Background There is intense interest about whether modulating gut microbiota can impact systemic metabolism. We investigated the safety of weekly oral fecal microbiota transplantation (FMT) capsules from healthy lean donors and their ability to alter gut microbiota and improve metabolic outcomes in patients with obesity. Methods and findings FMT-TRIM was a 12-week double-blind randomized placebo-controlled pilot trial of oral FMT capsules performed at a single US academic medical center. Between August 2016 and April 2018, we randomized 24 adults with obesity and mild-moderate insulin resistance (homeostatic model assessment of insulin resistance [HOMA-IR] between 2.0 and 8.0) to weekly healthy lean donor FMT versus placebo capsules for 6 weeks. The primary outcome, assessed by intention to treat, was change in insulin sensitivity between 0 and 6 weeks as measured by hyperinsulinemic euglycemic clamps. Additional metabolic parameters were evaluated at 0, 6, and 12 weeks, including HbA1c, body weight, body composition by dualenergy X-ray absorptiometry, and resting energy expenditure by indirect calorimetry. Fecal samples were serially collected and evaluated via 16S V4 rRNA sequencing. Our study population was 71% female, with an average baseline BMI of 38.8 ± 6.7 kg/m 2 and 41.3 ± 5.1 kg/m 2 in the FMT and placebo groups, respectively. There were no statistically significant improvements in insulin sensitivity in the FMT group compared to the placebo group (+5% ± 12% in FMT group versus −3% ± 32% in placebo group, mean difference 9%, 95% CI −5% to 28%, p = 0.16). There were no statistically significant differences between groups for most of the other secondary metabolic outcomes, including HOMA-IR (mean difference 0.2, 95% CI −0.9 to 0.9, p = 0.96) and body composition (lean mass mean difference −0.1 kg,

Through soft X-ray absorption spectroscopy, hard X-ray Raman scattering, and theoretical simulations, we provide the most in-depth and systematic study of the phase transformation and (de)lithiation effect on electronic structure in Li(x)FePO(4) nanoparticles and single crystals. Soft X-ray reveals directly the valence states of Fe 3d electrons in the vicinity of Fermi level, which is sensitive to the local lattice distortion, but more importantly offers detailed information on the evolution of electronic states at different electrochemical stages. The soft X-ray spectra of Li(x)FePO(4) nanoparticles evolve vividly with the (de)lithiation level. The spectra fingerprint the (de)lithiation process with rich information on Li distribution, valency, spin states, and crystal field. The high-resolution spectra reveal a subtle but critical deviation from two-phase transformation in our electrochemically prepared samples. In addition, we performed both first-principles calculations and multiplet simulations of the spectra and quantitatively determined the 3d valence states that are completely redistributed through (de)lithiation. This electronic reconfiguration was further verified by the polarization-dependent spectra collected on LiFePO(4) single crystals, especially along the lithium diffusion direction. The evolution of the 3d states is overall consistent with the local lattice distortion and provides a fundamental picture of the (de)lithiation effects on electronic structure in the Li(x)FePO(4) system.

Some studies on the hyperuricemia (HUA) have focused on intestinal bacteria. To better understand the correlation between gut microbiota and HUA, we established a HUA rat model with high-purine diet, and used 16S rRNA genes sequencing to analyze gut microbiota changes in HUA rats. To analyze the potential role played by gut microbiota in HUA, we altered the gut microbiota of HUA rats with antibiotics, and compared the degree of uric acid elevation between HUA and antibiotic-fed HUA rats (Ab+HUA). Finally, we established a recipient rat model, in which we transplanted fecal microbiota of HUA and normal rats into recipient rats. Three weeks later, we compared the uric acid content of recipient rats. As a result, the diversity and abundance of the gut microbiota had changed in HUA rats. The Ab-fed HUA rats had significantly lower uric acid content compared to the HUA rats, and gut microbiota from HUA rats increased uric acid content of recipient rats. The genera Vallitalea, Christensenella and Insolitispirillum may associate with HUA. Our findings highlight the association between gut microbiota and HUA, and the potential role played by gut microbiota in HUA. We hope that this finding will promote the isolation and culture of HUA-related bacteria and orient HUA-related studies from being correlational to mechanistic. These steps will therefore make it possible for us to treat HUA using gut microbiota as the target.

BackgroundFew published studies have evaluated the power of the oxygen uptake efficiency slope (OUES) to predict outcomes in patients with idiopathic pulmonary arterial hypertension (IPAH), who typically die of right‐sided heart failure. Our study sought to evaluate the power of OUES to predict clinical worsening and mortality in patients with IPAH.Methods and ResultsPatients with newly diagnosed IPAH who underwent symptom‐limited cardiopulmonary exercise testing from November 11, 2010, to June 25, 2015, in our hospital were prospectively enrolled and followed for up to 66 months. Clinical worsening and mortality were recorded. A total of 210 patients with IPAH (159 women; mean age, 32±10 years) were studied with a median follow‐up of 41 months. Thirty‐one patients died, 1 patient underwent lung transplantation, and 85 patients presented with clinical worsening. The univariate analysis revealed that OUES, OUESI (OUESI=OUES/body surface area), peak oxygen uptake (normalV˙normalO2), peak normalV˙normalO2/kg, ventilation (normalV˙E)/carbon dioxide output (normalV˙CO2) slope, peak systolic blood pressure, heart rate recovery, pulmonary vascular resistance, cardiac index, N‐terminal prohormone brain natriuretic peptide, and World Health Organization functional class were all predictive of clinical worsening and mortality (all P<0.05). Multivariate analysis demonstrated that OUESI and cardiac index were independently predictive of clinical worsening, and OUESI and N‐terminal prohormone brain natriuretic peptide were independently predictive of mortality. Patients with OUESI ≤0.52 m−2 had a worse 5‐year survival rate than patients with OUESI >0.52 m−2 (41.9% versus 89.8%, P<0.0001).ConclusionsThe OUES, a submaximal parameter obtained from cardiopulmonary exercise testing, provides prognostic information for predicting clinical worsening and mortality in patients with IPAH.

Background: Whether exercise can improve cardiovascular health in kidney transplant recipients (KTRs) is unclear. Therefore, we performed a systematic review of the effects of exercise on cardiovascular risk factors in this population setting. Methods: Randomized control trials (RCTs) evaluating the impact of exercise on major clinical outcomes in KTRs were identified by searches in Cochrane CENTRAL, PubMed, EMBASE, OVID and CBM updated to December 2018. The main outcomes of interest were blood pressure, lipid profile, blood glucose level, arterial stiffness, kidney function, body weight, body mass index, exercise tolerance (VO 2 peak) and quality of life (QOL). Results: After screening 445 studies in the database, we included 12 RCTs in the review and 11 RCTs for further qualitative analysis. The results indicate a significant improvement in small arterial stiffness [mean difference (MD): −1.14, 95% confidence interval (CI): −2.19–0.08, p = .03], VO 2 peak (MD: 2.25, 95% CI: 0.54–3.69, p = .01), and QOL (MD: 12.87, 95% CI: 6.80–18.94, p < .01) after exercise intervention in KTRs. However, there is no evidence for an improvement in blood pressure, lipid profile, blood glucose level, kidney function, body weight or body mass index. Conclusion: Exercise intervention in KTRs improves arterial stiffness but does not consistently contribute to the modification of other CVD risk factors like hypertension, dyslipidemia, hyperglycemia, decreased kidney function and obesity. Exercise also improves exercise tolerance and QOL in KTRs.