(Wh)olistic (E)ndocannabinoidome-Microbiome-Axis Modulation through (N)utrition (WHEN) to Curb Obesity and Related Disorders.

The discovery of the endocannabinoidome (eCBome) is evolving gradually with yet to be elucidated functional lipid mediators and receptors. The diet modulates these bioactive lipids and the gut microbiome, both working in an entwined alliance. Mounting evidence suggests that, in different ways and with a certain specialisation, lipid signalling mediators such as N-acylethanolamines (NAEs), 2-monoacylglycerols (2-MAGs), and N-acyl-amino acids (NAAs), along with endocannabinoids (eCBs), can modulate physiological mechanisms underpinning appetite, food intake, macronutrient metabolism, pain sensation, blood pressure, mood, cognition, and immunity. This knowledge has been primarily utilised in pharmacology and medicine to develop many drugs targeting the fine and specific molecular pathways orchestrating eCB and eCBome activity. Conversely, the contribution of dietary NAEs, 2-MAGs and eCBs to the biological functions of these molecules has been little studied. In this review, we discuss the importance of (Wh) olistic (E)ndocannabinoidome-Microbiome-Axis Modulation through (N) utrition (WHEN), in the management of obesity and related disorders.

Nutrient Intake and Dietary Inflammatory Potential in Current and Recovered Anorexia Nervosa.

Anorexia nervosa (AN) is characterised by disrupted and restrictive eating patterns. Recent investigations and meta-analyses have found altered concentrations of inflammatory markers in people with current AN. We aimed to assess nutrient intake in participants with current or recovered AN, as compared to healthy individuals, and explore group differences in dietary inflammatory potential as a possible explanation for the observed alterations in inflammatory markers. We recruited participants with current AN (n = 51), those recovered from AN (n = 23), and healthy controls (n = 49). We used the Food Frequency Questionnaire (FFQ), to calculate a Dietary Inflammatory Index (DII®) score and collected blood samples to measure serum concentrations of inflammatory markers. In current AN participants, we found lower intake of cholesterol, compared to HCs, and lower consumption of zinc and protein, compared to HC and recovered AN participants. A one-way ANOVA revealed no significant group differences in DII score. Multivariable regression analyses showed that DII scores were significantly associated with tumour necrosis factor (TNF)-α concentrations in our current AN sample. Our findings on nutrient intake are partially consistent with previous research. The lack of group differences in DII score, perhaps suggests that diet is not a key contributor to altered inflammatory marker concentrations in current and recovered AN. Future research would benefit from including larger samples and using multiple 24-h dietary recalls to assess dietary intake.

Effect on an Oral Nutritional Supplement with ß-Hydroxy-ß-methylbutyrate and Vitamin D on Morphofunctional Aspects, Body Composition, and Phase Angle in Malnourished Patients.

This is a retrospective study of data from clinical practice to observe the effect of a high-calorie, high-protein oral nutritional supplement (ONS) with ß-hydroxy-ß-methylbutyrate (HMB) on nutritional status, body weight, and muscle-related parameters in 283 adult patients with or at risk of malnutrition under standard of care, 63% being cancer patients. They were recommended to increase physical activity and energy and protein intake from regular diet plus two servings per day of a specialized ONS enriched with HMB or standard ONS for up to 6 months. Dietary records, adherence and tolerance to ONS, nutritional status, body composition, handgrip strength, and blood analysis at the beginning and the end of the intervention were recorded. This program improved nutritional status from 100% malnourished or at risk of malnutrition at baseline to 80% well-nourished at final visit. It also increased body weight by 3.6-3.8 kg, fat-free mass by 0.9 to 1.3 kg, and handgrip strength by 4.7 to 6.2 kg. In a subgroup of patients (n = 43), phase angle (PhA), and body cell mass (BCM) increased only in the patients receiving the ONS enriched with HMB (0.95 (0.13) vs. -0.36 (0.4), and 2.98 (0.5) vs. -0.6 (1.5) kg, mean difference (SE) from baseline for PhA and BCM, respectively), suggesting the potential efficacy of this supplement on muscle health.

How a Nutritional Deficiency Became Treated with Fluoride.

Ignoring evidence on causes of disease such as smoking can harm public health. This report explores how public health experts started to ignore evidence that pediatric vitamin D deficiencies are associated with dental caries. Historical analyses show that an organization of clinical specialists, the American Dental Association (ADA), initiated this view. The ADA was a world-leading organization and its governing bodies worked through political channels to make fluoride a global standard of care for a disease which at the time was viewed as an indicator of vitamin D deficiencies. The ADA scientific council was enlisted in this endeavor and authorized the statement saying that "claims for vitamin D as a factor in tooth decay are not acceptable". This statement was ghost-written, the opposite of what the ADA scientific council had endorsed for 15 years, and the opposite of what the National Academy of Sciences concluded. Internal ADA documents are informative on the origin of this scientific conundrum; the ADA scientific council had ignored their scientific rules and was assisting ADA governing bodies in conflicts with the medical profession on advertising policies. The evidence presented here suggests that professional organizations of clinical specialists have the power to create standards of care which ignore key evidence and consequently can harm public health.

Natural and Synthetic Bioactives for Skin Health, Disease and Management.

The skin is the largest organ of the integumentary system, strategically located at the interface of the body's internal and external environment. [...].

Nutrient Intake and Gut Microbial Genera Changes after a 4-Week Placebo Controlled Galacto-Oligosaccharides Intervention in Young Females.

Recent interest in the gut-brain-axis has highlighted the potential of prebiotics to impact wellbeing, and to affect behavioral change in humans. In this clinical trial, we examined the impact of four-weeks daily supplementation of galacto-oligosaccharides (GOS) on self-reported nutrient intake and relationships on gut microbiota in a four-week two-armed parallel double-blind placebo controlled GOS supplement trial in young adult females. Food diaries and stool samples were collected prior to and following 28 days of supplement consumption. It was found that four weeks of GOS supplementation influenced macronutrient intake, as evident by reduced carbohydrate and sugars and increased fats intake. Further analysis showed that the reduction in carbohydrates was predicted by increasing abundances of Bifidobacterium in the GOS group in comparison to the placebo group. This suggests that Bifidobacterium increase via GOS supplementation may help improve the gut microbiota composition by altering the desire for specific types of carbohydrates and boosting Bifidobacterium availability when fiber intake is below recommended levels, without compromising appetite for fiber from food.

Microbiome and Human Aging: Probiotic and Prebiotic Potentials in Longevity, Skin Health and Cellular Senescence.

The role of the microbiome in human aging is important: the microbiome directly impacts aging through the gastrointestinal system. However, the microbial impact on skin has yet to be fully understood. For example, cellular senescence is an intrinsic aging process that has been recently associated with microbial imbalance. With age, cells become senescent in response to stress wherein they undergo irreversible growth arrest while maintaining high metabolic activity. An accumulation of senescent cells has been linked to various aging and chronic pathologies due to an overexpression of the senescence-associated secretory phenotype (SASP) comprised of proinflammatory cytokines, chemokines, growth factors, proteases, lipids and extracellular matrix components. In particular, dermatological disorders may be promoted by senescence as the skin is a common site of accumulation. The gut microbiota influences cellular senescence and skin disruption through the gut-skin axis and secretion of microbial metabolites. Metabolomics can be used to identify and quantify metabolites involved in senescence. Moreover, novel anti-senescent therapeutics are warranted given the poor safety profiles of current pharmaceutical drugs. Probiotics and prebiotics may be effective alternatives, considering the relationship between the microbiome and healthy aging. However, further research on gut composition under a senescent status is needed to develop immunomodulatory therapies.

Nutrient Effects on Motor Neurons and the Risk of Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is an incurable chronic progressive neurodegenerative disease with the progressive degeneration of motor neurons in the motor cortex and lower motor neurons in the spinal cord and the brain stem. The etiology and pathogenesis of ALS are being actively studied, but there is still no single concept. The study of ALS risk factors can help to understand the mechanism of this disease development and, possibly, slow down the rate of its progression in patients and also reduce the risk of its development in people with a predisposition toward familial ALS. The interest of researchers and clinicians in the protective role of nutrients in the development of ALS has been increasing in recent years. However, the role of some of them is not well-understood or disputed. The objective of this review is to analyze studies on the role of nutrients as environmental factors affecting the risk of developing ALS and the rate of motor neuron degeneration progression. METHODS: We searched the PubMed, Springer, Clinical keys, Google Scholar, and E-Library databases for publications using keywords and their combinations. We analyzed all the available studies published in 2010-2020. DISCUSSION: We analyzed 39 studies, including randomized clinical trials, clinical cases, and meta-analyses, involving ALS patients and studies on animal models of ALS. This review demonstrated that the following vitamins are the most significant protectors of ALS development: vitamin B12, vitamin E > vitamin C > vitamin B1, vitamin B9 > vitamin D > vitamin B2, vitamin B6 > vitamin A, and vitamin B7. In addition, this review indicates that the role of foods with a high content of cholesterol, polyunsaturated fatty acids, urates, and purines plays a big part in ALS development. CONCLUSION: The inclusion of vitamins and a ketogenic diet in disease-modifying ALS therapy can reduce the progression rate of motor neuron degeneration and slow the rate of disease progression, but the approach to nutrient selection must be personalized. The roles of vitamins C, D, and B7 as ALS protectors need further study.

The Impact of Vegan and Vegetarian Diets on Physical Performance and Molecular Signaling in Skeletal Muscle.

Muscular adaptations can be triggered by exercise and diet. As vegan and vegetarian diets differ in nutrient composition compared to an omnivorous diet, a change in dietary regimen might alter physiological responses to physical exercise and influence physical performance. Mitochondria abundance, muscle capillary density, hemoglobin concentration, endothelial function, functional heart morphology and availability of carbohydrates affect endurance performance and can be influenced by diet. Based on these factors, a vegan and vegetarian diet possesses potentially advantageous properties for endurance performance. Properties of the contractile elements, muscle protein synthesis, the neuromuscular system and phosphagen availability affect strength performance and can also be influenced by diet. However, a vegan and vegetarian diet possesses potentially disadvantageous properties for strength performance. Current research has failed to demonstrate consistent differences of performance between diets but a trend towards improved performance after vegetarian and vegan diets for both endurance and strength exercise has been shown. Importantly, diet alters molecular signaling via leucine, creatine, DHA and EPA that directly modulates skeletal muscle adaptation. By changing the gut microbiome, diet can modulate signaling through the production of SFCA.

The Impact of Microbial Composition on Postprandial Glycaemia and Lipidaemia: A Systematic Review of Current Evidence.

Postprandial hyperglycaemia is associated with increased risk of cardiovascular disease. Recent studies highlight the role of the gut microbiome in influencing postprandial glycaemic (PPG) and lipidaemic (PPL) responses. The authors of this review sought to address the question: "To what extent does individual gut microbiome diversity and composition contribute to PPG and PPL responses?". CINAHL Plus, PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched from January 2010 to June 2020. Following screening, 22 studies were eligible to be included in the current review. All trials reported analysis of gut microbiome diversity and composition and PPG and/or PPL. Results were reported according to the 'Preferred Reporting Items for Systematic Reviews and Meta-Analysis' (PRISMA) statement. Individual microbiota structure was found to play a key role in determining postprandial metabolic responses in adults and is attributed to a complex interplay of diet, microbiota composition, and metagenomic activity, which may be predicted by metagenomic analysis. Alterations of gut microbiota, namely relative abundance of bacterial phylum Actinobacteria and Proteobacteria, along with Enterobacteriaceae, were associated with individual variation in postprandial glycaemic response in adults. The findings of the current review present new evidence to support a personalised approach to nutritional recommendations and guidance for optimal health, management, and treatment of common metabolic disorders. In conclusion, personalised nutrition approaches based on individual microbial composition may improve postprandial regulation of glucose and lipids, providing a potential strategy to ameliorate cardiometabolic health outcomes.

Flavonoid-Modifying Capabilities of the Human Gut Microbiome-An In Silico Study.

Flavonoids are a major group of dietary plant polyphenols and have a positive health impact, but their modification and degradation in the human gut is still widely unknown. Due to the rise of metagenome data of the human gut microbiome and the assembly of hundreds of thousands of bacterial metagenome-assembled genomes (MAGs), large-scale screening for potential flavonoid-modifying enzymes of human gut bacteria is now feasible. With sequences of characterized flavonoid-transforming enzymes as queries, the Unified Human Gastrointestinal Protein catalog was analyzed and genes encoding putative flavonoid-modifying enzymes were quantified. The results revealed that flavonoid-modifying enzymes are often encoded in gut bacteria hitherto not considered to modify flavonoids. The enzymes for the physiologically important daidzein-to-equol conversion, well studied in Slackiaisoflavoniconvertens, were encoded only to a minor extent in Slackia MAGs, but were more abundant in Adlercreutzia equolifaciens and an uncharacterized Eggerthellaceae species. In addition, enzymes with a sequence identity of about 35% were encoded in highly abundant MAGs of uncultivated Collinsella species, which suggests a hitherto uncharacterized daidzein-to-equol potential in these bacteria. Of all potential flavonoid modification steps, O-deglycosylation (including derhamnosylation) was by far the most abundant in this analysis. In contrast, enzymes putatively involved in C-deglycosylation were detected less often in human gut bacteria and mainly found in Agathobacter faecis (formerly Roseburia faecis). Homologs to phloretin hydrolase, flavanonol/flavanone-cleaving reductase and flavone reductase were of intermediate abundance (several hundred MAGs) and mainly prevalent in Flavonifractor plautii. This first comprehensive insight into the black box of flavonoid modification in the human gut highlights many hitherto overlooked and uncultured bacterial genera and species as potential key organisms in flavonoid modification. This could lead to a significant contribution to future biochemical-microbiological investigations on gut bacterial flavonoid transformation. In addition, our results are important for individual nutritional recommendations and for biotechnological applications that rely on novel enzymes catalyzing potentially useful flavonoid modification reactions.

Associations between Fasting Duration, Timing of First and Last Meal, and Cardiometabolic Endpoints in the National Health and Nutrition Examination Survey.

BACKGROUND: Research indicates potential cardiometabolic benefits of energy consumption earlier in the day. This study examined the association between fasting duration, timing of first and last meals, and cardiometabolic endpoints using data from the National Health and Nutrition Examination Survey (NHANES). METHODS: Cross-sectional data from NHANES (2005-2016) were utilized. Diet was obtained from one to two 24-h dietary recalls to characterize nighttime fasting duration and timing of first and last meal. Blood samples were obtained for characterization of C-reactive protein (CRP); glycosylated hemoglobin (HbA1c %); insulin; glucose; and high-density lipoprotein (HDL), low-density lipoprotein (LDL), and total cholesterol. Survey design procedures for adjusted linear and logistic regression were performed. RESULTS: Every one-hour increase in nighttime fasting duration was associated with a significantly higher insulin and CRP, and lower HDL. Every one-hour increase in timing of the last meal of the day was statistically significantly associated with higher HbA1c and lower LDL. Every one-hour increase in first mealtime was associated with higher CRP (ß = 0.044, p = 0.0106), insulin (ß = 0.429, p < 0.01), and glucose (ß = 0.662, p < 0.01), and lower HDL (ß = -0.377, p < 0.01). CONCLUSION: In this large public health dataset, evidence for the beneficial effect of starting energy consumption earlier in the day on cardiometabolic endpoints was observed.

The Window Matters: A Systematic Review of Time Restricted Eating Strategies in Relation to Cortisol and Melatonin Secretion.

Time-Restricted Eating is an eating pattern based on the circadian rhythm which limits daily food intake (usually to ≤12 h/day), unique in that no overt restriction is imposed on the quality, nor quantity, of food intake. This paper aimed to examine the effects of two patterns of TRE, traditional TRE, and Ramadan fasting, on two markers of circadian rhythm, cortisol and melatonin. PubMed and Web of Science were searched up to December 2020 for studies examining the effects of time restricted eating on cortisol and melatonin. Fourteen studies met our inclusion criteria. All Ramadan papers found statistically significant decrease in melatonin (p < 0.05) during Ramadan. Two out of the three Ramadan papers noted an abolishing of the circadian rhythm of cortisol (p < 0.05). The non-Ramadan TRE papers did not examine melatonin, and cortisol changes were mixed. In studies comparing TRE to control diets, Stratton et al. found increased cortisol levels in the non-TRE fasting group (p = 0.0018) and McAllister et al. noted no difference. Dinner-skipping resulted in significantly reduced evening cortisol and non-significantly raised morning cortisol. Conversely, breakfast skipping resulted in significantly reduced morning cortisol. This blunting indicates a dysfunctional HPA axis, and may be associated with poor cardio-metabolic outcomes. There is a paucity of research examining the effects of TRE on cortisol and melatonin. The contrasting effect of dinner and breakfast-skipping should be further examined to ascertain whether timing the feeding window indeed has an impact on circadian rhythmicity.

The Role of Diet in Bone and Mineral Metabolism and Secondary Hyperparathyroidism.

Bone disorders are a common complication of chronic kidney disease (CKD), obesity and gut malabsorption. Secondary hyperparathyroidism (SHPT) is defined as an appropriate increase in parathyroid hormone (PTH) secretion, driven by either reduced serum calcium or increased phosphate concentrations, due to an underlying condition. The available evidence on the effects of dietary advice on secondary hyperparathyroidism confirms the benefit of a diet characterized by decreased phosphate intake, avoiding low calcium and vitamin D consumption (recommended intakes 1000-1200 mg/day and 400-800 UI/day, respectively). In addition, low protein intake in CKD patients is associated with a better control of SHPT risk factors, although its strength in avoiding hyperphosphatemia and the resulting outcomes are debated, mostly for dialyzed patients. Ultimately, a consensus on the effect of dietary acid loads in the prevention of SHPT is still lacking. In conclusion, a reasonable approach for reducing the risk for secondary hyperparathyroidism is to individualize dietary manipulation based on existing risk factors and concomitant medical conditions. More studies are needed to evaluate long-term outcomes of a balanced diet on the management and prevention of secondary hyperparathyroidism in at-risk patients at.

Changes in peanut canopy structure and photosynthetic characteristics induced by an arbuscular mycorrhizal fungus in a nutrient-poor environment.

A well-developed canopy structure can increase the biomass accumulation and yield of crops. Peanut seeds were sown in a soil inoculated with an arbuscular mycorrhizal fungus (AMF) and uninoculated controls were also sown. Canopy structure was monitored using a 3-D laser scanner and photosynthetic characteristics with an LI-6400 XT photosynthesis system after 30, 45 and 70 days of growth to explore the effects of the AMF on growth, canopy structure and photosynthetic characteristics and yield. The AMF colonized the roots and AMF inoculation significantly increased the height, canopy width and total leaf area of the host plants and improved canopy structure. AMF reduced the tiller angle of the upper and middle canopy layers, increased that of the lower layer, reduced the leaf inclination of the upper, middle and lower layers, and increased the average leaf area and leaf area index after 45 days of growth, producing a well-developed and hierarchical canopy. Moreover, AMF inoculation increased the net photosynthetic rate in the upper, middle and lower layers. Plant height, canopy width, and total leaf area were positively correlated with net photosynthetic rate, and the inclination angle and tiller angle of the upper leaves were negatively correlated with net photosynthetic rate. Overall, the results demonstrate the effects of AMF inoculation on plant canopy structure and net photosynthetic rate.

The impact of dietary macronutrient intake on cognitive function and the brain.

Macronutrients - carbohydrates, fats, and proteins - supply the nutrients required for optimal functioning. Inadequate intake compromises both physical and brain health. We synthesized research on macronutrients from whole meals on cognitive function in healthy adults and identified underlying mechanisms. Intake of simple carbohydrates ('sugars') is consistently associated with decreased global cognition whereas consumption of complex carbohydrates correlates with successful brain aging and improved memory both in the short- and long-term. Saturated fatty acid intake correlates with decreased memory and learning scores whereas omega-3 intake correlates positively with memory scores. Protein intake boosts executive function and working memory when task-demands are high. Individual differences affecting the macronutrient-cognition relationship are age, physical activity, and glucose metabolism. Neural correlates reflect findings on cognitive functions: cortical thickness and cerebral amyloid burden correlate with sugar intake, inflammatory status and cerebral glucose metabolism correlate with fatty acid intake. Key mechanisms by which dietary macronutrients affect the brain and cognition include glucose and insulin metabolism, neurotransmitter actions, and cerebral oxidation and inflammation. In conclusion, macronutrient intake affects cognitive function both acutely and in the long-term, involving peripheral and central mechanisms. A healthy diet supports brain integrity and functionality, whereas inadequate nutrition compromises it. Studying diet can be key to nutritional recommendations, thereby improving the landscape of mental health and healthy brain aging.

Maternal overweight induced by reduced litter size impairs the behavioral neurodevelopment of offspring.

AIMS: We assessed the influence of maternal overweight on the behavioral neurodevelopment of male and female offspring in prepubertal age by reducing the litter size. MAIN METHODS: To reduce litter size in Wistar rats, the offspring of generation 0 (G0) were culled for 12 pups (6 males and 6 females: normal litter, NL-G1) or 4 pups (2 males and 2 females: small litter, SL-G1). In G1 dams, overweight was characterized, maternal behavior and locomotor activity were assessed. At G2, we quantified the ultrasonic vocalizations in post-natal day 5 (PND5); we evaluated olfactory discrimination in the homing behavior test on PND13; and in PND28-32 (prepubertal age), we performed the following tests: social play behavior, hole board, object recognition, and open field. At the end of the experiments, hippocampus and prefrontal cortex were dissected to quantify the synaptophysin by western blotting. KEY FINDINGS: Our data demonstrated that a reduction in litter size was able to induce maternal overweight without altering the parameters related to overweight in the offspring. The SL-G2 offspring showed deficits in early social communication, olfactory discrimination, social play behavior, and the exploration of objects, in addition to increasing repetitive and stereotyped movements. There were also changes in the synaptophysin levels in the hippocampus and prefrontal cortex of the offspring from reduced litter dams. In conclusion, maternal overweight caused by litter reduction impairs behavioral neurodevelopment, inducing autism-like symptoms in the offspring. SIGNIFICANCE: This study alerts the public about the negative consequences of maternal overweight in the descendants.

Nutrient-Induced Cellular Mechanisms of Gut Hormone Secretion.

The gastrointestinal tract can assess the nutrient composition of ingested food. The nutrient-sensing mechanisms in specialised epithelial cells lining the gastrointestinal tract, the enteroendocrine cells, trigger the release of gut hormones that provide important local and central feedback signals to regulate nutrient utilisation and feeding behaviour. The evidence for nutrient-stimulated secretion of two of the most studied gut hormones, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), along with the known cellular mechanisms in enteroendocrine cells recruited by nutrients, will be the focus of this review. The mechanisms involved range from electrogenic transporters, ion channel modulation and nutrient-activated G-protein coupled receptors that converge on the release machinery controlling hormone secretion. Elucidation of these mechanisms will provide much needed insight into postprandial physiology and identify tractable dietary approaches to potentially manage nutrition and satiety by altering the secreted gut hormone profile.

Milk Fatty Acid Profiles in Different Animal Species: Focus on the Potential Effect of Selected PUFAs on Metabolism and Brain Functions.

Milk contains several important nutrients that are beneficial for human health. This review considers the nutritional qualities of essential fatty acids (FAs), especially omega-3 (ω-3) and omega-6 (ω-6) polyunsaturated fatty acids (PUFAs) present in milk from ruminant and non-ruminant species. In particular, the impact of milk fatty acids on metabolism is discussed, including its effects on the central nervous system. In addition, we presented data indicating how animal feeding-the main way to modify milk fat composition-may have a potential impact on human health, and how rearing and feeding systems strongly affect milk quality within the same animal species. Finally, we have presented the results of in vivo studies aimed at supporting the beneficial effects of milk FA intake in animal models, and the factors limiting their transferability to humans were discussed.