BackgroundAsthma is the most prevalent chronic disease of childhood. Recently, we identified a critical window early in the life of both mice and Canadian infants during which gut microbial changes (dysbiosis) affect asthma development. Given geographic differences in human gut microbiota worldwide, we studied the effects of gut microbial dysbiosis on atopic wheeze in a population living in a distinct developing world environment.ObjectiveWe sought to determine whether microbial alterations in early infancy are associated with the development of atopic wheeze in a nonindustrialized setting.MethodsWe conducted a case-control study nested within a birth cohort from rural Ecuador in which we identified 27 children with atopic wheeze and 70 healthy control subjects at 5 years of age. We analyzed bacterial and eukaryotic gut microbiota in stool samples collected at 3 months of age using 16S and 18S sequencing. Bacterial metagenomes were predicted from 16S rRNA data by using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States and categorized by function with Kyoto Encyclopedia of Genes and Genomes ontology. Concentrations of fecal short-chain fatty acids were determined by using gas chromatography.ResultsAs previously observed in Canadian infants, microbial dysbiosis at 3 months of age was associated with later development of atopic wheeze. However, the dysbiosis in Ecuadorian babies involved different bacterial taxa, was more pronounced, and also involved several fungal taxa. Predicted metagenomic analysis emphasized significant dysbiosis-associated differences in genes involved in carbohydrate and taurine metabolism. Levels of the fecal short-chain fatty acids acetate and caproate were reduced and increased, respectively, in the 3-month stool samples of children who went on to have atopic wheeze.ConclusionsOur findings support the importance of fungal and bacterial microbiota during the first 100 days of life on the development of atopic wheeze and provide additional support for considering modulation of the gut microbiome as a primary asthma prevention strategy.
BackgroundThe 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.Materials and MethodsSchool 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.ResultsMicrobiota 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.DiscussionOur 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.
Whipworms are common soil-transmitted helminths that cause debilitating chronic infections in man. These nematodes are only distantly related to Caenorhabditis elegans and have evolved to occupy an unusual niche, tunneling through epithelial cells of the large intestine. Here we present the genome sequences of the human-infective Trichuris trichiura and the murine laboratory model T. muris. Based on whole transcriptome analyses we identify many genes that are expressed in a gender- or life stage-specific manner and characterise the transcriptional landscape of a morphological region with unique biological adaptations, namely bacillary band and stichosome, found only in whipworms and related parasites. Using RNAseq data from whipworm-infected mice we describe the regulated Th1-like immune response of the chronically infected cecum in unprecedented detail. In silico screening identifies numerous potential new drug targets against trichuriasis. Together, these genomes and associated functional data elucidate key aspects of the molecular host-parasite interactions that define chronic whipworm infection.
Asthma has emerged as an important public health problem in many Latin American countries over the past decade. In Brazil and Costa Rica, the prevalence of asthma and associated morbidity is as great or greater as reported in traditional high prevalence countries such as the US, but remains neglected as a public health priority. Asthma in Latin America is associated particularly with underprivileged populations living in cities but remains relatively rare in many rural populations. The causes of asthma in Latin America are likely to be associated with urbanization, migration, and the adoption of a modern ‘Westernized’ lifestyle and environmental changes that follow these processes that include changes in diet, physical activity, hygiene, and exposures to allergens, irritants, and outdoor and indoor pollutants. Because of the enormous social, genetic, and environmental contrasts within and between Latin American countries, and the large differences in prevalence associated with these differences, the investigation of asthma in Latin America provides important research opportunities to identify the social and biological mechanisms that underlie asthma development. Asthma in Latin America poses enormous challenges for health policy makers, health services, and researchers to respond to and alleviate the growing burden of asthma disability, particularly among marginalized urban populations.
ISAAC questionnaire-derived symptom prevalences are sufficiently precise for comparisons between populations. Where diagnostic precision at the individual level is important, questionnaires should be validated and potentially modified in those populations beforehand, or a standardized skin examination protocol should be used.
Summary Ruminococcus bromii is a dominant member of the human colonic microbiota that plays a ‘keystone’ role in degrading dietary resistant starch. Recent evidence from one strain has uncovered a unique cell surface ‘amylosome’ complex that organizes starch‐degrading enzymes. New genome analysis presented here reveals further features of this complex and shows remarkable conservation of amylosome components between human colonic strains from three different continents and a R. bromii strain from the rumen of Australian cattle. These R. bromii strains encode a narrow spectrum of carbohydrate active enzymes (CAZymes) that reflect extreme specialization in starch utilization. Starch hydrolysis products are taken up mainly as oligosaccharides, with only one strain able to grow on glucose. The human strains, but not the rumen strain, also possess transporters that allow growth on galactose and fructose. R. bromii strains possess a full complement of sporulation and spore germination genes and we demonstrate the ability to form spores that survive exposure to air. Spore formation is likely to be a critical factor in the ecology of this nutritionally highly specialized bacterium, which was previously regarded as ‘non‐sporing’, helping to explain its widespread occurrence in the gut microbiota through the ability to transmit between hosts.
This review provides an update on asthma in Hispanics, a diverse group tracing their ancestry to countries previously under Spanish rule. A marked variability in the prevalence and morbidity from asthma remains among Hispanic subgroups in the United States and Hispanic America. In the United States, Puerto Ricans and Mexican Americans have high and low burdens of asthma, respectively (the "Hispanic Paradox"). This wide divergence in asthma morbidity among Hispanic subgroups is multifactorial, likely reflecting the effects of known (secondhand tobacco smoke, air pollution, psychosocial stress, obesity, inadequate treatment) and potential (genetic variants, urbanization, vitamin D insufficiency, and eradication of parasitic infections) risk factors. Barriers to adequate asthma management in Hispanics include economic and educational disadvantages, lack of health insurance, and no access to or poor adherence with controller medications such as inhaled corticosteroids. Although considerable progress has been made in our understanding of asthma in Hispanic subgroups, many questions remain. Studies of asthma in Hispanic America should focus on environmental or lifestyle factors that are more relevant to asthma in this region (e.g., urbanization, air pollution, parasitism, and stress). In the United States, research studies should focus on risk factors that are known to or may diverge among Hispanic subgroups, including but not limited to epigenetic variation, prematurity, vitamin D level, diet, and stress. Clinical trials of culturally appropriate interventions that address multiple aspects of asthma management in Hispanic subgroups should be prioritized for funding. Ensuring high-quality healthcare for all remains a pillar of eliminating asthma disparities.
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