Variation In Microbiome Composition Research Articles

CLOUD: a non-parametric detection test for microbiome outliers

BackgroundDysbiosis of the human gut microbiome is defined as a maladaptive or clinically relevant deviation of the community profile from the healthy or normal state. Dysbiosis has been implicated in an extensive set of metabolic, auto-immune, and infectious diseases, and yet there is substantial inter-individual variation in microbiome composition even within body sites of healthy humans. An individual’s microbiome varies over time in a high-dimensional space to form their personal microbiome cloud. This cloud may or may not be similar to that of other people, both in terms of the average microbiome profile (conformity) and the diameter of the cloud (stability). However, there is currently no robust non-parametric test that determines whether a patient’s microbiome cloud is an outlier with respect to a reference group of healthy individuals with widely varying microbiome profiles.MethodsHere, we propose a test for outliers’ detection in the human gut microbiome that accounts for the wide range of microbiome phenotypes observed in a typical set of healthy individuals and for intra-individual temporal variation. Our robust nonparametric outlier detection test, the CLOUD test, performs two assessments of a patient’s microbiome health: conformity, the extent to which the patient’s microbiome cloud is ecologically similar to a subset of healthy subjects; and stability, which compares the cloud diameter of a patient to those of healthy subjects. The CLOUD test is based on locally linear embedded ecological distances, allowing it to account for widely varying microbiome compositions among reference individuals. It also leverages temporal variability within patients and reference individuals to increase the robustness of the test.ResultsWe describe the CLOUD test, and we apply it to one novel and two previously published cohorts of patients receiving fecal microbiota transplantation for recurrent Clostridium difficile colitis, as well as to two known healthy cohorts, demonstrating high concordance of the CLOUD conformity and stability indices with clinical outcomes.ConclusionsAlthough the CLOUD test is not, on its own, a test for clinical dysbiosis, it nonetheless provides a framework for outlier testing that could be incorporated into evaluation of suspected dysbiosis, which may play a role in diagnosis and prognosis of numerous pediatric and adult diseases.

Individual variation of natural D.melanogaster-associated bacterial communities.

Drosophila melanogaster has become an important model organism to study host-microbe interaction in the laboratory. However, the natural microbial communities that are associated with D. melanogaster have received less attention. Especially, information on inter-individual variation is still lacking, because most studies so far have used pooled material from several flies. Here, we collected bacterial 16S rRNA gene community profiles from a set of 32 individuals from a single population. We simulated pools from the individual data (i) to assess how well the microbiome of a host population is represented by pools, and (ii) to compare variation of Drosophila microbiomes within and between populations. Taxon richness was increased in simulated pools, suggesting that pools paint a more comprehensive picture of the taxa associated with a host population. Furthermore, microbiome composition varied less between pools than between individuals, indicating that differences even out in pools. Variation in microbiome composition was larger between populations than between simulated pools from a single population, adding to the notion that there are population-specific effects on the Drosophila microbiome. Surprisingly, samples from individuals clustered into two groups, suggesting that there are yet unknown factors that affect the composition of natural fly-associated microbial communities and need further research.

ABO antigen and secretor statuses are not associated with gut microbiota composition in 1,500 twins.

BackgroundHost genetics is one of several factors known to shape human gut microbiome composition, however, the physiological processes underlying the heritability are largely unknown. Inter-individual differences in host factors secreted into the gut lumen may lead to variation in microbiome composition. One such factor is the ABO antigen. This molecule is not only expressed on the surface of red blood cells, but is also secreted from mucosal surfaces in individuals containing an intact FUT2 gene (secretors). Previous studies report differences in microbiome composition across ABO and secretor genotypes. However, due to methodological limitations, the specific bacterial taxa involved remain unknown.ResultsHere, we sought to determine the relationship of the microbiota to ABO blood group and secretor status in a large panel of 1503 individuals from a cohort of twins from the United Kingdom. Contrary to previous reports, robust associations between either ABO or secretor phenotypes and gut microbiome composition were not detected. Overall community structure, diversity, and the relative abundances of individual taxa were not significantly associated with ABO or secretor status. Additionally, joint-modeling approaches were unsuccessful in identifying combinations of taxa that were predictive of ABO or secretor status.ConclusionsDespite previous reports, the taxonomic composition of the microbiota does not appear to be strongly associated with ABO or secretor status in 1503 individuals from the United Kingdom. These results highlight the importance of replicating microbiome-associated traits in large, well-powered cohorts to ensure results are robust.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3290-1) contains supplementary material, which is available to authorized users.

Comparative Assessment of Mediterranean Gorgonian-Associated Microbial Communities Reveals Conserved Core and Locally Variant Bacteria

Gorgonians are key habitat-forming species of Mediterranean benthic communities, but their populations have suffered from mass mortality events linked to high summer seawater temperatures and microbial disease. However, our knowledge on the diversity, dynamics and function of gorgonian-associated microbial communities is limited. Here, we analysed the spatial variability of the microbiomes of five sympatric gorgonian species (Eunicella singularis, Eunicella cavolini, Eunicella verrucosa, Leptogorgia sarmentosa and Paramuricea clavata), collected from the Mediterranean Sea over a scale of ∼1100km, using next-generation amplicon sequencing of the 16S rRNA gene. The microbiomes of all gorgonian species were generally dominated by members of the genus Endozoicomonas, which were at very low abundance in the surrounding seawater. Although the composition of the core microbiome (operational taxonomic units consistently present in a species) was found to be unique for each host species, significant overlap was observed. These spatially consistent associations between gorgonians and their core bacteria suggest intricate symbiotic relationships and regulation of the microbiome composition by the host. At the same time, local variations in microbiome composition were observed. Functional predictive profiling indicated that these differences could be attributed to seawater pollution. Taken together, our data indicate that gorgonian-associated microbiomes are composed of spatially conserved bacteria (core microbiome members) and locally variant members, and that local pollution may influence these local associations, potentially impacting gorgonian health.

Variation in Microbiome Composition and Stability for a Vancomycin Treated Primary Sclerosing Cholangitis Patient with Ulcerative Colitis Compared with Controls

The bacterial composition of the human intestines contributes to much more than just digestion. In the inflammatory, autoimmune conditions primary sclerosing cholangitis (PSC) and ulcerative colitis (UC), the microbiome may be, in some cases, a factor. To gain a better understanding of the composition and stability of the microbiome in a patient treated with vancomycin for PSC, terminal restriction fragment (TRF) analysis was performed on 13 controls and 1 patient, and 16s rRNA microbiome composition analysis was performed on 1 patient and 3 controls. Results showed similar levels of stability, with surprising differences in composition.

Escherichia coli O157:H7 super-shedder and non-shedder feedlot steers harbour distinct fecal bacterial communities.

Escherichia coli O157:H7 is a major foodborne human pathogen causing disease worldwide. Cattle are a major reservoir for this pathogen and those that shed E. coli O157:H7 at >104 CFU/g feces have been termed “super-shedders”. A rich microbial community inhabits the mammalian intestinal tract, but it is not known if the structure of this community differs between super-shedder cattle and their non-shedding pen mates. We hypothesized that the super-shedder state is a result of an intestinal dysbiosis of the microbial community and that a “normal” microbiota prevents E. coli O157:H7 from reaching super-shedding levels. To address this question, we applied 454 pyrosequencing of bacterial 16S rRNA genes to characterize fecal bacterial communities from 11 super-shedders and 11 contemporary pen mates negative for E. coli O157:H7. The dataset was analyzed by using five independent clustering methods to minimize potential biases and to increase confidence in the results. Our analyses collectively indicated significant variations in microbiome composition between super-shedding and non-shedding cattle. Super-shedders exhibited higher bacterial richness and diversity than non-shedders. Furthermore, seventy-two operational taxonomic units, mostly belonging to Firmicutes and Bacteroidetes phyla, were identified showing differential abundance between these two groups of cattle. The operational taxonomic unit affiliation provides new insight into bacterial populations that are present in feces arising from super-shedders of E. coli O157:H7.

Mechanistic links between gut microbial community dynamics, microbial functions and metabolic health.

Gut microbes comprise a high density, biologically active community that lies at the interface of an animal with its nutritional environment. Consequently their activity profoundly influences many aspects of the physiology and metabolism of the host animal. A range of microbial structural components and metabolites directly interact with host intestinal cells and tissues to influence nutrient uptake and epithelial health. Endocrine, neuronal and lymphoid cells in the gut also integrate signals from these microbial factors to influence systemic responses. Dysregulation of these host-microbe interactions is now recognised as a major risk factor in the development of metabolic dysfunction. This is a two-way process and understanding the factors that tip host-microbiome homeostasis over to dysbiosis requires greater appreciation of the host feedbacks that contribute to regulation of microbial community composition. To date, numerous studies have employed taxonomic profiling approaches to explore the links between microbial composition and host outcomes (especially obesity and its comorbidities), but inconsistent host-microbe associations have been reported. Available data indicates multiple factors have contributed to discrepancies between studies. These include the high level of functional redundancy in host-microbiome interactions combined with individual variation in microbiome composition; differences in study design, diet composition and host system between studies; and inherent limitations to the resolution of rRNA-based community profiling. Accounting for these factors allows for recognition of the common microbial and host factors driving community composition and development of dysbiosis on high fat diets. New therapeutic intervention options are now emerging.