Health-related quality of life is linked to the gut microbiome in kidney transplant recipients

Kidney transplant recipients (KTR) have impaired health-related quality of life (HRQoL) and suffer from intestinal dysbiosis. Increasing evidence shows that gut health and HRQoL are tightly related in the general population. Here, we investigate the association between the gut microbiome and HRQoL in KTR, using metagenomic sequencing data from fecal samples collected from 507 KTR. Multiple bacterial species are associated with lower HRQoL, many of which have previously been associated with adverse health conditions. Gut microbiome distance to the general population is highest among KTR with an impaired physical HRQoL (R = -0.20, P = 2.3 × 10 -65) and mental HRQoL (R = -0.14, P = 1.3 × 10 -3). Physical and mental HRQoL explain a significant part of variance in the gut microbiome (R 2  = 0.58%, FDR = 5.43 × 10 -4 and R 2  = 0.37%, FDR = 1.38 × 10 -3, respectively). Additionally, multiple metabolic and neuroactive pathways (gut brain modules) are associated with lower HRQoL. While the observational design of our study does not allow us to analyze causality, we provide a comprehensive overview of the associations between the gut microbiome and HRQoL while controlling for confounders. </p

Ruxolitinib for Glucocorticoid-Refractory Acute Graft-versus-Host Disease

BACKGROUND: Acute graft-versus-host disease (GVHD) remains a major limitation of allogeneic stem-cell transplantation; not all patients have a response to standard glucocorticoid treatment. In a phase 2 trial, ruxolitinib, a selective Janus kinase (JAK1 and JAK2) inhibitor, showed potential efficacy in patients with glucocorticoid-refractory acute GVHD. METHODS: We conducted a multicenter, randomized, open-label, phase 3 trial comparing the efficacy and safety of oral ruxolitinib (10 mg twice daily) with the investigator's choice of therapy from a list of nine commonly used options (control) in patients 12 years of age or older who had glucocorticoid-refractory acute GVHD after allogeneic stem-cell transplantation. The primary end point was overall response (complete response or partial response) at day 28. The key secondary end point was durable overall response at day 56. RESULTS: A total of 309 patients underwent randomization; 154 patients were assigned to the ruxolitinib group and 155 to the control group. Overall response at day 28 was higher in the ruxolitinib group than in the control group (62% [96 patients] vs. 39% [61]; odds ratio, 2.64; 95% confidence interval [CI], 1.65 to 4.22; P<0.001). Durable overall response at day 56 was higher in the ruxolitinib group than in the control group (40% [61 patients] vs. 22% [34]; odds ratio, 2.38; 95% CI, 1.43 to 3.94; P<0.001). The estimated cumulative incidence of loss of response at 6 months was 10% in the ruxolitinib group and 39% in the control group. The median failure-free survival was considerably longer with ruxolitinib than with control (5.0 months vs. 1.0 month; hazard ratio for relapse or progression of hematologic disease, non-relapse-related death, or addition of new systemic therapy for acute GVHD, 0.46; 95% CI, 0.35 to 0.60). The median overall survival was 11.1 months in the ruxolitinib group and 6.5 months in the control group (hazard ratio for death, 0.83; 95% CI, 0.60 to 1.15). The most common adverse events up to day 28 were thrombocytopenia (in 50 of 152 patients [33%] in the ruxolitinib group and 27 of 150 [18%] in the control group), anemia (in 46 [30%] and 42 [28%], respectively), and cytomegalovirus infection (in 39 [26%] and 31 [21%]). CONCLUSIONS: Ruxolitinib therapy led to significant improvements in efficacy outcomes, with a higher incidence of thrombocytopenia, the most frequent toxic effect, than that observed with control therapy

Cross-cohort gut microbiome associations with immune checkpoint inhibitor response in advanced melanoma

The composition of the gut microbiome has been associated with clinical responses to immune checkpoint inhibitor (ICI) treatment, but there is limited consensus on the specific microbiome characteristics linked to the clinical benefits of ICIs. We performed shotgun metagenomic sequencing of stool samples collected before ICI initiation from five observational cohorts recruiting ICI-naive patients with advanced cutaneous melanoma (n = 165). Integrating the dataset with 147 metagenomic samples from previously published studies, we found that the gut microbiome has a relevant, but cohort-dependent, association with the response to ICIs. A machine learning analysis confirmed the link between the microbiome and overall response rates (ORRs) and progression-free survival (PFS) with ICIs but also revealed limited reproducibility of microbiome-based signatures across cohorts. Accordingly, a panel of species, including Bifidobacterium pseudocatenulatum, Roseburia spp. and Akkermansia muciniphila, associated with responders was identified, but no single species could be regarded as a fully consistent biomarker across studies. Overall, the role of the human gut microbiome in ICI response appears more complex than previously thought, extending beyond differing microbial species simply present or absent in responders and nonresponders. Future studies should adopt larger sample sizes and take into account the complex interplay of clinical factors with the gut microbiome over the treatment course

Global maps of soil temperature

Research in global change ecology relies heavily on global climatic grids derived from estimates of air temperature in open areas at around 2 m above the ground. These climatic grids do not reflect conditions below vegetation canopies and near the ground surface, where critical ecosystem functions occur and most terrestrial species reside. Here, we provide global maps of soil temperature and bioclimatic variables at a 1-km2 resolution for 0–5 and 5–15 cm soil depth. These maps were created by calculating the difference (i.e. offset) between in situ soil temperature measurements, based on time series from over 1200 1-km2 pixels (summarized from 8519 unique temperature sensors) across all the world\u27s major terrestrial biomes, and coarse-grained air temperature estimates from ERA5-Land (an atmospheric reanalysis by the European Centre for Medium-Range Weather Forecasts). We show that mean annual soil temperature differs markedly from the corresponding gridded air temperature, by up to 10°C (mean = 3.0 ± 2.1°C), with substantial variation across biomes and seasons. Over the year, soils in cold and/or dry biomes are substantially warmer (+3.6 ± 2.3°C) than gridded air temperature, whereas soils in warm and humid environments are on average slightly cooler (−0.7 ± 2.3°C). The observed substantial and biome-specific offsets emphasize that the projected impacts of climate and climate change on near-surface biodiversity and ecosystem functioning are inaccurately assessed when air rather than soil temperature is used, especially in cold environments. The global soil-related bioclimatic variables provided here are an important step forward for any application in ecology and related disciplines. Nevertheless, we highlight the need to fill remaining geographic gaps by collecting more in situ measurements of microclimate conditions to further enhance the spatiotemporal resolution of global soil temperature products for ecological applications

Ecology, coevolution, and architecture of symbiotic prokaryote animal host interaction networks

2013 Workshop on Molecular Evolution, 21 January - 1 February 2013, Český Krumlov, Czech RepublicHow are prokaryote-host multi-species interaction networks organized & have evolved? What is the role of ecological & evolutionary processes in shaping these interaction networks? Which associations are likely to be symbiotic? Are within-host microbe-microbe interactions stable over time?Peer Reviewe

Specificity and temporal dynamics of complex bacteria-sponge symbiotic interactions

Microbes are known to form intricate and intimate relationships with most animal and plant taxa. Microbe-host symbiotic associations are poorly explored in comparison with other species interaction networks. The current paradigm on symbiosis research stems from species-poor systems where pairwise and reciprocally specialized interactions between a single microbe and a single host that coevolve are the norm. These symbioses involving just a few species are fascinating in their own right, but more diverse and complex host-associated microbial communities are increasingly found, with new emerging questions that require new paradigms and approaches. Here we adopt an intermediate complexity approach to study the specificity, phylogenetic community structure, and temporal variability of the subset of the most abundant bacteria associated with different sponge host species with diverse eco-evolutionary characteristics. We do so by using a monthly resolved annual temporal series of host-associated and free-living bacteria. Bacteria are very abundant and diverse within marine sponges, and these symbiotic interactions are hypothesized to have a very ancient origin. We show that host-bacteria reciprocal specialization depends on the temporal scale and level of taxonomic aggregation considered. Sponge hosts with similar ecoevolutionary characteristics (e.g., volume of tissue corresponding to microbes, water filtering rates, and microbial transmission type) have similar bacterial phylogenetic community structure when looking at interactions aggregated over time. In general, sponge hosts hypothesized to form more intricate relationships with bacteria show a remarkably persistent bacterial community over time. Other hosts, however, show a large turnover similar to that observed for free-living bacterioplankton. Our study highlights the importance of exploring temporal variability in host-microbe interaction networks if we aim to determine how specific and persistent these poorly explored but extremely common interactions are. © 2013 by the Ecological Society of AmericaPeer Reviewe

Appendix C. A table summarizing information about excised and sequenced DGGE bands, including GeneBank accesion numbers, taxonomic affiliation, and membership to sponge-specific clusters.

A table summarizing information about excised and sequenced DGGE bands, including GeneBank accesion numbers, taxonomic affiliation, and membership to sponge-specific clusters

Appendix B. A table showing the Jaccard index for different distance cut offs, corresponding to different taxonomic levels.

A table showing the Jaccard index for different distance cut offs, corresponding to different taxonomic levels

Appendix A. Figures showing different analyses conducted using denaturing gradient gel electrophoresis (DGGE) analysis and a dendrogram of the monthly Jaccard coefficient of similarity for the bacterioplankton.

Figures showing different analyses conducted using denaturing gradient gel electrophoresis (DGGE) analysis and a dendrogram of the monthly Jaccard coefficient of similarity for the bacterioplankton