Human milk oligosaccharides, antimicrobial drugs, and the gut microbiota of term neonates: observations from the KOALA birth cohort study.

The infant gut microbiota affects childhood health. This pioneer microbiota may be vulnerable to antibiotic exposures, but could be supported by prebiotic oligosaccharides found in breast milk and some infant formulas. We sought to characterize the effects of several exposures on the neonatal gut microbiota, including human milk oligosaccharides (HMOs), galacto-oligosaccharides (GOS), and infant/maternal antimicrobial exposures. We profiled the stool microbiota of 1023 one-month-old infants from the KOALA Birth Cohort using 16S rRNA gene amplicon sequencing. We quantified 15 HMOs in breast milk from the mothers of 220 infants, using high-performance liquid chromatography-mass spectrometry. Both breastfeeding and antibiotic exposure decreased gut microbial diversity, but each was associated with contrasting shifts in microbiota composition. Other factors associated with microbiota composition included C-section, homebirth, siblings, and exposure to animals. Neither infant exposure to oral antifungals nor maternal exposure to antibiotics during pregnancy were associated with infant microbiota composition. Four distinct groups of breast milk HMO compositions were evident, corresponding to maternal Secretor status and Lewis group combinations defined by the presence/absence of certain fucosylated HMOs. However, we found the strongest evidence for microbiota associations between two non-fucosylated HMOs: 6'-sialyllactose (6'-SL) and lacto-N-hexaose (LNH), which were associated with lower and higher relative abundances of Bifidobacterium, respectively. Among 111 exclusively formula-fed infants, the GOS-supplemented formula was associated with a lower relative abundance of Clostridium perfringens. In conclusion, the gut microbiota is sensitive to some prebiotic and antibiotic exposures during early infancy and understanding their effects could inform future strategies for safeguarding a health-promoting infant gut microbiota.

The intestinal microbiota composition and weight development in children: the KOALA Birth Cohort Study.

OBJECTIVE: To investigate whether the intestinal microbiota composition in early infancy is associated with subsequent weight development in children. METHODS: Analyses were conducted within the KOALA Birth Cohort Study (n = 2834). This cohort originates from two recruitments groups: pregnant women with a conventional lifestyle (no selection based on lifestyle) and pregnant women recruited through alternative channels (organic shops, anthroposophic clinicians/midwives, Steiner schools and relevant magazines). From 909 one-month-old infants, fecal samples were collected and analyzed by quantitative PCR targeting bifidobacteria, Bacteroides fragilis group, Clostridium difficile, Escherichia coli, Lactobacilli and total bacteria counts. Between the ages of 1 and 10 years, parent-reported weight and height was collected at 7 time points. Age- and gender-standardized body mass index (BMI) z-scores were calculated. Data were analyzed using generalized estimating equation. RESULTS: Colonization with B. fragilis group was borderline significantly associated with a higher BMI z-score of 0.15 (95% confidence interval (CI): -0.02 to 0.31), in the conventional subcohort. After stratification for fiber intake (P(forinteraction) = 0.003), colonization with B. fragilis group was associated with a 0.34 higher BMI z-score among children with a low-fiber intake in this subcohort (95% CI: 0.17-0.53). Higher counts among colonized children were positively associated with BMI z-score only in children within the conventional subcohort and a high-fiber diet (BMI z-score 0.08; 95% CI: 0.01-0.14), but inversely associated in children with a low-fiber diet (BMI z-score -0.05; 95% CI: -0.10 to 0.00), and in children recruited through alternative channels (BMI z-score -0.10; 95% CI: -0.17 to -0.03). The other bacteria were not associated with BMI z-scores, regardless of subcohort. CONCLUSION: Using a targeted approach, we conclude that the intestinal microbiota, particularly the B. fragilis group, is associated with childhood weight development. To identify the potential impact of additional bacterial taxa, further prospective studies applying an unconstrained in-depth characterization of the microbiota are needed.

Atherosclerosis and physical functioning in older men, a longitudinal study.

OBJECTIVE: Functional decline is a major threat to independency, progressing into functional limitations and eventually leading to disability. Chronic diseases, especially cardiovascular diseases, are important determinants of functional limitations and disability. Vascular damage exits long before it is clinically manifest and can have adverse effects on health, physical and cognitive functioning. The objective was to investigate the association between non-invasive atherosclerosis measures and physical functioning in older men. DESIGN: Prospective cohort study. SETTING: The study was conducted in the general community. PARTICIPANTS: 195 independently living older men. MEASUREMENTS: Atherosclerosis was measured by intima media thickness (CIMT) of the common carotid artery using ultrasonography and assessment for presence of atherosclerotic plaques. Physical functioning was measured by isometric handgrip strength and leg extensor strength using a hand held dynamometer, lower extremity function using the physical performance score and ability to perform activities of daily life using the modified Stanford health assessment questionnaire. Linear regression analysis was performed to estimate the associations between CIMT or plaques and physical functioning. RESULTS: After adjustment for confounders, higher baseline CIMT was associated with lower isometric handgrip strength at follow up (ßCIMT = -7.21, 95% CI[-13.64;-0.77]). No other associations were found between CIMT and physical functioning. In addition, no associations were found for the presence of plaques and physical functioning either at baseline, or at follow-up. CONCLUSION: Atherosclerosis, as measured by higher CIMT, is related to a lower isometric handgrip strength at follow-up, but no further associations with physical functioning were found in this longitudinal study among independently living older men.

Quantitative skeletal muscle ultrasound: diagnostic value in childhood neuromuscular disease.

UNLABELLED: In this study we investigated the diagnostic value of quantitative skeletal muscle ultrasonography in 150 consecutively referred children with symptoms suspect for a neuromuscular disorder. Muscle thickness and quantitatively determined echo intensity of four muscles and the distribution of these variables within the body were examined. RESULTS: Patients with and without a neuromuscular disorder could be discriminated with a positive predictive value of 91% and a negative predictive value of 86%. Patients with a neurogenic disorder could be distinguished from myopathies and non-neuromuscular disorders with a positive predictive value of 86% and a negative predictive of 84%, using the pattern of distribution of pathology within the body. CONCLUSIONS: Skeletal muscle ultrasound is a good, practical and non-invasive aid in the diagnosis of neuromuscular disorders in children, that is able to discriminate between children with and without a neuromuscular disorder and between neurogenic disorders and myopathies with high predictive values.

Chronic quercetin exposure affects fatty acid catabolism in rat lung.

Dietary quercetin intake is suggested to be health promoting, but this assumption is mainly based on mechanistic studies performed in vitro. Previously, we identified rat lung as a quercetin target tissue. To assess relevant in vivo health effects of quercetin, we analyzed mechanisms of effect in rat lungs of a chronic (41 weeks) 1% quercetin diet using whole genome microarrays. We show here that fatty acid catabolism pathways, like beta-oxidation and ketogenesis, are up-regulated by the long-term quercetin intervention. Up-regulation of genes (Hmgcs2, Ech1, Acox1, Pcca, Lpl and Acaa2) was verified and confirmed by quantitative real time PCR. In addition, free fatty acid levels were decreased in rats fed the quercetin diet, confirming that quercetin affects fatty acid catabolism. This in vivo study demonstrates for the first time that fatty acid catabolism is a relevant process that is affected in rats by chronic dietary quercetin.

Dietary intake of flavonoids and asthma in adults.

Epidemiological studies have suggested that a high consumption of apples may protect against asthma and chronic obstructive pulmonary disease. This effect has been attributed to their high flavonoid content, but few studies have investigated the relationship between flavonoid intake and obstructive lung disease directly. In a population-based, case-control study of 1,471 adults aged 16-50 yrs in London (UK), the present study examined whether dietary intake of catechins, flavonols and flavones was negatively associated with asthma, asthma severity and chronic sputum production. Asthma was defined by positive responses to a standard screening questionnaire in 1996 and information about usual diet was obtained by a food frequency questionnaire in 1997. After controlling for potential confounders, dietary intake of these three flavonoid subclasses was not significantly associated with asthma, (odds ratio per quintile (95% confidence interval) = 0.94 (0.86-1.02); 1.00 (0.92-1.09); 0.98 (0.88 -1.08) for flavones, flavonols and total catechins, respectively) nor was it associated with asthma severity, or chronic sputum production. In conclusion, no evidence was found for a protective effect of three major subclasses of dietary flavonoids on asthma. It is possible that other flavonoids or polyphenols present in apples may explain the protective effect of apples on obstructive lung disease.

Dietary catechins in relation to coronary heart disease death among postmenopausal women.

Catechins, one of the major groups of flavonoids, are bioactive compounds present in a variety of plant foods and beverages. Experimental data suggest that they might prevent chronic diseases in humans. We studied whether the intake of catechins was inversely associated with the risk of coronary heart disease death in a prospective study of postmenopausal women from Iowa. Between 1986 and 1998, 767 of 34,492 participants initially free of cardiovascular diseases died from coronary heart disease. There was a strong inverse association between the intake of (+)-catechin and (-)-epicatechin and coronary heart disease death, which was somewhat attenuated after multivariate adjustment (risk ratios from lowest to highest quintile: 1.00, 0.95, 0.97, 0.77, 0.76). This inverse association was most pronounced in women at low risk of coronary heart disease (non-smokers, free of diabetes mellitus and cardiovascular diseases). A high intake of "gallates," catechins typical of tea, was not associated with coronary heart disease death. Of the major catechin sources, apples and wine were inversely associated with coronary heart disease death. Our data suggest that preventive effects might be limited to certain types of catechins, or that these are indicators of other dietary components or a healthy lifestyle in general.

Chronic obstructive pulmonary disease and intake of catechins, flavonols, and flavones: the MORGEN Study.

Flavonoids have been suggested to protect against chronic lung disease. We studied intake of catechins, flavonols, and flavones in relation to pulmonary function and COPD symptoms in 13,651 adults from three Dutch cities examined from 1994 to 1997. Dietary intake was estimated using a food frequency questionnaire, and flavonoid intake was calculated using specific food composition tables. Pulmonary function (FEV1) was determined by spirometry and COPD symptoms by questionnaire. Associations were presented for the fifth versus the first quintile of intake (Q5-Q1), adjusted for age, height (for FEV1 only), sex, smoking, BMI, and energy intake. Smoking was strongly associated with COPD, independent of dietary effects. Average catechin, flavonol, and flavone intake was 58 mg/d (SD = 46) with tea and apples as main sources. Total catechin, flavonol, and flavone intake was positively associated with FEV1 (beta(Q5-Q1) = 44 ml, 95% CI = 18-69) and inversely associated with chronic cough (OR(Q5-Q1) = 0.80, 95% CI = 0.66-0.97) and breathlessness (OR(Q5-Q1) = 0.74, 95% CI = 0.58- 0.94), but not chronic phlegm. Catechin intake was independently associated with FEV1 (beta(Q5-Q1) = 130 ml, 95% CI = 101-159) and all three COPD symptoms (OR(Q5-Q1) = 0.60-0.72, p < 0.001). Flavonol and flavone intake was independently associated with chronic cough only. Solid fruit, but not tea, intake was beneficially associated with COPD. Our results suggest a beneficial effect of a high intake of catechins and solid fruits against COPD.

Catechin intake might explain the inverse relation between tea consumption and ischemic heart disease: the Zutphen Elderly Study.

BACKGROUND: Epidemiologic studies suggest that tea consumption may reduce the risk of cardiovascular diseases, but results are inconsistent. Catechins, which belong to the flavonoid family, are the main components of tea and may be responsible for the alleged protective effect. Taking catechin sources other than tea into account might clarify the reported associations. OBJECTIVE: The objective was to evaluate the association between catechin intake and the incidence of and mortality from ischemic heart disease and stroke. DESIGN: We evaluated the effect of a high catechin intake by using data from the Zutphen Elderly Study, a prospective cohort study of 806 men aged 65-84 y at baseline in 1985. RESULTS: The mean (+/-SD) catechin intake at baseline was 72 +/- 47.8 mg, mainly from black tea, apples, and chocolate. A total of 90 deaths from ischemic heart disease were documented. Catechin intake was inversely associated with ischemic heart disease mortality; the multivariate-adjusted risk ratio in the highest tertile of intake was 0.49 (95% CI: 0.27, 0.88; P for trend: 0.017). After multivariate adjustment, catechin intake was not associated with the incidence of myocardial infarction (risk ratio in the highest tertile of intake: 0.70; 95% CI: 0.39, 1.26; P for trend: 0.232). After adjustment for tea consumption and flavonol intake, a 7.5-mg increase in catechin intake from sources other than tea was associated with a tendency for a 20% reduction in ischemic heart disease mortality risk (P = 0.114). There was no association between catechin intake and stroke incidence or mortality. CONCLUSION: Catechins, whether from tea or other sources, may reduce the risk of ischemic heart disease mortality but not of stroke.

Dietary catechins and epithelial cancer incidence: the Zutphen elderly study.

The flavonoids, a group of more than 4,000 polyphenolic antioxidants, are potential cancer preventive components of fruits and vegetables. Catechins, one of the 6 major groups of flavonoids, are present in high concentrations in tea as well. Our objective was to evaluate the association between intake of catechins and incidence of epithelial cancers with data from the Zutphen Elderly Study, a prospective cohort study among 728 men aged 65-84 years in 1985. The average catechin intake at baseline was 72 mg/day (range, 0-355 mg/day). After 10 years of follow-up, 96 incident epithelial cancers were recorded, including 42 cases of lung cancer. After multivariate adjustment, catechin intake was not associated with epithelial cancer (risk ratio [RR] from lowest to highest tertile: 1.00, 0.75, 0.94; p for trend: 0.82), or lung cancer (RR from lowest to highest tertile: 1.00, 0.72, 0.92; p for trend: 0.80). Catechins not from tea were borderline significantly inversely associated with lung cancer incidence (RR and 95% confidence interval [CI] for a 7.5-mg increase in intake: 0.66, 0.42-1.05), whereas catechins from tea were not. Catechins from apple, the major source of non-tea catechins, were also related to lung cancer incidence (RR and 95% CI for a 7.5-mg catechin increase: 0.67, 0.38-1.17). Because tea, the major catechin source in this population, was not associated with cancer risk, it seems unlikely that catechins are responsible for the observed inverse trend between non-tea catechins and lung cancer incidence. However, differences in bioavailability of the various catechins may play a role; effects on individual cancer sites cannot be excluded and merit further investigation.

Catechin intake and associated dietary and lifestyle factors in a representative sample of Dutch men and women.

OBJECTIVE: To study the intake of catechins in the Dutch population and to assess the relation between catechin intake and other dietary factors. Catechins, dietary components that belong to the flavonoid family, potentially protect against chronic diseases such as cancer and cardiovascular diseases. Catechins are the major components of tea, but they are present in many other plant foods as well. DESIGN: Data were used from a nationwide dietary survey carried out in 1998 among a representative sample of 6200 Dutch men and women aged 1-97y. Dietary data were collected using a 2 day dietary record method. RESULTS: The average daily catechin intake was 50 mg (s.d. 56 mg/day). Catechin intake increased with age, and the intake was higher in women (60 mg/day) than in men (40 mg/day). Tea was the main catechin source in all age groups, whereas chocolate was second in children, and apples and pears were second in adults and elderly. Catechin intake was lower in smokers than in non-smokers, and increased with socio-economic status. A high intake was associated with a high intake of fiber (r = 0.20), vitamin C (r = 0.17) and beta-carotene (r = 0.10). CONCLUSIONS: Catechins are quantitatively important bioactive components of the daily diet, which should be taken into account when studying the relation between diet and chronic diseases. Catechin intake is only moderately associated with the intake of other nutrients, but much stronger with certain health behaviours such as smoking.

Catechin contents of foods commonly consumed in The Netherlands. 1. Fruits, vegetables, staple foods, and processed foods.

Catechins, compounds that belong to the flavonoid class, are potentially beneficial to human health. To enable epidemiological evaluation of these compounds, data on their contents in foods are required. HPLC with UV and fluorescence detection was used to determine the levels of (+)-catechin, (-)-epicatechin, (+)-gallocatechin (GC), (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECg), and (-)-epigallocatechin gallate (EGCg) in 24 types of fruits, 27 types of vegetables and legumes, some staple foods, and processed foods commonly consumed in The Netherlands. Most fruits, chocolate, and some legumes contained catechins. Levels varied to a large extent: from 4.5 mg/kg in kiwi fruit to 610 mg/kg in black chocolate. (+)-Catechin and (-)-epicatechin were the predominant catechins; GC, EGC, and ECg were detected in some foods, but none of the foods contained EGCg. The data reported here provide a base for the epidemiological evaluation of the effect of catechins on the risk for chronic diseases.

Catechin contents of foods commonly consumed in The Netherlands. 2. Tea, wine, fruit juices, and chocolate milk.

Catechins, compounds that belong to the flavonoid class, are potentially beneficial to human health. To enable an epidemiological evaluation of catechins, data on their contents in foods are required. HPLC with UV and fluorescence detection was used to determine the levels of (+)-catechin, (-)-epicatechin, (+)-gallocatechin (GC), (-)-epigallocatechin (EGC), (-)-epicatechin gallate (ECg), and (-)-epigallocatechin gallate (EGCg) in 8 types of black tea, 18 types of red and white wines, apple juice, grape juice, iced tea, beer, chocolate milk, and coffee. Tea infusions contained high levels of catechins (102-418 mg of total catechins/L), and tea was the only beverage that contained GC, EGC, ECg, and EGCg in addition to (+)-catechin and (-)-epicatechin. Catechin concentrations were still substantial in red wine (27-96 mg/L), but low to negligible amounts were found in white wine, commercially available fruit juices, iced tea, and chocolate milk. Catechins were absent from beer and coffee. The data reported here provide a base for the epidemiological evaluation of the effect of catechins on the risk for chronic diseases.

Chocolate as a source of tea flavonoids.

The antioxidant catechin content of chocolate is four times that of tea. Chocolate contributed 20% of the catechin intake in a representative sample of the Dutch population, and tea contributes 55%. Epidemiological assessments of health effects of tea should include other foods that are sources of catechins.

Short-term effects of the flavour of drinks on ingestive behaviours in man.

To examine the influence of the oro-sensory properties of different beverages on spontaneous intake of drinks, and the consequence of the volume of fluid ingested on subsequent food intake, 24 subjects (12 men, 12 women), slightly dehydrated, had access ad libitum, during four different experimental sessions in a cross-over design, to one of four commercial beverages without any other drink. The four beverages differed in flavour and caloric content: mineral water; the same mineral water flavoured with orange and unsweetened; the same mineral water flavoured with orange and sweetened with 100 g/l sucrose; or equally sweetened with 50 mg/l aspartame. Ad libitum: lunch was served 15 min after the subjects had access to the beverages and dinner was served when they spontaneously requested it, about 6 h after the end of lunch. The nature of the beverage exerted a small but significant effect on the cumulative fluid intake of the subjects. They consumed slightly more of the two sweetened beverages than the mineral water, and slightly less of the orange-flavoured beverage. However, energy intake and macronutrient selection during lunch and dinner on the experimental days and on the following day did not differ significantly between the different conditions. This resulted in a significantly higher total energy intake when the imposed beverage contained sucrose. Moreover, in such experimental conditions, with only one type of beverage to drink, the flavour of this beverage had little influence on the amount of fluid consumed, and the volume consumed did not influence subsequent food intake. As a consequence, the energy provided by the sucrose-sweetened beverage was not taken in account in the overall energy balance by the subjects, at least in the short term.

Catch-up growth in children fed a macrobiotic diet in early childhood.

To study the relationship between diet and growth, a longitudinal anthropometric study was conducted in a Dutch population consuming a macrobiotic diet. Measurements (anthropometry and food habit questionnaire) were taken in 1985 (0-7 y), 1987, and in 1993 (7-16 y, n = 209). Z-scores were calculated for anthropometric measures and changes expressed as the differences between 1993 and the mean of 1985 and 1987. Analysis indicated significant (P < 0.002) catch-up in height [(mean Z-score +/-sEM) +0.59 +/- 0.071 and arm circumference (+0.34 +/- 0.09) for age (boys and girls combined). In 1993, both girls and boys were still significantly (P < 0.05) below the reference for height and sum of four skinfolds for age, and girls were below reference for weight-for-height and arm circumference for age. In girls, multiple regression analyses showed a significant positive effect of the consumption frequency of dairy products on catch-up growth in height, weight and arm circumference, after adjustment for menarche, age, and baseline height, weight and arm circumference (P < 0.05). The addition of moderate amounts of dairy products to a vegan type of diet improved growth of children, especially girls.