The intestinal microbiota has been implicated in insulin resistance, although evidence regarding causality in humans is scarce. We therefore studied the effect of lean donor (allogenic) versus own ...(autologous) fecal microbiota transplantation (FMT) to male recipients with the metabolic syndrome. Whereas we did not observe metabolic changes at 18 weeks after FMT, insulin sensitivity at 6 weeks after allogenic FMT was significantly improved, accompanied by altered microbiota composition. We also observed changes in plasma metabolites such as γ-aminobutyric acid and show that metabolic response upon allogenic FMT (defined as improved insulin sensitivity 6 weeks after FMT) is dependent on decreased fecal microbial diversity at baseline. In conclusion, the beneficial effects of lean donor FMT on glucose metabolism are associated with changes in intestinal microbiota and plasma metabolites and can be predicted based on baseline fecal microbiota composition.
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•Lean donor FMT in obese metabolic syndrome patients improves insulin sensitivity•Beneficial effects of lean donor FMT are transient•Improvement in insulin sensitivity is linked to changes in plasma metabolites•Response to lean donor FMT is driven by baseline fecal microbiota composition
Kootte et al. show that fecal microbiota transplantation from lean donors to obese patients with metabolic syndrome improves insulin sensitivity, a transient effect associated with changes in microbiota composition and fasting plasma metabolites. Baseline fecal microbiota composition in recipients predicts the response to lean donor fecal microbiota transplantation.
The metabolic effects of omega-6 polyunsaturated fatty acids (PUFAs) remain contentious, and little evidence is available regarding their potential role in primary prevention of type 2 diabetes. We ...aimed to assess the associations of linoleic acid and arachidonic acid biomarkers with incident type 2 diabetes.
We did a pooled analysis of new, harmonised, individual-level analyses for the biomarkers linoleic acid and its metabolite arachidonic acid and incident type 2 diabetes. We analysed data from 20 prospective cohort studies from ten countries (Iceland, the Netherlands, the USA, Taiwan, the UK, Germany, Finland, Australia, Sweden, and France), with biomarkers sampled between 1970 and 2010. Participants included in the analyses were aged 18 years or older and had data available for linoleic acid and arachidonic acid biomarkers at baseline. We excluded participants with type 2 diabetes at baseline. The main outcome was the association between omega-6 PUFA biomarkers and incident type 2 diabetes. We assessed the relative risk of type 2 diabetes prospectively for each cohort and lipid compartment separately using a prespecified analytic plan for exposures, covariates, effect modifiers, and analysis, and the findings were then pooled using inverse-variance weighted meta-analysis.
Participants were 39 740 adults, aged (range of cohort means) 49-76 years with a BMI (range of cohort means) of 23·3-28·4 kg/m
, who did not have type 2 diabetes at baseline. During a follow-up of 366 073 person-years, we identified 4347 cases of incident type 2 diabetes. In multivariable-adjusted pooled analyses, higher proportions of linoleic acid biomarkers as percentages of total fatty acid were associated with a lower risk of type 2 diabetes overall (risk ratio RR per interquintile range 0·65, 95% CI 0·60-0·72, p<0·0001; I
=53·9%, p
=0·002). The associations between linoleic acid biomarkers and type 2 diabetes were generally similar in different lipid compartments, including phospholipids, plasma, cholesterol esters, and adipose tissue. Levels of arachidonic acid biomarker were not significantly associated with type 2 diabetes risk overall (RR per interquintile range 0·96, 95% CI 0·88-1·05; p=0·38; I
=63·0%, p
<0·0001). The associations between linoleic acid and arachidonic acid biomarkers and the risk of type 2 diabetes were not significantly modified by any prespecified potential sources of heterogeneity (ie, age, BMI, sex, race, aspirin use, omega-3 PUFA levels, or variants of the FADS gene; all p
≥0·13).
Findings suggest that linoleic acid has long-term benefits for the prevention of type 2 diabetes and that arachidonic acid is not harmful.
Funders are shown in the appendix.
Chronic kidney disease (CKD) patients undergoing hemodialysis (HD) therapy have an increased risk of developing cognitive impairment and dementia, which are known relevant factors in disease ...prognosis and therapeutic success, but still lack adequate screening in clinical routine. We evaluated the Montreal Cognitive Assessment (MoCA) for suitability in assessing cognitive performance in HD patients in comparison to the commonly used Mini-Mental State Examination (MMSE) and a detailed neuropsychological test battery, used as gold standard.
43 HD patients and 42 healthy controls with an average age of 58 years, were assessed with the MoCA, the MMSE and a detailed neuropsychological test battery, covering the domains of memory, attention, language, visuospatial and executive functions. Composite scores were created for comparison of cognitive domains and test results were analyzed using Spearman's correlation and linear regression. Cognitive dysfunction was defined using z-score values and predictive values were calculated. Sensitivity and specificity of the MoCA were determined using receiver operating characteristic (ROC) analysis.
HD patients performed worse in all cognitive domains, especially in memory recall and executive functions. The MoCA correlated well with the detailed test battery and identified patients with cognitive impairment with a sensitivity of 76.7% and specificity of 78.6% for a cut-off value of ≤24 out of 30 points. In the detailed assessment executive functions accounted significantly for performance in the MoCA. The MMSE only discriminated weakly between groups.
The MoCA represents a suitable cognitive screening tool for hemodialysis patients, demonstrating good sensitivity and specificity levels, and covering executive functions, which appear to play an important role in cognitive performance of HD patients.
Autism spectrum disorder (ASD) is a neurodevelopmental condition in which children show reduced attention to social aspects of the environment. However in adults with ASD, evidence for social ...attentional deficits is equivocal. One problem is that many paradigms present social information in an unrealistic, isolated way. This study presented adults and adolescents, with and without ASD, with a complex social scene alongside another, non-social scene, and measured eye-movements during a 3-s viewing period. Analyses first identified viewing time to different regions and then investigated some more complex issues. These were: the location of the very first fixation in a trial (indicating attentional priority); the effect of a task instruction on scan paths; the extent to which gaze-following was evident; and the degree to which participants’ scan paths were influenced by the low-level properties of a scene. Results indicate a superficially normal attentional preference for social information in adults with ASD. However, more sensitive measures show that ASD does entail social attention problems across the lifespan, supporting accounts of the disorder which emphasise lifelong neurodevelopmental atypicalities. These subtle abnormalities may be sufficient to produce serious difficulties in real-life scenarios.
The worldwide increase in obesity and related chronic diseases has largely been driven by global trade liberalization, economic growth and rapid urbanization. These factors continue to fuel dramatic ...changes in living environments, diets and lifestyles in ways that promote positive energy balance. Nutritional transitions in low-income and middle-income countries are typically characterized by increases in the consumption of animal fat and protein, refined grains, and added sugar. This change is coupled with reductions in physical activity owing to more mechanized and technologically driven lifestyles. Given the high costs of obesity and comorbidities in terms of health-care expenditure and quality of life, prevention strategies are paramount, particularly in low-income and middle-income countries that must manage coexisting infectious diseases and undernutrition in addition to the obesity epidemic. As countries become increasingly urbanized, undernutrition and obesity can exist side by side within the same country, community or household, which is a particular challenge for health systems with limited resources. Owing to the scope and complexity of the obesity epidemic, prevention strategies and policies across multiple levels are needed in order to have a measurable effect. Changes should include high-level global policies from the international community and coordinated efforts by governments, organizations, communities and individuals to positively influence behavioural change.
Similar to other positive-strand RNA viruses, rhinovirus, the causative agent of the common cold, replicates on a web of cytoplasmic membranes, orchestrated by host proteins and lipids. The host ...pathways that facilitate the formation and function of the replication membranes and complexes are poorly understood. We show that rhinovirus replication depends on host factors driving phosphatidylinositol 4-phosphate (PI4P)-cholesterol counter-currents at viral replication membranes. Depending on the virus type, replication required phosphatidylinositol 4-kinase class 3beta (PI4K3b), cholesteryl-esterase hormone-sensitive lipase (HSL) or oxysterol-binding protein (OSBP)-like 1, 2, 5, 9, or 11 associated with lipid droplets, endosomes, or Golgi. Replication invariably required OSBP1, which shuttles cholesterol and PI4P between ER and Golgi at membrane contact sites. Infection also required ER-associated PI4P phosphatase Sac1 and phosphatidylinositol (PI) transfer protein beta (PITPb) shunting PI between ER-Golgi. These data support a PI4P-cholesterol counter-flux model for rhinovirus replication.
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•Lipid kinase PI4K3b is enriched at rhinovirus replication sites and supports replication•Lipid droplet-derived cholesterol is enriched on rhinovirus (HRV) replication sites•Oxysterol-binding protein 1 (OSBP1) broadly supports enterovirus infections•Fueled by storage cholesterol, the PI4K3b-OSBP1-Sac1-PITPb cycle drives HRV replication
Roulin et al. present evidence for a lipid counter-current model boosting rhinovirus infection. High concentrations of phosphatidyl-inositol (PI) 4-phosphate are built-up on Golgi membranes and used by oxysterol-binding protein-1, a sterol-dependent transducer in cytokine signaling to load cholesterol onto viral replication membranes at ER-Golgi contact sites using lipid droplet cholesteryl-esters.
The placenta is the extraembryonic organ that supports the fetus during intrauterine life. Although placental dysfunction results in major disorders of pregnancy with immediate and lifelong ...consequences for the mother and child, our knowledge of the human placenta is limited owing to a lack of functional experimental models
. After implantation, the trophectoderm of the blastocyst rapidly proliferates and generates the trophoblast, the unique cell type of the placenta. In vivo, proliferative villous cytotrophoblast cells differentiate into two main sub-populations: syncytiotrophoblast, the multinucleated epithelium of the villi responsible for nutrient exchange and hormone production, and extravillous trophoblast cells, which anchor the placenta to the maternal decidua and transform the maternal spiral arteries
. Here we describe the generation of long-term, genetically stable organoid cultures of trophoblast that can differentiate into both syncytiotrophoblast and extravillous trophoblast. We used human leukocyte antigen (HLA) typing to confirm that the organoids were derived from the fetus, and verified their identities against four trophoblast-specific criteria
. The cultures organize into villous-like structures, and we detected the secretion of placental-specific peptides and hormones, including human chorionic gonadotropin (hCG), growth differentiation factor 15 (GDF15) and pregnancy-specific glycoprotein (PSG) by mass spectrometry. The organoids also differentiate into HLA-G
extravillous trophoblast cells, which vigorously invade in three-dimensional cultures. Analysis of the methylome reveals that the organoids closely resemble normal first trimester placentas. This organoid model will be transformative for studying human placental development and for investigating trophoblast interactions with the local and systemic maternal environment.
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