Influence of microbially fermented 2´-fucosyllactose on neuronal-like cell activity in an in vitro co-culture system.

Scope: 2´-Fucosyllactose (2´-FL), the most abundant oligosaccharide in human milk, plays an important role in numerous biological functions, including improved learning. It is not clear, however, whether 2´-FL or a cleavage product could influence neuronal cell activity. Thus, we investigated the effects of 2´-FL, its monosaccharide fucose (Fuc), and microbial fermented 2´-FL and Fuc on the parameters of neuronal cell activity in an intestinal-neuronal transwell co-culture system in vitro. Methods: Native 13C-labeled 2´-FL and 13C-Fuc or their metabolites, fermented with Bifidobacterium (B.) longum ssp. infantis and B. breve, which were taken from the lag-, log- and stationary (stat-) growth phases of batch cultures, were applied to the apical compartment of the co-culture system with Caco-2 cells representing the intestinal layer and all-trans-retinoic acid-differentiated SH-SY5Y (SH-SY5YATRA) cells mimicking neuronal-like cells. After 3 h of incubation, the culture medium in the basal compartment was monitored for 13C enrichment by using elemental analysis isotope-ratio mass spectrometry (EA-IRMS) and effects on cell viability, plasma, and mitochondrial membrane potential. The neurotransmitter activation (BDNF, GABA, choline, and glutamate) of SH-SY5YATRA cells was also determined. Furthermore, these effects were also measured by the direct application of 13C-2´-FL and 13C-Fuc to SH-SY5YATRA cells. Results: While no effects on neuronal-like cell activities were observed after intact 2´-FL or Fuc was incubated with SH-SY5YATRA cells, supernatants from the stat-growth phase of 2´-FL, fermented by B. longum ssp. infantis alone and together with B. breve, significantly induced BDNF release from SH-SY5YATRA cells. No such effects were found for 2´-FL, Fuc, or their fermentation products from B. breve. The BDNF release occurred from an enhanced vesicular release, which was confirmed by the use of the Ca2+-channel blocker verapamil. Concomitant with this event, 13C enrichment was also observed in the basal compartment when supernatants from the stat-growth phase of fermentation by B. longum ssp. infantis alone or together with B. breve were used. Conclusion: The results obtained in this study suggest that microbial products of 2´-FL rather than the oligosaccharide itself may influence neuronal cell activities.

Effect of a QTL on wheat chromosome 5B associated with enhanced root dry mass on transpiration and nitrogen uptake under contrasting drought scenarios in wheat.

BACKGROUND: A sufficient nitrogen supply is crucial for high-quality wheat yields. However, the use of nitrogen fertilization can also negatively influence ecosystems due to leaching or volatile atmospheric emissions. Drought events, increasingly prevalent in many crop production areas, significantly impact nitrogen uptake. Breeding more efficient wheat varieties is necessary to achieve acceptable yields with limited nitrogen and water. Crop root systems play a crucial role as the primary organ for absorbing water and nutrients. To investigate the impact of an enhanced root system on nitrogen and water use efficiency in wheat under various irrigation conditions, this study conducted two experiments using precision phenotyping platforms for controlled drought stress treatment. Experiment 1 involved four contrasting winter wheat genotypes. It included the Chinese variety Ning0604, carrying a quantitative trait locus (QTL) on chromosome 5B associated with a higher root dry biomass, and three elite German varieties, Elixer, Genius, and Leandrus. Experiment 2 compared near-isogenic lines (NIL) of the three elite varieties, each containing introgressions of the QTL on chromosome 5B linked to root dry mass. In both experiments, nitrogen partitioning was tracked via isotope discrimination after fertilization with 5 Atom % 15N-labeled KNO3-. RESULTS: In experiment 1 the quantification by 15N isotope discrimination revealed significantly (p < 0.05) higher nitrogen derived from fertilizer in the root organ for Ning0604 than those of the three German varieties. In experiment 2, two out of three NILs showed a significantly (p < 0.05) higher uptake of N derived from fertilizer than their respective recipient line under well-watered conditions. Furthermore, significantly lower transpiration rates (p < 0.1) were observed in one NIL compared to its respective recipient. CONCLUSIONS: The combination of the DroughtSpotter facility coupled with 15N tracer-based tracking of N uptake and remobilization extends the insight into the impact of genetically altered root biomass on wheat NUE and WUE under different water availability scenarios. The study shows the potential for how a modified genetic constitution of the locus on wheat chromosome 5B can reduce transpiration and enhance N uptake. The dependence of the observations on the recipient and water availability suggests a need for further research to investigate the interaction with genetic background traits.

Inhibition of Transglutaminase 2 as a Therapeutic Strategy in Celiac Disease-In Vitro Studies in Intestinal Cells and Duodenal Biopsies.

Enzymatic modification of gliadin peptides by human transglutaminase 2 (TG2) is a key mechanism in the pathogenesis of celiac disease (CD) and represents a potential therapeutic target. Recently, we have identified the small oxidative molecule PX-12 as an effective inhibitor of TG2 in vitro. In this study, we further investigated the effect of PX-12 and the established active-site directed inhibitor ERW1041 on TG2 activity and epithelial transport of gliadin peptides. We analyzed TG2 activity using immobilized TG2, Caco-2 cell lysates, confluent Caco-2 cell monolayers and duodenal biopsies from CD patients. TG2-mediated cross-linking of pepsin-/trypsin-digested gliadin (PTG) and 5BP (5-biotinamidopentylamine) was quantified by colorimetry, fluorometry and confocal microscopy. Cell viability was tested with a resazurin-based fluorometric assay. Epithelial transport of promofluor-conjugated gliadin peptides P31-43 and P56-88 was analyzed by fluorometry and confocal microscopy. PX-12 reduced TG2-mediated cross-linking of PTG and was significantly more effective than ERW1041 (10 µM, 15 ± 3 vs. 48 ± 8%, p < 0.001). In addition, PX-12 inhibited TG2 in cell lysates obtained from Caco-2 cells more than ERW1041 (10 µM; 12 ± 7% vs. 45 ± 19%, p < 0.05). Both substances inhibited TG2 comparably in the intestinal lamina propria of duodenal biopsies (100 µM, 25 ± 13% vs. 22 ± 11%). However, PX-12 did not inhibit TG2 in confluent Caco-2 cells, whereas ERW1041 showed a dose-dependent effect. Similarly, epithelial transport of P56-88 was inhibited by ERW1041, but not by PX-12. Cell viability was not negatively affected by either substance at concentrations up to 100 µM. PX-12 did not reduce TG2 activity or gliadin peptide transport in confluent Caco-2 cells. This could be caused by rapid inactivation or degradation of the substance in the Caco-2 cell culture. Still, our in vitro data underline the potential of the oxidative inhibition of TG2. The fact that the TG2-specific inhibitor ERW1041 reduced the epithelial uptake of P56-88 in Caco-2 cells further strengthens the therapeutic potential of TG2 inhibitors in CD.

Plasma anthocyanins and their metabolites reduce in vitro migration of pancreatic cancer cells, PANC-1, in a FAK- and NF-kB dependent manner: Results from the ATTACH-study a randomized, controlled, crossover trial in healthy subjects.

Pancreatic cancer is primarily considered to be a metastatic disease with a low 5-year survival rate. We aimed to detect if plasma-isolated anthocyanins and their metabolites (PAMs) modulate pancreatic cancer cells migration and to describe molecular targets of PAMs in this process. Plasma metabolites were isolated by solid-phase extraction before and after a 28-days intervention trial involving 35 healthy subjects comparing effects of a daily anthocyanin-rich juice intake vs. placebo. Plasma extracts were used for migration and mechanistic in vitro studies as well as for metabolomic analysis. Pancreatic PANC-1 and AsPC-1 were used for migration studies in a Boyden chamber co-cultured with endothelial cells. Expression of adhesion molecules on cancer and endothelial cells were determined by flow cytometry and NF-kB (nuclear factor-kappa B) p65 and focal adhesion kinase activation were measured by immunoassays. UHPLC-MS/MS metabolomics was done in plasma and urine samples. Plasma extracts isolated after the intake of the anthocyanin-rich juice significantly reduced PANC-1 migration, but not AsPC-1 migration. In PANC-1, and to a lower extent in endothelial cells, plasma extracts after juice intake decreased the expression of ß1- and ß4-integrins and intercellular adhesion molecule-1. Pooled plasma from volunteers with the highest inhibition of PANC-1 migration (n = 10) induced a reduction of NF-kB-p65 and FAK-phosphorylation in cancer and in endothelial cells. Concerning metabolites, 14 were significantly altered by juice intervention and PANC-1 migration was inversely associated with the increase of o-coumaric acid and peonidin-3-galactoside. PAMs were associated with lower PANC-1 cell migration opening new strategies for metastatic pancreatic cancer treatment.

Influence of Plasma-Isolated Anthocyanins and Their Metabolites on Cancer Cell Migration (HT-29 and Caco-2) In Vitro: Results of the ATTACH Study.

Cancer mortality is mainly due to metastasis. Therefore, searching for new therapeutic agents suppressing cancer cell migration is crucial. Data from human studies regarding effects of anthocyanins on cancer progression, however, are scarce and it is unclear whether physiological concentrations of anthocyanins and their metabolites reduce cancer cell migration in vivo. In addition, interactions with chemotherapeutics like 5-fluorouracil (5-FU) are largely unknown. Thus, we combined a placebo-controlled, double-blinded, cross-over study with in vitro migration studies of colon cancer cell lines to examine the anti-migratory effects of plasma-isolated anthocyanins and their metabolites (PAM). Healthy volunteers (n = 35) daily consumed 0.33 L of an anthocyanin-rich grape/bilberry juice and an anthocyanin-depleted placebo juice for 28 days. PAM were isolated before and after intervention by solid-phase extraction. HT-29 and Caco-2 cells were incubated with PAM in a Boyden chamber. Migration of HT-29 cells was significantly inhibited by PAM from juice but not from placebo. In contrast, Caco-2 migration was not affected. Co-incubation with 5-FU and pooled PAM from volunteers (n = 10), which most effectively inhibited HT-29 migration, further reduced HT-29 migration in comparison to 5-FU alone. Therefore, PAM at physiological concentrations impairs colon cancer cell migration and may support the effectiveness of chemotherapeutics.

Infant formulas with synthetic oligosaccharides and respective marketing practices.

Human milk contains more than 150 different oligosaccharides, which together are among to the quantitatively predominant solid components of breast milk. The oligosaccharide content and composition of human milk show large inter-individual differences. Oligosaccharide content is mostly influenced by genetic variants of the mother's secretor status. Oligosaccharides in human milk are utilized by infants' intestinal bacteria, affecting bacterial composition and metabolic activity. Maternal secretor status, and respective differing fucosylated oligosaccharide content, has been associated both with reduced and increased risk of infection in different populations of breastfed infants, possibly due to environmental conditions and the infant's genotype. There are no safety concerns regarding the addition of previously approved oligosaccharides to infant formula; however, no firm conclusions can be drawn about clinically relevant benefits either. Therefore, infant formulas with synthetic oligosaccharide additives are currently not preferentially recommended over infant formulas without such additives. We consider the use of terms such as "human milk oligosaccharides" and corresponding abbreviations such as "HMO" in any advertising of infant formula to be an inappropriate idealization of infant formula. Manufacturers should stop this practice, and such marketing practices should be prevented by responsible supervisory authorities. Pediatricians should inform families that infant formulas supplemented with synthetic oligosaccharides do not resemble the complex oligosaccharide composition of human milk.

Respiratory and Intestinal Microbiota in Pediatric Lung Diseases-Current Evidence of the Gut-Lung Axis.

The intestinal microbiota is known to influence local immune homeostasis in the gut and to shape the developing immune system towards elimination of pathogens and tolerance towards self-antigens. Even though the lung was considered sterile for a long time, recent evidence using next-generation sequencing techniques confirmed that the lower airways possess their own local microbiota. Since then, there has been growing evidence that the local respiratory and intestinal microbiota play a role in acute and chronic pediatric lung diseases. The concept of the so-called gut-lung axis describing the mutual influence of local microbiota on distal immune mechanisms was established. The mechanisms by which the intestinal microbiota modulates the systemic immune response include the production of short-chain fatty acids (SCFA) and signaling through pattern recognition receptors (PRR) and segmented filamentous bacteria. Those factors influence the secretion of pro- and anti-inflammatory cytokines by immune cells and further modulate differentiation and recruitment of T cells to the lung. This article does not only aim at reviewing recent mechanistic evidence from animal studies regarding the gut-lung axis, but also summarizes current knowledge from observational studies and human trials investigating the role of the respiratory and intestinal microbiota and their modulation by pre-, pro-, and synbiotics in pediatric lung diseases.

Tissue Transglutaminase but Not Microbial Transglutaminase Is Inhibited by Exogenous Oxidative Substances in Celiac Disease.

Enzymatic modification of gliadin peptides by human transglutaminase 2 (TG2) is a central step in celiac disease (CD) pathogenesis. Microbial transglutaminase (mTG) mimics the enzymatic function of TG2 and might play a role in CD. TG2 is inhibited by endogenous oxidative endoplasmic reticulum-resident protein 57 (ERp57), but data about mTG are lacking. We investigated the localization of ERp57 in duodenal biopsies and examined inhibition of TG2, and mTG by competitive, and oxidative molecules. Localization of ERp57 was investigated in duodenal biopsies from CD, and control patients by electron microcopy. Inhibition of TG2 and mTG was analyzed on an in vitro level using a photometric assay. ERp57 was observed within the lamina propria and its abundance within the endoplasmic reticulum (ER) was reduced in CD patients. TG2 was oxidatively inhibited by up to 95% by PX12 (p < 0.001) and L-cystine (p < 0.001), whereas mTG remained unaffected. The reduced presence of ERp57 within the ER of CD biopsies suggests a regulatory function of this protein within CD pathogenesis. PX12 and L-cystine oxidatively inhibit TG2 and might serve as treatment options in CD. mTG is poorly regulated and could contribute to the accumulation of immunogenic peptides within the gut with potential pathogenic effects.

The role of breastfeeding promotion in German hospitals for exclusive breastfeeding duration.

Breastfeeding promotion and support in hospitals is expected to have a positive impact on maternal breastfeeding outcomes. The objective of this study is to examine the association between breastfeeding promotion in maternity hospitals in Germany and exclusive breastfeeding (EBF) rates during the first 4 months. Thus, a nationwide cross-sectional web-based survey of breastfeeding promotion was conducted in 103 hospitals. Mother-infant pairs (n = 962) were recruited at these hospitals for a prospective web-based survey of breastfeeding status at five-time points, that is, during a hospital stay, at discharge as well as after 0.5, 2, and 4 months. The hospital analysis was based on the "10 Steps to Successful Breastfeeding" of the World Health Organization and the United Nations Children's Fund, adapted for Germany. Their degree of implementation was stratified by a breastfeeding promotion index (BPI) as low (≤5 steps), medium (6-8 steps), and high (≥9 steps). The association between the BPI and the odds of EBF at each of the five-time points was estimated by multivariable regression models, adjusting for various maternal factors. At all time points, the proportion of EBF among mothers from high BPI hospitals exceeded the proportion of those from medium or low BPI hospitals. A high BPI was associated with higher odds of EBF during the hospital stay and at discharge, while maternal factors for EBF such as breastfeeding experience and no early use of a pacifier persisted beyond. The high commitment of hospitals and tailored support of mothers is essential for EBF.

Adrenal Steroid Metabolism and Blood Pressure in 5- to 7-Year-Old Children Born Preterm as Compared to Peers Born at Term.

Background: Previous studies indicated preterm birth to be a risk factor for hypertension in adolescence and adulthood. However, studies in children investigating the underlying mechanisms are scarce. Objective: We hypothesized children born preterm to have higher excretion of cortisol and/or androgen metabolites per day concomitantly with higher blood pressure as compared to peers born at term. We thus aimed to compare urinary steroid profiles and blood pressure between 5- to 7-year-old children born preterm and peers born at term. Furthermore, aldosterone precursor excretion per day was compared between both groups. Methods: Blood pressure was measured in 236 children (preterms n = 116; gestational age 29.8 ± 2.6 (30; 24-33) weeks [mean ± standard deviation (median; range)]) using an automatic oscillometric device. Urinary steroid profiles were determined in 24-h urine samples (preterms n = 109; terms n = 113) using gas chromatographic-mass spectrometric analysis. To assess excretion of cortisol and androgen metabolites per day, major cortisol and androgen metabolites were summed, respectively. To assess aldosterone excretion per day tetrahydrocorticosterone, 5α-tetrahydrocorticosterone, and tetrahydro-11-deydrocorticosterone were summed. Results: Multiple regression analyses showed prematurity to be associated with systolic but not with diastolic blood pressure. When adjusted for potential confounders (prematurity, gender, age at day of examination, being born small for gestational age, breastfeeding, accelerated weight gain during infancy, family history of cardiovascular disease, parental hypertension, and body mass index) prematurity was shown to be associated with an increase in systolic blood pressure by 2.87 mmHg (95% confidence interval 0.48-5.27; p = 0.02). Cortisol, androgen metabolite, and aldosterone precursor excretion per day were not higher in individuals born preterm. In contrast to our hypothesis, multiple regression analysis showed prematurity to independently decrease cortisol and aldosterone precursor excretion per day (p < 0.001 and 0.04, respectively). Conclusion: This study provides further evidence for systolic blood pressure to be higher after preterm birth as early as at the age of 5 to 7 years. However, this seems not to be explained by elevated excretion of cortisol and/or androgen metabolites.

Solanum anguivi Lam. fruit preparations counteract the negative effects of a high-sugar diet on the glucose metabolism in Drosophila melanogaster.

Solanum anguivi Lam. fruits (SALF) are traditionally consumed as a remedy for type 2 diabetes mellitus (T2DM). However, data regarding the potential anti-diabetic effect of SALF and its underlying mechanisms are scarce. As the fruit fly's energy metabolism has been suggested to be comparable with mammals including the secretion of insulin-like peptides, we fed Drosophila melanogaster a high-sugar diet (HSD) to induce a T2DM-like phenotype and subsequently exposed them to a HSD supplemented with SALF. Following, flies were analyzed for various biomarkers in relation to energy metabolism. The HSD-induced glucose levels were significantly down-regulated in flies exposed to a HSD supplemented with SALF. In addition, flies exposed to SALF-supplemented HSD exhibited a better survival in comparison to HSD-fed counterparts. Other parameters of the energy metabolism such as triglyceride levels, weights, and fitness were not affected by SALF supplementation. This was also true for the expression levels of the insulin-like-peptides 3 and 6 as well as for spargel, the Drosophila homolog of PPARγ-co-activator 1α, a central player in mitochondrial biogenesis. Overall, the present study shows that SALF significantly lowered the HSD-induced glucose levels and increased the survival while the biomarkers of the energy metabolism were not affected.

Fucose as a Cleavage Product of 2'Fucosyllactose Does Not Cross the Blood-Brain Barrier in Mice.

SCOPE: To further examine the role of the human milk oligosaccharide 2'fucosyllactose (2´FL) and fucose (Fuc) in cognition. Using 13 C-labeled 2'FL,thestudy previously showed in mice that 13 C-enrichment of the brain is not caused by 13 C1 -2´FL itself, but rather by microbial metabolites. Here, the study applies 13 C1 -Fuc in the same mouse model to investigate its uptake into the brain. METHODS AND RESULTS: Mice received 13 C1 -Fuc via oral gavage (2 mmol 13 C1 -Fuc/kg-1 body weight) or intravenously (0.4 mmol/kg-1 body weight). 13 C-enrichment is measured in organs, including various brain regions, biological fluids and excrements. By EA-IRMS, the study observes an early rise of 13 C-enrichment in plasma, 30 min after oral dosing. However, 13 C-enrichment in the brain does not occur until 3-5 h post-dosing, when the 13 C-Fuc bolus has already reached the lower gut. Therefore, the researcher assume that 13 C-Fuc is absorbed in the upper small intestine but cannot cross the blood-brain barrier which is also observed after intravenous application of 13 C1 -Fuc. CONCLUSIONS: Late 13 C-enrichment in the rodent brain may be derived from 13 C1 -Fuc metabolites derived from bacterial fermentation. The precise role that Fuc or 2´FL metabolites might play in gut-brain communication needs to be investigated in further studies.

Absence of neocytolysis in humans returning from a 3-week high-altitude sojourn.

AIMS: Total haemoglobin mass (tot-Hb) increases during high-altitude acclimatization. Normalization of tot-Hb upon descent is thought to occur via neocytolysis, the selective destruction of newly formed erythrocytes. Because convincing experimental proof of neocytolysis is lacking, we performed a prospective study on erythrocyte survival after a stay at the Jungfraujoch Research Station (JFJRS; 3450 m). METHODS: Newly formed erythrocytes of 12 male subjects (mean age 23.3 years) were age cohort labelled in normoxia (110 m) and during a 19-day high-altitude sojourn by ingestion of 13 C2- and 15 N-labelled glycine respectively. Elimination dynamics for erythrocytes produced in normoxia and at high altitude were measured by isotope ratio mass spectrometry of haem, by determining tot-Hb, reticulocyte counts, erythrocyte membrane protein 4.1a/4.1b ratio and by mathematical modelling. RESULTS: Tot-Hb increased by 4.7% ± 2.7% at high altitude and returned to pre-altitude values within 11 days after descent. Elimination of 13 C- (normoxia) and 15 N- (high altitude) labelled erythrocytes was not different. Erythropoietin levels and counts of CD71-positive reticulocytes decreased rapidly after descent. The band 4.1a/4.1b ratio decreased at altitude and remained low for 3-4 days after descent and normalized slowly. There was no indication of haemolysis. CONCLUSION: We confirm a rapid normalization of tot-Hb upon descent. Based on the lack of accelerated removal of age cohorts of erythrocytes labelled at high altitude, on patterns of changes in reticulocyte counts and of the band 4.1a/4.1b ratio and on modelling, this decrease did not occur via neocytolysis, but by a reduced rate of erythropoiesis along with normal clearance of senescent erythrocytes.

Breast-feeding promotion in hospitals and prospective breast-feeding rates during the first year of life in two national surveys 1997-1998 and 2017-2019 in Germany.

OBJECTIVES: The present study aimed to assess the current state of breast-feeding promotion in hospitals and the prevalence of breast-feeding during the first year of life in Germany and to compare the results with a study 20 years earlier. DESIGN: In the studies on 'breast-feeding and infant nutrition in Germany' named 'SuSe', a cross-sectional survey in hospitals was combined with a subsequent prospective survey of breast-feeding and infant nutrition during the first year of life (0·5, 2, 4, 6 and 12 months after birth) in mother-infant pairs who were recruited in the hospitals. Written questionnaires and phone calls were used in SuSe I and web-based questionnaires in SuSe II. Breast-feeding promotion and prevalence were evaluated using recommendations from the WHO and the UNICEF. SETTING: Two nationwide surveys SuSe I (1997-1998) and SuSe II (2017-2019). PARTICIPANTS: In SuSe I, 177 hospitals and 1717 mother-infant pairs and in SuSe II 109 hospitals and 962 mother-infant pairs were included. RESULTS: In SuSe II, hospitals implemented seven of the WHO 'Ten Steps to Successful Breastfeeding' to a greater extent than the hospitals in SuSe I. More mothers exclusively breastfed for 4 months (57 % v. 33 %) and continued breast-feeding until 6 (78 % v. 48 %) and 12 months (41 % v. 13 %). In both studies, exclusive breast-feeding decreased between 4 and 6 months of age due to the introduction of complementary feeding. CONCLUSIONS: In Germany, breast-feeding habits have come closer to the recommendations over the last 20 years.

Fructose Consumption-Free Sugars and Their Health Effects.

BACKGROUND: The excessive consumption of free sugars, including fructose, is considered a cause of overweight and metabolic syndrome throughout the Western world. In Germany, the prevalence of overweight and obesity among adults (54%, 18%) and children (15%, 6%) has risen in the past few decades and has now become stable at a high level. The causative role of fructose is unclear. METHODS: This review is based on publications retrieved by a selective search in PubMed and the Cochrane Library, with special attention to international guidelines and expert recommendations. RESULTS: The hepatic metabolism of fructose is insulin-independent; because of the lack of a feedback mechanism, it leads to substrate accumulation, with de novo lipogenesis and gluconeogenesis. Recent meta-analyses with observation periods of one to ten weeks have shown that the consumption of fructose in large amounts leads to weight gain (+ 0.5 kg [0.26; 0.79]), elevated triglyceride levels (+ 0.3 mmol/L [0.11; 0.41]), and steatosis hepatis (intrahepatocellular fat content: + 54% [29; 79%]) when it is associated with a positive energy balance (fructose dose + 25-40% of the total caloric requirement). Meta-analyses in the isocaloric setting have not shown any comparable effects. Children, with their preference for sweet foods and drinks, are prone to excessive sugar consumption. Toddlers under age two are especially vulnerable. CONCLUSION: The effects that have been observed with the consumption of large amounts of fructose cannot be reliably distinguished from the effects of a generally excessive caloric intake. Further randomized and controlled intervention trials of high quality are needed in order to determine the metabolic effects of fructose consumed under isocaloric conditions. To lessen individual consumption of sugar, sugary dietary items such as sweetened soft drinks, fruit juice, and smoothies should be avoided in favor of water as a beverage and fresh fruit.

Nutrient Restriction has Limited Short-Term Effects on Gut, Immunity, and Brain Development in Preterm Pigs.

BACKGROUND: Extrauterine growth restriction (EUGR) in preterm infants is associated with higher morbidity and impaired neurodevelopment. Early nutrition support may prevent EUGR in preterm infants, but it is not known if this improves organ development and brain function in the short and long term. OBJECTIVE: Using pigs as models for infants, we hypothesized that diet-induced EUGR impairs gut, immunity, and brain development in preterm neonates during the first weeks after birth. METHODS: Forty-four preterm caesarean-delivered pigs (Danish Landrace × Large White × Duroc, birth weight 975 ± 235 g, male:female ratio 23:21) from 2 sows were fed increasing volumes [32-180 mL/(kg·d)] of dilute bovine milk (EUGR group) or the same diet fortified with powdered bovine colostrum for 19 d (CONT group, 50-100% higher protein and energy intake than the EUGR group). RESULTS: The EUGR pigs showed reduced body growth (-39%, P < 0.01), lower plasma albumin, phosphate, and creatine kinase concentrations (-35 to 14%, P < 0.05), increased cortisol and free iron concentrations (+130 to 700%, P < 0.05), and reduced relative weights of the intestine, liver, and spleen (-38 to 19%, all P < 0.05). The effects of EUGR on gut structure, function, microbiota, and systemic immunity were marginal, although EUGR temporarily increased type 1 helper T cell (Th1) activity (e.g. more blood T cells and higher Th1-related cytokine concentrations on day 8) and reduced colon nutrient fermentation (lower SCFA concentration; -45%, P < 0.01). Further, EUGR pigs showed increased relative brain weights (+19%, P < 0.01), however, memory and learning, as tested in a spatial T-maze, were not affected. CONCLUSION: Most of the measured organ growth, and digestive, immune, and brain functions showed limited effects of diet-induced EUGR in preterm pigs during the first weeks after birth. Likewise, preterm infants may show remarkable physiological adaptation to deficient nutrient supply during the first weeks of life although early life malnutrition may exert negative consequences later.

Digestive enzyme expression in the large intestine of children with short bowel syndrome in a late stage of adaptation.

BACKGROUND AND AIMS: Intestinal adaptation in short bowel syndrome (SBS) includes morphologic processes and functional mechanisms. This study investigated whether digestive enzyme expression in the duodenum and colon is upregulated in SBS patients. METHOD: Sucrase-isomaltase (SI), lactase-phlorizin hydrolase (LPH), and neutral Aminopeptidase N (ApN) were analyzed in duodenal and colonic biopsies from nine SBS patients in a late stage of adaptation as well as healthy and disease controls by immunoelectron microscopy (IEM), Western blots, and enzyme activities. Furthermore, proliferation rates and intestinal microbiota were analyzed in the mucosal specimen. RESULTS: We found significantly increased amounts of SI, LPH, and ApN in colonocytes in most SBS patients with large variation and strongest effect for SI and ApN. Digestive enzyme expression was only partially elevated in duodenal enterocytes due to a low proliferation level measured by Ki-67 staining. Microbiome analysis revealed high amounts of Lactobacillus resp. low amounts of Proteobacteria in SBS patients with preservation of colon and ileocecal valve. Colonic expression was associated with a better clinical course in single cases. CONCLUSION: In SBS patients disaccharidases and peptidases can be upregulated in the colon. Stimulation of this colonic intestinalization process by drugs, nutrients, and pre- or probiotics might offer better therapeutic approaches.