Bacteroides vulgatus SNUG 40005 Restores Akkermansia Depletion by Metabolite Modulation.

BACKGROUND & AIMS: Weight loss and exercise intervention have been reported to increase the interaction between Bacteroides spp and Akkermansiamuciniphila (Am), although the underlying mechanisms and consequences of the interaction remain unknown. METHODS: Using a healthy Korean twin cohort (n = 582), we analyzed taxonomic associations with host body mass index. B vulgatus strains were isolated from mice and human subjects to investigate the strain-specific effect of B vulgatus SNUG 40005 (Bvul) on obesity. The mechanisms underlying Am enrichment by Bvul administration were investigated by multiple experiments: (1) in vitro cross-feeding experiments, (2) construction of Bvul mutants with the N-acetylglucosaminidase gene knocked out, and (3) in vivo validation cohorts with different metabolites. Finally, metabolite profiling in mouse and human fecal samples was performed. RESULTS: An interaction between Bvul and Am was observed in lean subjects but was disrupted in obese subjects. The administration of Bvul to mice fed a high-fat diet decreased body weight, insulin resistance, and gut permeability. In particular, Bvul restored the abundance of Am, which decreased significantly after a long-term high-fat diet. A cross-feeding analysis of Am with cecal contents or Bvul revealed that Am enrichment was attributed to metabolites produced during mucus degradation by Bvul. The metabolome profile of mouse fecal samples identified N-acetylglucosamine as contributing to Am enrichment, which was confirmed by in vitro and in vivo experiments. Metabolite network analysis of the twin cohort found that lysine serves as a bridge between N-acetylglucosamine, Bvul, and Am. CONCLUSIONS: Strain-specific microbe-microbe interactions modulate the mucosal environment via metabolites produced during mucin degradation in the gut.

Clinical, gut microbial and neural effects of a probiotic add-on therapy in depressed patients: a randomized controlled trial.

A promising new treatment approach for major depressive disorder (MDD) targets the microbiota-gut-brain (MGB) axis, which is linked to physiological and behavioral functions affected in MDD. This is the first randomized controlled trial to determine whether short-term, high-dose probiotic supplementation reduces depressive symptoms along with gut microbial and neural changes in depressed patients. Patients with current depressive episodes took either a multi-strain probiotic supplement or placebo over 31 days additionally to treatment-as-usual. Assessments took place before, immediately after and again four weeks after the intervention. The Hamilton Depression Rating Sale (HAM-D) was assessed as primary outcome. Quantitative microbiome profiling and neuroimaging was used to detect changes along the MGB axis. In the sample that completed the intervention (probiotics N = 21, placebo N = 26), HAM-D scores decreased over time and interactions between time and group indicated a stronger decrease in the probiotics relative to the placebo group. Probiotics maintained microbial diversity and increased the abundance of the genus Lactobacillus, indicating the effectivity of the probiotics to increase specific taxa. The increase of the Lactobacillus was associated with decreased depressive symptoms in the probiotics group. Finally, putamen activation in response to neutral faces was significantly decreased after the probiotic intervention. Our data imply that an add-on probiotic treatment ameliorates depressive symptoms (HAM-D) along with changes in the gut microbiota and brain, which highlights the role of the MGB axis in MDD and emphasizes the potential of microbiota-related treatment approaches as accessible, pragmatic, and non-stigmatizing therapies in MDD. Trial Registration: www.clinicaltrials.gov , identifier: NCT02957591.

Fecal Microbiota Transplantation (FMT) as an Adjunctive Therapy for Depression-Case Report.

Depression is a debilitating disorder, and at least one third of patients do not respond to therapy. Associations between gut microbiota and depression have been observed in recent years, opening novel treatment avenues. Here, we present the first two patients with major depressive disorder ever treated with fecal microbiota transplantation as add-on therapy. Both improved their depressive symptoms 4 weeks after the transplantation. Effects lasted up to 8 weeks in one patient. Gastrointestinal symptoms, constipation in particular, were reflected in microbiome changes and improved in one patient. This report suggests further FMT studies in depression could be worth pursuing and adds to awareness as well as safety assurance, both crucial in determining the potential of FMT in depression treatment.

Long-term life history predicts current gut microbiome in a population-based cohort study.

Extensive scientific and clinical microbiome studies have explored contemporary variation and dynamics of the gut microbiome in human health and disease1-3, yet the role of long-term life history effects has been underinvestigated. Here, we analyzed the current, quantitative microbiome composition in the older adult Bruneck Study cohort (Italians, Bruneck, n = 304 (male, 154; female, 150); age 65-98 years) with extensive clinical, demographic, lifestyle and nutritional data collected over the past 26 years4. Multivariate analysis of historical variables indicated that medication history, historical physical activity, past dietary habits and specific past laboratory blood parameters explain a significant fraction of current quantitative microbiome variation in older adults, enlarging the explanatory power of contemporary covariates by 33.4%. Prediction of current enterotype by a combination of past and contemporary host variables revealed good levels of predictability (area under the curve (AUC), 0.78-0.83), with Prevotella and dysbiotic Bacteroides 2 being the best predicted enterotypes. These findings demonstrate long-term life history effects on the microbiota and provide insights into lifestyle variables and their role in maintaining a healthy gut microbiota in later life.

Interactions between soil compositions and the wheat root microbiome under drought stress: From an in silico to in planta perspective.

As wheat (Triticum aestivum) is an important staple food across the world, preservation of stable yields and increased productivity are major objectives in breeding programs. Drought is a global concern because its adverse impact is expected to be amplified in the future due to the current climate change. Here, we analyzed the effects of edaphic, environmental, and host factors on the wheat root microbiomes collected in soils from six regions in Belgium. Amplicon sequencing analysis of unplanted soil and wheat root endosphere samples indicated that the microbial community variations can be significantly explained by soil pH, microbial biomass, wheat genotype, and soil sodium and iron levels. Under drought stress, the biodiversity in the soil decreased significantly, but increased in the root endosphere community, where specific soil parameters seemingly determine the enrichment of bacterial groups. Indeed, we identified a cluster of drought-enriched bacteria that significantly correlated with soil compositions. Interestingly, integration of a functional analysis further revealed a strong correlation between the same cluster of bacteria and ß-glucosidase and osmoprotectant proteins, two functions known to be involved in coping with drought stress. By means of this in silico analysis, we identified amplicon sequence variants (ASVs) that could potentially protect the plant from drought stress and validated them in planta. Yet, ASVs based on 16S rRNA sequencing data did not completely distinguish individual isolates because of their intrinsic short sequences. Our findings support the efforts to maintain stable crop yields under drought conditions through implementation of root microbiome analyses.

Wheat bran with reduced particle size increases serum SCFAs in obese subjects without improving health parameters compared with a maltodextrin placebo.

BACKGROUND: Wheat bran (WB) has been associated with improved gastrointestinal health and a reduced risk of metabolic disorders. Reducing the particle size of WB might increase its fermentability and facilitate cross-feeding between the gut bacteria and in this way produce health effects. OBJECTIVES: We investigated the impact of WB with reduced particle size (WB RPS) on colonic fermentation and host health in normal-weight (NW) and obese (OB) participants compared with placebo (PL). METHODS: During 1 mo, 36 NW and 14 OB participants daily consumed 20 g WB RPS or PL (maltodextrin). Before and after the intervention, fasting serum and fecal SCFAs, fecal metabolite profiles, and microbiota composition were measured as fermentation parameters. Fecal output, fecal dry weight (%), fat excretion, transit, stool consistency, intestinal permeability, and serum total cholesterol, triglyceride, and C-reactive protein concentrations were measured as health parameters. The impact of WB RPS on the fermentation of other carbohydrates was assessed by quantifying postprandial cumulative serum 13C-SCFA after a challenge with 13C-inulin. RESULTS: WB RPS increased fasting serum acetate (P < 0.05) and total SCFA (P < 0.05) concentrations in OB participants. Fasting serum propionate concentrations were lower in OB than in NW participants at baseline (NW: 1.57 ± 0.75 µmol/L; OB: 0.89 ± 0.52 µmol/L; P < 0.01), but not after WB RPS (NW: 1.75 ± 0.77 µmol/L; OB: 1.35 ± 0.63 µmol/L; P = not significant). WB RPS did not enhance colonic fermentation of 13C-inulin and did not affect microbiota composition. Health parameters were not affected by the WB RPS intervention, either in NW or in OB participants. CONCLUSIONS: WB RPS increased fasting serum SCFA concentrations in OB participants. These changes were not associated with beneficial effects on host health.

Fecal Microbiota Transplantation Reduces Symptoms in Some Patients With Irritable Bowel Syndrome With Predominant Abdominal Bloating: Short- and Long-term Results From a Placebo-Controlled Randomized Trial.

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder associated with intestinal dysbiosis. Given the reported promising results of open-label fecal microbiota transplantation (FMT) therapy in patients with predominant abdominal bloating, we studied efficacy of this treatment in a randomized, placebo-controlled trial. METHODS: Patients with refractory IBS, defined as failure of ≥3 conventional therapies, were randomly assigned to single-dose nasojejunal administration of donor stools (n = 43) or autologous stools (n = 19) in a double-blind study, performed from December 2015 through October 2017, and were followed up for 1 year. IBS-related symptoms were assessed by using a daily symptom diary to determine general abdominal discomfort, abdominal bloating, abdominal pain, and flatulence on a scale of 1-6. Number of daily bowel movements, consistency of the stools, and abdominal circumference were also recorded. Patients completed the IBS-specific quality of life questionnaire. Primary endpoints were improvement of IBS symptoms and bloating at 12 weeks (response). Secondary endpoints were changes in IBS symptom scores and quality of life. Stool samples were collected for microbiota amplicon sequencing. Open-label retransplantation was offered after the trial. RESULTS: At week 12, 56% of patients given donor stool reported improvement in both primary endpoints compared with 26% of patients given placebo (P = .03). Patients given donor stool had significant improvements in level of discomfort (mean reduction, 19%; median score before FMT, 3.98; range, 2.13-6.00; median score after FMT, 3.1; range, 951.29-5.90), stool frequency (mean reduction, 13%; median score before FMT, 2.10; range, 0.57-14.29; median score after FMT 1.7; range, 0.71-4.29), urgency (mean reduction, 38%; median score before FMT, 0.61; range, 0.00-1.00; median score after FMT, 0.37; range, 0.00-1.00), abdominal pain (mean reduction, 26%; median score before FMT, 3.88; range, 1.57-5.17; median score after FMT, 2.80; range, 1.14-4.94), flatulence (mean reduction, 10%; median score before FMT, 3.42; range, 0.71-6.00; median score after FMT, 3.07; range, 0.79-4.23), and quality of life (mean increase, 16%; median score before FMT 32.6; range, 11-119; median score after FMT, 43.1; range, 32.25-99). A significantly higher proportion of women given donor stool (69%) had a response than men (29%) (P = .01). Fecal samples from responders had higher diversity of microbiomes before administration of donor material than fecal samples from nonresponders (P = .04) and distinct baseline composition (P = .04), but no specific marker taxa were associated with response. After single FMT, 21% of patients given donor stool reported effects that lasted for longer than 1 year compared with 5% of patients given placebo stool. A second FMT reduced symptoms in 67% of patients with an initial response to donor stool but not in patients with a prior nonresponse. CONCLUSIONS: In a randomized trial of patients with treatment-refractory IBS with predominant bloating, FMT relieved symptoms compared with placebo (autologous transplant), although the effects decreased over 1 year. A second FMT restored the response patients with a prior response. Response was associated with composition of the fecal microbiomes before FMT; this might be used to as a biomarker to select patients for this treatment. ClinicalTrials.gov, Number: NCT02299973.

Design of synthetic microbial consortia for gut microbiota modulation.

The use of and interest in probiotics to modulate the human intestinal microbiota have strongly increased in recent years. However, most of the current probiotic products have been limited to single-strain formulations of easily culturable food-grade microorganisms and often resulted in mixed results or limited effects on host health. Therefore, a revision of current probiotic strategies by using synthetic human-derived microbial multispecies consortia is necessary. In light of this ongoing evolution of the field, novel approaches are needed to design and assemble bacterial cocktails targeted to restore dysbiotic states in microbiota-associated diseases. This review discusses the steps in the process for identifying effective targets, predicting putative multistrain communities, assembling ecosystems in silico and in vitro and monitoring stability and outputs before in vivo trials.

Oxidative stress in the oral cavity is driven by individual-specific bacterial communities.

The term "bacterial dysbiosis" is being used quite extensively in metagenomic studies, however, the identification of harmful bacteria often fails due to large overlap between the bacterial species found in healthy volunteers and patients. We hypothesized that the pathogenic oral bacteria are individual-specific and they correlate with oxidative stress markers in saliva which reflect the inflammatory processes in the oral cavity. Temporally direct and lagged correlations between the markers and bacterial taxa were computed individually for 26 volunteers who provided saliva samples during one month (21.2 ± 2.7 samples/volunteer, 551 samples in total). The volunteers' microbiomes differed significantly by their composition and also by their degree of microbiome temporal variability and oxidative stress markers fluctuation. The results showed that each of the marker-taxa pairs can have negative correlations in some volunteers while positive in others. Streptococcus mutans, which used to be associated with caries before the metagenomics era, had the most prominent correlations with the oxidative stress markers, however, these correlations were not confirmed in all volunteers. The importance of longitudinal samples collections in correlation studies was underlined by simulation of single sample collections in 1000 different combinations which produced contradictory results. In conclusion, the distinct intra-individual correlation patterns suggest that different bacterial consortia might be involved in the oxidative stress induction in each human subject. In the future, decreasing cost of DNA sequencing will allow to analyze multiple samples from each patient, which might help to explore potential diagnostic applications and understand pathogenesis of microbiome-associated oral diseases.

Interplay between gut microbiota metabolism and inflammation in HIV infection.

HIV infection causes a disruption of gut-associated lymphoid tissue, driving a shift in the composition of gut microbiota. A deeper understanding of the metabolic changes and how they affect the interplay with the host is needed. Here, we assessed functional modifications of HIV-associated microbiota by combining metagenomic and metatranscriptomic analyses. The transcriptionally active microbiota was well-adapted to the inflamed environment, overexpressing pathways related to resistance to oxidative stress. Furthermore, gut inflammation was maintained by the Gram-negative nature of the HIV-associated microbiota and underexpression of anti-inflammatory processes, such as short chain fatty acid biosynthesis or indole production. We performed co-occurrence and metabolic network analyses that showed relevance in the microbiota structure of both taxonomic and metabolic HIV-associated biomarkers. The Bayesian network revealed the most determinant pathways for maintaining the structure stability of the bacterial community. In addition, we identified the taxa's contribution to metabolic activities and their interactions with host health.

Effects of HIV, antiretroviral therapy and prebiotics on the active fraction of the gut microbiota.

OBJECTIVE: In a recent blinded randomized study, we found that in HIV-infected individuals a short supplementation with prebiotics (scGOS/lcFOS/glutamine) ameliorates dysbiosis of total gut bacteria, particularly among viremic untreated patients. Our study goal was to determine the fraction of the microbiota that becomes active during the intervention and that could provide additional functional information. DESIGN: A total of six healthy individuals, and 16 HIV-infected patients comprising viremic untreated patients (n = 5) and antiretroviral therapy-treated patients that are further divided into immunological responders (n = 7) and immunological nonresponders (n = 4) completed the 6-week course of prebiotic treatment, including six patients receiving a placebo. METHODS: Alpha and beta diversity of potentially active and total gut microbiota was evaluated using shotgun proteomics and 16S rRNA gene sequencing. RESULTS: HIV infection decreased dormancy and increased alpha diversity of active bacteria in comparison with the healthy controls, whose richness was not further influenced by the prebiotic intervention. The effect of the prebiotics was most evident at the beta-diversity of active bacteria, particularly within viremic untreated patients. We found that the prebiotics did not only ameliorate dysbiosis of total bacteria in viremic untreated patients but also increased the abundance of active bacteria with strong immunomodulatory properties and amino acids metabolism, namely Bifidobacteriaceae, at similar levels to those in healthy individuals. This effect was attenuated in ART-treated individuals. CONCLUSION: The effect of prebiotics was greater among ART-naive HIV-infected individuals than in ART-treated patients and healthy controls. This highlights the importance of therapies aimed at manipulating the microbiome in this group of patients.

Gut Bacteria Metabolism Impacts Immune Recovery in HIV-infected Individuals.

While changes in gut microbial populations have been described in human immuno-deficiency virus (HIV)-infected patients undergoing antiretroviral therapy (ART), the mechanisms underlying the contributions of gut bacteria and their molecular agents (metabolites and proteins) to immune recovery remain unexplored. To study this, we examined the active fraction of the gut microbiome, through examining protein synthesis and accumulation of metabolites inside gut bacteria and in the bloodstream, in 8 healthy controls and 29 HIV-infected individuals (6 being longitudinally studied). We found that HIV infection is associated to dramatic changes in the active set of gut bacteria simultaneously altering the metabolic outcomes. Effects were accentuated among immunological ART responders, regardless diet, subject characteristics, clinical variables other than immune recovery, the duration and type of ART and sexual preferences. The effect was found at quantitative levels of several molecular agents and active bacteria which were herein identified and whose abundance correlated with HIV immune pathogenesis markers. Although, we cannot rule out the possibility that some changes are partially a random consequence of the disease status, our data suggest that most likely reduced inflammation and immune recovery is a joint solution orchestrated by both the active fraction of the gut microbiota and the host.

Active and Secretory IgA-Coated Bacterial Fractions Elucidate Dysbiosis in Clostridium difficile Infection.

The onset of Clostridium difficile infection (CDI) has been associated with treatment with wide-spectrum antibiotics. Antibiotic treatment alters the activity of gut commensals and may result in modified patterns of immune responses to pathogens. To study these mechanisms during CDI, we separated bacteria with high cellular RNA content (the active bacteria) and their inactive counterparts by fluorescence-activated cell sorting (FACS) of the fecal bacterial suspension. The gut dysbiosis due to the antibiotic treatment may result in modification of immune recognition of intestinal bacteria. The immune recognition patterns were assessed by FACS of bacterial fractions either coated or not with intestinal secretory immunoglobulin A (SIgA). We described the taxonomic distributions of these four bacterial fractions (active versus inactive and SIgA coated versus non-SIgA coated) by massive 16S rRNA gene amplicon sequencing and quantified the proportion of C. difficile toxin genes in the samples. The overall gut microbiome composition was more robustly influenced by antibiotics than by the C. difficile toxins. Bayesian networks revealed that the C. difficile cluster was preferentially SIgA coated during CDI. In contrast, in the CDI-negative group Fusobacterium was the characteristic genus of the SIgA-opsonized fraction. Lactobacillales and Clostridium cluster IV were mostly inactive in CDI-positive patients. In conclusion, although the proportion of C. difficile in the gut is very low, it is able to initiate infection during the gut dysbiosis caused by environmental stress (antibiotic treatment) as a consequence of decreased activity of the protective bacteria. IMPORTANCE C. difficile is a major enteric pathogen with worldwide distribution. Its expansion is associated with broad-spectrum antibiotics which disturb the normal gut microbiome. In this study, the DNA sequencing of highly active bacteria and bacteria opsonized by intestinal secretory immunoglobulin A (SIgA) separated from the whole bacterial community by FACS elucidated how the gut dysbiosis promotes C. difficile infection (CDI). Bacterial groups with inhibitory effects on C. difficile growth, such as Lactobacillales, were mostly inactive in the CDI patients. C. difficile was typical for the bacterial fraction opsonized by SIgA in patients with CDI, while Fusobacterium was characteristic for the SIgA-opsonized fraction of the controls. The study demonstrates that sequencing of specific bacterial fractions provides additional information about dysbiotic processes in the gut. The detected patterns have been confirmed with the whole patient cohort independently of the taxonomic differences detected in the nonfractionated microbiomes.

HIV infection results in metabolic alterations in the gut microbiota different from those induced by other diseases.

Imbalances in gut bacteria have been associated with multiple diseases. However, whether there are disease-specific changes in gut microbial metabolism remains unknown. Here, we demonstrate that human immunodeficiency virus (HIV) infection (n = 33) changes, at quantifiable levels, the metabolism of gut bacteria. These changes are different than those observed in patients with the auto-immune disease systemic lupus erythaematosus (n = 18), and Clostridium difficile-associated diarrhoea (n = 6). Using healthy controls as a baseline (n = 16), we demonstrate that a trend in the nature and directionality of the metabolic changes exists according to the type of the disease. The impact on the gut microbial activity, and thus the metabolite composition and metabolic flux of gut microbes, is therefore disease-dependent. Our data further provide experimental evidence that HIV infection drastically changed the microbial community, and the species responsible for the metabolism of 4 amino acids, in contrast to patients with the other two diseases and healthy controls. The identification in this present work of specific metabolic deficits in HIV-infected patients may define nutritional supplements to improve the health of these patients.

Carriage of Enterobacteria Producing Extended-Spectrum ß-Lactamases and Composition of the Gut Microbiota in an Amerindian Community.

Epidemiological and individual risk factors for colonization by enterobacteria producing extended-spectrum beta-lactamases (E-ESBL) have been studied extensively, but whether such colonization is associated with significant changes in the composition of the rest of the microbiota is still unknown. To address this issue, we assessed in an isolated Amerindian Guianese community whether intestinal carriage of E-ESBL was associated with specificities in gut microbiota using metagenomic and metatranscriptomic approaches. While the richness of taxa of the active microbiota of carriers was similar to that of noncarriers, the taxa were less homogeneous. In addition, species of four genera, Desulfovibrio, Oscillospira, Parabacteroides, and Coprococcus, were significantly more abundant in the active microbiota of noncarriers than in the active microbiota of carriers, whereas such was the case only for species of Desulfovibrio and Oscillospira in the total microbiota. Differential genera in noncarrier microbiota could either be associated with resistance to colonization or be the consequence of the colonization by E-ESBL.

Effect of daily intake of pomegranate juice on fecal microbiota and feces metabolites from healthy volunteers.

SCOPE: The purpose of the study was to evaluate the effect, regarding the metabolic and microbial profile of feces, of diet supplementation of healthy adults with pomegranate juice (PJ). METHODS AND RESULTS: Twelve healthy adults were recruited to the study, which consisted of the intake of 200 mL/day of PJ during 4 weeks. Feces were collected before and after the supplementation with PJ. Metabolites (phenolic catabolites, short-chain fatty acids, and fecal steroids) and microbial profile were analyzed at baseline and at 4 weeks. Fecal phenolic metabolites, 3-phenylpropionic acid, catechol, hydroxytyrosol, and urolithin A, showed a significant increase in their concentration after supplementation with PJ. Among fecal steroids, parallel to the significant increase of cholesterol concentration, a significant decrease of coprostanol was observed. Although no significant changes in the microbiota profile were observed, different relationships between initial microbiota and the metabolites produced were found. Catechol showed positive and negative correlation with Oscillospora and Paraprevotella genera, respectively, and 3-phenylpropionic acid was positively correlated with Odoribacter genus. CONCLUSION: Inclusion of PJ in the diet did not significantly alter the gut microbiota composition in healthy adults, but the individual bacterial composition could contribute to the generation of potential health-promoting phenolic metabolites.

Estudios de epidemiología molecular en población inmigrante en España / Molecular epidemiology studies on the immigrant population in Spain

Fundamentos: La epidemiología molecular es una nueva disciplina que permite la integración de la información sobre la variabilidad genética de patógenos infecciosos con su difusión en la población y subgrupos de la misma incluyendo, por ejemplo, las mutaciones de resistencia a antibióticos y antivirales. El objetivo es conocer qué posibles diferencias existe en las características genéticas de los agentes infecciosos que afectan a las poblaciones inmigrante y autóctoctona en España.. Métodos: Se revisaron artículos originales publicados entre 1998- 2013, con las palabras clave "epidemiología molecular", "tipado molecular", "secuenciación", "inmigrante", "España". Resultados: De un total de 267 artículos identificados inicialmente, 50 pasaron los diferentes filtros establecidos. De ellos, 36 analizan las infecciones por Mycobacterium tuberculosis y VIH, seguidos de los que analizan infecciones por Staphylococcus aureus (3) y el Virus de la Hepatitis B (3). Conclusiones: Los objetivos principales de estos trabajos fueron el tipado del patógeno y la determinación de la frecuencia de mutaciones de resistencia. Los estudios más frecuentes correspondieron a cohortes retrospectivas, seguidos por los estudios ecológicos y los ensayos clínicos. En general los estudios son descriptivos y su ámbito por el tipo y tamaño de muestra es bastante restringido. En varios se determina que las cepas o variantes del patógeno encontradas en inmigrantes tienen su origen más probable en sus países de origen, si bien otros también ponen de manifiesto la transmisión desde la población autóctona a la inmigrante (AU)

Background: Molecular epidemiology is a new scientific discipline which allows to integrate information on the genetic variation of infectious pathogens with their diffusion in a population and its subgroups including, for instance, resistance mutations to antibiotics and antiretrovirals. We present the results of an analysis of scientific publications that analyze the health status of the immigrant population in Spain from a molecular epidemiology perspective. Methods:We reviewed original articles published in 1998-2014 with he keywords "molecular epidemiology", "molecular typing", "sequencing", "immigrant", and "Spain". Results: Froma total of 267 articles identified initially, only 50 passed through the established filters. Most of them (36) analyzed infections by Mycobacterium tuberculosis (3) and HIV (3), followed at a large distance by Staphylococcus aureus and hepatitis B virus. The main goal of these works was the typing of the pathogen and to determine the frequency of resistance mutations. Conclusion: Is difficult to generalize the conclusions from the analyzed articles because most of them have a purely descriptive and quite restricted scope, considering the type and size of the samples studied. Several studies are focused on the most likely origin for the strains or variants of the pathogen but others also reveal transmissions from the local to the immigrant populations (AU)

[Molecular epidemiology studies on the immigrant population in Spain]. / Estudios de epidemiología molecular en población inmigrante en España.

BACKGROUND: Molecular epidemiology is a new scientific discipline which allows to integrate information on the genetic variation of infectious pathogens with their diffusion in a population and its subgroups including, for instance, resistance mutations to antibiotics and antiretrovirals. We present the results of an analysis of scientific publications that analyze the health status of the immigrant population in Spain from a molecular epidemiology perspective. METHODS: We reviewed original articles published in 1998-2014 with the keywords "molecular epidemiology", "molecular typing", "sequencing", "immigrant", and "Spain". RESULTS: From a total of 267 articles identified initially, only 50 passed through the established filters. Most of them (36) analyzed infections by Mycobacterium tuberculosis (3) and HIV (3), followed at a large distance by Staphylococcus aureus and hepatitis B virus. The main goal of these works was the typing of the pathogen and to determine the frequency of resistance mutations. CONCLUSION: Is difficult to generalize the conclusions from the analyzed articles because most of them have a purely descriptive and quite restricted scope, considering the type and size of the samples studied. Several studies are focused on the most likely origin for the strains or variants of the pathogen but others also reveal transmissions from the local to the immigrant populations.

Comparison of different assembly and annotation tools on analysis of simulated viral metagenomic communities in the gut.

BACKGROUND: The main limitations in the analysis of viral metagenomes are perhaps the high genetic variability and the lack of information in extant databases. To address these issues, several bioinformatic tools have been specifically designed or adapted for metagenomics by improving read assembly and creating more sensitive methods for homology detection. This study compares the performance of different available assemblers and taxonomic annotation software using simulated viral-metagenomic data. RESULTS: We simulated two 454 viral metagenomes using genomes from NCBI's RefSeq database based on the list of actual viruses found in previously published metagenomes. Three different assembly strategies, spanning six assemblers, were tested for performance: overlap-layout-consensus algorithms Newbler, Celera and Minimo; de Bruijn graphs algorithms Velvet and MetaVelvet; and read probabilistic model Genovo. The performance of the assemblies was measured by the length of resulting contigs (using N50), the percentage of reads assembled and the overall accuracy when comparing against corresponding reference genomes. Additionally, the number of chimeras per contig and the lowest common ancestor were estimated in order to assess the effect of assembling on taxonomic and functional annotation. The functional classification of the reads was evaluated by counting the reads that correctly matched the functional data previously reported for the original genomes and calculating the number of over-represented functional categories in chimeric contigs. The sensitivity and specificity of tBLASTx, PhymmBL and the k-mer frequencies were measured by accurate predictions when comparing simulated reads against the NCBI Virus genomes RefSeq database. CONCLUSIONS: Assembling improves functional annotation by increasing accurate assignations and decreasing ambiguous hits between viruses and bacteria. However, the success is limited by the chimeric contigs occurring at all taxonomic levels. The assembler and its parameters should be selected based on the focus of each study. Minimo's non-chimeric contigs and Genovo's long contigs excelled in taxonomy assignation and functional annotation, respectively.tBLASTx stood out as the best approach for taxonomic annotation for virus identification. PhymmBL proved useful in datasets in which no related sequences are present as it uses genomic features that may help identify distant taxa. The k-frequencies underperformed in all viral datasets.

Study of the viral and microbial communities associated with Crohn's disease: a metagenomic approach.

OBJECTIVES: This study aimed to analyze and compare the diversity and structure of the viral and microbial communities in fecal samples from a control group of healthy volunteers and from patients affected by Crohn's disease (CD). METHODS: Healthy adult controls (n=8) and patients affected by ileocolic CD (n=11) were examined for the viral and microbial communities in their feces and, in one additional case, in the intestinal tissue. Using two different approaches, we compared the viral and microbial communities in several ways: by group (patients vs. controls), entity (viruses vs. bacteria), read assembly (unassembled vs. assembled reads), and methodology (our approach vs. an existing pipeline). Differences in the viral and microbial composition, and abundance between the two groups were analyzed to identify taxa that are under- or over-represented. RESULTS: A lower diversity but more variability between the CD samples in both virome and microbiome was found, with a clear distinction between groups based on the microbiome. Only ≈5% of the differential viral biomarkers are more represented in the CD group (Synechococcus phage S CBS1 and Retroviridae family viruses), compared with 95% in the control group. Unrelated patterns of bacteria and bacteriophages were observed. CONCLUSIONS: Our use of an extensive database is critical to retrieve more viral hits than in previous approaches. Unrelated patterns of bacteria and bacteriophages may be due to uneven representation of certain viruses in databases, among other factors. Further characterization of Retroviridae viruses in the CD group could be of interest, given their links with immunodeficiency and the immune responses. To conclude, some methodological considerations underlying the analysis of the viral community composition and abundance are discussed.