,
reveal that by 11 months, the phylotypes detected in the infant are distinct
from those in the mother, although the maternal Bacteroides
phylotypes were transiently present at 1 month of age. The configuration of
genetic variants within these genera reveals populations far from equilibrium
and likely to be undergoing rapid growth, consistent with recent population
turnovers. Such compositional turnovers and the associated loss of maternal
phylotypes should limit the potential for long-term coadaptation between
specific bacterial and host genotypes.
Bacteroides; Bifidobacterium; gut microbiota; community genomics; bacterial population genetics
To help investigate the relationship between inflammatory and other diseases and the composition of the gut microbiota, we propose that a positive-feedback loop exists between the preferences of the host for a particular dietary regimen, the composition of the gut microbiota that depends on this regimen, and the preferences of the host as influenced by the gut microbiota. We cite evidence in support of this hypothesis and make testable predictions.
There has been a dramatic rise in the prevalence of IgE-mediated food allergy over recent decades, particularly among infants and young children. The cause of this increase is unknown but one putative factor is a change in the composition, richness and balance of the microbiota that colonize the human gut during early infancy. The coevolution of the human gastrointestinal tract and commensal microbiota has resulted in a symbiotic relationship in which gut microbiota play a vital role in early life immune development and function, as well as maintenance of gut wall epithelial integrity. Since IgE mediated food allergy is associated with immune dysregulation and impaired gut epithelial integrity there is substantial interest in the potential link between gut microbiota and food allergy. Although the exact link between gut microbiota and food allergy is yet to be established in humans, recent experimental evidence suggests that specific patterns of gut microbiota colonization may influence the risk and manifestations of food allergy. An understanding of the relationship between gut microbiota and food allergy has the potential to inform both the prevention and treatment of food allergy. In this paper we review the theory and evidence linking gut microbiota and IgE-mediated food allergy in early life. We then consider the implications and challenges for future research, including the techniques of measuring and analyzing gut microbiota, and the types of studies required to advance knowledge in the field.
gut microbiota; immune development; food allergy
Background: Recent data have outlined a relationship between the composition of the intestinal microflora and allergic inflammation, and demonstrated the competence of probiotics in downregulation of such inflammation.
Aims: Our aims were to characterise the relationship between gut microbes and the extent of allergic sensitisation and to assess whether the efficacy of bifidobacterial supplementation in the treatment of allergy could relate to modulation of the intestinal microbiota.
Methods: This randomised study included 21 infants with early onset atopic eczema of whom eight were intolerant (highly sensitised group (HSG)) and 13 tolerant (sensitised group (SG)) to extensively hydrolysed whey formula (EHF). In the SG, six were weaned to EHF without (placebo group (PG)) and seven to EHF with Bifidobacterium lactis Bb-12 supplementation (bifidobacteria treated group (BbG)). The faecal microflora of infants in the HSG was analysed only before weaning whereas in the SG the faecal microflora was analysed both before and after weaning.
Results: Infants in the HSG had greater numbers of lactobacilli/enterococci than those in the SG. Serum total IgE concentration correlated directly with Escherichia coli counts in all infants and with bacteroides counts in the HSG, indicating that the presence of these bacteria is associated with the extent of atopic sensitisation. The effect of supplementation was characterised as a decrease in the numbers of Escherichia coli and protection against an increase in bacteroides numbers during weaning.
Conclusions: These data indicate that bifidobacterial supplementation appears to modify the gut microbiota in a manner that may alleviate allergic inflammation. Further studies are needed to confirm this conclusion.
intestinal microflora; breast feeding; whey formula; probiotics; bifidobacteria; allergy; infants