Article

Helminths and the microbiota: Parts of the hygiene hypothesis

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

In modern societies, diseases that are driven by dysregulated immune responses are increasing at an alarming pace, such as inflammatory bowel diseases and diabetes. There is an urgent need to understand these epidemiological trends, which are likely to be driven by the changing environment of the last few decades. There are complex interactions between human genetic factors and this changing environment that is leading to the increasing prevalence of metabolic and inflammatory diseases. Alterations to human gut bacterial communities (the microbiota) and lowered prevalence of helminth infections are potential environmental factors contributing to immune dysregulation. Helminths have co-evolved with the gut microbiota and their mammalian hosts. This three-way interaction is beginning to be characterized and the knowledge gained may enable the design of new therapeutic strategies to treat metabolic and inflammatory diseases. However, these complex interactions need to be carefully investigated in the context of host genetic backgrounds in order to identify optimal treatment strategies. The complex nature of these interactions raises the possibility that only with highly personalized treatment, with knowledge of individual genetic and microbiota communities, will therapeutic interventions be successful for a majority of the individuals suffering from these complex diseases of immune dysregulation. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... Ello ha conducido al desarrollo de respuestas defensivas por parte de los primeros y al estímulo de complejos mecanismos inmunomoduladores por parte de los segundos. 4,[9][10][11][12][13][14][15][16][17] ...
... La coevolución milenaria entre hospederos y parásitos, que los ha llevado a adaptarse los unos a los otros, y el carácter potencialmente patógeno de muchas de esas respuestas, han resultado en el desarrollo de mecanismos reguladores de las respuestas inmunitarias del hospedero. 4,[9][10][11][12][13][14][15][16][17] En la modulación de las respuestas inmunitarias del hospedero participan mediadores solubles, de manera particular IL-10 y TGF-β, y diferentes tipos celulares, también de la inmunidad innata y de la adquirida. A los primeros, ya se hizo referencia en los acápites precedentes. ...
... 10 Sin embargo, la regulación por los helmintos de las respuestas inmunitarias de los hospederos que parasitan puede tener consecuencias clínicas y epidemiológicas adicionales. A saber: incremento en la susceptibilidad a otras infecciones, cambios en la frecuencia e intensidad de fenómenos alérgicos y autoinmunes, insuficiencias en las respuestas a vacunas contra otros microorganismos y, sin que aún esté suficientemente documentado, desarrollo de algunos tipos de tumores 4,[9][10][11][12][13][14][15][16][17] (Fig. 2). ...
... 37 At the same time, human hosts have co-evolved an immune system (IS) innate response to produce Th2-mediated type 2 immune response in order to minimize helminth virulence and promote intestinal tolerance. 38 Recently, the presence of certain helminths has been correlated with increased BGM diversity, as well as low occurrence of inflammatory and autoimmune diseases. 10,38 In endemic countries, for instance in Malaysia, indigenous populations colonized by a variety of helminths including Trichuris spp. ...
... 38 Recently, the presence of certain helminths has been correlated with increased BGM diversity, as well as low occurrence of inflammatory and autoimmune diseases. 10,38 In endemic countries, for instance in Malaysia, indigenous populations colonized by a variety of helminths including Trichuris spp. ...
... 41 The ability of helminths to promote protective bacterial species in the gut is already being tested as a novel therapeutic strategy for inflammatory diseases. 38,40 In spite of these substantial evidences, the molecular mechanisms by which parasites alter BGM and vice versa remains largely unknown. Besides, we must not forget that these organisms are wired to be pathogenic by nature. ...
Article
Full-text available
The human gut microbiome (GM) is a complex ecosystem that includes numerous prokaryotic and eukaryotic inhabitants. The composition of GM can influence an array of host physiological functions including immune development. Accumulating evidence suggest that several members of non-bacterial microbiota, including protozoa and helminths, that were earlier considered as pathogens, could have a commensal or beneficial relationship with the host. Here we examine the most recent data from omics studies on prokaryota-meiofauna-host interaction as well as the impact of gut parasitome on gut bacterial ecology and its role as ‘immunological driver’ in health and disease to glimpse new therapeutic perspectives.
... Los resultados hoy disponibles permiten concluir que esa protección contra enfermedades autoinmunes e inflamatorias es consecuencia de dos fenómenos inducidos por estos parásitos: la regulación de las respuestas inmunitarias del hospederoy cambios en la flora bacteriana de este. [2][3]5,7,9,[22][23][24][25][26][27][28] ...
... La población de microorganismos normalmente presente en el intestino de los mamíferos es considerada su microbiota. 27 Observaciones diversas evidencian de manera creciente que esos microorganismos son importantes en la regulación de la homeostasis de sus hospederos y, consecuentemente, en el desarrollo de numerosas enfermedades 53 . Diferentes funciones fisiológicas, entre ellas las respuestas inmunitarias, el metabolismo y el desarrollo cognoscitivo, están afectadas por la composición de la microbiota. ...
... [62][63] Estos hallazgos podrían proveer una explicación a la contribución de algunos hábitos alimentarios de la vida moderna (por ejemplo, dietas ricas en grasas y pobres en fibras) al incremento de la susceptibilidad a enfermedades inflamatorias. 27 Aunque los helmintos pueden modular directamente el sistema inmunitario de sus respectivos hospederos, tal como se ha descrito anteriormente, también estos parásitos pueden influir sobre las respuestas inmunitarias mediante sus efectos sobre la flora bacteriana intestinal 22,64 . Los resultados de trabajos recientes sugieren que la infección crónica por helmintos afecta la composición de la microbiota: ...
Article
Full-text available
Epidemiological, clinical and immunological evidence from human studies and data obtained from experiments in animal models offer increased support to the view that helminth infections have a protective effect against pathological entities that run with deregulation of the immune system, such as illness idiopathic autoimmune and inflammatory changes some. From this precedent, the objective of this study was to review and analyze the literature on helminth infections, regulation of immune responses and autoimmune and inflammatory events. Studies support the conclusion that regulation of immune responses by helminth hosts affects frequency and intensity of autoimmune and inflammatory events. In order to better quality medical practice, clinical and therapeutic implications of these impacts should be known by professionals in diagnosis and treatment of idiopathic autoimmune diseases and inflammatory disorders.
... In this context, helminth infection has been associated with remission of immunopathologies for immune-related diseases (e.g., allergy and IBD) or impaired immunity to coinfection with various microbial agents (e.g., bacteria and viruses), leading to increased susceptibility and attenuated immunopathology (12,13). Furthermore, recent studies have demonstrated that the presence of helminths alters the microbiota composition and the metabolic signature of the host, and conversely, bacterial microbiota contributes to regulating host immune response to helminth or pathology (14,15), highlighting interactions between the gut microbiome and helminth infection. However, the impacts of these diseases on the gut fungal compositions have not been established. ...
... The area under the ROC curve (AUC) was used to designate the ROC effect. Multidimensional scaling of proximity matrix from randomForest for the 32 optimal markers was plotted by MDSPlot (R package randomForest 4. [6][7][8][9][10][11][12][13][14]. ...
Article
Full-text available
Helminth infection affects over 1 billion people worldwide. However, its relationship with the gut mycobiome remains unknown.
... Further, the presence of some protozoa, such as the common Blastocystis, has been associated with reduced risk of gastrointestinal disease [63]. Finally, although multicellular eukaryotes such as helminths have generally been eliminated from gut microbiomes in Western cultures, they have been a component of the gut microbiome for a significant portion of our recent evolutionary history [64]. Given their potent immunomodulatory capabilities and interactions with the other inhabitants of the normal gut microbiome (such as Lactobacilli [65]), their elimination may have removed an important educator of our immune systems [64]. ...
... Finally, although multicellular eukaryotes such as helminths have generally been eliminated from gut microbiomes in Western cultures, they have been a component of the gut microbiome for a significant portion of our recent evolutionary history [64]. Given their potent immunomodulatory capabilities and interactions with the other inhabitants of the normal gut microbiome (such as Lactobacilli [65]), their elimination may have removed an important educator of our immune systems [64]. ...
Article
Full-text available
Humans are virtually identical in their genetic makeup, yet the small differences in our DNA give rise to tremendous phenotypic diversity across the human population. By contrast, the metagenome of the human microbiome-the total DNA content of microbes inhabiting our bodies-is quite a bit more variable, with only a third of its constituent genes found in a majority of healthy individuals. Understanding this variability in the "healthy microbiome" has thus been a major challenge in microbiome research, dating back at least to the 1960s, continuing through the Human Microbiome Project and beyond. Cataloguing the necessary and sufficient sets of microbiome features that support health, and the normal ranges of these features in healthy populations, is an essential first step to identifying and correcting microbial configurations that are implicated in disease. Toward this goal, several population-scale studies have documented the ranges and diversity of both taxonomic compositions and functional potentials normally observed in the microbiomes of healthy populations, along with possible driving factors such as geography, diet, and lifestyle. Here, we review several definitions of a 'healthy microbiome' that have emerged, the current understanding of the ranges of healthy microbial diversity, and gaps such as the characterization of molecular function and the development of ecological therapies to be addressed in the future.
... Fewer intestinal helminth (Trichuris trichiura), hepatitis A virus (HAV), and protozoa (T. gondii) infections and lower bacterial (Helicobacter pylori) load have been shown to be related to the increased frequency of atopic disease (5)(6)(7). Some findings also suggest that measles, HAV, and tuberculosis infections prevent atopic disorders (5). ...
... pylori antibodies were significantly higher in nonatopic subjects compared to atopic and that, while not a significant difference, anti-HAV antibodies tended to be higher in nonatopic compared to atopic subjects. Several studies have shown that infections that are transmitted through ingestion, such as HAV, T. gondii, and H. pylori, decrease the risk of atopy (5)(6)(7). In a study of 240 atopic and 240 nonatopic young adults from Italy, Matricardi et al. (13) found a lower prevalence of HAV and H. pylori, as well as T. gondii, in atopic subjects. ...
Article
Background/aim: We investigated the role of body flora and chronic inflammatory infections in the etiology of allergic disorders in Turkish children. Materials and methods: Forty pediatric asthma patients with positive skin prick tests and 40 age-matched healthy subjects with negative skin prick tests were enrolled in this cross-sectional study. Serum H. pylori IgG, viral hepatitis serology, IL-10, and TGF-beta levels were measured. Stool and throat cultures were taken and tested for occurrence of microorganisms. Results: A significantly higher percentage of nonatopic subjects tested positive for anti-H. pylori antibodies compared to atopic subjects (60% vs. 20%). Serum IL-10 levels were also significantly higher in nonatopic subjects. No significant differences in direct microscopy and culture specimens of stools were observed. Examination of throat flora showed significantly higher occurrences of Neisseria and beta-hemolytic Streptococcus in nonatopic subjects, but higher occurrences of gram-positive bacilli in atopic subjects. Conclusion: Higher prevalence of anti-H. pylori antibody and higher serum levels of IL-10 in nonatopic subjects suggest that chronic infection and inflammation may protect against atopic disease. Higher occurrences of Neisseria and beta-hemolytic Streptococcus in throat cultures from nonatopic subjects are novel findings that lend further support to the hygiene hypothesis.
... One aspect of this idea is encapsulated in the hygiene hypothesis, which proposes improved sanitation and subsequently reduced exposure to microbes has raised the incidence of allergic and autoimmune diseases in industrialized countries, whereas regular exposure to foreign antigens (including infections) derails induction or maintenance of pathological Th1 and Th2 responses (Strachan 1989;Blaser and Falkow 2009;Loke and Lim 2015). This idea has caught on, such that some individuals deliberately inoculate themselves with chronic but curable helminth infections to reap the proposed benefits of this immunological experience (Loke and Lim 2015). ...
... One aspect of this idea is encapsulated in the hygiene hypothesis, which proposes improved sanitation and subsequently reduced exposure to microbes has raised the incidence of allergic and autoimmune diseases in industrialized countries, whereas regular exposure to foreign antigens (including infections) derails induction or maintenance of pathological Th1 and Th2 responses (Strachan 1989;Blaser and Falkow 2009;Loke and Lim 2015). This idea has caught on, such that some individuals deliberately inoculate themselves with chronic but curable helminth infections to reap the proposed benefits of this immunological experience (Loke and Lim 2015). Very recent studies suggest more subtlety to this concept-studies of rural farmers revealed that exposure to the "right kind of dust" (from Amish but not Hutterite farms) protected children against asthma, an effect that was mimicked in mice (Stein et al. 2016), whereas other mouse studies suggested that periodic exposure to lipopolysaccharide (LPS) blocks asthma induction (Schuijs et al. 2015). ...
Article
Much of what we understand about immunology, including the response to vaccines, come from studies in mice because they provide many practical advantages compared with research in higher mammals and humans. Nevertheless, modalities for preventing or treating disease do not always translate from mouse to humans, which has led to increasing scrutiny of the continued merits of mouse research. Here, we summarize the pros and cons of current laboratory mouse models for immunology research and discuss whether overreliance on nonphysiological, ultra-hygienic animal husbandry approaches has limited the ultimate translation potential of mouse-derived data to humans. Alternative approaches are discussed that may extend the use of the mouse model for preclinical studies.
... Here, we propose that the lower bacterial diversity in industrialized countries is, in part, an indirect consequence of the lower prevalence of helminths and protozoa. The related changes in the gut microbiota might even be one of the mechanisms behind the ever-increasing incidence of some modern diseases, an extension of the Hygiene/Old Friends hypothesis [17,22,23]. The question is therefore whether gut eukaryotes are simply parasites that are detrimental to human health or whether, on the contrary, they could provide, after millions of years of coevolution, some beneficial effects to their hosts. ...
... idea of helminthic therapy [23]. Given that both naturally [39,40] and experimentally [37,41,42] infected humans have an increased gut microbiome diversity, and that diversity decreases after deworming treatment [38], it has been proposed that helminths indirectly influence human health through the gut microbiome [43]. ...
Article
The importance of the gut microbiota for human health has sparked a strong interest in the study of the factors that shape its composition and diversity. Despite the growing evidence suggesting that helminths and protozoa significantly interact with gut bacteria, gut microbiome studies remain mostly focused on prokaryotes and on populations living in industrialized countries that typically have a low parasite burden. We argue that protozoa, like helminths, represent an important factor to take into account when studying the gut microbiome, and that their presence - especially considering their long coevolutionary history with humans - may be beneficial. From this perspective, we examine the relationship between the protozoa and their hosts, as well as their relevance for public health.
... Such responses are characterized by the production of cytokines like interleukin-4 (IL-4), IL-5, IL-9, and IL-13 that are necessary for helminth expulsion by the host and tolerance of helminth infections, activating the mechanisms of down-streaming effects (Allen and Maizels 2011;Pulendran and Artis 2012). Another study has suggested that deworming during pregnancy might promote allergic disease in offspring (Loke and Lim 2015). It has been clinically proven that during pregnancy helminth infection may protect children from immune dysregulation, and that it does not have a negative effect on the offspring (Loke and Lim 2015). ...
... Another study has suggested that deworming during pregnancy might promote allergic disease in offspring (Loke and Lim 2015). It has been clinically proven that during pregnancy helminth infection may protect children from immune dysregulation, and that it does not have a negative effect on the offspring (Loke and Lim 2015). Perhaps helmiths inhabiting gastrointestinal habitats should be considered to be having crosstalks with their hosts (Chow, Tang and Mazmanian 2011). ...
Article
Full-text available
The peaceful phenomenon of the co-evolution between the prokaryotes (microbiota) and the eukaryotes (parasites including protozoa and helminths) in the animal gut has drawn the researchers’ attention. Importantly, exploring the potential of helminths for therapeutic uses was one of the reasons behind understanding the physiological and immunological crosstalk existing between them. Here we discuss the interactive immunological associations of helminths and microbial responses individually and in combination with their hosts. Considering that there is probably crosstalk between eukaryotic organisms like helminths and protozoa with their host’s gut microbiota, in this review we searched the literature identifying the privileged and favourable relationship generated between them in the host. Understanding the possibilities of the role of helminths along with gut microbiota as a black box would certainly help decode the therapeutic intrusion with helminths in experimental clinical trials, and a successful trial could be used to consider possible future and safe treatments for various immune-inflammatory diseases in humans.
... Conversely, helminths actively secrete molecules affecting bacteria (Hewitson et al. 2011), and also modulate host immune response (Broadhurst et al. 2012;Osborne et al. 2014), both of which can lead to changes in microbiota composition. It is not yet known how adaptive these changes are from the host, parasite, or microbiota perspective, or how species-specific these interactions are (Loke & Lim 2015). Two previous studies have looked specifically for the effect of Cestode species also had a negative constrained association with strong statistical support between each other (Figure 2a). ...
... Different modes of transmission could be a likely explanation, as the closest match via BLAST for PS1 is Strongyloides sp.(Aivelo et al. 2015), which means that it is soil transmitted, whereas PS3-6 are more likely to be transmitted through foraging on their intermediate hosts. Nevertheless, if these nematode species are identified to species, the different transmission modes can be deduced.Parasite-microbiota studies are complicated by the need to take into account interactions with the host(Kreisinger et al. 2015;Loke & Lim 2015) ...
Article
Full-text available
1. Detecting interaction between species is notoriously difficult, and disentangling species associations in host-related gut communities is especially challenging. Nevertheless, due to contemporary methods, including metabarcoding and 16S sequencing, collecting observational data on community composition has become easier and much more common. 2. We studied the previously collected data sets of intestinal bacterial microbiota and parasite compositions within longitudinally followed mouse lemurs by analysing the potential interactions with diversity metrics and novel joint species distribution modelling. 3. Both methods showed statistical association between certain parasite species and bacterial microbiota composition. Unicellular Eimeria sp. had an effect on diversity of gut microbiota. The cestode Hymenolepis diminuta had negative associations with several bacterial orders, whereas closely related species H. nana had positive associations with several bacterial orders. 4. Our results reveal potential interactions between some, but not all, intestinal parasites and gut bacterial microbiota. Host variables contributed over half of the total variation explained with the model, and sex was the most important single host variable; especially with microbiota, there were sex-related differences in the community composition. 5. This study shows how joint species distribution modelling can incorporate both within-host dynamics of several taxa and host characteristics to model potential interactions in intestinal community. These results provide new hypothesis for interactions between and among parasites and bacterial microbiota to be tested further with experimental studies.
... 87,88 However, an industrialized lifestyle has also been associated with the rise in incidences of IBD, 89,90 and some hypothesize that exposure to certain intestinal parasites may be beneficial for maintaining a healthy and diverse microbiome. [90][91][92] Macroparasites, namely helminths, and their purified antigens have been used to treat IBD in mice [93][94][95] and in controversial human trials with some success. [96][97][98][99] Protozoa have received far less attention in relation to IBD, although there are several protozoan species that are able to commensally colonize and reside in the human intestine. ...
Article
Full-text available
The gut microbiome has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Studies suggest that the IBD gut microbiome is less diverse than that of the unaffected population, a phenomenon often referred to as dysbiosis. However, these studies have heavily focused on bacteria, while other intestinal microorganisms—fungi, protozoa, and bacteriophages—have been neglected. Of the nonbacterial microbes that have been studied in relation to IBD, most are thought to be pathogens, although there is evidence that some of these species may instead be harmless commensals. In this review, we discuss the nonbacterial gut microbiome of IBD, highlighting the current biases, limitations, and outstanding questions that can be addressed with high-throughput DNA sequencing methods. Further, we highlight the importance of studying nonbacterial microorganisms alongside bacteria for a comprehensive view of the whole IBD biome and to provide a more precise definition of dysbiosis in patients. With the rise in popularity of microbiome-altering therapies for the treatment of IBD, such as fecal microbiota transplantation, it is important that we address these knowledge gaps to ensure safe and effective treatment of patients.
... As interactions between microbiota and the immune system are key to the development of a functional immune system [40] such events may have lasting effects on the development of intestinal and immune functions. As such alterations have been described for other intestinal parasitic infections [21], a role of intestinal parasitic infections in gut health should be re-evaluated in pigs, too. ...
Article
Full-text available
Although vaccination against various pathogens is integral to health management of swine, vaccines against parasites have not yet been commercialized for the use in pigs. The incentive to develop and commercialize anti-parasitic vaccines in swine are twofold; on the one hand parasitic diseases which are economically important, such as ascarosis and neonatal coccidiosis, could be controlled in a sustainable manner; on the other hand, the transmission of zoonotic parasites, such as Toxoplasma gondii or Cysticercus cellulosae, could be effectively interrupted. Although experimental research indicates that vaccination against a number of porcine parasites is feasible, development and commercialization of potential vaccines so far has been very slow, as our knowledge on the host-parasite interplay in porcine parasitic infections is still very limited. In the light of growing concerns regarding consumer health and antiparasitic drug resistance, however, it is timely to re-direct R&D efforts to the development of biological control options.
... Although competition between helminths for food resources [12], secretion of bacterial growth inhibitors by some species [13,14], and host age and diet [6,15] have all been proposed as mechanisms altering the gut microbiota, the interplay between host, helminths and microbiota has attracted much attention owing to the potential for helminths to induce direct or indirect changes in the microbiota, for example, via host immunity [6,16]. An absence of helminths or an incomplete microbiota community, known as biome depletion, within human populations has been widely cited as a mechanism leading to the increased prevalence of auto-and hyper-immune diseases [9,17]. As such, helminth modification of the gut microbiota may have the potential to be harnessed for valuable therapeutic approaches ( [18,19] but see Rausch et al. [20]), hence the potential effects of helminths on host-microbiota composition and diversity deserve further investigation. ...
Article
Full-text available
The gut microbiota is vital to host health and, as such, it is important to elucidate the mechanisms altering its composition and diversity. Intestinal helminths are host immunomodulators and have evolved both temporally and spatially in close association with the gut microbiota, resulting in potential mechanistic interplay. Host-helminth and host-microbiota interactions are comparatively well-examined, unlike microbiota-helminth relationships, which typically focus on experimental infection with a single helminth species in laboratory animals. Here, in addition to a review of the literature on helminth-microbiota interactions, we examined empirically the association between microbiota diversity and composition and natural infection of multiple helminth species in wild mice (Apodemus flavicollis), using 16S rRNA gene catalogues (metataxonomics). In general, helminth presence is linked with high microbiota diversity, which may confer health benefits to the host. Within our wild rodent system variation in the composition and abundance of gut microbial taxa associated with helminths was specific to each helminth species and occurred both up- and downstream of a given helminth's niche (gut position). The most pronounced helminth-microbiota association was between the presence of tapeworms in the small intestine and increased S24-7 (Bacteroidetes) family in the stomach. Helminths clearly have the potential to alter gut homeostasis. Free-living rodents with a diverse helminth community offer a useful model system that enables both correlative (this study) and manipulative inference to elucidate helminth-microbiota interactions.
... We animal models, such as mice or rats (Cortés et al., 2019;Peachey et al., 2017;Reynolds et al., 2015). Limited research has previously been done on characterizing these interactions in NHPs (Broadhurst et al., 2012;de Winter et al., 2020;Loke & Lim, 2015). ...
Article
Full-text available
Western lowland gorillas (Gorilla gorilla gorilla) are Critically Endangered and show continued population decline. Consequently, pressure mounts to better understand their conservation threats and ecology. Gastrointestinal symbionts, such as bacterial and eukaryotic communities, are believed to play vital roles in the physiological landscape of the host. Gorillas host a broad spectrum of eucaryotes, so called parasites, with strongylid nematodes being particularly prevalent. While these communities are partially consistent, they are also shaped by various ecological factors, such as diet or habitat type. To investigate gastrointestinal symbionts of wild western lowland gorillas, we analysed 215 faecal samples from individuals in five distinct localities across the Congo Basin, using high‐throughput sequencing techniques. We describe the gut bacterial microbiome and genetic diversity of strongylid communities, including strain‐level identification of amplicon sequence variants (ASVs). We identified strongylid ASVs from eight genera and bacterial ASVs from twenty phyla. We compared these communities across localities, with reference to varying environmental factors among populations, finding differences in alpha diversity and community compositions of both gastrointestinal components. Moreover, we also investigated covariation between strongylid nematodes and the bacterial microbiome, finding correlations between strongylid taxa and Prevotellaceae and Rikenellaceae ASVs that were consistent across multiple localities. Our research highlights complexity of the bacterial microbiome and strongylid communities in several gorilla populations and emphasizes potential interactions between these two symbiont communities. This study provides a framework for ongoing research into strongylid nematode diversity, and their interactions with the bacterial microbiome, amongst great apes.
... This interaction provokes profound changes in the composition and structure of the microbiota allowing the parasite to establish, thrive and progress to chronic stages of infection. These changes promote a favorable metabolic, microbial and immunological environment for these parasites, which may lead to a greater susceptibility to acquire superinfections by other pathogenic bacteria such as Campylobacter, as has been demonstrated in swine models (Glendinning et al., 2014;Kreisinger et al., 2015;Loke and Lim, 2015;Giacomin et al., 2016;Midha et al., 2017Midha et al., , 2021Williams et al., 2017;Leung et al., 2018;Lawson et al., 2021;Rosa et al., 2021). In light of these observations, it is essential to continue to conduct studies that allow us assess the potential benefits of probiotics as a novel and effective therapeutic alternative against helminth infections. ...
Article
Full-text available
Helminth infections remain a global public health issue, particularly in low- and middle-income countries, where roundworms from theTrichuris and Ascaris genera are most prevalent. These geohelminths not only impact human health but most importantly also affect animal well-being, in particular the swine industry. Host-helminth parasite interactions are complex and at the same time essential to understand the biology, dynamics and pathophysiology of these infections. Within these interactions, the immunomodulatory capacity of these helminths in the host has been extensively studied. Moreover, in recent years a growing interest on how helminths interact with the intestinal microbiota of the host has sparked, highlighting how this relationship plays an essential role in the establishment of initial infection, survival and persistence of the parasite, as well as in the development of chronic infections. Identifying the changes generated by these helminths on the composition and structure of the host intestinal microbiota constitutes a field of great scientific interest, since this can provide essential and actionable information for designing effective control and therapeutic strategies. Helminths like Trichuris and Ascaris are a focus of special importance due to their high prevalence, higher reinfection rates, resistance to anthelmintic therapy and unavailability of vaccines. Therefore, characterizing interactions between these helminths and the host intestinal microbiota represents an important approach to better understand the nature of this dynamic interface and explore novel therapeutic alternatives based on management of host microbiota. Given the extraordinary impact this may have from a biological, clinical, and epidemiological public health standpoint, this review aims to provide a comprehensive overview of current knowledge and future perspectives examining the parasite-microbiota interplay and its impact on host immunity.
... Indeed, helminth co-infection may influence outcome of other infections and many studies have investigated the influence of previous helminth infections on the pathogenesis of other infectious diseasesincluding bacterial, protozoan, and viral diseases (120)(121)(122)(127)(128)(129)(130)(131)(132)(133)(134). This experimental study design stems from the idea that mammals have co-evolved with helminth parasites and they could be part of the natural macrobiota of the host (135,136). However, pre-existing disease and co-infections may also influence outcomes during helminth infection. ...
Article
Full-text available
Helminth infection currently affect over 2 billion people worldwide, with those with the most pathologies and morbidities, living in regions with unequal and disproportionate access to effective healthcare solutions. Host genetics and environmental factors play critical roles in modulating and regulating immune responses following exposure to various pathogens and insults. However, the interplay of environment and genetic factors in influencing who gets infected and the establishment, persistence, and clearance of helminth parasites remains unclear. Inbred strains of mice have long been used to investigate the role of host genetic factors on pathogenesis and resistance to helminth infection in a laboratory setting. This review will discuss the use of ecological and environmental mouse models to study helminth infections and how this could be used in combination with host genetic variation to explore the relative contribution of these factors in influencing immune response to helminth infections. Improved understanding of interactions between genetics and the environment to helminth immune responses would be important for efforts to identify and develop new prophylactic and therapeutic options for the management of helminth infections and their pathogenesis.
... Additionally, ties between immunity, metabolism, and the gut microbiome are increasingly recognized (18,19), and the low diversity microbiomes and low activation state of T cells of lab mice most closely resemble neonates (20) and diverge widely from wild mice (21). Furthermore, gastrointestinal (GI) helminths also play a role in training and modulating immunity (22,23), with increasing risks of allergic and autoimmune conditions in human populations devoid of their coevolved worms (24). Thus, this and other studies of helminth infection in rewilded mice 1 provide the opportunity to study how these key components of immunological regulation interact to affect the health of humans and other animals. ...
Article
Full-text available
Resources are a core currency of species interactions and ecology in general (e.g., think of food webs or competition). Within parasite-infected hosts, resources are divided among the competing demands of host immunity and growth as well as parasite reproduction and growth. Effects of resources on immune responses are increasingly understood at the cellular level (e.g., metabolic predictors of effector function), but there has been limited consideration of how these effects scale up to affect individual energetic regimes (e.g., allocation trade-offs), susceptibility to infection, and feeding behavior (e.g., responses to local resource quality and quantity). We experimentally rewilded laboratory mice (strain C57BL/6) in semi-natural enclosures to investigate the effects of dietary protein and gastrointestinal nematode (Trichuris muris) infection on individual-level immunity, activity, and behavior. The scale and realism of this field experiment, as well as the multiple physiological assays developed for laboratory mice, enabled us to detect costs, trade-offs, and potential compensatory mechanisms that mice employ to battle infection under different resource conditions. We found that mice on a low-protein diet spent more time feeding, which led to higher body fat stores (i.e., concentration of a satiety hormone, leptin) and altered metabolite profiles, but which did not fully compensate for the effects of poor nutrition on albumin or immune defenses. Specifically, immune defenses measured as interleukin 13 (IL13) (a primary cytokine coordinating defense against T. muris) and as T. muris-specific IgG1 titers were lower in mice on the low-protein diet. However, these reduced defenses did not result in higher worm counts in mice with poorer diets. The lab mice, living outside for the first time in thousands of generations, also consumed at least 26 wild plant species occurring in the enclosures, and DNA metabarcoding revealed that the consumption of different wild foods may be associated with differences in leptin concentrations. When individual foraging behavior was accounted for, worm infection significantly reduced rates of host weight gain. Housing laboratory mice in outdoor enclosures provided new insights into the resource costs of immune defense to helminth infection and how hosts modify their behavior to compensate for those costs.
... There is now great interest in understanding the extent to which well-known immunomodulatory effects of helminths may be mediated by effects on the microbiota (Giacomin et al., 2015;Gause and Maizels, 2016). While various incarnations of the hygiene hypothesis have implicated either disruptions to the commensal flora or reduced helminth exposure in the rise of autoimmunity and allergy, interactions between the two may be an important piece of this puzzle (Loke and Lim, 2015). The emerging view is that immune homeostasis is a complex trait with inputs from several elements of the gut ecosystem including gut microbes, eukaryotic parasites, and diet, which all interact with one other to shape host health and disease. ...
Article
Full-text available
The vertebrate gut teems with a large, diverse, and dynamic bacterial community that has pervasive effects on gut physiology, metabolism, and immunity. Under natural conditions, these microbes share their habitat with a similarly dynamic community of eukaryotes (helminths, protozoa, and fungi), many of which are well-known parasites. Both parasites and the prokaryotic microbiota can dramatically alter the physical and immune landscape of the gut, creating ample opportunities for them to interact. Such interactions may critically alter infection outcomes and affect overall host health and disease. For instance, parasite infection can change how a host interacts with its bacterial flora, either driving or protecting against dysbiosis and inflammatory disease. Conversely, the microbiota can alter a parasite's colonization success, replication, and virulence, shifting it along the parasitism-mutualism spectrum. The mechanisms and consequences of these interactions are just starting to be elucidated in an emergent transdisciplinary area at the boundary of microbiology and parasitology. However, heterogeneity in experimental designs, host and parasite species, and a largely phenomenological and taxonomic approach to synthesizing the literature have meant that common themes across studies remain elusive. Here, we use an ecological perspective to review the literature on interactions between the prokaryotic microbiota and eukaryotic parasites in the vertebrate gut. Using knowledge about parasite biology and ecology, we discuss mechanisms by which they may interact with gut microbes, the consequences of such interactions for host health, and how understanding parasite-microbiota interactions may lead to novel approaches in disease control.
... One of these potential mechanisms is likely to rely on the production of immune-modulatory excretory/ secretory products (ES) by hookworms, which include homologues of mammalian C-type lectins, galectins and cytokines [9][10][11] ; however, it is likely that other biological and environmental factors are involved in these processes. In particular, given the primary role played by gastrointestinal dysbiosis in the pathogenesis of CeD 12 , it has been proposed that one of the mechanisms by which hookworms can support intestinal immune homeostasis in inflammatory disorders (such as CeD), is via the alteration of the composition of the gut microbiota and relative abundance of individual microbial species 8,[13][14][15][16][17] . This hypothesis is based on the results of recent studies by us and others, in which experimental infections with gastrointestinal helminths were accompanied by detectable changes in commensal bacterial composition of both human and animal hosts 13,14,[17][18][19][20] , as well as of the metabolic profiles of bacterial communities which indirectly promote the development of host regulatory T-cell responses 21 . ...
Article
Full-text available
A reduced diversity of the gastrointestinal commensal microbiota is associated with the development of several inflammatory diseases. Recent reports in humans and animal models have demonstrated the beneficial therapeutic effects of infections by parasitic worms (helminths) in some inflammatory disorders, such as inflammatory bowel disease (IBD) and coeliac disease (CeD). Interestingly, these studies have described how helminths may alter the intestinal microbiota, potentially representing a mechanism by which they regulate inflammation. However, for practical reasons, these reports have primarily analysed the faecal microbiota. In the present investigation, we have assessed, for the first time, the changes in the microbiota at the site of infection by a parasitic helminth (hookworm) and gluten-dependent inflammation in humans with CeD using biopsy tissue from the duodenum. Hookworm infection and gluten exposure were associated with an increased abundance of species within the Bacteroides phylum, as well as increases in the richness and diversity of the tissue-resident microbiota within the intestine, results that are consistent with previous reports using other helminth species in humans and animal models. Hence, this may represent a mechanism by which parasitic helminths may restore intestinal immune homeostasis and exert a therapeutic benefit in CeD, and potentially other inflammatory disorders.
... But a bigger study, controlling also for the baseline diet, is needed to better characterize the effect of diet changes. Finally, in comparing visitors to villagers, the presence of intestinal protozoa and helminths in villagers (Table S2) is likely to have an effect on the composition of their fecal microbiota (28). ...
Article
Full-text available
People living traditional lifestyles have higher gut microbiota diversity than urban subjects. We hypothesized that shifting lifestyles from an urban environment to a traditional rainforest village would lead to changes in the microbiota of visitors, which would become more similar to the microbiota of villagers. Here, we characterized at different time points the microbiota of 7 urban visitors (5 adults and 2 children) staying in a rainforest Amerindian village for 16 days and compared them with a reference collection of samples from age-matched local villagers. We performed a 16S rRNA gene survey of samples from multiple body sites (including fecal, oral, nasal, and skin samples) using Illumina MiSeq sequencing. The main factor segregating the microbiotas of each body site was the human group (i.e., visitors versus villagers), with the visitor microbiota tending to have lower alpha diversity; the lowered alpha diversity was statistically significant in the microbiota of skin and in the children’s fecal and oral microbiota. During the rainforest period, all visitors experienced microbiota changes within their personal cloud of variation. For all body sites, the microbiota conformations in the visitor children better matched the microbiota conformations in villagers of the same age than did those of the visitor adults, which showed a lower “microbiota age” than the microbiota of the villagers. The results suggest higher stability in the adult microbiota, with the less resilient children’s microbiota responding more to dietary changes. IMPORTANCE Despite the limitations of a small study, our results evidence higher resilience of the gut microbiota with respect to dietary manipulation in adults than in children and urge further studies to understand the extent of microbiota plasticity in response to dietary changes and the mechanisms underlying microbiota resilience. These studies are relevant to the potential of future human pre- and probiotics in preventing or curing microbiota-associated diseases.
... As intestinal helminths co-habitate with the most abundant and diverse microbial community in the host, important interactions occur between these organisms that reside in the same niche (77). Although commensal bacteria and multicellular helminths occupy very different taxonomic space, they have both responded to evolutionary forces by developing strategies of host immunomodulation. ...
Article
Full-text available
Parasitic helminths are among the most pervasive pathogens of the animal kingdom. To complete their life cycle, these intestinal worms migrate through host tissues causing significant damage in their wake. As a result, infection can lead to malnutrition, anemia and increased susceptibility to co-infection. Despite repeated deworming treatment, individuals living in endemic regions remain highly susceptible to re-infection by helminths, but rarely succumb to excessive tissue damage. The chronicity of infection and inability to resist numerous species of parasitic helminths that have co-evolved with their hosts over millenia suggests that mammals have developed mechanisms to tolerate this infectious disease. Distinct from resistance where the goal is to destroy and eliminate the pathogen, disease tolerance is an active process whereby immune and structural cells restrict tissue damage to maintain host fitness without directly affecting pathogen burden. Although disease tolerance is evolutionary conserved and has been well-described in plant systems, only recently has this mode of host defense, in its strictest sense, begun to be explored in mammals. In this review, we will examine the inter- and intracellular networks that support disease tolerance during enteric stages of parasitic helminth infection and why this alternative host defense strategy may have evolved to endure the presence of non-replicating pathogens and maintain the essential functions of the intestine.
... Helminths have coexisted with human beings and our ancestors for over a million years [72]. Helminths are complex multicellular organisms which have achieved the ability to cause chronic infections by modulating the host immune response [73][74][75][76]. Epidemiological data suggests that helminth infections may play a protective role in various inflammatory diseases such as allergic disorders, asthma, inflammatory bowel disease, and multiple sclerosis, and therapeutic applications are being investigated [77]. ...
Article
Full-text available
First described by Paul Ehrlich in 1879, who noted its characteristic staining by acidophilic dyes, for many years, the eosinophil was considered to be an end-effector cell associated with helminth infections and a cause of tissue damage. Over the past 30 years, research has helped to elucidate the complexity of the eosinophil's function and establish its role in host defense and immunity. Eosinophils express an array of ligand receptors which play a role in cell growth, adhesion, chemotaxis, degranulation, and cell-to-cell interactions. They play a role in activation of complement via both classical and alternative pathways. Eosinophils synthesize, store and secrete cytokines, chemokines, and growth factors. They can process antigen, stimulate T cells, and promote humoral responses by interacting with B cells. Eosinophils can function as antigen presenting cells and can regulate processes associated with both T1 and T2 immunity. Although long known to play a role in defense against helminth organisms, the interactions of eosinophils with these parasites are now recognized to be much more complex. In addition, their interaction with other pathogens continues to be investigated. In this paper, we review the eosinophil's unique biology and structure, including its characteristic granules and the effects of its proteins, our developing understanding of its role in innate and adaptive immunity and importance in immunomodulation, and the part it plays in defense against parasitic, viral, fungal and bacterial infections. Rather than our worst enemy, the eosinophil may, in fact, be one of the most essential components in host defense and immunity.
... One of these potential mechanisms is likely to rely on the production of immune-modulatory excretory/ secretory products (ES) by hookworms, which include homologues of mammalian C-type lectins, galectins and cytokines [9][10][11] ; however, it is likely that other biological and environmental factors are involved in these processes. In particular, given the primary role played by gastrointestinal dysbiosis in the pathogenesis of CeD 12 , it has been proposed that one of the mechanisms by which hookworms can support intestinal immune homeostasis in inflammatory disorders (such as CeD), is via the alteration of the composition of the gut microbiota and relative abundance of individual microbial species 8,[13][14][15][16][17] . This hypothesis is based on the results of recent studies by us and others, in which experimental infections with gastrointestinal helminths were accompanied by detectable changes in commensal bacterial composition of both human and animal hosts 13,14,[17][18][19][20] , as well as of the metabolic profiles of bacterial communities which indirectly promote the development of host regulatory T-cell responses 21 . ...
Article
Full-text available
A reduced diversity of the gastrointestinal commensal microbiota is associated with the development of several inflammatory diseases. Recent reports in humans and animal models have demonstrated the beneficial therapeutic effects of infections by parasitic worms (helminths) in some inflammatory disorders, such as inflammatory bowel disease (IBD) and coeliac disease (CeD). Interestingly, these studies have described how helminths may alter the intestinal microbiota, potentially representing a mechanism by which they regulate inflammation. However, for practical reasons, these reports have primarily analysed the faecal microbiota. In the present investigation, we have assessed, for the first time, the changes in the microbiota at the site of infection by a parasitic helminth (hookworm) and gluten-dependent inflammation in humans with CeD using biopsy tissue from the duodenum. Hookworm infection and gluten exposure were associated with an increased abundance of species within the Bacteroides phylum, as well as increases in the richness and diversity of the tissue-resident microbiota within the intestine, results that are consistent with previous reports using other helminth species in humans and animal models. Hence, this may represent a mechanism by which parasitic helminths may restore intestinal immune homeostasis and exert a therapeutic benefit in CeD, and potentially other inflammatory disorders.
... For 2 decades, the hygiene hypothesis -which proposes that the lack of early childhood exposure to infectious agents increases susceptibility to allergic diseases in later life -provided the conceptual framework for unravelling the mechanisms that could account for the increased incidence of allergic diseases [1]. Based on the "hygiene hypothesis", as people migrate to a more hygienic environment, there are less opportunities to encounter the sources of infection [2]. The difference in the occurrence of allergic and immune-mediated disorders between developing and developed countries may be attributed to the prevalence of helminth infections [3,4]. ...
Article
Full-text available
As most infections by the helminth parasite elicit the recruitment of CD4+CD25+Foxp3+ T (Treg) cells, many scientists have suggested that these cells could be used for the treatment of immune-mediated inflammation and associated diseases. In order to investigate the distribution and alteration of activated Treg cells, we compared the expression levels of Treg cell activation markers in the ileum and gastrocnemius tissues 1, 2, and 4 weeks after infection. The number of Treg cells was monitored using GFP-coded Foxp3 transgenic mice. In mice at 1 week after Trichinella spiralis infection, the number of activated Treg cells was higher than in the control group. In mice at 2 weeks after infection, there was a significant increase in the number of cells expressing Foxp3 and CTLA-4 when compared to the control group and mice at 1 week after infection. At 4 weeks after infection, T. spiralis was easily identifiable in nurse cells in mouse muscles. In the intestine, the expression of Gzmb and Klrg1 decreased over time and that of Capg remained unchanged for the first and second week, then decreased in the 4th week. However, in the muscles, the expression of most chemokine genes was increased due to T. spiralis infection, in particular the expression levels of Gzmb, OX40, and CTLA-4 increased until week 4. In addition, increased gene expression of all chemokine receptors in muscle, CXCR3, CCR4, CCR5, CCR9, and CCR10, was observed up until the 4th week. In conclusion, various chemokine receptors showed increased expressions combined with recruitment of Treg cells in the muscle tissue.
... Gastrointestinal parasitic worms (mainly helminths) represent the most prevalent infectious agents affecting nearly one-third of the human population, as well as most livestock and wildlife, especially in the tropics and in developing countries [1,2,3]. Although helminths cause considerable human morbidity and mortality worldwide [4] with a notable economic impact, their absence in the gut biota of humans consuming a 'western' diet has been widely associated with an increased prevalence of auto-and hyper-immune diseases [5,6]. This suggests that helminths are an essential player in host gut homeostasis and health. ...
Article
Full-text available
Gastrointestinal parasites colonizing the mammalian gut influence the host immune system and health. Parasite infections, mainly helminths, have been studied intensively in both humans and non-human animals, but relatively rarely within a conservation framework. The Udzungwa red colobus monkey (Procolobus gordonorum) is an endangered endemic primate species living in the Udzungwa Mountains of Tanzania, a global biodiversity hotspot. Since this endemic primate species is highly sensitive to human disturbance, here we investigate whether habitat type (driven by natural and human-induced factors) is associated with helminth diversity. Using standard flotation and sedimentation techniques, we analyzed 251 fecal samples belonging to 25 social groups from four different forest blocks within the Udzungwa Mountains. Five parasitic helminth taxa were recovered from Udzungwa red colobus, including Trichuris sp., Strongyloides fulleborni, S. stercoralis, a strongylid nematode and Colobenterobius sp. We used Generalized Linear Mixed Models to explore the contribution of habitat type, altitude and fecal glucocorticoid levels (as biomarkers of stress) in predicting gut parasite variation. Although some parasites (e.g., Trichuris sp.) infected more than 50% of individuals, compared to others (e.g., Colobenterobius sp.) that infected less than 3%, both parasite richness and prevalence did not differ significantly across forests, even when controlling for seasonality. Stress hormone levels also did not predict variation in parasite richness, while altitude could explain it resulting in lower richness at lower altitudes. Because human activities causing disturbance are concentrated mainly at lower altitudes, we suggest that protection of primate forest habitat preserves natural diversity at both macro- and microscales, and that the importance of the latter should not be underestimated.
... Helminths and protozoa residing in the gut may alter the composition of the gut microbiome [13][14][15][16][17][18][19], and those interactions may have important downstream effects on host immunity and gut homeostasis [2,[20][21][22][23]. Little, however, is known about larval stages of helminths that are transmitted faecal-orally, the presence of which in the gut is transitory because they penetrate the gut epithelium and migrate to other host tissues. ...
Article
Full-text available
Host-parasite interactions may be modulated by host- or parasite-associated microbes, but the role of these are often overlooked. Particularly for parasites with intestinal stages (either larval or adult), the host gut microbiome may play a key role for parasite establishment; moreover, the microbiome may change in response to invading parasites. Hypothesis testing at the organismal level may be hampered, particularly in mammalian definitive hosts, by ethical, logistical, and economical restrictions. Thus, invertebrates naturally serving as intermediate hosts to parasites with complex life cycles may inform the development of mammalian models as an early-stage host-parasite model. In addition, several important pathogens are vectored by insects, and insect gut microbiome-pathogen interactions may provide essential base-line knowledge, which may be used to control vectorborne pathogens. Here, we used the grain beetle, Tenebrio molitor, a host of the tapeworm Hymenolepis diminuta, to explore interactions between infection status and resident gut microbiota at two pre-determined time points (day two and seven) post infection. Using 16S/18S microbial profiling, we measured key parameters of the composition, relative abundance, and diversity of the host gut bacteriome and mycobiome. In addition, we quantified the systemic beetle immune response to infection by Phenoloxidase activity and hemocyte abundance. We found significant changes in the gut bacteriome and mycobiome in relation to infection status and beetle age. Thus, the relative abundance of Proteobacteria was significantly higher in the gut of infected beetles and driven mostly by an increased abundance of Acinetobacter. In addition, the mycobiome was less abundant in infected beetles but maintained higher Shannon diversity in infected compared with non-infected beetles. Beetles treated with a broad-spectrum antibiotic (Tetracycline) exhibited significantly reduced parasite establishment compared with the untreated control group, indicating that the host microbiome may greatly influence hatching of eggs and subsequent establishment of H. diminuta larvae. Our results suggest that experimental work using invertebrates may provide a platform for explorative studies of host-parasite-microbe interactions and their underlying mechanisms.
... These inconsistent findings of host-helminth-microbiota studies suggest there exist additional variables that modulate the outcome of these interactions. Identifying these other variables may facilitate treatment of dysbiosis or helminthiasis [14][15][16]. ...
Article
Vertebrates’ gut microbial communities can be altered by the hosts’ parasites. Helminths inhabiting the gut lumen can interact directly with their host’s microbiota via physical contact, chemical products, or competition for nutrients. Indirect interactions can also occur, for instance when helminths induce or suppress host immunity in ways that have collateral effects on the microbiota. If there is genetic variation in host immune responses to parasites, we would expect such indirect effects to be conditional on host genotype. To test for such genotype by infection interactions, we experimentally exposed Gasterosteus aculeatus to their naturally co-evolved parasite, Schistocephalus solidus. The host microbiota differed in response to parasite exposure, and between infected and uninfected fish. The magnitude and direction of microbial responses to infection differed between host sexes, and also differed between variants at autosomal quantitative trait loci. These results indicate that host genotype and sex regulate the effect of helminth infection on a vertebrate gut microbiota. If this result holds in other taxa, especially humans, then helminth-based therapeutics for dysbiosis might need to be tailored to host genotype and sex.
... There is a gradual increase in the prevalence of various immunological disorders in developed countries [88,89]. The link between parasites and allergies or autoimmune diseases has been described as the "hygiene hypothesis" [90,91]. This hypothesis suggests that lack of exposure to parasites in childhood suppresses an immature immune system, resulting in a higher frequency of allergic and immunological diseases: asthma, allergic diseases, RA, cardiovascular disease, multiple sclerosis, type 1 diabetes, and inflammatory bowel disease (IBD) [92][93][94][95][96]. Animal studies have shown that parasite homogenates or secretions can suppress the immune response in the host, suggesting that immunosuppressive activity is induced by the parasite [97]. ...
Article
Full-text available
One of the adaptations of nematodes, which allows long-term survival in the host, is the production of proteins with immunomodulatory properties. The parasites secrete numerous homologs of human immune mediators, such as macrophage migration inhibitory factor (MIF), which is a substantial regulator of the inflammatory immune response. Homologs of mammalian MIF have been recognized in many species of nematode parasites, but their role has not been fully understood. The application of molecular biology and genetic engineering methods, including the production of recombinant proteins, has enabled better characterization of their structure and properties. This review provides insight into the current state of knowledge on MIF homologs produced by nematodes, as well as their structure, enzymatic activity, tissue expression pattern, impact on the host immune system, and potential use in the treatment of parasitic, inflammatory, and autoimmune diseases.
... In humans, most of the identified microbes can be found in the gastrointestinal tract [2,3], which contains approximately 10 14 microbes, collectively defined as the human gut microbiota [1,2,4]. Overall, a healthy gut microbiota is mainly dominated by bacteria belonging to two main phyla -Bacteroidetes and Firmicutes [1,5,6] -and additionally contains eukaryotes (such as Candida, Malassezia, and Saccharomyces) [1,7], Archaea (mostly belonging to the Methanobrevibacter genus) [1,8] and viruses (consisting primarily of bacteriophages) [1,9,10]. ...
Article
Full-text available
During the last decade, the advent of modern sequencing methods (next generation techniques, NGS) has helped describe the composition of the human gut microbiome, enabling us to understand the main characteristics of a healthy gut microbiome and, conversely, the magnitude of its disease-related changes. This new knowledge has revealed that healthy gut microbiota allow the maintenance of several crucial physiological functions, such as the ability to regulate the innate and adaptive immune systems. Increasing evidence has pointed out a condition of dysbiosis in several autoimmune/immune mediated dermatological conditions and specific gut microbial signatures have also been reported to correlate with clinical and prognostic parameters of such diseases. Based on a literature search of relevant published articles, this review debates the current knowledge and the possible pathogenic implications of bacterial gut microbiota composition assessed through NGS techniques in systemic lupus erythematosus, atopic dermatitis, psoriasis, and alopecia areata. Evidence of a potential role of specific gut microbiota signatures in modulating the clinical course of such diseases and their main comorbidities has been also reviewed.
... Association of dysbiosis of the microbiome and mental diseases such autism, schizophrenia, anxiety, depression and bipolar disease has been already reported (Meyer et al., 2011;Foster and McVey Neufeld 2013;Flowers et al., 2020). Moreover, parasitic gut infection alters the composition of microflora (Loke and Lim 2015). The relation of helminth infection with cognition and behaviour via gut microbiota has been discussed already (Guernier et al., 2017). ...
Article
Full-text available
Galectins are a family of proteins that bind β-galactosides and play key roles in a variety of cellular processes including host defense and entry of parasites into the host cells. They have been well studied in hosts but less so in parasites. As both host and parasite galectins are highly upregulated proteins following infection, galectins are an area of increasing interest and their role in immune modulation has only recently become clear. Correlation of CNS parasitic diseases with mental disorders as a result of direct or indirect interaction has been observed. Therefore, galectins produced by the parasite should be taken into consideration as potential therapeutic agents.
... Millions of years of coevolution have enabled helminths to evade mammalian host responses and persist without causing severe disease in most individuals (Allen and Maizels, 2011). A benefit of this commensal-like relationship to the mammalian host may be a tempered immune response, because eradication of helminths correlates with higher prevalence of dysregulated immune disorders such as asthma, allergy, and autoimmunity (Cheng and Locksley, 2014;Loke and Lim, 2015). Nonetheless, helminth-endemic areas also have higher incidences of some systemic infections including HIV, malaria, and Mycobacterium tuberculosis (Mtb), raising the possibility that helminth infection can impair host immunity against certain pathogens (Salgame et al., 2013). ...
Article
Although enteric helminth infections modulate immunity to mucosal pathogens, their effects on systemic microbes remain less established. Here, we observe increased mortality in mice coinfected with the enteric helminth Heligmosomoides polygyrus bakeri (Hpb) and West Nile virus (WNV). This enhanced susceptibility is associated with altered gut morphology and transit, translocation of commensal bacteria, impaired WNV-specific T cell responses, and increased virus infection in the gastrointestinal tract and central nervous system. These outcomes were due to type 2 immune skewing, because coinfection in Stat6 −/− mice rescues mortality, treatment of helminth-free WNV-infected mice with interleukin (IL)-4 mirrors coinfection, and IL-4 receptor signaling in intestinal epithelial cells mediates the susceptibility phenotypes. Moreover, tuft cell-deficient mice show improved outcomes with coinfection, whereas treatment of helminth-free mice with tuft cell-derived cytokine IL-25 or ligand succinate worsens WNV disease. Thus, helminth activation of tuft cell-IL-4-receptor circuits in the gut exacerbates infection and disease of a neurotropic flavivirus.
... As intestinal helminths share a niche with intestinal commensal microbes, the presence of helminths alters the composition of intestinal microbiota through their direct contact and the secretion of ES product, which influences the extent of host immunity to diseases such as allergies and inflammatory bowel disease [147,148]. Intuitively, the shaping of intestinal microbiota by helminths can favour both resistance and susceptibility; however, it still strongly relies on whether the changes in microbiota promote protective type 2 response or favour parasite survival. Recently, it is shown that specific pathogen-free and germ-free mice generate similar levels of Th2 responses, with effective worm expulsion of intestinal Hymenolepis dimunita [149]. ...
Article
Full-text available
The current approaches to reduce the burden of chronic helminth infections in endemic areas are adequate sanitation and periodic administration of deworming drugs. Yet, resistance against some deworming drugs and reinfection can still rapidly occur even after treatment. A vaccine against helminths would be an effective solution at preventing reinfection. However, vaccines against helminth parasites have yet to be successfully developed. While T helper cells and innate lymphoid cells have been established as important components of the protective type 2 response, the roles of B cells and antibodies remain the most controversial. Here, we review the roles of B cells during intestinal helminth infection. We discuss the potential factors that contribute to the context-specific roles for B cells in protection against diverse intestinal helminth parasite species, using evidence from well-defined murine model systems. Understanding the precise roles of B cells during resistance and susceptibility to helminth infection may offer a new perspective of type 2 protective immunity.
... While in animal models, helminth infections have been shown to increase microbial diversity, data from human studies are more complex. Several studies assessing helminthinduced intestinal microbial changes have indicated an increase in microbial diversity and abundance, while others report no significant changes [17]. Nevertheless, the most common feature of worm infections is increased abundance of Lactobacilli species, which are capable of inducing host regulatory responses [16]. ...
... Helminths alter the commensal bacteria diversity, 98 and viral infections are affected by perturbations in commensal bacteria. 41 Thus, it is likely that helminth-mediated changes to the microbiome can affect viral pathogenesis. ...
Article
Full-text available
Viral infections are often studied in model mammalian organisms under specific pathogen-free conditions. However, in nature, coinfections are common, and infection with one organism can alter host susceptibility to infection with another. Helminth parasites share a long coevolutionary history with mammalian hosts and have shaped host physiology, metabolism, immunity, and the composition of the microbiome. Published studies suggest that helminth infection can either be beneficial or detrimental during viral infection. Here, we discuss coinfection studies in mouse models and use them to define key determinants that impact outcomes, including the type of antiviral immunity, the tissue tropism of both the helminth and the virus, and the timing of viral infection in relation to the helminth lifecycle. We also explore the current mechanistic understanding of how helminth-virus coinfection impacts host immunity and viral pathogenesis. While much attention has been placed on the impact of the gut bacterial microbiome on immunity to infection, we suggest that enteric helminths, as a part of the eukaryotic macrobiome, also represent an important modulator of disease pathogenesis and severity following virus infection.
... A healthy gut microbiota is characterized by resistance and resilience, defined as the ability to resist an external perturbation and to return to the pre-perturbation state after a change occurs, respectively [7]; therefore, gut microbiota exhibiting high plasticity towards the environment [8] could be a double-edged sword ( Figure 1). Indeed, if an external factor is stronger than the stability of the gut ecosystem to an extent exceeding the resistance and resilience capabilities [9], the return of the microbial community to the previous state can be compromised, leading to the development of permanent dysbiotic states [5,10] in either the bacteria composition or functionality [9,11]. At this point, whereby dysbiosis predominates over balanced states, the consequences can be detrimental for host health [9]. ...
Article
Full-text available
It is widely known that a good balance and healthy function for bacteria groups in the colon are necessary to maintain homeostasis and preserve health. However, the lack of consensus on what defines a healthy gut microbiota and the multitude of factors that influence human gut microbiota composition complicate the development of appropriate dietary recommendations for our gut microbiota. Furthermore, the varied response to the intake of probiotics and prebiotics observed in healthy adults suggests the existence of potential inter- and intra-individual factors, which might account for gut microbiota changes to a greater extent than diet. The changing dietary habits worldwide involving consumption of processed foods containing artificial ingredients, such as sweeteners; the coincident rise in emotional disorders; and the worsening of other lifestyle habits, such as smoking habits, drug consumption, and sleep, can together contribute to gut dysbiosis and health impairment, as well as the development of chronic diseases. This review summarizes the current literature on the effects of specific dietary ingredients (probiotics, prebiotics, alcohol, refined sugars and sweeteners, fats) in the gut microbiota of healthy adults and the potential inter- and intra-individual factors involved, as well as the influence of other potential lifestyle factors that are dramatically increasing nowadays.
Article
Full-text available
Background: Many lines of scientific research suggest that Autism Spectrum Disorders (ASDs) may be associated with alterations in the enteric ecosystem, including alterations of the enteric macrobiome (i.e. helminthes and fauna) and changes in predominant microbiome species, particularly a reduction in microbiome diversity. Methods: We performed and comprehensive review of the literature and summarized the major findings. Results: These alterations are believed to be due to a variety of factors including changes in the post-industrial society related to decreased exposure to symbiotic organisms, increased human migration, overuse of antibiotics and changes in dietary habits. Changes in the enteric ecosystem are believed to alter metabolic and immune system function and epigenetic regulation. If these changes occur during critical developmental windows, the trajectory of brain development, as well as brain function, can be altered. This paper reviews theoretical models that explain how these perturbations may in isolation or in combination be causative for ASDs as well as the preclinical and clinical studies that support these models. We discuss how these alterations may converge to trigger or exacerbate the formation of an ASD phenotype. We focus on possible preconception, prenatal, perinatal and postnatal factors that may alter the enteric ecosystem leading to physiological disruptions, potentially through triggering events. Conclusion: If these theoretical models prove to be valid, they may lead to the development of practical interventions which could decrease ASD prevalence and/or morbidity.
Article
Full-text available
In human medicine, the prevalence of allergies has increased during the last decades. A similar tendency is suspected in small animal veterinary medicine. Unfortunately, only little information is available about the prevalence of allergies in dogs in Flanders. In this study, veterinarians and owners were asked about the five most common types of allergy, i.e. atopy, flea allergy, food allergy, contact allergy and allergy to medication and injections. The median prevalence, estimated by the veterinarians, was respectively 15%, 10%, 5%, 2% and 1%. Some remarkable differences with the literature were noticed. A blood test was mentioned by the owners as the most frequently used test to diagnose food allergies. Living in an urban environment could not be linked with an increased risk to develop allergies, and 11% of the veterinarians reported washing-powder as a contact allergen. In the opinion of more than half of the veterinarians, the number of dogs with an allergy has increased during his/her career.
Article
There has been increasing recognition that the alarming surge in allergy and autoimmunity in the industrialised and developing worlds shadows the rapid eradication of pathogens, such as parasitic helminths. Appreciation of this has fuelled an explosion in research investigating the therapeutic potential of these worms. This review considers the current state-of-play with a particular focus on exciting recent advances in the identification of potential novel targets for immunomodulation that can be exploited therapeutically. Furthermore, we contemplate the prospects for designing worm-derived immunotherapies for an ever-widening range of inflammatory diseases, including, for example, obesity, cardiovascular disease, and ageing as well as neurodevelopmental disorders like autism.
Article
Innate lymphoid cells (ILC) are a recently identified group of innate lymphocytes that are preferentially located at barrier surfaces. Barrier surfaces are in direct contact with complex microbial ecosystems, collectively referred to as the microbiota. It is now believed that the interplay of the microbiota with host components (i.e. epithelial cells and immune cells) promotes host fitness by regulating organ homeostasis, metabolism, and host defense against pathogens. In this review, we will give an overview of this multifaceted interplay between ILC and components of the microbiota.
Article
The applications of nanoparticles (NPs) are increasing exponentially in consumer products, biotechnology and biomedicine, and humans, as well as the environment, are increasingly being exposed to NPs. Analogously, various (pathogenic) microorganisms are present at all the major exposure and entry sites for NPs in the human body as well as in environmental habitats. However, the field has just started to explore the complex interplay between NPs and microbes and the (patho)biological consequences. Based on recent insights, herein, we critically reviewed the available knowledge about the interaction of NPs with microbes and the analytical investigations including the latest intravital imaging tools. We have commented on how the NPs’ characteristics influence complex formation with microorganisms, presented the underlying physicochemical forces, and provided examples of how this knowledge can be used to rationally control the NP–microbe interaction. We concluded by discussing the role of the biomolecule corona in NP–microbe crosstalk and speculated the impact of NP–microbe complex formation on the (patho)biological outcome and fate of microbial pathogens. The presented insights will not only support the field in engineering NPs with improved anti-microbial activity but also stimulate research on the biomedical and toxicological relevance of nanomaterial–microbiome complex formation for the anthropocene in general.
Article
Full-text available
The parasitic helminthes are a group of invertebrates and including animals which have been adapted themselves to the parasitic mode of life. These are belonging to two important phyla namely, platyhelminthes and Aschelminthes. The parasites are those organism which lives at the expense of other organism, and in return causes injury or harm to the host. Thus it is an association in which one organism i.e. the parasite, is benefited while another one, the host, is harmed is called parasitism; however, behavior, occurrence, establishment and cuases of of parasitism known as parasitocoenosis. The parasitism has evolved accidently as a result of contact between different forms of animals, mainly for the purpose of obtaining nourishment and receiving shelter. An ideal parasite never causes too much harm to its host because if the host dies the parasite depending upon the host will also have to die. The parasitism and parasitocoenosis is a matter of conflict and ambiguity either it is structured association based on ecosegregation and microhabitat specificity or a stochastic assemblages and accidental contact due to utilization of common habitat and life style. The helminthes zoonotic infections are among the most common on erath and are responsible for major human infectious diseases. Some of the most important and well known human zoonoses are caused by parasitic helminthes including anisakiasis, trichinellosis, cysticercosis, echinococcosis, schistosomiasis, etc. However, along with social, epidemiological and environmental changes, together with improvements in our ability to diagnose helminth infections, several neglected parasite species are now fast-becoming recognized as important zoonotic diseases of humans, e.g., anasakiasis, several fish-borne trematodiasis and fasciolosis. In the present review, we discuss the current status of the primary helminth zoonotic infections with particular emphasis on their ecosegregation and parasitocoenosis. Advances in molecular biology, proteomics and the release of helminth genome-sequencing project data are revolutionizing parasitology research.
Article
Full-text available
Helminth parasites infect an alarmingly large proportion of the world’s population, primarily within tropical regions, and their ability to down‐modulate host immunity is key to their persistence. Helminths have developed multiple mechanisms that induce a state of hyporesponsiveness or immune suppression within the host; of particular interest are mechanisms that drive the induction of regulatory T cells (Tregs). Helminths actively induce Tregs either directly by secreting factors, such as the TGF‐β mimic Hp‐TGM, or indirectly by interacting with bystander cell types such as dendritic cells and macrophages which then induce Tregs. Expansion of Tregs not only enhances parasite survival but in cases such as filarial infection, Tregs also play a role in preventing parasite‐associated pathologies. Furthermore, Tregs generated during helminth infection have been associated with suppression of bystander immunopathologies in a range of inflammatory conditions such as allergy and autoimmune disease. In this review we discuss evidence from natural and experimental infections that point to the pathways and molecules involved in helminth Treg induction, and postulate how parasite‐derived molecules and/or Tregs might be applied as anti‐inflammatory therapies in the future.
Article
Cardiovascular diseases are rising in developing countries with increasing urbanization and lifestyle changes and remains a major cause of death in the developed world. In this mini review, we discuss the possibility that the effect of helminth infections on the immune system and the microbiota may affect risk factors in cardiovascular diseases such as atherosclerosis, as part of the hygiene hypothesis. The effects of Type 2 immune responses induced by helminths and helminth derived molecules on regulating metabolism and Mϕ function could be a mechanistic link for further investigation. We emphasize the complexity and difficulties in determining indirect or direct and causal relationships between helminth infection status and cardiovascular diseases. New experimental models, such as rewilding laboratory mice, whereby different aspects of the environment and host genetics can be carefully dissected may provide further mechanistic insights and therapeutic strategies for treating cardiovascular diseases. Reviews helminth infection's impact on the immune system and the microbiota; provides mechanistic insight that may aid in finding new approaches for treating cardiovascular disease.
Article
Gut bacteria may coexist with other groups of organisms, such as nematode parasites, that inhabit the gastrointestinal tract of primates; however, the possible effects of endoparasites on bacterial communities are frequently overlooked. Here we explored whether infection with Trypanoxyuris, an oxyurid gastrointestinal parasite, is associated with changes in the gut bacterial community of wild black howler monkeys (Alouatta pigra), by comparing gut bacterial communities of consistently infected individuals and individuals that never tested positive for Trypanoxyuris throughout different months across the year. We additionally controlled for other sources of variation reported to influence the primate microbiome including individual identity, social group, and seasonality. Trypanoxyuris infection was not related to differences in gut bacterial alpha diversity, but was weakly associated with differences in gut bacterial community structure. In contrast, among the covariates considered, both individual identity and social group were more strongly associated with variation in the howler gut bacterial community. Our results suggest that gastrointestinal parasites may be associated, to some extent, with shifts in the gut bacterial communities hosted by free-ranging primates, although a causal link still needs to be established. Further studies of wild primate hosts infected with parasite species with different pathogenicity are needed to better elucidate health-related consequences from the parasite-microbiome interplay. Research highlights • 1. Pinworm (Trypanoxyuris) infection was associated with slight shifts in the gut bacterial community of black howler monkeys. • 2. The individual ID and social group played a stronger role shaping bacterial communities in this Alouatta pigra population. • 3. Bacterial taxa associated with colonic inflammation were increased in parasite-infected individuals.
Article
По данным ВОЗ, гельминтозы занимают третье место в структуре инфекционных заболеваний. Рост заболеваемости обусловлен сбросом сточных вод в поверхностные водные объекты или непосредственно на землю, повышением миграции населения из стран с теплым климатом, увеличение численности домашних животных. В последнее время получена информация о развивающейся у гельминтов устойчивости к лекарственным средствам. В первой части статьи приводится понятие и классификация гельминтов, систематизирована информация о клинической картине наиболее часто встречающихся гельминтозов. Вторая часть посвящена 17 противогельминтным лекарственным средствам, зарегистрированным в Республике Беларусь. Приводится актуальная и систематизированная информация о показаниях и противопоказаниях по применению, побочных реакциях и лекарственных взаимодействиях с позиции причинно-следственных связей, опирающихся на фармакодинамические и фармакокинетические особенности лекарственных средств. Приведен алгоритм оказания фармацевтическим работником грамотной фармацевтической помощи (в т. ч. фармацевтического консультирования) посетителю, обратившемуся в аптеку с вопросом о приобретении противогельминтных средств. Аccording to WHO, helminthiases rank the third place in the structure of infectious diseases. In addition, the increasing of the incidence is due to the discharge of wastewater into other water bodies or onto the ground, an increasing the population migration from countries with a warm climate, and an increasing the number of domestic animals. The increase of morbidity of helminthiasis is associated with the discharge of wastewater into other water objects or onto the ground, the migration of people from countries with a warm climate, and the large number of domestic animals. Recently the reports about helminths with drug resistance are received. In the first part, the concept and classification of helminths is given, and clinical information on the most common helminthiases is systematized. The second part of the article is devoted to 17 anthelmintic medicines that are registered in the Republic of Belarus. Actual and systematic information about medical uses and contraindications, adverse reactions and drug interactions were systematizedaccording to pharmacodynamic and pharmacokinetic of medicines, and cause-effect relationships. An algorithm of pharmaceutical consulting has been developed to help pharmacists give advices to a visitor with helminthiasis.
Article
Humans have co‐existed with parasites for virtually the entirety of our existence as a species. Today, nearly one‐third of the human population is infected with at least one helminthic species, most of which reside in the intestinal tract, where they have co‐evolved alongside the human gut microbiota. Appreciation for the interconnected relationship between helminths and the gut microbiota has increased in recent years. Here, we review the evidence of how helminths and the gut microbiota can influence various aspects of childhood development and the onset of pediatric diseases. We discuss the emerging evidence of how many of the changes that parasitic worms inflict on their host is enacted through gut microbes. In this light, we argue that helminth‐induced microbiome modifications are of great importance in both facing the global challenge of overcoming parasitic infections, and in replicating helminthic protective effects against inflammatory diseases. We propose that deepening our knowledge of helminth‐microbiome interactions will uncover novel, safer and more effective therapeutic strategies in combatting an array of childhood disorders.
Article
The 19(th) century has been termed the "Golden Age of Parasitology" as during this period the life cycles of many parasites were identified, public health strategies were proposed to prevent transmission, and therapeutic strategies initiated to provide a cure for those infected (1). However, if the 19(th) century was the Golden Age, surely we should declare that in the last decade, we have entered into a Platinum Age of Parasitology where we appreciate not only how parasitic infection negatively impacts humans, but also how humans and parasites have co-evolved, in many cases, to minimize the pathological impact of infection on the host (2). This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
Article
Full-text available
The intestinal microbiota are pivotal in determining the developmental, metabolic and immunological status of the mammalian host. However, the intestinal tract may also accommodate pathogenic organisms, including helminth parasites which are highly prevalent in most tropical countries. Both microbes and helminths must evade or manipulate the host immune system to reside in the intestinal environment, yet whether they influence each other's persistence in the host remains unknown. We now show that abundance of Lactobacillus bacteria correlates positively with infection with the mouse intestinal nematode, Heligmosomoides polygyrus, as well as with heightened regulatory T cell (Treg) and Th17 responses. Moreover, H. polygyrus raises Lactobacillus species abundance in the duodenum of C57BL/6 mice, which are highly susceptible to H. polygyrus infection, but not in BALB/c mice, which are relatively resistant. Sequencing of samples at the bacterial gyrB locus identified the principal Lactobacillus species as L. taiwanensis, a previously characterized rodent commensal. Experimental administration of L. taiwanensis to BALB/c mice elevates regulatory T cell frequencies and results in greater helminth establishment, demonstrating a causal relationship in which commensal bacteria promote infection with an intestinal parasite and implicating a bacterially-induced expansion of Tregs as a mechanism of greater helminth susceptibility. The discovery of this tripartite interaction between host, bacteria and parasite has important implications for both antibiotic and anthelmintic use in endemic human populations.
Article
Full-text available
The mammalian intestine is colonized by beneficial commensal bacteria and is a site of infection by pathogens, including helminth parasites. Helminths induce potent immunomodulatory effects, but whether these effects are mediated by direct regulation of host immunity or indirectly through eliciting changes in the microbiota is unknown. We tested this in the context of virus-helminth coinfection. Helminth coinfection resulted in impaired antiviral immunity and was associated with changes in the microbiota and STAT6-dependent helminth-induced alternative activation of macrophages. Notably, helminth-induced impairment of antiviral immunity was evident in germ-free mice, but neutralization of Ym1, a chitinase-like molecule that is associated with alternatively activated macrophages, could partially restore antiviral immunity. These data indicate that helminth-induced immunomodulation occurs independently of changes in the microbiota but is dependent on Ym1.
Article
Full-text available
Hosts may mitigate the impact of parasites by two broad strategies: resistance, which limits parasite burden, and tolerance, which limits the fitness or health cost of increasing parasite burden. The degree and causes of variation in both resistance and tolerance are expected to influence host-parasite evolutionary and epidemiological dynamics and inform disease management, yet very little empirical work has addressed tolerance in wild vertebrates. Here, we applied random regression models to longitudinal data from an unmanaged population of Soay sheep to estimate individual tolerance, defined as the rate of decline in body weight with increasing burden of highly prevalent gastrointestinal nematode parasites. On average, individuals lost weight as parasite burden increased, but whereas some lost weight slowly as burden increased (exhibiting high tolerance), other individuals lost weight significantly more rapidly (exhibiting low tolerance). We then investigated associations between tolerance and fitness using selection gradients that accounted for selection on correlated traits, including body weight. We found evidence for positive phenotypic selection on tolerance: on average, individuals who lost weight more slowly with increasing parasite burden had higher lifetime breeding success. This variation did not have an additive genetic basis. These results reveal that selection on tolerance operates under natural conditions. They also support theoretical predictions for the erosion of additive genetic variance of traits under strong directional selection and fixation of genes conferring tolerance. Our findings provide the first evidence of selection on individual tolerance of infection in animals and suggest practical applications in animal and human disease management in the face of highly prevalent parasites.
Article
Full-text available
Immune responses to gastrointestinal nematodes have been studied extensively for over 80 years and intensively investigated over the last 30-40 years. The use of laboratory models has led to the discovery of new mechanisms of protective immunity and made major contributions to our fundamental understanding of both innate and adaptive responses. In addition to host protection, it is clear that immunoregulatory processes are common in infected individuals and resistance often operates alongside modulation of immunity. This review aims to discuss the recent discoveries in both host protection and immunoregulation against gastrointestinal nematodes, placing the data in context of the specific life cycles imposed by the different parasites studied and the future challenges of considering the mucosal/immune axis to encompass host, parasite, and microbiome in its widest sense.
Article
Full-text available
Therapeutic food interventions have reduced mortality in children with severe acute malnutrition (SAM) but incomplete restoration of healthy growth remains a major problem1,2. The relationships between the type of nutritional intervention, the gut microbiota, and therapeutic responses are unclear. In the current study, bacterial species whose proportional representation define a healthy gut microbiota as it assembles during the first two postnatal years were identified by applying a machine-learning-based approach to 16S rRNA datasets generated from monthly fecal samples obtained from a birth-cohort of children, living in an urban slum of Dhaka, Bangladesh, who exhibited consistently healthy growth. These age-discriminatory bacterial species were incorporated into a model that computes a ‘relative microbiota maturity index’ and ‘microbiota-for-age Z-score’ that compare development (defined here as maturation) of a child’s fecal microbiota relative to healthy children of similar chronologic age. The model was applied to twins and triplets (to test for associations of these indices with genetic and environmental factors including diarrhea), children with SAM enrolled in a randomized trial of two food interventions, and children with moderate acute malnutrition. Our results indicate that SAM is associated with significant relative microbiota immaturity that is only partially ameliorated following two widely used nutritional interventions. Immaturity is also evident in less severe forms of malnutrition and correlates with anthropometric measurements. Microbiota maturity indices provide a microbial measure of human postnatal development, a way of classifying malnourished states, and a parameter for judging therapeutic efficacy. More prolonged interventions with existing or new therapeutic foods and/or addition of gut microbes may be needed to achieve enduring repair of gut microbiota immaturity in childhood malnutrition and improve clinical outcomes.
Article
Full-text available
Soil-transmitted helminths colonize more than 1.5 billion people worldwide, yet little is known about how they interact with bacterial communities in the gut microbiota. Differences in the gut microbiota between individuals living in developed and developing countries may be partly due to the presence of helminths, since they predominantly infect individuals from developing countries, such as the indigenous communities in Malaysia we examine in this work. We compared the composition and diversity of bacterial communities from the fecal microbiota of 51 people from two villages in Malaysia, of which 36 (70.6%) were infected by helminths. The 16S rRNA V4 region was sequenced at an average of nineteen thousand sequences per samples. Helminth-colonized individuals had greater species richness and number of observed OTUs with enrichment of Paraprevotellaceae, especially with Trichuris infection. We developed a new approach of combining centered log-ratio (clr) transformation for OTU relative abundances with sparse Partial Least Squares Discriminant Analysis (sPLS-DA) to enable more robust predictions of OTU interrelationships. These results suggest that helminths may have an impact on the diversity, bacterial community structure and function of the gut microbiota.
Article
Full-text available
Metabolites from intestinal microbiota are key determinants of host-microbe mutualism and, consequently, the health or disease of the intestinal tract. However, whether such host-microbe crosstalk influences inflammation in peripheral tissues, such as the lung, is poorly understood. We found that dietary fermentable fiber content changed the composition of the gut and lung microbiota, in particular by altering the ratio of Firmicutes to Bacteroidetes. The gut microbiota metabolized the fiber, consequently increasing the concentration of circulating short-chain fatty acids (SCFAs). Mice fed a high-fiber diet had increased circulating levels of SCFAs and were protected against allergic inflammation in the lung, whereas a low-fiber diet decreased levels of SCFAs and increased allergic airway disease. Treatment of mice with the SCFA propionate led to alterations in bone marrow hematopoiesis that were characterized by enhanced generation of macrophage and dendritic cell (DC) precursors and subsequent seeding of the lungs by DCs with high phagocytic capacity but an impaired ability to promote T helper type 2 (TH2) cell effector function. The effects of propionate on allergic inflammation were dependent on G protein-coupled receptor 41 (GPR41, also called free fatty acid receptor 3 or FFAR3), but not GPR43 (also called free fatty acid receptor 2 or FFAR2). Our results show that dietary fermentable fiber and SCFAs can shape the immunological environment in the lung and influence the severity of allergic inflammation.
Article
Full-text available
Long-term dietary intake influences the structure and activity of the trillions of microorganisms residing in the human gut, but it remains unclear how rapidly and reproducibly the human gut microbiome responds to short-term macronutrient change. Here we show that the short-term consumption of diets composed entirely of animal or plant products alters microbial community structure and overwhelms inter-individual differences in microbial gene expression. The animal-based diet increased the abundance of bile-tolerant microorganisms (Alistipes, Bilophila and Bacteroides) and decreased the levels of Firmicutes that metabolize dietary plant polysaccharides (Roseburia, Eubacterium rectale and Ruminococcus bromii). Microbial activity mirrored differences between herbivorous and carnivorous mammals, reflecting trade-offs between carbohydrate and protein fermentation. Foodborne microbes from both diets transiently colonized the gut, including bacteria, fungi and even viruses. Finally, increases in the abundance and activity of Bilophila wadsworthia on the animal-based diet support a link between dietary fat, bile acids and the outgrowth of microorganisms capable of triggering inflammatory bowel disease. In concert, these results demonstrate that the gut microbiome can rapidly respond to altered diet, potentially facilitating the diversity of human dietary lifestyles.
Article
Full-text available
Intestinal microbes provide multicellular hosts with nutrients and confer resistance to infection. The delicate balance between pro- and anti-inflammatory mechanisms, essential for gut immune homeostasis, is affected by the composition of the commensal microbial community. Regulatory T cells (Treg cells) expressing transcription factor Foxp3 have a key role in limiting inflammatory responses in the intestine. Although specific members of the commensal microbial community have been found to potentiate the generation of anti-inflammatory Treg or pro-inflammatory T helper 17 (TH17) cells, the molecular cues driving this process remain elusive. Considering the vital metabolic function afforded by commensal microorganisms, we reasoned that their metabolic by-products are sensed by cells of the immune system and affect the balance between pro- and anti-inflammatory cells. We tested this hypothesis by exploring the effect of microbial metabolites on the generation of anti-inflammatory Treg cells. We found that in mice a short-chain fatty acid (SCFA), butyrate, produced by commensal microorganisms during starch fermentation, facilitated extrathymic generation of Treg cells. A boost in Treg-cell numbers after provision of butyrate was due to potentiation of extrathymic differentiation of Treg cells, as the observed phenomenon was dependent on intronic enhancer CNS1 (conserved non-coding sequence 1), essential for extrathymic but dispensable for thymic Treg-cell differentiation. In addition to butyrate, de novo Treg-cell generation in the periphery was potentiated by propionate, another SCFA of microbial origin capable of histone deacetylase (HDAC) inhibition, but not acetate, which lacks this HDAC-inhibitory activity. Our results suggest that bacterial metabolites mediate communication between the commensal microbiota and the immune system, affecting the balance between pro- and anti-inflammatory mechanisms.
Article
Full-text available
The soil-transmitted helminth (STH), Trichuris trichiura colonises the human large intestine where it may modify inflammatory responses, an effect possibly mediated through alterations in the intestinal microbiota. We hypothesised that patent T. trichiura infections would be associated with altered faecal microbiota and that anthelmintic treatment would induce a microbiota resembling more closely that observed in uninfected individuals. School children in Ecuador were screened for STH infections and allocated to 3 groups: uninfected, T. trichiura only, and mixed infections with T. trichiura and Ascaris lumbricoides. A sample of uninfected children and those with T. trichiura infections only were given anthelmintic treatment. Bacterial community profiles in faecal samples were studied by 454 pyrosequencing of 16 S rRNA genes. Microbiota analyses of faeces were done for 97 children: 30 were uninfected, 17 were infected with T. trichiura, and 50 with T. trichiura and A. lumbricoides. Post-treatment samples were analyzed for 14 children initially infected with T. trichiura alone and for 21 uninfected children. Treatment resulted in 100% cure of STH infections. Comparisons of the microbiota at different taxonomic levels showed no statistically significant differences in composition between uninfected children and those with T. trichiura infections. We observed a decreased proportional abundance of a few bacterial genera from the Clostridia class of Firmicutes and a reduced bacterial diversity among children with mixed infections compared to the other two groups, indicating a possible specific effect of A. lumbricoides infection. Anthelmintic treatment of children with T. trichiura did not alter faecal microbiota composition. Our data indicate that patent human infections with T. trichiura may have no effect on faecal microbiota but that A. lumbricoides colonisation might be associated with a disturbed microbiota. Our results also catalogue the microbiota of rural Ecuadorians and indicate differences with individuals from more urban industrialised societies.
Article
Full-text available
Parasitic nematodes are potent modulators of immune reactivity in mice and men. Intestinal nematodes live in close contact with commensal gut bacteria, provoke biased Th2 immune responses upon infection, and subsequently lead to changes in gut physiology. We hypothesized that murine nematode infection is associated with distinct changes of the intestinal bacterial microbiota composition. We here studied intestinal inflammatory and immune responses in mice following infection with the hookworm Heligmosomoidespolygyrusbakeri and applied cultural and molecular techniques to quantitatively assess intestinal microbiota changes in the ileum, cecum and colon. At day 14 post nematode infection, mice harbored significantly higher numbers of γ-Proteobacteria/Enterobacteriaceae and members of the Bacteroides/Prevotella group in their cecum as compared to uninfected controls. Abundance of Gram-positive species such as Lactobacilli, Clostridia as well as the total bacterial load was not affected by worm infection. The altered microbiota composition was independent of the IL-4/-13 - STAT6 signaling axis, as infected IL-4Rα(-/-) mice showed a similar increase in enterobacterial loads. In conclusion, infection with an enteric nematode is accompanied by distinct intestinal microbiota changes towards higher abundance of gram-negative commensal species at the small intestinal site of infection (and inflammation), but also in the parasite-free large intestinal tract. Further studies should unravel the impact of nematode-induced microbiota changes in inflammatory bowel disease to allow for a better understanding of how theses parasites interfere with intestinal inflammation and bacterial communities in men.
Article
Full-text available
Opisthorchis viverrini is a fish-borne trematode endemic in East Asia. Following ingestion, the flukes locate to the biliary treȩ where chronic infection frequently leads to cholangiocarcinoma (CCA). The mechanisms by which O. viverrini infection culminates in CCA remain unknown. An unexplored aspect is its influence on the host microbiome. In the hamster, infection with this pathogen reliably leads to CCA. Genomic DNAs of microbiota from colorectal contents and bile of hamsters and from whole O. viverrini were examined in this model of fluke-induced CCA. Microbial communities were characterized by high-throughput sequencing of variable regions 7-9 of prokaryotic 16S ribosomal DNA Of ∼1 million sequences, 536,009 with useable reads were assignable to 29,776 operational taxonomy units (OTUs) and, in turn, to 20 phyla and 273 genera of Bacteria or Archaea. Microbial community analyses revealed that fluke infection perturbed the gastrointestinal tract microbiome, increasing Lachnospiraceae, Ruminococcaceae, and Lactobacillaceae, while decreasing Porphyromonadaceae, Erysipelotrichaceae, and Eubacteriaceae (P≤0.05). More than 60 OTUs were detected in the biliary system, which confirmed bacteriobilia and a noteworthy community of microbes associated with the parasites. The fluke-associated microorganisms included potential pathogens from the Enterobacteriaceae and Listeriaceae and others, including Cyanobacteria and Deinococci, usually found in external environments. Given that opisthorchiasis is distinguished from other helminth infections by a robust inflammatory phenotype with conspicuously elevated IL-6, and that inflammation of the biliary system leads to periductal fibrosis, which is a precursor of CCA, the flukes and their microbiota may together drive this distinctive immune response.
Article
Full-text available
Regulatory T cells (Tregs) that express the transcription factor Foxp3 are critical for regulating intestinal inflammation. Candidate microbe approaches have identified bacterial species and strain-specific molecules that can affect intestinal immune responses, including species that modulate Treg responses. Because neither all humans nor mice harbor the same bacterial strains, we posited that more prevalent factors exist that regulate the number and function of colonic Tregs. We determined that short-chain fatty acids, gut microbiota–derived bacterial fermentation products, regulate the size and function of the colonic Treg pool and protect against colitis in a Ffar2-dependent manner in mice. Our study reveals that a class of abundant microbial metabolites underlies adaptive immune microbiota coadaptation and promotes colonic homeostasis and health.
Article
Full-text available
Helminth-induced type 2 immune responses, which are characterized by the T helper 2 cell-associated cytokines interleukin-4 (IL-4) and IL-13, mediate host protection through enhanced tissue repair, the control of inflammation and worm expulsion. In this Opinion article, we consider type 2 immunity in the context of helminth-mediated tissue damage. We examine the relationship between the control of helminth infection and the mechanisms of wound repair, and we provide a new understanding of the adaptive type 2 immune response and its contribution to both host tolerance and resistance.
Article
Full-text available
Kwashiorkor, an enigmatic form of severe acute malnutrition, is the consequence of inadequate nutrient intake plus additional environmental insults. To investigate the role of the gut microbiome, we studied 317 Malawian twin pairs during the first 3 years of life. During this time, half of the twin pairs remained well nourished, whereas 43% became discordant, and 7% manifested concordance for acute malnutrition. Both children in twin pairs discordant for kwashiorkor were treated with a peanut-based, ready-to-use therapeutic food (RUTF). Time-series metagenomic studies revealed that RUTF produced a transient maturation of metabolic functions in kwashiorkor gut microbiomes that regressed when administration of RUTF was stopped. Previously frozen fecal communities from several discordant pairs were each transplanted into gnotobiotic mice. The combination of Malawian diet and kwashiorkor microbiome produced marked weight loss in recipient mice, accompanied by perturbations in amino acid, carbohydrate, and intermediary metabolism that were only transiently ameliorated with RUTF. These findings implicate the gut microbiome as a causal factor in kwashiorkor.
Article
Full-text available
Helminth infections may modulate immune responses to unrelated pathogens and allergens; these effects may commence prenatally. We addressed the hypothesis that anthelminthic treatment in pregnancy and early childhood would improve responses to immunisation and modulate disease incidence in early childhood with both beneficial and detrimental effects. A randomised, double-blind, placebo-controlled trial was conducted in Entebbe, Uganda [ISRCTN32849447]. In three independent randomisations, 2507 pregnant women were allocated to receive single-dose albendazole or placebo, and praziquantel or placebo; 2016 of their offspring were randomised to receive quarterly single-dose albendazole or placebo from age 15 months to 5 years. Primary outcomes were post-immunisation recall responses to BCG and tetanus antigens, and incidence of malaria, diarrhoea, and pneumonia; incidence of eczema was an important secondary outcome. Analysis was by intention-to-treat. Of 2345 live births, 1622 (69%) children remained in follow-up at age 5 years. 68% of mothers at enrolment, and 11% of five-year-olds, had helminth infections. Maternal hookworm and Schistosoma mansoni were effectively treated by albendazole and praziquantel, respectively; and childhood hookworm and Ascaris by quarterly albendazole. Incidence rates of malaria, diarrhoea, pneumonia, and eczema were 34, 65, 10 and 5 per 100 py, respectively. Albendazole during pregnancy caused an increased rate of eczema in the children (HR 1.58 (95% CI 1.15-2.17), p = 0.005). Quarterly albendazole during childhood was associated with reduced incidence of clinical malaria (HR 0.85 (95% CI 0.73-0.98), p = 0.03). There were no consistent effects of the interventions on any other outcome. Routine use of albendazole in pregnancy may not always be beneficial, even in tropical developing countries. By contrast, regular albendazole treatment in preschool children may have an additional benefit for malaria control where helminths and malaria are co-endemic. Given the low helminth prevalence in our children, the effect of albendazole on malaria is likely to be direct. Current Controlled Trials ISRCTN32849447.
Article
Full-text available
Idiopathic chronic diarrhea (ICD) is a leading cause of morbidity amongst rhesus monkeys kept in captivity. Here, we show that exposure of affected animals to the whipworm Trichuris trichiura led to clinical improvement in fecal consistency, accompanied by weight gain, in four out of the five treated monkeys. By flow cytometry analysis of pinch biopsies collected during colonoscopies before and after treatment, we found an induction of a mucosal T(H)2 response following helminth treatment that was associated with a decrease in activated CD4(+) Ki67+ cells. In parallel, expression profiling with oligonucleotide microarrays and real-time PCR analysis revealed reductions in T(H)1-type inflammatory gene expression and increased expression of genes associated with IgE signaling, mast cell activation, eosinophil recruitment, alternative activation of macrophages, and worm expulsion. By quantifying bacterial 16S rRNA in pinch biopsies using real-time PCR analysis, we found reduced bacterial attachment to the intestinal mucosa post-treatment. Finally, deep sequencing of bacterial 16S rRNA revealed changes to the composition of microbial communities attached to the intestinal mucosa following helminth treatment. Thus, the genus Streptophyta of the phylum Cyanobacteria was vastly increased in abundance in three out of five ICD monkeys relative to healthy controls, but was reduced to control levels post-treatment; by contrast, the phylum Tenericutes was expanded post-treatment. These findings suggest that helminth treatment in primates can ameliorate colitis by restoring mucosal barrier functions and reducing overall bacterial attachment, and also by altering the communities of attached bacteria. These results also define ICD in monkeys as a tractable preclinical model for ulcerative colitis in which these effects can be further investigated.
Article
Full-text available
Helminth parasites are highly prevalent in human communities in developing countries. In an endemic area an infected individual may harbour parasitic worms for most of his or her life, and the ability of these infections to survive immunological attack has long been a puzzle. But new techniques are starting to expose the diverse mechanisms by which these agents modulate or evade their hosts' defences, creating a dynamic interaction between the human immune system and the parasite population.
Article
Full-text available
Helminth parasites infect almost one-third of the world's population, primarily in tropical regions. However, regions where helminth parasites are endemic record much lower prevalences of allergies and autoimmune diseases, suggesting that parasites may protect against immunopathological syndromes. Most helminth diseases are spectral in nature, with a large proportion of relatively asymptomatic cases and a subset of patients who develop severe pathologies. The maintenance of the asymptomatic state is now recognized as reflecting an immunoregulatory environment, which may be promoted by parasites, and involves multiple levels of host regulatory cells and cytokines; a breakdown of this regulation is observed in pathological disease. Currently, there is much interest in whether helminth-associated immune regulation may ameliorate allergy and autoimmunity, with investigations in both laboratory models and human trials. Understanding and exploiting the interactions between these parasites and the host regulatory network are therefore likely to highlight new strategies to control both infectious and immunological diseases.
Article
Full-text available
The human skin harbors complex bacterial communities. Prior studies showing high inter-individual variation focused on subjects from developed countries. We therefore compared cutaneous bacterial communities of Amerindians in the Venezuelan Amazon with subjects in the United States. Forearm skin specimens were studied from healthy Amerindians in Platanillal village in Amazonas State, and from healthy persons in New York and Colorado. All skin sampling used similar swab/buffer techniques. Multiplexed V2-targeted 16S rRNA gene pyrosequencing yielded high quality sequences from 112 samples. The results show 20 phyla, with three (Proteobacteria, Firmicutes, Actinobacteria) predominating. US residents and Venezuelan Amerindians had significantly different forearm skin bacterial community compositions, with United States dominated by Propionibacterium. Among the Amerindians, there was a deep split based on bacterial community membership, with 30 and 42 samples, respectively, falling into each of the two groups, not associated with age, gender, or body mass index. One Amerindian group had diversity similar to the United States, but was dominated by Staphylococcus rather than Propionibacterium. The other Amerindian group was significantly more diverse and even than the US or the other Amerindian group, and featured a broad range of Proteobacteria. The results provide evidence that ethnicity, lifestyle and/or geography are associated with the structure of human cutaneous bacterial communities.The ISME Journal advance online publication, 16 August 2012; doi:10.1038/ismej.2012.81.
Article
Full-text available
Gut microbial communities represent one source of human genetic and metabolic diversity. To examine how gut microbiomes differ among human populations, here we characterize bacterial species in fecal samples from 531 individuals, plus the gene content of 110 of them. The cohort encompassed healthy children and adults from the Amazonas of Venezuela, rural Malawi and US metropolitan areas and included mono- and dizygotic twins. Shared features of the functional maturation of the gut microbiome were identified during the first three years of life in all three populations, including age-associated changes in the genes involved in vitamin biosynthesis and metabolism. Pronounced differences in bacterial assemblages and functional gene repertoires were noted between US residents and those in the other two countries. These distinctive features are evident in early infancy as well as adulthood. Our findings underscore the need to consider the microbiome when evaluating human development, nutritional needs, physiological variations and the impact of westernization.
Article
Full-text available
Studies of the human microbiome have revealed that even healthy individuals differ remarkably in the microbes that occupy habitats such as the gut, skin and vagina. Much of this diversity remains unexplained, although diet, environment, host genetics and early microbial exposure have all been implicated. Accordingly, to characterize the ecology of human-associated microbial communities, the Human Microbiome Project has analysed the largest cohort and set of distinct, clinically relevant body habitats so far. We found the diversity and abundance of each habitat's signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals. The project encountered an estimated 81-99% of the genera, enzyme families and community configurations occupied by the healthy Western microbiome. Metagenomic carriage of metabolic pathways was stable among individuals despite variation in community structure, and ethnic/racial background proved to be one of the strongest associations of both pathways and microbes with clinical metadata. These results thus delineate the range of structural and functional configurations normal in the microbial communities of a healthy population, enabling future characterization of the epidemiology, ecology and translational applications of the human microbiome.
Article
Purpose of review: The gut microbiota has become a focus of research for those interested in the brain and behaviour. Here, we profile the gut microbiota in a variety of neuropsychiatric syndromes. Recent findings: Multiple routes of communication between the gut and brain have been established and these include the vagus nerve, immune system, short chain fatty acids and tryptophan. Developmentally, those born by caesarean section have a distinctly different microbiota in early life to those born per vaginum. At the other extreme, individuals who age with considerable ill-heath tend to show narrowing in microbial diversity. Recently, the gut microbiota has been profiled in a variety of conditions including autism, major depression and Parkinson's disease. There is still debate as to whether or not these changes are core to the pathophysiology or merely epiphenomenal. Summary: The current narrative suggests that certain neuropsychiatric disorders might be treated by targeting the microbiota either by microbiota transplantation, antibiotics or psychobiotics.
Article
Recent studies have suggested that there may be a strong link between the gut microbiota, energy extraction and body metabolism. Evidence is accumulating that the intestinal microbiota, in addition to other major factors such as diet and host genetics, contributes to obesity, metabolic dysfunction and diabetes. Both preclinical experimental and human studies have shown that obesity and metabolic dysfunction are characterized by a profound dysbiosis. Several human metagenome-wide association studies have demonstrated highly significant correlations of certain members of intestinal microbiota with obesity and type 2 diabetes. In addition dietary factors that substantially affect microbial composition, microbiota disruption, and the consequence of early-life antibiotic use, may contribute to childhood obesity and metabolic dysfunction. Further evidence for an association between microbiota and metabolic dysfunction has been derived from studies in pregnancy demonstrating that major gut microbial shifts occur during pregnancy thereby affecting host metabolism. In particular, the high rate of obesity following caesarean section could be partially explained by functional alterations in the intestinal microbiota. Obesity and associated metabolic dysfunction emerge from disturbed interactions between the intestinal microbiota, dietary changes and host immune functions. A better understanding of this relationship might lead to better therapies for human metabolic and inflammatory diseases in the future.
Article
Context The Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III) highlights the importance of treating patients with the metabolic syndrome to prevent cardiovascular disease. Limited information is available about the prevalence of the metabolic syndrome in the United States, however.Objective To estimate the prevalence of the metabolic syndrome in the United States as defined by the ATP III report.Design, Setting, and Participants Analysis of data on 8814 men and women aged 20 years or older from the Third National Health and Nutrition Examination Survey (1988-1994), a cross-sectional health survey of a nationally representative sample of the noninstitutionalized civilian US population.Main Outcome Measures Prevalence of the metabolic syndrome as defined by ATP III (≥3 of the following abnormalities): waist circumference greater than 102 cm in men and 88 cm in women; serum triglycerides level of at least 150 mg/dL (1.69 mmol/L); high-density lipoprotein cholesterol level of less than 40 mg/dL (1.04 mmol/L) in men and 50 mg/dL (1.29 mmol/L) in women; blood pressure of at least 130/85 mm Hg; or serum glucose level of at least 110 mg/dL (6.1 mmol/L).Results The unadjusted and age-adjusted prevalences of the metabolic syndrome were 21.8% and 23.7%, respectively. The prevalence increased from 6.7% among participants aged 20 through 29 years to 43.5% and 42.0% for participants aged 60 through 69 years and aged at least 70 years, respectively. Mexican Americans had the highest age-adjusted prevalence of the metabolic syndrome (31.9%). The age-adjusted prevalence was similar for men (24.0%) and women (23.4%). However, among African Americans, women had about a 57% higher prevalence than men did and among Mexican Americans, women had about a 26% higher prevalence than men did. Using 2000 census data, about 47 million US residents have the metabolic syndrome.Conclusions These results from a representative sample of US adults show that the metabolic syndrome is highly prevalent. The large numbers of US residents with the metabolic syndrome may have important implications for the health care sector.
Article
Inflammatory bowel disease (IBD), especially Crohn's disease (CD), probably results from failure to downregulate a chronic Th1 intestinal inflammatory process. Induction of a Th2 immune response by intestinal helminths diminishes Th1 responsiveness. This study evaluates the safety and effectiveness of helminthic ova in the treatment of active IBD.Methods We studied four patients with active CD and three with ulcerative colitis (UC). In an initial treatment and observation period, a single dose of 2500 live Trichuris suis eggs was given orally, and patients were followed every 2 wk for 12 wk. Baseline medications were continued at the same dose throughout the study. Safety was monitored by following the patients' clinical status and laboratory studies at regular intervals. Patients also were monitored regularly using the Crohn's Disease Activity Index, Simple Clinical Colitis Activity Index (SCCAI), and the Inflammatory Bowel Disease Quality of Life Index (IBDQ). To assess safety and efficacy with repetitive doses, two patients with CD and two with UC were given 2500 ova at 3-wk intervals as maintenance treatment using the same evaluation parameters.ResultsDuring the treatment and observation period, all patients improved clinically without any adverse clinical events or laboratory abnormalities. Three of the four patients with CD entered remission according to the Crohn's Disease Activity Index; the fourth patient experienced a clinical response (reduction of 151) but did not achieve remission. Patients with UC experienced a reduction of the Clinical Colitis Activity Index to 57% of baseline. According to the IBD Quality of Life Index, six of seven patients (86%) achieved remission. The benefit derived from the initial dose was temporary. In the maintenance period, multiple doses again caused no adverse effects and sustained clinical improvement in all patients treated every 3 wk for >28 wk.Conclusions This open trial demonstrates that it is safe to administer eggs from the porcine whipworm, Trichuris suis, to patients with CD and UC. It also demonstrates improvement in the common clinical indices used to describe disease activity. The benefit was temporary in some patients with a single dose, but it could be prolonged with maintenance therapy every 3 wk. The study suggests that it is possible to downregulate aberrant intestinal inflammation in humans with helminths.