BMI, Alcohol Consumption and Gut Microbiome Species Richness Are Related to Structural and Functional Neurological Abnormalities

The incidence of neurological diseases is increasing throughout the world. The aim of the present study was to identify nutrition and microbiome factors related to structural and functional neurological abnormalities to optimize future preventive strategies. Methods: Two hundred thirty-eight patients suffering from (1) structural (neurodegeneration) or (2) functional (epilepsy) neurological abnormalities or (3) chronic pain (migraine) and 612 healthy control subjects were analyzed by validated 12-month food frequency questionnaire (FFQ) and 16S rRNA micro- biome sequencing (from stool samples). A binomial logistic regression model was applied for risk calculation and functional pathway analysis to show which functional pathway could discriminate cases and healthy controls. Results: Detailed analysis of more than 60 macro- and micronutrients revealed no distinct significant difference between cases and controls, whereas BMI, insulin resistance and metabolic inflammation in addition to alcohol consumption were major drivers of an overall neurological disease risk. The gut microbiome analysis showed decreased alpha diversity (Shannon index: p = 9.1× 10 −7 ) and species richness (p = 1.2 × 10 −8 ) in the case group as well as signifi- cant differences in beta diversity between cases and controls (Bray–Curtis: p = 9.99 × 10 −4 ; Jaccard: p = 9.99 × 10 −4 ). The Shannon index showed a beneficial effect (OR = 0.59 (95%-CI (0.40, 0.87); p = 8 × 10 −3 ). Cases were clearly discriminated from healthy controls by environmental information processing, signal transduction, two component system and membrane transport as significantly different functional pathways. Conclusions: In conclusion, our data indicate that an overall healthy lifestyle, in contrast to supplementation of single micro- or macronutrients, is most likely to reduce overall neurological abnormality risk and that the gut microbiome is an interesting target to develop novel preventive strategies

Precision Nutrition in Chronic Inflammation

The molecular foundation of chronic in fl ammatory diseases (CIDs) can differ markedly between individuals. As our understanding of the biochemical mechanisms underlying individual disease manifestations and progressions expands, new strategies to adjust treatments to the patient ’ s characteristics will continue to profoundly transform clinical practice. Nutrition has long been recognized as an important determinant of in fl ammatory disease phenotypes and treatment response. Yet empirical work demonstrating the therapeutic effectiveness of patient-tailored nutrition remains scarce. This is mainly due to the challenges presented by long-term effects of nutrition, variations in inter-individual gastrointestinal microbiota, the multiplicity of human metabolic pathways potentially affected by food ingredients, nutrition behavior, and the complexity of food composition. Historically, these challenges have been addressed in both human studies and experimental model laboratory studies primarily by using individual nutrition data collection in tandem with large- scale biomolecular data acquisition (e.g. genomics, metabolomics, etc.). This review highlights recent fi ndings in the fi eld of precision nutrition and their potential implications for the development of personalized treatment strategies for CIDs. It emphasizes the importance of computational approaches to integrate nutritional information into multi- omics data analysis and to predict which molecular mechanisms may explain how nutrients intersect with disease pathways. We conclude that recent fi ndings point towards the unexhausted potential of nutrition as part of personalized medicine in chronic in fl ammation

Genetische und Umweltfaktoren und ihre Zusammenhänge mit der Geschmackswahrnehmung des Menschen

Taste perception is important in health and disease. From an evolutionary perspective, the ability to make competent decisions between nutritious and toxic food elements was crucial in survival. Living in a westernized world, hedonic feeding seems to have overgrown homeostatic signals of satiety and fullness, leading to overconsumption of energy dense, unhealthy food and with this contributing to the obesity pandemic. On the other hand, a reduction of taste perception affects the quality of life and has even been linked to depression and other diseases. Therefore, this work aimed at contributing to a deeper understanding of taste perception in humans. To this goal, comprehensive analysis of genetic and environmental data from a large human cohort was conducted with respect to bitter and salty taste perception. The study revealed novel insights into human taste perception: In general, bitter taste sensitivity was more closely linked to genetic traits than salty while salty taste sensitivity demonstrated more associations with environmental factors. In genetic analyses nucleotide polymorphisms as well as haplotypes involved in taste perception of specific bitter compounds popped up, which is in accordance with previous studies and by this strengthening the validity of the herein presented cohort. This work further suggests an ion exchanger to be involved in salty taste perception in taste bud cells, which might be of interest since transduction mechanisms of salty taste are not fully understood yet. Furthermore, an intestinal oligosaccharide digesting enzyme which is a target of anti-diabetic drugs was linked to bitter taste and seems to be under regulatory control of bitter tasting nutrients as shown in other studies. Despite the fact that only few associations of taste and nutrition could be found, an overall trend was observable in that a less taste sensitive phenotype seems to be connected with a healthier diet. Matching these findings, probands with high bitter as well as salty taste sensitivity exhibited a higher BMI. Furthermore, genes involved in neuron development and functionality have been detected to be in association with taste and might be of interest in conjunction with BMI and taste processing brain regions, which indeed revealed a direct link with obesity but not with taste perception in a subcohort of this study. Several gut bacterial species showed associations with taste. In high salt sensitivity, two candidate bacteria showed strong associations with a gut bacterial composition low in diverse species richness, being in line with a reduction in α-diversity in obese subjects – which also exhibited a rather salt sensitive phenotype in this cohort. Akkermansia, known for a variety of health promoting effects, was reduced in states of bitter sensitivity. In conclusion this work provides novel insights into taste perception in humans, with promising candidates which might be worth further investigations in follow up studies

Glioblastoma multiforme: Metabolic differences to peritumoral tissue and IDH-mutated gliomas revealed by mass spectrometry imaging.

Kampa JM, Kellner U, Marsching C, et al. Glioblastoma multiforme: Metabolic differences to peritumoral tissue and IDH-mutated gliomas revealed by mass spectrometry imaging. Neuropathology : official journal of the Japanese Society of Neuropathology. 2020;40(6):546-558.Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor. High infiltration rates and poor therapy responses make it the deadliest glioma. The tumor metabolism is known to differ from normal one and is influenced through various factors which can lead to longer survival. Metabolites are small molecules (<1500Da) that display the metabolic pathways in the tissue. To determine the metabolic alterations between tumor and peritumoral tissue in human GBMs, mass spectrometry imaging (MSI) was performed on thin sections from 25 resected tumors. In addition, the GBMs were compared with six gliomas harboring a mutation in the isocitrate dehydrogenase (IDH1) gene (IDH1). With this technique, a manifold of analytes can be easily visualized on a single tissue section. Metabolites were annotated based on their accurate mass using high resolution MSI. Differences in their mean intensities in the tumor and peritumoral areas were statistically evaluated and abundances were visualized on the tissue. Enhanced levels of the antioxidants ascorbic acid, taurine, and glutathione in tumor areas suggest protective effects on the tumor. Increased levels of purine and pyrimidine metabolism compounds in GBM areas indicate the high energy demand. In accordance with these results, enhanced abundances of lactate and glutamine were detected. Moreover, decreased abundance of N-acetylaspartate, a marker for neuronal health, was measured in tumor areas. Obtained metabolic information could potentially support and personalize therapeutic approaches, hence emphasizing the suitability of MSI for GBM research. © 2020 The Authors. Neuropathology published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Neuropathology

Vitamin C and Omega-3 Fatty Acid Intake Is Associated with Human Periodontitis&mdash;A Nested Case-Control Study

Vitamins and omega-3 fatty acids (&#8486;3FA) modulate periodontitis-associated inflammatory processes. The aim of the current investigation was to evaluate associations of oral nutrient intake and corresponding serum metabolites with clinical severity of human periodontitis. Within the Food Chain Plus cohort, 373 periodontitis patients&mdash;245 without (POL) and 128 with tooth loss (PWL)&mdash;were matched to 373 controls based on sex, smoking habit, age and body mass index in a nested case-control design. The amount of oral intake of vitamins and &#8486;3FAs was assessed from nutritional data using a Food Frequency Questionnaire. Oral intake and circulatory bioavailability of vitamins and &#8486;3FA serum metabolomics were compared, using ultra-high-resolution mass spectrometry. Periodontitis patients exhibited a significantly higher oral intake of vitamin C and &#8486;3FA Docosapentaenoic acid (p &lt; 0.05) compared to controls. Nutritional intake of vitamin C was higher in PWL, while the intake of Docosapentaenoic acid was increased in POL (p &lt; 0.05) compared to controls. In accordance, serum levels of Docosapentaenoic acid were also increased in POL (p &lt; 0.01) compared to controls. Vitamin C and the &#8486;3FA Docosapentaenoic acid might play a role in the pathophysiology of human periodontitis. Further studies on individualized nutritional intake and periodontitis progression and therapy are necessary

Effects of lifestyle and associated diseases on serum CC16 suggest complex interactions among metabolism, heart and lungs

Introduction: Clara cell 16-kDa protein (CC16) is an anti-inflammatory, immunomodulatory secreted pulmonary protein with reduced serum concentrations in obesity according to recent data. Objective: Studies focused solely on bodyweight, which does not properly reflect obesity-associated implications of the metabolic and reno-cardio-vascular system. The purpose of this study was therefore to examine CC16 in a broad physiological context considering cardio-metabolic comorbidities of primary pulmonary diseases. Methods: CC16 was quantified in serum samples in a subset of the FoCus (N = 497) and two weight loss intervention cohorts (N = 99) using ELISA. Correlation and general linear regression analyses were applied to assess CC16 effects of lifestyle, gut microbiota, disease occurrence and treatment strategies. Importance and intercorrelation of determinants were validated using random forest algorithms. Results: CC16 A38G gene mutation, smoking and low microbial diversity significantly decreased CC16. Pre-menopausal female displayed lower CC16 compared to post-menopausal female and male participants. Biological age and uricosuric medications increased CC16 (all p < 0.01). Adjusted linear regression revealed CC16 lowering effects of high waist-to-hip ratio (est. −11.19 [−19.4; −2.97], p = 7.99 × 10−3), severe obesity (est. −2.58 [−4.33; −0.82], p = 4.14 × 10−3) and hypertension (est. −4.31 [−7.5; −1.12], p = 8.48 × 10−3). ACEi/ARB medication (p = 2.5 × 10−2) and chronic heart failure (est. 4.69 [1.37; 8.02], p = 5.91 × 10−3) presented increasing effects on CC16. Mild associations of CC16 were observed with blood pressure, HOMA-IR and NT-proBNP, but not manifest hyperlipidemia, type 2 diabetes, diet quality and dietary weight loss intervention. Conclusion: A role of metabolic and cardiovascular abnormalities in the regulation of CC16 and its modifiability by behavioral and pharmacological interventions is indicated. Alterations by ACEi/ARB and uricosurics could point towards regulatory axes comprising the renin-angiotensin-aldosterone system and purine metabolism. Findings altogether strengthen the importance of interactions among metabolism, heart and lungs