Interplay between Intestinal Bacterial Communities and Unicellular Parasites in a Morbidly Obese Population: A Neglected Trinomial

Obesity is an epidemic causing a metabolic health crisis. Herein, the interactions between the gut prokaryotic and eukaryotic communities, metabolic comorbidities and diet were studied. Stool samples from 56 subjects, 47 with type III obesity and 9 with type II obesity and cardiovascular risk or metabolic disease, were assessed for the richness, diversity and ecology of the bacterial gut community through metagenomics, together with the study of the presence of common unicellular eukaryote parasites (Blastocystis sp., Dientamoeba fragilis and Giardia intestinalis) by qPCR. Clinical information regarding metabolic comorbidities and non-alcoholic hepatic fatty liver disease was gathered. To assess the quality of the patients' diet, each participant filled in three dietary questionnaires. The most prevalent parasite Blastocystis sp. (46.4%), together with D. fragilis (8.9%), was found to be associated with higher mean diversity indexes regarding non-colonized subjects; the opposite of that which was observed in those with G. intestinalis (16.1%). In terms of phyla relative abundance, with Blastocystis sp. and D. fragilis, very slight differences were observed; on the contrary, G. intestinalis was related to an increase in Bacteroidetes and Proteobacteria, and a decrease in Firmicutes and Actinobacteria, presenting the lowest Firmicutes/Bacteroidetes ratio. At genus level, Blastocystis sp. and/or D. fragilis was accompanied with an increase in Lactobacillus spp., and a decrease in Akkermansia spp., Bifidobacterium spp. and Escherichia spp., while G. intestinalis was associated with an increase in Bacteroides spp., and a decrease in Faecalibacterium spp., Prevotella spp. and Lactobacillus spp., and the highest Bacteroides spp./Prevotella spp. ratio. Participants with non-alcoholic hepatic fatty liver presented a higher Firmicutes/Bacteroidetes ratio, and those with type 2 diabetes displayed a significantly lower Faecalibacterium spp./Escherichia spp. ratio, due to an overrepresentation of the genus Escherichia spp. The presence of parasites was associated with variations in the richness, diversity and distribution of taxa in bacterial communities, confirming a gain in diversity associated with Blastocystis sp. and providing different functioning of the microbiota with a potential positive effect on comorbidities such as type 2 diabetes, insulin resistance and metabolic syndrome. Future basic and clinical studies should assess the beneficial or pathogenic effect of these eukaryotes on obese subjects and focus on deciphering whether they may imply a healthier metabolic profile

Toward a Standardized Strategy of Clinical Metabolomics for the Advancement of Precision Medicine

Despite the tremendous success, pitfalls have been observed in every step of a clinical metabolomics workflow, which impedes the internal validity of the study. Furthermore, the demand for logistics, instrumentations, and computational resources for metabolic phenotyping studies has far exceeded our expectations. In this conceptual review, we will cover inclusive barriers of a metabolomics-based clinical study and suggest potential solutions in the hope of enhancing study robustness, usability, and transferability. The importance of quality assurance and quality control procedures is discussed, followed by a practical rule containing five phases, including two additional "pre-pre-" and "post-post-" analytical steps. Besides, we will elucidate the potential involvement of machine learning and demonstrate that the need for automated data mining algorithms to improve the quality of future research is undeniable. Consequently, we propose a comprehensive metabolomics framework, along with an appropriate checklist refined from current guidelines and our previously published assessment, in the attempt to accurately translate achievements in metabolomics into clinical and epidemiological research. Furthermore, the integration of multifaceted multi-omics approaches with metabolomics as the pillar member is in urgent need. When combining with other social or nutritional factors, we can gather complete omics profiles for a particular disease. Our discussion reflects the current obstacles and potential solutions toward the progressing trend of utilizing metabolomics in clinical research to create the next-generation healthcare system.11Ysciescopu

Early Chronic Kidney Disease (G1-G3a) in Combination with Steatosis as a Predictor of Incident Ischemic Heart Disease: A Longitudinal Study in Non-Diabetic Koreans

Hepatic steatosis and chronic kidney disease (CKD) in the advanced stages are closely related to cardiovascular diseases. Despite the potential connection between early CKD (G1-G3a) and hepatic steatosis on cardiometabolic risks, few studies have revealed their causal link to ischemic heart disease (IHD). We prospectively investigated the combined effect of CKD in earlier stages and hepatic steatosis on incident IHD risk in large-scale, non-diabetic Koreans. Data were assessed from 16,531 participants without diabetes from the Health Risk Assessment Study (HERAS) and Korea Health Insurance Review and Assessment (HIRA) data. We divided the study population into four groups according to the existence of early CKD and hepatic steatosis: controls, early CKD only, hepatic steatosis only, and both early CKD and hepatic steatosis. We prospectively assessed hazard ratios (HRs) with 95% confidence intervals (CIs) for IHD using multivariate Cox proportional-hazard regression models over a 50-month period. During the follow-up period, 326 (2.0%) patients developed IHD. HRs of IHD in the four groups were 1.00 (controls), 1.26 (95% CI 0.72-2.19), 1.19 (95% CI 0.90-1.57) and 1.76 (95% CI 1.04-2.97), respectively, after adjusting for potential confounding variables. Even less than stage 3A, CKD could precede and predict IHD in patients with hepatic steatosis.ope

The UK Biobank imaging enhancement of 100,000 participants: rationale, data collection, management and future directions

UK Biobank is a population-based cohort of half a million participants aged 40–69 years recruited between 2006 and 2010. In 2014, UK Biobank started the world’s largest multi-modal imaging study, with the aim of re-inviting 100,000 participants to undergo brain, cardiac and abdominal magnetic resonance imaging, dual-energy X-ray absorptiometry and carotid ultrasound. The combination of large-scale multi-modal imaging with extensive phenotypic and genetic data offers an unprecedented resource for scientists to conduct health-related research. This article provides an in-depth overview of the imaging enhancement, including the data collected, how it is managed and processed, and future direction

Studies on clinical and epidemiological factors associated with peripheral neuropathy and severe hyperlactatemia or lactic acidosis in HIV-infected adults exposed to nucleoside analogues reverse transcriptase inhibitors.

Studies on mitochondrial dysfunction in HIV-infected adults exposed to anti-retroviral therapy. A significant proportion of HIV-infected patients who require anti-retroviral therapy are or have been exposed to nucleoside analogue reverse transcriptase inhibitors (NRTIs). It has been consistently suggested that most of the NRTI-attributed adverse drug reactions (ADR) are due to mitochondrial dysfunction. In a sub-analysis of a large randomised clinical trial (Delta) the incidence of peripheral neuropathy (PN) was constant over time in all study arms, which does not support the hypothesis of cumulative toxicity previously proposed for NRTI-induced ADR. Patients taking zidovudine (AZT)/zalcitabine (ddC) combination were more likely to develop PN than patients on AZT monotherapy (RH= 2.30 95%CI= 1.62 - 3.28). The incidence of PN among patients exposed to zidovudine/didanosine (AZT/ddl) combination was not different from that observed in patients on AZT. In a multi-centre case-control study including 110 cases of lactic acidosis (LA) or severe hyperlactataemia (HL) patients with < 200 CD4 cell/pl were more likely to develop HL/LA than patients with higher levels of CD4 cells (OR=3.44 95%CI= 1.64 - 7.22). Female patients were found to be at higher risk for HULA than men (OR= 4.75 95%CI= 1.96 - 11.53). Patients exposed to either d4T, ddl or the combination of these two were four to six times more likely to develop HL/LA than patients taking other NRTIs based combinations. Interestingly, cases of HL/LA were exposed to d4T for shorter periods of time than controls. Almost 10 % of the cases included in the study were asymptomatic at the time of diagnosis. All these symptom-free cases had blood lactate ranging between 5 and 7 mmol/l. Therefore, case definitions for HL or LA based on clinical presentation may underestimate the magnitude of the problem

Postprandial Dysmetabolism and Non-Alcoholic Fatty Liver Disease in Relation to Type 2 Diabetes Mellitus and Cardiovascular Risk

Het aantal gevallen van “ouderdomssuikerziekte” (type 2 diabetes mellitus) neemt in de Westerse wereld snel toe als gevolg van veranderingen in leefstijl (verhoogde consumptie van vet- en energierijke voeding en verminderde lichaamsbeweging), en als gevolg van de vergrijzing van de bevolking. Mensen met type 2 diabetes mellitus hebben een verhoogd risico op het krijgen van hart- en vaatziekten. Dit verhoogde risico kan voor een deel verklaard worden door reeds bekende risicofactoren voor hart- en vaatziekten, zoals hoge bloeddruk (hypertensie), roken, afwijkende vetspiegels in het bloed (een verhoogd LDL-cholesterol (het “slechte” cholesterol), laag HDL cholesterol (goede cholesterol) en verhoogde hoeveelheden triglyceriden), alsook hoge glucose (suiker) concentraties in het bloed. Met name bij vrouwen na de menopauze (overgang) is het risico op hart- en vaatziekten hoger dan bij vrouwen vóór de menopauze. Na de overgang stijgt de hoeveelheid triglyceriden en daalt de hoeveelheid HDL-cholesterol in het bloed. Dit heeft ons aangespoord de effecten van maaltijden te bestuderen bij vrouwen na menopauze. Het is al langer bekend dat glucose en triglyceriden, en verbindingen die hieruit gevormd kunnen worden, schadelijk kunnen zijn voor de bloedvaten en daardoor kunnen bijdragen aan het ontwikkelen van hart- en vaatziekten. Ruim een kwart eeuw geleden is geopperd dat verstoringen in de vet- en glucosestofwisseling die optreden na een maaltijd mogelijk kunnen bijdragen aan het verhoogde risico op hart- en vaatziekten. Na het eten van een maaltijd stijgen de triglyceriden- en glucoseconcentraties in het bloed. De triglyceriden en de glucose worden gebruikt als bouwstoffen of als brandstoffen voor het lichaam. De mate waarin deze stoffen worden verwerkt en opgeslagen verschilt tussen gezonde mensen en mensen met type diabetes mellitus. De lever speelt hierbij een belangrijke rol. Een verhoogde hoeveelheid vet in de lever (steatose), een aandoening die vaker voorkomt bij mensen met diabetes en overgewicht, kan deze processen verstoren, alsook het risico op hart- en vaatziekten verhogen. Het hormoon insuline speelt een belangrijke rol bij het verwerken van de triglyceriden en de glucose. Bij mensen met type 2 diabetes mellitus werkt het insuline minder goed waardoor de triglyceriden en de glucose trager worden opgenomen en verwerkt. De vraag is welke stof schadelijker is voor de vaatwand: de glucose of de triglyceriden? De onderzoeken die in dit proefschrift beschreven zijn, proberen antwoord te geven op de volgende vragen: 1a) hoe is het beloop van glucose en triglyceriden in het bloed na twee vetrijke en twee koolhydraatrijke maaltijden, 1b) wat is de relatieve bijdrage van glucose en triglyceriden in relatie tot hart- en vaatziekten en 1c) welke mechanismen kunnen het verhoogde risico op hart- en vaatzieken verklaren bij patiënten met type 2 diabetes mellitus; 2a) hebben mensen met leververvetting een verhoogde kans op het risico van hart- en vaatzieken en 2b) wat zijn de mogelijke mechanismen waardoor dit verklaard kan worden?Heine, R.J. [Promotor]Diamant, M. [Copromotor]Teerlink, T. [Copromotor