Gut microbiota and allergy/asthma: From pathogenesis to new therapeutic strategies

Asthma and atopy, classically associated with hyper-activation of the T helper 2 (Th2) arm of adaptive immunity, are among the most common chronic illnesses worldwide. Emerging evidence relates atopy and asthma to the composition and function of gut microbiota composition. Moreover, certain gut microbial strains have been shown to inhibit or attenuate immune responses associated with chronic inflammation in experimental models. Although still a relatively nascent field of research, evidence to date suggests that the gut microbiome may represent fertile targets for prevention or management of allergic asthma and other diseases in which adaptive immune dysfunction is a prominent feature. The oral probiotics/prebiotic represents a possible therapeutic for improving asthma and allergic disease. Especially, recent technological developments that permit identification of microbes and their products using culture-independent molecular detection techniques. In this review, we literaturely summarise the aggravation or improvement of metabolic diseases by role of gut microbiota, probiotics/prebiotic treatment.     

The Relationship Between Advances in Understanding the Microbiome and the Maturing Hygiene Hypothesis

Expanding knowledge about an interaction of the bacterial colonization with pathogenic and non-pathogenic bacteria and the human immune system leads to speculation on potential effects on health and disease. Recent advances in sequencing technologies and new bioinformatic possibilities now allow investigating the microbes that colonize the human gut, skin and airways in more detail. In light of the hygiene hypothesis, the impact of the microbial composition of individuals with allergic sensitization and/or atopic diseases, i.e., allergic asthma or atopic eczema, were investigated in several clinical trials. Altered diversity of gut microbiota during infancy as well as colonization with specific pathogenic and apathogenic bacteria has been linked with an elevated risk for allergy. There are ongoing attempts to establish intervention strategies aimed at modifying initial colonization patterns in early life. While results from animal models, in-vitro data and epidemiological studies encourage the concept of a relationship between the microbiome and the development of allergic diseases, the transfer of these findings to intervention strategies still seems to be a major challenge.     

Lactobacillus rhamnosus probiotic prevents airway function deterioration and promotes gut microbiome resilience in a murine asthma model

ABSTRACT

Allergic asthma is a highly prevalent inflammatory disease of the lower airways, clinically characterized by airway hyperreactivity and deterioration of airway function. Immunomodulatory probiotic bacteria are increasingly being explored to prevent asthma development, alone or in combination with other treatments.

In this study, wild-type and recombinant probiotic Lactobacillus rhamnosus GR-1 were tested as preventive treatment of experimental allergic asthma in mice. Recombinant L. rhamnosus GR-1 was designed to produce the major birch pollen allergen Bet v 1, to promote allergen-specific immunomodulation. Administration of wild-type and recombinant L. rhamnosus GR-1 prevented the development of airway hyperreactivity. Recombinant L. rhamnosus GR-1 also prevented elevation of airway total cell counts, lymphocyte counts and lung IL-1β levels, while wild-type L. rhamnosus GR-1 inhibited airway eosinophilia. Of note, a shift in gut microbiome composition was observed after asthma development, which correlated with the severity of airway inflammation and airway hyperreactivity. In the groups that received L. rhamnosus GR-1, this asthma-associated shift in gut microbiome composition was not observed, indicating microbiome-modulating effects of this probiotic.

These data demonstrate that L. rhamnosus GR-1 can prevent airway function deterioration in allergic asthma. Bet v 1 expression by L. rhamnosus GR-1 further contributed to lower airway inflammation, although not solely through the expected reduction in T helper 2-associated responses, suggesting involvement of additional mechanisms. The beneficial effects of L. rhamnosus GR-1 correlate with increased gut microbiome resilience, which in turn is linked to protection of airway function, and thus further adds support to the existence of a gut-lung axis.     

下呼吸道微生态在支气管哮喘中的研究进展

随着二代测序的不断发展,过去人们认为无菌的下呼吸道现已被证实有多种不同的微生物群落定植.同时,越来越多的研究也证明,微生态在宿主免疫系统的发生发展中起着重要的作用.呼吸道微生态紊乱可能与多种呼吸道疾病密切相关,包括肺结核、COPD及支气管哮喘(简称哮喘)等.该研究主要回顾了近年来对哮喘患者及健康人群呼吸道微生态的研究,探讨在哮喘患者中呼吸道菌群定植的改变趋势,以及呼吸道微生态的改变与哮喘发病机制之间的关系,并且对呼吸道微生态在哮喘治疗中的研究进展进行讨论.     

Gut microbiome in multiple sclerosis: The players involved and the roles they play

The human gut contains trillions of bacteria (microbiome) that play a major role in maintaining a healthy state for the host. Perturbation of this healthy gut microbiome might be an important environmental factor in the pathogenesis of inflammatory autoimmune diseases such as multiple sclerosis (MS). Others and we have recently reported that MS patients have gut microbial dysbiosis (altered microbiota) with the depletion of some and enrichment of other bacteria. However, the significance of gut bacteria that show lower or higher abundance in MS is unclear. The majority of gut bacteria are associated with certain metabolic pathways, which in turn help in the maintenance of immune homeostasis of the host. Here we discuss recent MS microbiome studies and the possible mechanisms through which gut microbiome might contribute to the pathogenesis of MS.     

TLR Activation and Allergic Disease: Early Life Microbiome and Treatment

Purpose of Review

Allergy and asthma are growing problems in the developed world. The accelerated increase of these diseases may be related to microbiome modification that leads to aberrant activation of Toll-like receptors (TLRs). Current research supports the concept that changes in microbial communities in early life impact TLR activation, resulting in an altered risk for the development of asthma and allergies.

Recent Findings

Prenatal and early childhood events that generate microbiome modification are closely related with TLR activation. Early childhood exposure to a rich array of TLR agonists, particularly lipopolysaccharide, strongly predicts protection against allergic disease later in life even when other lifestyle factors are accounted for. Genetic deletion of TLR signaling components in mice results in reduced function of tolerogenic cell populations in the gut. In contrast, weak TLR signaling can promote allergic sensitization later in life.

Summary

This review summarizes the role of TLR signaling in microbiome-mediated protection against allergy.

     

Asthma Microbiome Studies and the Potential for New Therapeutic Strategies

Recent applications of culture-independent tools for microbiome profiling have revealed significant relationships between asthma and microbiota associated with the environment, gut, or airways. Studies of the airway microbiome in particular represent a new frontier in pulmonary research. Although these studies are relatively new, current evidence suggests the possibility of new therapeutic strategies for the treatment or prevention of asthma. In this article, recent literature on microbiota and asthma are critically reviewed, with a particular focus on studies of the airway microbiome. Perspectives are presented on how growing knowledge of relationships between the microbiome and asthma is likely to translate into improved understanding of asthma pathogenesis, its heterogeneity, and opportunities for novel treatment approaches.     

Influence of the gut microbiota on satiety signaling

Recent studies show a link between the gut microbiota and the regulation of satiety and energy intake, processes that contribute to the development and pathophysiology of metabolic diseases. However, this link is predominantly established in animal and in vitro studies, whereas human intervention studies are scarce. In this review we focus on recent evidence linking satiety and the gut microbiome, with specific emphasis on gut microbial short-chain fatty acids (SCFAs). Based on a systematic search we provide an overview of human studies linking the intake of prebiotics with gut microbial alterations and satiety signaling. Our outcomes highlight the importance of in-depth examination of the gut microbiota in relation to satiety and provide insights into recent and future studies in this field.     

Juvenile idiopathic arthritis and the gut microbiome: Where are we now?

In recent decades, because of advances in technology there has been an explosion of knowledge on how microbiome affects human health. In most chronic immune-inflammatory diseases, alterations in gut microbiome has been shown. The successful use of faecal microbial transplants for the treatment of clostridium difficile associated diarrhoea has also paved the way for novel therapies.Gut microbiome is affected by early life events like the mode of delivery, breast feeding, the use of antibiotics, etc. and that may have an indirect effect on the developing immune system as well as on the predisposition to juvenile idiopathic arthritis (JIA). Multiple studies have found altered gut microbiome in JIA though no single organism or microbial community has been found to be associated with JIA. In JIA, attempts to modify gut microbiome by using probiotics, exclusive enteral nutrition and other modalities have had variable success.The current review discusses the current data available on gut microbiome in different categories of JIA and how this knowledge can translate into new therapies.     

Gut Immunity and Type 1 Diabetes: a Mélange of Microbes,Diet, and Host Interactions?

Type 1 diabetes (T1D) is a complex autoimmune disease, and first stages of the disease typically develop early in life. Genetic as well as environmental factors are thought to contribute to the risk of developing autoimmunity against pancreatic beta cells. Several environmental factors, such as breastfeeding or early introduction of solid food, have been associated with increased risk for developing T1D. During the first years of life, the gut microbial community is shaped by the environment, in particular by dietary factors. Moreover, the gut microbiome has been described for its role in shaping the immune system early in life and early data suggest associations between T1D risk and alterations in gut microbial communities. In this article, we discuss environmental factors influencing the colonization process of the gut microbial community. Furthermore, we review possible interactions between the microbiome and the host that might contribute to the risk of developing T1D.     

Overgrowth of the indigenous gut microbiome and irritable bowel syndrome

Culture-independent molecular techniques have demonstrated that the majority of the gut microbiota is uncultivable.Application of these molecular techniques to more accurately identify the indigenous gut microbiome has moved with great pace over recent years,leading to a substantial increase in understanding of gut microbial communities in both health and a number of disorders,including irritable bowel syndrome(IBS).Use of culture-independent molecular techniques already employed to characterise faecal and,to a lesser extent,colonic mucosal microbial populations in IBS,without reliance on insensitive,traditional microbiological culture techniques,has the potential to more accurately determine microbial composition in the small intestine of patients with this disorder,at least that occurring proximally and within reach of sampling.Current data concerning culture-based and culture-independent analyses of the small intestinal microbiome in IBS are considered here.     

Interactions between respiratory tract infections and atopy in the aetiology of asthma.

The prevalence of asthma, in particular atopic asthma, has markedly increased in recent years. Accumulating evidence suggests that environmental factors associated with allergic sensitization and exposure to microbial stimuli during infancy and early childhood, are associated with these changes in prevalence. However, considerable controversy surrounds the role of microbial agents, as evidence has been presented for both positive and negative effects in this context. The review below focuses upon interactions between immune competence during infancy, the development of T-helper (Th)1-polarized versus Th2-polarized memory against inhalant allergens, and susceptibility to virus infection. In particular, recent finding are highlighted which suggest that delayed postnatal maturation of Th1 function is associated with increased risk for early postnatal sensitization to inhalant allergens, and also with risk for viral bronchiolitis during infancy. Variations in the kinetics of postnatal maturation of T-helper 1 function may in part be attributable to polymorphisms in the CD14 gene, which influence host responsiveness both to bacterial as well as viral stimuli.     

Life-long dynamics of the swine gut microbiome and their implications in probiotics development and food safety

ABSTRACT

The swine gut microbiome has received remarkable attention in recent years given that pigs serve not only as important sources for animal-derived food but also as excellent biomedical models for human health. However, despite recent advances in the understanding of the swine gut microbiome, many important biological and ecological questions are still largely unanswered. In a recent study, we characterized the life-long dynamics of the swine gut microbiome from birth to market. We showed distinct shifts in gut microbiome structure along different growth stages mainly driven by diet. Here, we summarize these discoveries and provide additional data related to the core swine gut microbiome, probiotics development in the swine industry, and foodborne pathogens in the pork supply chain.     

Environmental determinants associated with the development of asthma in childhood.

Asthma is a common chronic respiratory disease, and many epidemiological studies have documented an increasing trend over the past few decades. Comparative studies have shown that asthma is more prevalent in Westernised societies than in rural or developing regions. Environmental factors are likely to be important in explaining such disparities and increasing trends. Although allergen exposure and atopic sensitisation have been thought to be important in the pathogenesis of asthma, recent cross-sectional and longitudinal studies suggest that allergic sensitisation is likely a marker rather than a causative factor for asthma. There is accumulating evidence confirming the role of early exposure to infections in altering the regulation of cytokine production and reduction of subsequent development of atopic disorders. The consistent finding of a lower prevalence of asthma in subjects brought up in a farming environment and the inverse relationship between microbial exposure and asthma symptoms further support the importance of early environmental exposure affecting the risk of subsequent development of asthma. Confirmation of the pathogenetic role of these environmental determinants may allow us to develop primary preventive strategies against the development of asthma and related atopic diseases.     

The bidirectional capacity of bacterial antigens to modulate allergy and asthma.

In recent decades, the prevalence of allergic diseases including bronchial asthma, hay fever and atopic dermatitis, has risen steadily in high-income countries. The underlying mechanisms for this phenomenon remain largely unknown. Since the natural mutation rate is low, altered environmental and lifestyle conditions are thought to play an important role. Epidemiological and clinical studies have provided indirect evidence that infections may prevent the development of atopy and atopic disease. This is referred to as the "hygiene hypothesis". According to the hygiene hypothesis, viral and/or bacterial infections could inhibit the T-helper (Th)-2 immune response associated with atopic reactions by stimulating a Th-1 response involved in defence of bacterial infections and delayed-type hypersensitivity reactions. In particular, the prenatal period and early childhood are considered to be critical for the establishment and maintenance of a normal Th-1/Th-2 balance. On the other hand, several studies suggested that infections exacerbate established allergic diseases, e.g. bronchial asthma, airway hyperresponsiveness and atopic dermatitis. Therefore, viral and/or microbial infections and/or their products may have bidirectional effects on the development of allergy and asthma. This review will focus on recent findings related to the interaction between allergic disorders and infectious diseases, with the main emphasis on bacterial infections.     

Probiotics drive gut microbiome triggering emotional brain signatures

ABSTRACT

Experimental manipulation of the gut microbiome was found to modify emotional and cognitive behavior, neurotransmitter expression and brain function in rodents, but corresponding human data remain scarce. The present double-blind, placebo-controlled randomised study aimed at investigating the effects of 4 weeks’ probiotic administration on behavior, brain function and gut microbial composition in healthy volunteers. Forty-five healthy participants divided equally into three groups (probiotic, placebo and no intervention) underwent functional MRI (emotional decision-making and emotional recognition memory tasks). In addition, stool samples were collected to investigate the gut microbial composition. Probiotic administration for 4 weeks was associated with changes in brain activation patterns in response to emotional memory and emotional decision-making tasks, which were also accompanied by subtle shifts in gut microbiome profile. Microbiome composition mirrored self-reported behavioral measures and memory performance. This is the first study reporting a distinct influence of probiotic administration at behavioral, neural, and microbiome levels at the same time in healthy volunteers. The findings provide a basis for future investigations into the role of the gut microbiota and potential therapeutic application of probiotics.     

Therapeutic modulation of gut microbiota in inflammatory bowel disease: More questions to be answered

Patients with inflammatory bowel disease (IBD) exhibit impaired control of the microbiome in the gut, and ‘dysbiosis’ is commonly observed. Western diet is a risk factor for the development of IBD, but it may have different effects on gut microbiota between IBD and non‐IBD individuals. Exclusive enteral nutrition (EEN) can induce remission in pediatric Crohn's disease with a decrease in gut microbial diversity. Although there are some theoretical benefits, actual treatment effects of prebiotics and probiotics in IBD vary. High‐quality studies have shown that VSL#3 (a high‐potency probiotic medical food containing eight different strains) exhibits benefits in treating ulcerative colitis, and gut microbial diversity is reduced after treated with VSL#3 in animal models. The effect of fecal microbiome transplantation on IBD is controversial. Increasing microbial diversity compared with impaired handling of bacteria presents a dilemma. Antibiotics are the strongest factors in the reduction of microbiome ecological diversity. Some antibiotics may help to induce remission of the disease. Microbiome alteration has been suggested to be an intrinsic property of IBD and a potential predictor in diagnosis and prognosis. However, the effects of therapeutic modulations are variable; thus, more questions remain to be answered.     

Triclosan,a common antimicrobial ingredient,on gut microbiota and gut health

Triclosan (TCS) is an antimicrobial compound incorporated into more than 2,000 consumer products. This compound is frequently detected in the human body and causes ubiquitous contamination in the environment, raising concerns about its impact on human health and environmental pollution. Our recent research showed that exposure to TCS exaggerates colonic inflammation and exacerbates development of colitis-associated colon tumorigenesis, via gut microbiome-dependent mechanisms. In this review, we discussed recent research about TCS, as well as other consumer antimicrobials, on the gut microbiome and gut health.     

Significance of the Gut Microbiome for Viral Diarrheal and Extra-Intestinal Diseases

The composition of the mammalian gut microbiome is very important for the health and disease of the host. Significant correlations of particular gut microbiota with host immune responsiveness and various infectious and noninfectious host conditions, such as chronic enteric infections, type 2 diabetes, obesity, asthma, and neurological diseases, have been uncovered. Recently, research has moved on to exploring the causalities of such relationships. The metabolites of gut microbiota and those of the host are considered in a ‘holobiontic’ way. It turns out that the host’s diet is a major determinant of the composition of the gut microbiome and its metabolites. Animal models of bacterial and viral intestinal infections have been developed to explore the interrelationships of diet, gut microbiome, and health/disease phenotypes of the host. Dietary fibers can act as prebiotics, and certain bacterial species support the host’s wellbeing as probiotics. In cases of Clostridioides difficile-associated antibiotic-resistant chronic diarrhea, transplantation of fecal microbiomes has sometimes cured the disease. Future research will concentrate on the definition of microbial/host/diet interrelationships which will inform rationales for improving host conditions, in particular in relation to optimization of immune responses to childhood vaccines.     

Gut microbiome in acute pancreatitis: A review based on current literature

The gut microbiome is a complex microbial community, recognized for its potential role in physiology, health, and disease. The available evidence supports the role of gut dysbiosis in pancreatic disorders, including acute pancreatitis (AP). In AP, the presence of gut barrier damage resulting in increased mucosal permeability may lead to translocation of intestinal bacteria, necrosis of pancreatic and peripancreatic tissue, and infection, often accompanied by multiple organ dysfunction syndrome. Preserving gut microbial homeostasis may reduce the systemic effects of AP. A growing body of evidence suggests the possible involvement of the gut microbiome in various pancreatic diseases, including AP. This review discusses the possible role of the gut microbiome in AP. It highlights AP treatment and supplementation with prebiotics, synbiotics, and probiotics to maintain gastrointestinal microbial balance and effectively reduce hospitalization, morbidity and mortality in an early phase. It also addresses novel therapeutic areas in the gut microbiome, personalized treatment, and provides a roadmap of human microbial contributions to AP that have potential clinical benefit.