Free threonine in human breast milk is related to infant intestinal microbiota composition.

BACKGROUND: Accumulating evidence indicates that free amino acids (FAA) might be bioactive compounds with potential immunomodulatory capabilities. However, the FAA composition in human milk is still poorly characterized with respect to its correlation to maternal serum levels and its physiological significance for the infant. Studies addressing the relation of human milk FAA to the infants' intestinal microbiota are still missing. METHODS: As part of a pilot study, maternal serum and breast milk FAA concentrations as well as infant intestinal microbiota (16S rRNA) were determined 2 months after birth. The study cohort consisted of 41 healthy mothers and their term delivered, healthy infants with normal birthweight. The relationship between maternal serum and milk FAA was determined by correlation analyses. Associations between (highly correlated) milk FAA and infant intestinal beta diversity were tested using PERMANOVA, LefSe and multivariate regression models adjusted for common confounders. RESULTS: Seven breast milk FAA correlated significantly with serum concentrations. One of these, threonine showed a negative association with abundance of members of the class Gammaproteobacteria (R2adj = 17.1%, p = 0.006; ß= - 0.441). In addition, on the level of families and genera, threonine explained 23.2% of variation of the relative abundance of Enterobacteriaceae (R2adj; p = 0.001; ß = - 0.504) and 11.1% of variability in the abundance of Escherichia/Shigella (R2adj, p = 0.025; ß = - 0.368), when adjusted for confounders. CONCLUSION: Our study is the first to suggest potential interactions between breast milk FAA and infant gut microbiota composition during early lactation. The results might be indicative of a potential protective role of threonine against members of the Enterobacteriaceae family in breast-fed infants. Still, results are based on correlation analyses and larger cohorts are needed to support the findings and elucidate possible underlying mechanisms to assess the complex interplay between breast milk FAA and infant intestinal microbiota in detail.

Looking to the horizon: the role of bilirubin in the development and prevention of age-related chronic diseases.

Bilirubin, the principal tetrapyrrole, bile pigment and catabolite of haem, is an emerging biomarker of disease resistance, which may be related to several recently documented biological functions. Initially believed to be toxic in infants, the perception of bilirubin has undergone a transformation: it is now considered to be a molecule that may promote health in adults. Data from the last decade demonstrate that mildly elevated serum bilirubin levels are strongly associated with reduced prevalence of chronic diseases, particularly cardiovascular diseases (CVDs), as well as CVD-related mortality and risk factors. Recent data also link bilirubin to other chronic diseases, including cancer and Type 2 diabetes mellitus, and to all-cause mortality. Therefore, there is evidence to suggest that bilirubin is a biomarker for reduced chronic disease prevalence and a predictor of all-cause mortality, which is of important clinical significance. In the present review, detailed information on the association between bilirubin and all-cause mortality, as well as the pathological conditions of CVD, cancer, diabetes and neurodegenerative diseases, is provided. The mechanistic background concerning how bilirubin and its metabolism may influence disease prevention and its clinical relevance is also discussed. Given that the search for novel biomarkers of these diseases, as well as for novel therapeutic modalities, is a key research objective for the near future, bilirubin represents a promising candidate, meeting the criteria of a biomarker, and should be considered more carefully in clinical practice as a molecule that might provide insights into disease resistance. Clearly, however, greater molecular insight is warranted to support and strengthen the conclusion that bilirubin can prevent disease, with future research directions also proposed.

Nuclear anomalies in exfoliated buccal cells in healthy and diabetic individuals and the impact of a dietary intervention.

This study aimed to compare the frequencies of nuclear anomalies in buccal cells between diabetic and non-diabetic individuals and to assess the impact of a 'healthy diet'-a cornerstone in the treatment of diabetes. Seventy-six diabetic and 21 non-diabetic individuals participated in this parallel, randomised, intervention trial. All participants received information about the importance of a healthy diet, while participants randomly assigned to the intervention group received additionally 300g of vegetables and 25ml of plant oil rich in polyunsaturated fatty acids (PUFA) per day for 8 weeks. Cytogenetic damage in buccal cells was assessed at baseline and after 8 weeks using the buccal micronucleus cytome assay. Micronucleus (MN) frequency at baseline was significantly higher in participants with diabetes (0.58±0.30‰) compared with non-diabetic individuals (0.28±0.29‰). Further analysis of baseline data revealed significantly higher MN levels in participants of the highest tertile of waist circumference (+40%), fasting plasma glucose (+55%), glycated haemoglobin (+41%) and cardiovascular disease risk (+39%) relative to participants of the lowest tertile. The dietary intervention had no effect on MN frequencies. Glycated haemoglobin and biomarkers reflecting cytokinetic defect or acute cell death were reduced in both the intervention and 'information only' groups. The results of this study suggest a strong impact of abdominal obesity and glucose metabolism on genomic stability. Similar effects on nuclear anomalies were observed in the 'information only' group and the intervention group receiving vegetables and PUFA-rich plant oil.

In vitro DNA-damaging effects of intestinal and related tetrapyrroles in human cancer cells.

Epidemiological studies report a negative association between circulating bilirubin concentrations and the risk for cancer and cardiovascular disease. Structurally related tetrapyrroles also possess in vitro anti-genotoxic activity and may prevent mutation prior to malignancy. Furthermore, few data suggest that tetrapyrroles exert anti-carcinogenic effects via induction of cell cycle arrest and apoptosis. To further investigate whether tetrapyrroles provoke DNA-damage in human cancer cells, they were tested in the single cell gel electrophoresis assay (SCGE). Eight tetrapyrroles (unconjugated bilirubin, bilirubin ditaurate, biliverdin, biliverdin-/bilirubin dimethyl ester, urobilin, stercobilin and protoporphyrin) were added to cultured Caco2 and HepG2 cells and their effects on comet formation (% tail DNA) were assessed. Flow cytometric assessment (apoptosis/necrosis, cell cycle, intracellular radical species generation) assisted in revealing underlying mechanisms of intracellular action. Cells were incubated with tetrapyrroles at concentrations of 0.5, 5 and 17µM for 24h. Addition of 300µM tertiary-butyl hydroperoxide to cells served as a positive control. Tetrapyrrole incubation mostly resulted in increased DNA-damage (comet formation) in Caco2 and HepG2 cells. Tetrapyrroles that are concentrated within the intestine, including protoporphyrin, urobilin and stercobilin, led to significant comet formation in both cell lines, implicating the compounds in inducing DNA-damage and apoptosis in cancer cells found within organs of the digestive system.

A Special Issue on "Food Perception and Preferences in the Context of Health and Sustainability".

In a rapidly changing world with increasing environmental and health issues, it is necessary to steer research in an appropriate direction while keeping our health in mind [...].

Haem catabolism: a novel modulator of inflammation in Gilbert's syndrome.

BACKGROUND: Moderately elevated unconjugated bilirubin concentrations protect against inflammatory diseases and are present in individuals with Gilbert's syndrome. This study examined the relationship between circulating haem oxygenase catabolites, unconjugated bilirubin, carboxy haemoglobin, iron and inflammatory parameters. MATERIALS AND METHODS: Seventy-six matched individuals were allocated to Gilbert's syndrome (GS) or control group (unconjugated bilirubin ≥ or < 17.1 µM). Iron, carboxy haemoglobin and high-sensitivity C-reactive protein were analysed using routine diagnostic tests. Unconjugated bilirubin and haem were analysed using high-performance liquid chromatography. The cytokines IL-1ß, TNF-α and IL-6 were assessed using high-sensitivity enzyme-linked immunosorbent assays. RESULTS: Gilbert's syndrome subjects had significantly greater levels of unconjugated bilirubin (P < 0.05), carboxy haemoglobin (P < 0.05), iron (P < 0.05), IL-1ß (P < 0.05), a significantly lower body mass index (P < 0.05) and IL-6 concentrations (P < 0.05) vs. controls. Regression analysis revealed that unconjugated bilirubin mainly explained IL-1ß results (16%), and body mass index+IL-6 predicted 26% of the variance in C-reactive protein concentrations. CONCLUSIONS: A positive relationship between unconjugated bilirubin and free plasma haem, iron and carboxy haemoglobin indicated a positive feedback loop of haem oxygenase induction possibly mediated by unconjugated bilirubin. Furthermore, reduced body mass index in Gilbert's syndrome individuals was linked to reduced inflammation status, which could be influenced by circulating haem oxygenase catabolites and contribute to reduced risk of noncommunicable diseases in this population.

Protection from age-related increase in lipid biomarkers and inflammation contributes to cardiovascular protection in Gilbert's syndrome.

Recent epidemiological and clinical data show protection from CVD (cardiovascular disease), all-cause mortality and cancer in subjects with GS (Gilbert's syndrome), which is characterized by a mildly elevated blood bilirubin concentration. The established antioxidant effect of bilirubin, however, contributes only in part to this protection. Therefore we investigated whether mildly elevated circulating UCB (unconjugated bilirubin) is associated with altered lipid metabolism. The study was performed on GS and age- and gender-matched healthy subjects (n=59 per group). Full lipoprotein profile, TAG (triacylglycerols), Apo (apolipoprotein)-A1, Apo-B, lipoprotein(a), the subfractions of LDL (low-density lipoprotein) and selected pro-inflammatory mediators were analysed. A hyperbilirubinaemic rodent model (Gunn rats, n=40) was investigated to further support the presented human data. GS subjects had significantly (P<0.05) improved lipid profile with reduced total cholesterol, LDL-C (LDL-cholesterol), TAG, low- and pro-atherogenic LDL subfractions (LDL-1+LDL-2), Apo-B, Apo-B/Apo-A1 ratio and lower IL-6 (interleukin 6) and SAA (serum amyloid A) concentrations (P=0.094). When the control and GS groups were subdivided into younger and older cohorts, older GS subjects demonstrated reduced lipid variables (total cholesterol and LDL-C, TAG and LDL-C subfractions, Apo-B/Apo-A1 ratio; P<0.05; Apo-B: P<0.1) compared with controls. These data were supported by lipid analyses in the rodent model showing that Gunn rat serum had lower total cholesterol (2.29±0.38 compared with 1.27±0.72 mM; P<0.001) and TAG (1.66±0.67 compared with 0.99±0.52 mM; P<0.001) concentrations compared with controls. These findings indicate that the altered lipid profile and the reduced pro-inflammatory status in hyperbilirubinaemic subjects, particularly in the older individuals, probably contribute additionally to the commonly accepted beneficial antioxidant effects of bilirubin in humans.

Genome damage in peripheral blood lymphocytes of diabetic and non-diabetic individuals after intervention with vegetables and plant oil.

Recent studies suggest increased cancer risk in patients with type 2 diabetes mellitus (T2DM) compared with healthy individuals. The present study aims to assess whether T2DM is associated with increased genome instability and whether a healthy diet with natural foods can improve genome stability in peripheral blood lymphocytes (PBLs). Seventy-six diabetic and 21 non-diabetic individuals were randomly assigned to either an 'intervention' or an 'information only' group. All participants received information about the beneficial effects of a healthy diet, while subjects of the intervention group received additionally 300g of vegetables and 25ml of plant oil rich in polyunsaturated fatty acids per day for 8 weeks. Chromosomal damage was assessed using the cytokinesis-block micronucleus (MN) cytome assay. Levels of chromosomal damage did not differ between diabetic and non-diabetic individuals. However, diabetic individuals with MN frequency above the high 50th percentile had significantly higher levels of fasting plasma glucose, glycosylated haemoglobin and were at higher risk for cardiovascular disease (CVD), assessed by the Framingham general cardiovascular risk score. Non-diabetic individuals with MN frequency above the 50th percentile had significantly lower vitamin B12 levels. The intervention with vegetables and plant oil led to significant increases in folate, γ-tocopherol, α- and ß-carotene while vitamin B12 was significantly reduced. Levels of chromosomal damage were not altered, only apoptosis was slightly increased. The results suggest interactions between glycaemic control, CVD risk and genome stability in individuals with T2DM. However, a healthy diet does not improve genome damage in PBLs.

Bilirubin and related tetrapyrroles inhibit food-borne mutagenesis: a mechanism for antigenotoxic action against a model epoxide.

Bilirubin exhibits antioxidant and antimutagenic effects in vitro. Additional tetrapyrroles that are naturally abundant were tested for antigenotoxicity in Salmonella. Un-/conjugated bilirubin (1 and 2), biliverdin (4), bilirubin and biliverdin dimethyl esters (3 and 5), stercobilin (6), urobilin (7), and protoporphyrin (8) were evaluated at physiological concentrations (0.01-2 µmol/plate; 3.5-714 µM) against the metabolically activated food-borne mutagens aflatoxin B1 (9) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (10). Compound 8 most effectively inhibited the mutagenic effects of 9 in strain TA102 and 10 in TA98. Compound 7 inhibited 9-induced mutagenesis in strain TA98 most effectively, while 1 and 4 were promutagenic in this strain. This is likely due to their competition with mutagens for phase-II detoxification. Mechanistic investigations into antimutagenesis demonstrate that tetrapyrroles react efficiently with a model epoxide of 9, styrene epoxide (11), to form covalent adducts. This reaction is significantly faster than that of 11 with guanine. Hence, the evaluated tetrapyrroles inhibited genotoxicity induced by poly-/heterocyclic amines found in foods, and novel evidence obtained in the present investigation suggests this may occur via chemical scavenging of genotoxic metabolites of the mutagens investigated. This may have important ramifications for maintaining health, especially with regard to cancer prevention.

Liking and Description of Pasta Sauces with Varying Mealworm Content.

Entomophagy is directly connected with culture, explaining why it is commonly rejected in Western countries. Due to increased meat consumption in recent years with its associated negative impacts on health and sustainability, the development of products based on alternative protein sources has become urgent. The larval form of Tenebrio molitor (mealworm) has the potential to substitute meat as it requires less resources and produces less emissions compared to other forms of meat production. Therefore, in this project we have aimed to develop pasta sauces with differing mealworm contents based on a common meat sauce and to test the acceptance with 91 consumers in Austria. Three sauces (100% mealworm, 50% mealworm and 50% meat, 100% meat) were developed and tested using a 9-point hedonic scale for acceptance, and the CATA (Check-All-That-Apply) method was integrated to also receive descriptive information. The analysis of the liking data revealed that the liking for the hybrid sauce with meat and mealworm content was comparable to the meat sauce (6.9 ± 1.8. vs. 6.5 ± 1.8, p > 0.05). Less liked was the sauce with the highest mealworm content (5.7 ± 1.8, p < 0.05). The CATA analysis demonstrated the strongest positive effects on the mean in terms of how much the products were liked for the attribute "fleshy" (0.8). On the other hand, the attributes "brownish" (-0.9) or "mushy" (-1.0) had the strongest negative effects on the mean of the liking of products. We have seen that meat cannot be substituted by mealworm immediately and completely. The results suggest a stepwise substitution and the further adaptation of products regarding the (negative and positive effecting) attributes to increase consumer acceptance.

Investigating the Relationships between Taste Preferences and Beverage Intake in Preadolescents.

Sugar-sweetened beverages are known promotors of adverse health outcomes. This study aimed to find a relation between taste perception, preferences for beverages, anthropometric parameters, and frequency of beverage consumption. Taste perception of sweetness was tested using an adopted sensitivity test with sucrose and different concentrations of sugar-sweetened apple juice. Furthermore, bitter-compound 6-n-propylthiouracil (PROP) and salty perception were tested and accompanied by a questionnaire on beverage intake. We did not find a clear relationship between taste perception, anthropometrics, and beverage intake. Nevertheless, in males, the bitter intensity perception of PROP was positively correlated with the BMI percentiles (CDC, r = 0.306, p ≤ 0.043) and the waist circumference (r = 0.326, p = 0.031). Furthermore, the liking of sweet taste (p < 0.05) and sweet intensity rating (p < 0.05) of apple juice increased with intensity, and adolescents with overweight or obesity had a higher intake of free sugars from beverages (p < 0.001). The role of taste perception on anthropometric measures and beverage intake remains unclear and requires further investigation.

Distinct maternal amino acids and oxylipins predict infant fat mass and fat-free mass indices.

Interested in maternal determinants of infant fat mass index (FMI) and fat-free mass index (FFMI), considered as predictors for later development of obesity, we analysed amino acids (AA) and oxylipins in maternal serum and breast milk (BM). FMI and FFMI were calculated in 47 term infants aged 4 months (T4). Serum AA were analysed in pregnancy (T1, T2) and 6-8 weeks postpartum (T3). At T3, AA and oxylipins were analysed in BM. Biomarker-index-associations were identified by regression analysis. Infant FMI (4.1 ± 1.31 kg/m2; MW ± SD) was predicted by T2 proline (R2 adj.: 7.6%, p = .036) and T3 BM 11-hydroxy-eicosatetraenoic-acid (11-HETE) and 13-hydroxy-docosahexaenoic-acid (13-HDHA; together:35.5% R2 adj., p < .001). Maternal peripartum antibiotics (AB) emerged as confounders (+AB: 23.5% higher FMI; p = .025). Infant FFMI (12.1 ± 1.19 kg/m2; MW ± SD) was predicted by histidine (R2 adj.: 14.5%, p < .001) and 17-HDHA (BM, R2 adj.:19.3%, p < .001), determined at T3. Confirmed in a larger cohort, the parameters could elucidate connections between maternal metabolic status, nutrition, and infant body development.

Investigating New Sensory Methods Related to Taste Sensitivity, Preferences, and Diet of Mother-Infant Pairs and Their Relationship With Body Composition and Biomarkers: Protocol for an Explorative Study.

BACKGROUND: Early experiences with different flavors play an important role in infant development, including food and taste acceptance. Flavors are already perceived in utero with the development of the taste and olfactory system and are passed on to the child through breast and bottle feeding. Therefore, the first 1000 days of life are considered a critical window for infant developmental programming. OBJECTIVE: The objective of our study is to investigate, both in the prenatal and postnatal period, taste sensitivity, preferences, and dietary diversity of mother-infant pairs. The explorative study design will also report on the impact of these variables on body composition (BC) and biomarkers. In contrast to conventional methods, this study involves long-term follow-up data collection from mother-infant pairs; moreover, the integration of audiovisual tools for recording infants' expressions pertaining to taste stimuli is a novelty of this study. Considering these new methodological approaches, the study aims to assess taste-related data in conjunction with BC parameters like fat-free mass or fat mass, biomarkers, and nutritional intake in infants and children. METHODS: Healthy pregnant women aged between 18 and 50 years (BMI≥18.5 kg/m2 to ≤30 kg/m2; <28 weeks of gestation) were recruited from January 2014 to October 2014. The explorative design implies 2 center visits during pregnancy (24-28 weeks of gestation and 32-34 weeks of gestation) and 2 center visits after delivery (6-8 weeks postpartum and 14-16 weeks postpartum) as well as follow-up visits at 1, 3-3.5, and 6 years after delivery. Data collection encompasses anthropometric and biochemical measurements as well as BC analyses with air displacement plethysmography, taste perception assessments, and multicomponent questionnaires on demographics, feeding practices, and nutritional and lifestyle behaviors. Audiovisual data from infants' reactions to sensory stimuli are collected and coded by trained staff using Baby Facial Action Coding and the Body Action Posture System. Birth outcomes and weight development are obtained from medical records, and additional qualitative data are gathered from 24 semistructured interviews. RESULTS: Our cohort represents a homogenous group of healthy women with stringent exclusion criteria. A total of 54 women met the eligibility criteria, whereas 47 mother-child pairs completed data collection at 4 center visits during and after pregnancy. Follow-up phases, data analyses, and dissemination of the findings are scheduled for the end of 2023. The study was approved by the ethics committee of the Medical University of Graz (EC No 26-066 ex 13/14), and all participants provided informed consent. CONCLUSIONS: The results of this study could be useful for elucidating the connections between maternal and infant statuses regarding diet, taste, biomarkers, and prenatal and postnatal weight development. This study may also be relevant to the establishment of further diagnostic and interventional strategies targeting childhood obesity and early body fat development. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/37279.

Oxidative Stress and Related Biomarkers in Gilbert's Syndrome: A Secondary Analysis of Two Case-Control Studies.

Bilirubin is an important antioxidant and a modulator of biological functions. However, most of the protection against oxidative stress was shown in vitro or ex vivo. The aim of this case-control study was to investigate whether subjects with Gilbert's syndrome (GS) experience different levels of lipid and protein oxidation (as well as differences in oxidative stress related markers) compared to healthy controls. GS subjects (n =119) demonstrated higher serum levels of unconjugated bilirubin (p < 0.001), a lower BMI (p < 0.001), 37% higher antioxidant potential assessed as ferric reducing ability potential (p < 0.001), higher advanced oxidation protein products (p < 0.01) andlower apolipoprotein B (p < 0.05), hs-C-reactive protein (p < 0.05), interleukin 6 (p < 0.001) and interleukin 1 beta (p < 0.05) values compared to healthy controls (n =119). Furthermore, the resting heart rate was significantly lower in the GS group (p < 0.05). Stronger protective effects for GS subjects were demonstrated in the older subgroup (n =104, average age 50 years) compared to those of the younger group (n =134, average age 27 years). Although not all markers related to oxidative stress were different between the groups (e.g., malondialdehyde, homocysteine, oxLDL, and myeloperoxidase; p >0.05), the observed differences contribute to the explanation of why GS serves as an important protector in the pathogenesis of metabolic, oxidative stress related diseases.

Gilbert's Syndrome and the Gut Microbiota - Insights From the Case-Control BILIHEALTH Study.

The heme catabolite bilirubin has anti-inflammatory, anti-oxidative and anti-mutagenic effects and its relation to colorectal cancer (CRC) risk is currently under evaluation. Although the main metabolic steps of bilirubin metabolism, including the formation of stercobilin and urobilin, take place in the human gastrointestinal tract, potential interactions with the human gut microbiota are unexplored. This study investigated, whether gut microbiota composition is altered in Gilbert's Syndrome (GS), a mild form of chronically elevated serum unconjugated bilirubin (UCB) compared to matched controls. Potential differences in the incidence of CRC-associated bacterial species in GS were also assessed. To this end, a secondary investigation of the BILIHEALTH study was performed, assessing 45 adults with elevated UCB levels (GS) against 45 age- and sex-matched controls (C). Fecal microbiota analysis was performed using 16S rRNA gene sequencing. No association between mildly increased UCB and the composition of the gut microbiota in this healthy cohort was found. The alpha and beta diversity did not differ between C and GS and both groups showed a typical representation of the known dominant phyla. Furthermore, no difference in abundance of Firmicutes and Proteobacteria, which have been associated with the mucosa of CRC patients were observed between the groups. A sequence related to the Christensenella minuta strain YIT 12065 was identified with a weak association value of 0.521 as an indicator species in the GS group. This strain has been previously associated with a lower body mass index, which is typical for the GS phenotype. Overall, sex was the only driver for an identifiable difference in the study groups, as demonstrated by a greater bacterial diversity in women. After adjusting for confounding factors and multiple testing, we can conclude that the GS phenotype does not affect the composition of the human gut microbiota in this generally healthy study group.

Intake of Fibre-Associated Foods and Texture Preferences in Relation to Weight Status Among 9-12 Years Old Children in 6 European Countries.

Plant foods, rich in fibre, can offer textures that children find difficult to orally manipulate, resulting in low preferences but are important for a healthy diet and prevention of overweight in children. Our aim was to investigate preferences for food texture, intake of fibre-associated foods and the relation to BMI. Three hundred thirty European children (9-12 years, 54% female) indicated their texture preferences using the Child-Food-Texture-Preference- Questionnaire (CFTPQ), and their parents responded on fibre-associated food consumption and anthropometric information. BMI was significantly lower for children with higher intake of wholegrain alternatives of common foods; in addition to being significantly influenced by country and the wearing of a dental brace. Overall BMI-for-age-percentiles (BMI_pct) were negatively associated with the consumption of wholegrain cereals, white pasta and wholemeal products and positively associated with the intake of legumes and white biscuits. In males, BMI_pct were negatively associated with wholegrain products and dried fruits, and in females, positively with legume consumption. A few country-related associations were found for BMI_pct and wholegrain biscuits, seeds and nuts and refined products. No overall correlation was found between BMI_pct and the texture preference of soft/hard foods by CFTPQ, except in Austria. We conclude that this study revealed evidence of a connection between fibre-associated foods and children's BMI at a cross-cultural level and that sex is an important determinant of fibre-associated food intake and the development of overweight in childhood.

Serum metabolomics analysis reveals increased lipid catabolism in mildly hyperbilirubinemic Gilbert's syndrome individuals.

BACKGROUND: The protective role of mildly elevated bilirubin against CVD and diabetes mellitus type 2 (DMT2) is associated with a favorable lipid phenotype. As the mechanistic understanding of this protection in humans remains elusive, we aimed to assess the metabolomics profile of mildly hyperbilirubinemic (Gilbert's syndrome; GS) individuals especially targeting lipid catabolism. METHODS AND RESULTS: Using NMR serum metabolomics of 56 GS individuals and 56 age and gender-matched healthy controls, GS individuals demonstrated significantly greater concentrations of acetylcarnitine (+20%, p < 0.001) and the ketone bodies, 3-hydroxybutyric acid (+132%, p < 0.001), acetoacetic acid (+95%, p < 0.001) and acetone (+46%, p < 0.001). Metabolites associated with an increased mitochondrial lipid metabolism such as citrate (+15%, p < 0.001), anaplerotic amino acid intermediates and creatinine were significantly greater and creatine significantly reduced in GS individuals. Stimulators of lipid catabolism including AMPK (+59%, p < 0.001), pPPARα (+24%, p < 0.001) and T3 (+9%, p = 0.009) supported the metabolomics data while concomitantly blood glucose and insulin (-33%, p = 0.002) levels were significantly reduced. We further showed that the increased lipid catabolism partially mediates the favorable lipid phenotype (lower triglycerides) of GS individuals. Increased trimethylamine (+35%, p < 0.001) indicated changes in trimethylamine metabolism, an emerging predictor of metabolic health. CONCLUSION: We showed an enhanced lipid catabolism in mildly hyperbilirubinemic individuals, novel evidence as to why these individuals are leaner and protected against chronic metabolic diseases emphasizing bilirubin to be a promising future target in obese and dyslipidemia patients.

Chromosomal stability in buccal cells was linked to age but not affected by exercise and nutrients - Vienna Active Ageing Study (VAAS), a randomized controlled trial.

The purpose of this study was to investigate the effect of six months strength training with or without supplementing protein and vitamins, on chromosomal integrity of buccal cells in institutionalized elderly. One hundred seventeen women and men (65-98 years) performed either resistance training (RT), RT combined with a nutritional supplement (RTS) or cognitive training (CT) twice per week for six months. Participants' fitness was measured using the 6 min walking, the chair rise, and the handgrip strength test. Genotoxicity and cytotoxicity parameters were investigated with the Buccal Micronucleus Cytome (BMcyt) assay. Six minutes walking and chair rise performance improved significantly, however, no changes of the parameters of the BMcyt were detected. Age and micronuclei (MN) frequency correlated significantly, for both women (r = 0.597, p = 0.000) and men (r = 0.508, p = 0.000). Squared regressions revealed a significant increase in the MN frequency of buccal cells with age (R2 = 0.466, p = 0.000). Interestingly and contrary to what was shown in blood lymphocytes, chromosomal damage in buccal cells increases until very old age, which might qualify them as a valid biomarker for aging. Unexpectedly, in this group of institutionalized elderly, resistance training using elastic bands had no effect on chromosomal damage in buccal cells.

Yuck, This Biscuit Looks Lumpy! Neophobic Levels and Cultural Differences Drive Children's Check-All-That-Apply (CATA) Descriptions and Preferences for High-Fibre Biscuits.

Food neophobia influences food choice in school-aged children. However, little is known about how children with different degrees of food neophobia perceive food and to what extent different sensory attributes drive their liking. This paper explores liking and sensory perception of fibre-rich biscuits in school-aged children (n = 509, age 9-12 years) with different degrees of food neophobia and from five different European countries (Finland, Italy, Spain, Sweden and United Kingdom). Children tasted and rated their liking of eight commercial biscuits and performed a Check-All-That-Apply task to describe the samples and further completed a Food Neophobia Scale. Children with a higher degree of neophobia displayed a lower liking for all tasted biscuits (p < 0.001). Cross-cultural differences in liking also appeared (p < 0.001). A negative correlation was found between degree of neophobia and the number of CATA-terms used to describe the samples (r = -0.116, p = 0.009). Penalty analysis showed that degree of food neophobia also affected drivers of biscuit liking, where particularly appearance terms were drivers of disliking for neophobic children. Cross-cultural differences in drivers of liking and disliking were particularly salient for texture attributes. Further research should explore if optimizing appearance attributes could be a way to increase liking of fibre-rich foods in neophobic children.

Mild hyperbilirubinaemia as an endogenous mitigator of overweight and obesity: Implications for improved metabolic health.

BACKGROUND AND AIMS: Mild endogenous elevation of unconjugated bilirubin (UCB) as seen in Gilbert's syndrome (GS), might mitigate cardiovascular disease (CVD) risk factors including overweight/obesity. This study aimed to determine whether hyperbilirubinaemia is linked to improved anthropometric data and lipid profile. METHODS: Our study considered GS and age-/gender-matched healthy controls (n = 248). Additionally, obese female type 2 diabetic patients (DM2) (n = 26) were included as a "disease control group". RESULTS: BMI, hip circumference (HC), and lipid profile were significantly lower in GS. UCB was inversely correlated with BMI (p <0 .001), HC as well as with fat mass (FM) and lipid variables (p < 0.05). Moreover, DM2 patients had significantly lower UCB compared to GS and healthy controls. Older GS subjects (≥35 years) had significantly reduced anthropometric data and improved lipid profile. CONCLUSIONS: Our results propose that the health promoting potential of mild hyperbilirubinaemia may extend to protection from age-related weight gain and dyslipidaemia.