Scope
Western type of diets are characterized by high animal protein intake and are associated with various chronic inflammatory diseases. With a higher protein consumption, excess undigested protein ...will reach the colon and be subsequently metabolized by gut microbiota. Depending on the type of protein, fermentation in the colon generates different metabolites with varying biological effects. This study aims to compare the impact of protein fermentation products from different sources on gut health.
Methods and results
Three high protein diets (vital wheat gluten VWG, lentil, or casein) are submitted to the in vitro model of colon. Fermentation of excess lentil protein for 72 h results in highest production of short‐chain fatty acids and lowest production of branched‐chain fatty acids. Exposure of Caco‐2 monolayers or Caco‐2 monolayers co‐cultured with THP‐1 macrophages to luminal extracts of fermented lentil protein results in less cytotoxicity of Caco‐2 monolayers and less damage to barrier integrity, when compared to VWG and casein. Lowest induction of interleukin‐6 is observed in THP‐1 macrophages after treatment with lentil luminal extracts, which is identified to be regulated by aryl hydrocarbon receptor signaling.
Conclusion
The findings indicate that protein sources affect the health effects of high protein diet in the gut.
Three different high protein diets are submitted to the in vitro model of colon (TIM‐2). Cumulative short‐chain fatty acids and branched‐chain fatty acids produced during fermentation are measured. The aqueous phases of lumen samples are collected after 72 h and are used to treat different cell models to assess their effects on cell viability, epithelial barrier integrity, and cytokine secretion.
Current technological developments have allowed for a significant increase and availability of data. Consequently, this has opened enormous opportunities for the machine learning and data science ...field, translating into the development of new algorithms in a wide range of applications in medical, biomedical, daily-life, and national security areas. Ensemble techniques are among the pillars of the machine learning field, and they can be defined as approaches in which multiple, complex, independent/uncorrelated, predictive models are subsequently combined by either averaging or voting to yield a higher model performance. Random forest (RF), a popular ensemble method, has been successfully applied in various domains due to its ability to build predictive models with high certainty and little necessity of model optimization. RF provides both a predictive model and an estimation of the variable importance. However, the estimation of the variable importance is based on thousands of trees, and therefore, it does not specify which variable is important for which sample group.
The present study demonstrates an approach based on the pseudo-sample principle that allows for construction of bi-plots (i.e. spin plots) associated with RF models. The pseudo-sample principle for RF. is explained and demonstrated by using two simulated datasets, and three different types of real data, which include political sciences, food chemistry and the human microbiome data. The pseudo-sample bi-plots, associated with RF and its unsupervised version, allow for a versatile visualization of multivariate models, and the variable importance and the relation among them.
Display omitted
•Pseudo-samples enable visualization of the variable importance in random forest (RF).•Interpretation of variable importance in RF and unsupervised random forest (URF).•Possibility of obtaining so called bi-plot for RF and URF.•Relation between variables are obtained using principal coordinates analysis.
Analysis of exhaled breath for asthma phenotyping using endogenously generated volatile organic compounds (VOCs) offers the possibility of noninvasive diagnosis and therapeutic monitoring. Induced ...sputum is indeed not widely available and markers of neutrophilic asthma are still lacking.
To determine whether analysis of exhaled breath using endogenously generated VOCs can be a surrogate marker for recognition of sputum inflammatory phenotypes.
We conducted a prospective study on 521 patients with asthma recruited from the University Asthma Clinic of Liege. Patients underwent VOC measurement, fraction of exhaled nitric oxide (Fe
) spirometry, sputum induction, and gave a blood sample. Subjects with asthma were classified in three inflammatory phenotypes according to their sputum granulocytic cell count.
In the discovery study, seven potential biomarkers were highlighted by gas chromatography-mass spectrometry in a training cohort of 276 patients with asthma. In the replication study (
= 245), we confirmed four VOCs of interest to discriminate among asthma inflammatory phenotypes using comprehensive two-dimensional gas chromatography coupled to high-resolution time-of-flight mass spectrometry. Hexane and 2-hexanone were identified as compounds with the highest classification performance in eosinophilic asthma with accuracy comparable to that of blood eosinophils and Fe
. Moreover, the combination of Fe
, blood eosinophils, and VOCs gave a very good prediction of eosinophilic asthma (area under the receiver operating characteristic curve, 0.9). For neutrophilic asthma, the combination of nonanal, 1-propanol, and hexane had a classification performance similar to Fe
or blood eosinophils in eosinophilic asthma. Those compounds were found in higher levels in neutrophilic asthma.
Our study is the first attempt to characterize VOCs according to sputum granulocytic profile in a large population of patients with asthma and provide surrogate markers for neutrophilic asthma.
Smoking is a major risk factor for bladder cancer (BC). This meta-analysis updates previous reviews on smoking characteristics and BC risk, and provides a more quantitative estimation of the ...dose-response relationship between smoking characteristics and BC risk.
In total, 89 studies comprising data from 57 145 BC cases were included and summary odds ratios (SORs) were calculated. Dose-response meta-analyses modelled relationships between smoking intensity, duration, pack-years and cessation and BC risk. Sources of heterogeneity were explored and sensitivity analyses were conducted to test the robustness of findings.
Current smokers (SOR = 3.14, 95% CI = 2.53-3.75) and former smokers(SOR = 1.83, 95% CI = 1.52-2.14) had an increased risk of BC compared with never smokers. Age at first exposure was negatively associated with BC risk. BC risk increased gradually by smoking duration and a risk plateau at smoking 15 cigarettes a day and 50 pack-years was observed. Smoking cessation is most beneficial from 20 years before diagnosis. The population-attributable risk of BC for smokers has decreased from 50% to 43% in men and from 35% to 26% in women from Europe since estimated in 2000. Results were homogeneous between sources of heterogeneity, except for lower risk estimates found in studies of Asian populations.
Active smokers are at an increased risk of BC. Dose-response meta-analyses showed a BC risk plateau for smoking intensity and indicate that even after long-term smoking cessation, an elevated risk of bladder cancer remains.
Hypertension is an established risk factor for renal cell cancer (RCC). The renin‐angiotensin‐aldosterone system (RAAS) regulates blood pressure and is closely linked to hypertension. RAAS ...additionally influences homeostasis of electrolytes (e.g. sodium and potassium) and fluid. We investigated single nucleotide polymorphisms (SNPs) in RAAS and their interactions with hypertension and intakes of sodium, potassium and fluid regarding RCC risk in the Netherlands Cohort Study (NLCS), which was initiated in 1986 and included 120,852 participants aged 55 to 69 years. Diet and lifestyle were assessed by questionnaires and toenail clippings were collected. Genotyping of toenail DNA was performed using the SEQUENOM® MassARRAY® platform for a literature‐based selection of 13 candidate SNPs in seven key RAAS genes. After 20.3 years of follow‐up, Cox regression analyses were conducted using a case‐cohort approach including 3,583 subcohort members and 503 RCC cases. Two SNPs in AGTR1 were associated with RCC risk. AGTR1_rs1492078 (AA vs. GG) decreased RCC risk hazard ratio (HR) (95% confidence interval (CI)): 0.70(0.49–1.00), whereas AGTR1_rs5186 (CC vs. AA) increased RCC risk HR(95%CI): 1.49(1.08–2.05). Associations were stronger in participants with hypertension. The RCC risk for AGT_rs3889728 (AG + AA vs. GG) was modified by hypertension (p interaction = 0.039). SNP‐diet interactions were not significant, although HRs suggested interaction between SNPs in ACE and sodium intake. SNPs in AGTR1 and AGT influenced RCC susceptibility, and their effects were modified by hypertension. Sodium intake was differentially associated with RCC risk across genotypes of several SNPs, yet some analyses had probably inadequate power to show significant interaction. Results suggest that RAAS may be a candidate pathway in RCC etiology.
What's new?
The renin‐angiotensin‐aldosterone system (RAAS) regulates blood pressure and salt homeostasis in the kidney and may, therefore, reflect a mechanism potentially underlying associations between hypertension or sodium intake and risk of renal cell cancer (RCC). In this prospective cohort study, several polymorphisms in RAAS genes, specifically in AGT, AGTR1, and ACE, were found to be associated with RCC risk. For polymorphisms in AGT and AGTR1, associations may be modified by hypertension, while for variants in ACE, suggestive biologic interaction with sodium intake was observed.
Evidence is emerging for the role of intestinal tryptophan metabolism in the development of inflammatory bowel disease (IBD). In order to identify the role of altered intestinal tryptophan metabolism ...in IBD pathogenesis, a meta-analysis of the transcriptome was performed to identify differentially expressed genes involved in the tryptophan metabolism pathways in intestinal biopsies of IBD as compared to non-IBD controls. Moreover, a systematic review of the metabolome was performed to identify the concurrent changes in tryptophan metabolites. Integration of the transcriptome and metabolome identified various alterations in intestinal tryptophan metabolism during active disease in IBD patients, including decreased intestinal tryptophan absorption, enhanced kynurenine pathway, increased interstitial serotonin availability, changed indole pathway, and activated aryl hydrocarbon receptor signaling. Therefore, a network of intestinal tryptophan metabolism pathways in IBD could be established, helping to assess the potential of genes and metabolites involved in these pathways as diagnostic markers and targets for IBD management.
Medical diagnosis and phenotyping increasingly incorporate information from complex biological samples. This has promoted the development and clinical application of non-invasive metabolomics in ...exhaled air (breathomics). In respiratory medicine, expired volatile organic compounds (VOCs) are associated with inflammatory, oxidative, microbial, and neoplastic processes. After recent proof of concept studies demonstrating moderate to good diagnostic accuracies, the latest efforts in breathomics are focused on optimization of sensor technologies and analytical algorithms, as well as on independent validation of clinical classification and prediction. Current research strategies are revealing the underlying pathophysiological pathways as well as clinically-acceptable levels of diagnostic accuracy. Implementing recent guidelines on validating molecular signatures in medicine will enhance the clinical potential of breathomics and the development of point-of-care technologies.
Early and reliable determination of bacterial strain specificity and antibiotic resistance is critical to improve sepsis treatment. Previous research demonstrated the potential of headspace analysis ...of volatile organic compounds (VOCs) to differentiate between various microorganisms associated with pulmonary infections in vitro. This study evaluates whether VOC analysis can also discriminate antibiotic sensitive from resistant bacterial strains when cultured on varying growth media.
Both antibiotic-sensitive and -resistant strains of Pseudomonas aeruginosa, Staphylococcus aureus and Klebsiella pneumonia were cultured on 4 different growth media, i.e. Brain Heart Infusion, Marine Broth, Müller-Hinton and Trypticase Soy Agar. After overnight incubation at 37°C, the headspace air of the cultures was collected on stainless steel desorption tubes and analyzed by gas chromatography time-of-flight mass spectrometry (GC-tof-MS). Statistical analysis was performed using regularized multivariate analysis of variance and cross validation.
The three bacterial species could be correctly recognized based on the differential presence of 14 VOCs (p<0.001). This discrimination was not influenced by the different growth media. Interestingly, a clear discrimination could be made between the antibiotic-resistant and -sensitive variant of Pseudomonas aeruginosa (p<0.001) based on their species-specific VOC signature.
This study demonstrates that isolated microorganisms, including antibiotic-sensitive and -resistant strains of Pseudomonas aeruginosa, could be identified based on their excreted VOCs independent of the applied growth media. These findings suggest that the discriminating volatiles are associated with the microorganisms themselves rather than with their growth medium. This study exemplifies the potential of VOC analysis as diagnostic tool in medical microbiology. However, validation of our results in appropriate in vivo models is critical to improve translation of breath analysis to clinical applications.
Human smoking behavior influences exposure to smoke toxicants and is important for risk assessment. In a prospective observational study, the smoking behavior of Marlboro smokers was measured for 36 ...h. Puff volume, duration, frequency, flow and inter-puff interval were recorded with the portable CReSSmicro™ device, as has often been done by other scientists. However, the use of the CReSSmicro™ device may lead to some registration pitfalls since the method of insertion of the cigarette may influence the data collection. Participants demonstrated consistent individual characteristic puffing behavior over the course of the day, enabling the creation of a personalized puffing profile. These puffing profiles were subsequently used as settings for smoking machine experiments and tar, nicotine and carbon monoxide (TNCO) emissions were generated. The application of human puffing profiles led to TNCO exposures more in the range of Health Canada Intense (HCI)-TNCO emissions than for those of the International Standardization Organization (ISO). Compared to the ISO regime, which applies a low puff volume relative to human smokers, the generation of TNCO may be at least two times higher than when human puffing profiles were applied on the smoking machine. Human smokers showed a higher puffing intensity than HCI and ISO because of higher puffing frequency, which resulted in more puffs per cigarette, than both HCI and ISO.
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