ObjectivePatients with renal failure suffer from symptoms caused by uraemic toxins, possibly of gut microbial origin, as deduced from studies in animals. The aim of the study is to characterise relationships between the intestinal microbiome composition, uraemic toxins and renal failure symptoms in human end-stage renal disease (ESRD).DesignCharacterisation of gut microbiome, serum and faecal metabolome and human phenotypes in a cohort of 223 patients with ESRD and 69 healthy controls. Multidimensional data integration to reveal links between these datasets and the use of chronic kidney disease (CKD) rodent models to test the effects of intestinal microbiome on toxin accumulation and disease severity.ResultsA group of microbial species enriched in ESRD correlates tightly to patient clinical variables and encode functions involved in toxin and secondary bile acids synthesis; the relative abundance of the microbial functions correlates with the serum or faecal concentrations of these metabolites. Microbiota from patients transplanted to renal injured germ-free mice or antibiotic-treated rats induce higher production of serum uraemic toxins and aggravated renal fibrosis and oxidative stress more than microbiota from controls. Two of the species, Eggerthella lenta and Fusobacterium nucleatum, increase uraemic toxins production and promote renal disease development in a CKD rat model. A probiotic Bifidobacterium animalis decreases abundance of these species, reduces levels of toxins and the severity of the disease in rats.ConclusionAberrant gut microbiota in patients with ESRD sculpts a detrimental metabolome aggravating clinical outcomes, suggesting that the gut microbiota will be a promising target for diminishing uraemic toxicity in those patients.Trial registration numberThis study was registered at ClinicalTrials.gov (NCT03010696).

This study investigated the changes in chemical composition, nitrogen fraction distribution, and AA profile of milk samples obtained during lactation from the Jiangyue breed of donkey in Northwest China. Results showed that donkey milk contained 9.53% total solids, 1.57% protein, 1.16% fat, 6.33% lactose, and 0.4% ash on average, which is more similar to mare and human milk than to the milk of other mammals. Throughout the lactation investigated, pH and density were constant, protein and ash content showed an apparent negative trend (an increase in lactose content during 120 d postpartum, followed by a decrease), fat content exhibited wide variability, and variations in the content and percentage of whey protein, casein, and AA were small. The casein to whey protein ratio of 52:37 was between the lower value of human milk and the higher value of cow milk. Sodium dodecyl sulfate-PAGE results demonstrated that donkey milk is rich in beta-lactoglobulin and lysozyme. The percentages of 8 essential AA in protein of donkey milk were 38.2%, higher than those of mare and cow milk; donkey milk also had higher levels of serine (6.2%), glutamic acid (22.8%), arginine (4.6%), and valine (6.5%) and a lower level of cystine (0.4%).

Background and Purpose— Trimethylamine N-oxide (TMAO)—a gut derived metabolite—has been shown to be atherogenic. It remains unknown whether TMAO is associated with the risk of first stroke. We aimed to determine the association between serum TMAO levels and first stroke in hypertensive patients without major cardiovascular diseases and examine any possible effect modifiers. Methods— We used a nested case-control design, using data from the CSPPT (China Stroke Primary Prevention Trial), including 622 patients with first stroke and 622 matched controls. The study was conducted from May 2008 to August 2013. The primary outcome was a first stroke. Results— After adjusting for choline, L-carnitine, and other important covariates, including baseline systolic blood pressure and time-averaged systolic blood pressure, during the treatment period, the risk of first stroke increased with each increment of TMAO level (per natural log [TMAO] increment: odds ratio, 1.22; 95% CI, 1.02–1.46). Consistently, compared with participants in the lowest tertile (<1.79 μmol/L) of serum TMAO levels, a significantly higher risk of first stroke was found in those in higher TMAO tertiles (≥1.79 μmol/L; odds ratio, 1.34; 95% CI, 1.00–1.81) or in TMAO tertile 3 (≥3.19 μmol/L; odds ratio, 1.43; 95% CI, 1.02–2.01). In the exploratory analysis, we observed an interaction between TMAO and folate levels (≥7.7 [median] versus <7.7 ng/mL) on first stroke ( P for interaction, 0.030). Conclusions— Higher TMAO levels were associated with increased risk of first stroke in hypertensive patients. Our finding, if further confirmed, calls for a carefully designed clinical trial to further evaluate the role of higher TMAO levels on outcomes in hypertensive patients. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT00794885.

Polysaccharide CharacterizationImmunomodulatory activity A B S T R A C TThe crude polysaccharide from the stem of Dendrobium officinale (DOP) was obtained by water extraction and ethanol precipitation. Two fractions of DOP, DOP-1 and DOP-2, were fractioned by DEAE cellulose and Sephacryl S-400 gel filtration column chromatography.Their molecular weights and monosaccharide compositions were studied. The immunomodulatory activity of DOP, DOP-1 and DOP-2 was evaluated with in vitro cell models.The results showed that the 533.7 kDa DOP-1 and 159.5 kDa DOP-2 were mainly composed of mannose and glucose. Both DOP and its purified fractions significantly (P < 0.05) promoted splenocyte proliferation, enhanced natural killer cell-mediated cytotoxicity, and increased the phagocytosis and nitric oxide production of macrophages. Moreover, these two fractions caused a significant (P < 0.05) stimulation of cytokine secretion of both splenocytes and macrophages. These findings suggest that Dendrobium officinale polysaccharides should be explored as novel potential immunomodulators.