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Despite a marked impact on society in terms of patient suffering and healthcare expenditure, colonic diverticulitis has a relative scarcity of published literature examining its pathophysiology. Based on preliminary studies, akin to other gastrointestinal diseases, alterations of the microbiome appear to be associated with diverticulitis. In fact, these perturbations in the microbiome can be detected when comparing segments of diseased and non-diseased colonic tissues within the same individual. Unfortunately, differentiating cause from effect is not feasible without longitudinal studies. While the use of antibiotics for the treatment of uncomplicated diverticulitis is waning, studies utilizing rifaximin, probiotics, and even fecal microbiota transplantation are growing. At present, treatment recommendations are limited by significant heterogeneity in the study populations as well as confounding bias. Ultimately, while dysbiosis is likely to play a role in diverticulitis, a lack of animal models upon which to perform mechanistic study has limited evidence-based recommendations.

Streptococcus pyogenes causes 700 million human infections annually worldwide, yet, despite a century of intensive effort, there is no licensed vaccine against this bacterium. Although a number of large-scale genomic studies of bacterial pathogens have been published, the relationships among the genome, transcriptome, and virulence in large bacterial populations remain poorly understood. We sequenced the genomes of 2,101 emm28 S. pyogenes invasive strains, from which we selected 492 phylogenetically diverse strains for transcriptome analysis and 50 strains for virulence assessment. Data integration provided a novel understanding of the virulence mechanisms of this model organism. Genome-wide association study, expression quantitative trait loci analysis, machine learning, and isogenic mutant strains identified and confirmed a one-nucleotide indel in an intergenic region that significantly alters global transcript profiles and ultimately virulence. The integrative strategy that we used is generally applicable to any microbe and may lead to new therapeutics for many human pathogens. This study presents the genomes of 2,101 emm28 Streptococcus pyogenes invasive strains, of which 492 were transcriptionally profiled, and 50 were assessed for virulence. GWAS, eQTL analysis, and study of isogenic mutant strains identified an intergenic region that alters global transcript profiles and bacterial virulence.

Summary Studies in mice and humans have revealed intriguing associations between host genetics and the microbiome. Here we report a 16S rRNA-based analysis of the gut microbiome in 1,126 twin pairs, a subset of which was previously reported. Tripling the sample narrowed the confidence intervals around heritability estimates and uncovered additional heritable taxa, some of which are validated in other studies. Repeat sampling of subjects showed heritable taxa to be temporally stable. A candidate gene approach uncovered associations between heritable taxa and genes related to diet, metabolism, and olfaction. We replicate an association between Bifidobacterium and the lactase (LCT) gene locus and identify an association between the host gene ALDH1L1 and the bacteria SHA-98, suggesting a link between formate production and blood pressure. Additional genes detected are involved in barrier defense and self/non-self recognition. Our results indicate that diet-sensing, metabolism, and immune defense are important drivers of human-microbiome co-evolution.

Background Variation in the human fecal microbiota has previously been associated with body mass index (BMI). Although obesity is a global health burden, the accumulation of abdominal visceral fat is the specific cardio-metabolic disease risk factor. Here, we explore links between the fecal microbiota and abdominal adiposity using body composition as measured by dual-energy X-ray absorptiometry in a large sample of twins from the TwinsUK cohort, comparing fecal 16S rRNA diversity profiles with six adiposity measures. Results We profile six adiposity measures in 3666 twins and estimate their heritability, finding novel evidence for strong genetic effects underlying visceral fat and android/gynoid ratio. We confirm the association of lower diversity of the fecal microbiome with obesity and adiposity measures, and then compare the association between fecal microbial composition and the adiposity phenotypes in a discovery subsample of twins. We identify associations between the relative abundances of fecal microbial operational taxonomic units (OTUs) and abdominal adiposity measures. Most of these results involve visceral fat associations, with the strongest associations between visceral fat and Oscillospira members. Using BMI as a surrogate phenotype, we pursue replication in independent samples from three population-based cohorts including American Gut, Flemish Gut Flora Project and the extended TwinsUK cohort. Meta-analyses across the replication samples indicate that 8 OTUs replicate at a stringent threshold across all cohorts, while 49 OTUs achieve nominal significance in at least one replication sample. Heritability analysis of the adiposity-associated microbial OTUs prompted us to assess host genetic-microbe interactions at obesity-associated human candidate loci. We observe significant associations of adiposity-OTU abundances with host genetic variants in the FHIT, TDRG1 and ELAVL4 genes, suggesting a potential role for host genes to mediate the link between the fecal microbiome and obesity. Conclusions Our results provide novel insights into the role of the fecal microbiota in cardio-metabolic disease with clear potential for prevention and novel therapies. Electronic supplementary material The online version of this article (doi:10.1186/s13059-016-1052-7) contains supplementary material, which is available to authorized users.

The composition of the human gut microbiome is influenced by many environmental factors. Diet is thought to be one of the most important determinants, though we have limited understanding of the extent to which dietary fluctuations alter variation in the gut microbiome between individuals. In this study, we examined variation in gut microbiome composition between winter and summer over the course of one year in 60 members of a founder population, the Hutterites. Because of their communal lifestyle, Hutterite diets are similar across individuals and remarkably stable throughout the year, with the exception that fresh produce is primarily served during the summer and autumn months. Our data indicate that despite overall gut microbiome stability within individuals over time, there are consistent and significant population-wide shifts in microbiome composition across seasons. We found seasonal differences in both (i) the abundance of particular taxa (false discovery rate

The bacterial composition of the human fecal microbiome is influenced by many lifestyle factors, notably diet. It is less clear, however, what role host genetics plays in dictating the composition of bacteria living in the gut. In this study, we examined the association of ~200K host genotypes with the relative abundance of fecal bacterial taxa in a founder population, the Hutterites, during two seasons (n = 91 summer, n = 93 winter, n = 57 individuals collected in both). These individuals live and eat communally, minimizing variation due to environmental exposures, including diet, which could potentially mask small genetic effects. Using a GWAS approach that takes into account the relatedness between subjects, we identified at least 8 bacterial taxa whose abundances were associated with single nucleotide polymorphisms in the host genome in each season (at genome-wide FDR of 20%). For example, we identified an association between a taxon known to affect obesity (genus Akkermansia) and a variant near PLD1, a gene previously associated with body mass index. Moreover, we replicate a previously reported association from a quantitative trait locus (QTL) mapping study of fecal microbiome abundance in mice (genus Lactococcus, rs3747113, P = 3.13 x 10−7). Finally, based on the significance distribution of the associated microbiome QTLs in our study with respect to chromatin accessibility profiles, we identified tissues in which host genetic variation may be acting to influence bacterial abundance in the gut.

T U E S D A Y 890 Decrease in Diversity of Nasal Microbiota during Wheezing Episodes in Preschool Children Gorka Alkorta-Aranburu, PhD, Catherine Igartua, Emily R. Davenport, Katherine Naughton, So Watanabe, MD, PhD, Yoav Gilad, PhD, Robert F. Lemanske, Jr, MD, FAAAAI, David M. Mauger, PhD, Carole Ober, PhD, Daniel J. Jackson, MD, Jayant M. Pinto, MD; The University of Chicago, Showa University, Toyko, Japan, University of Chicago, University of Wisconsin School of Medicine and Public Health, Madison, WI, Penn State University College of Medicine, Hershey, PA, University of Chicago, Chicago, IL, Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, WI, The University of Chicago, Chicago, IL. RATIONALE: Wheezing episodes are responsible for significant morbidity in children and are closely associated with respiratory tract infections (RTIs).We hypothesized that the composition of airway bacteria would be altered during these illnesses. METHODS: Using DNA from nasal lavage samples prospectively collected in the Maintenance and Intermittent Inhaled Corticosteroids in Wheezing Toddlers (MIST) clinical trial, we sequenced the 16S rRNA gene (V4 region) to analyze the bacterial microbiome of 33 children at baseline and during RTI. 160,000 sequence reads per sample were subsampled at random and classified using Mothur (RDP database) in order to generate standard ecologic metrics and identify the abundance of specific bacteria. RESULTS: Among the 18 males and 15 females (mean age 36 months), a majority had allergic sensitization (51.5%) or a parent with asthma (57.6%). Microbial diversity was significantly decreased during RTIs (Shannon Index 1.17 vs. 0.71, P50.018), particularly episodes severe enough to be treated with oral corticosteroids. The relative abundance of the phyla Bacteroidetes and Fusobacteria were lower during RTIs (Bonferroni P 0.01). CONCLUSIONS: Severe RTIs are associated with decreased bacterial diversity in the upper airway, indicating that the composition of nasal microbiota may influence wheezing episodes. Future studies should define the role of specific bacterial populations in these episodes. The nose is an accessible site to assess these relationships.