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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.
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Microbioma Gastrointestinal , Leche Humana , Femenino , Microbioma Gastrointestinal/genética , Humanos , Lactante , Leche Humana/química , Leche Humana/metabolismo , Leche Humana/microbiología , Proyectos Piloto , ARN Ribosómico 16S/genética , Treonina/metabolismoRESUMEN
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.
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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.
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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.
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Microbioma Gastrointestinal , Enfermedad de Gilbert , Estudios de Casos y Controles , Clostridiales , Femenino , Enfermedad de Gilbert/genética , Humanos , ARN Ribosómico 16S/genéticaRESUMEN
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.
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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%, pâ¯<â¯0.001) and the ketone bodies, 3-hydroxybutyric acid (+132%, pâ¯<â¯0.001), acetoacetic acid (+95%, pâ¯<â¯0.001) and acetone (+46%, pâ¯<â¯0.001). Metabolites associated with an increased mitochondrial lipid metabolism such as citrate (+15%, pâ¯<â¯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%, pâ¯<â¯0.001), pPPARα (+24%, pâ¯<â¯0.001) and T3 (+9%, pâ¯=â¯0.009) supported the metabolomics data while concomitantly blood glucose and insulin (-33%, pâ¯=â¯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%, pâ¯<â¯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.
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Bilirrubina/sangre , Enfermedad de Gilbert/sangre , Metabolismo de los Lípidos/fisiología , Metaboloma/fisiología , Adulto , Femenino , Humanos , Masculino , Metabolómica , Persona de Mediana Edad , Adulto JovenRESUMEN
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.