ALBERT

Description: © The Author(s), 2015. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in American Journal of Gastroenterology 110 (2015): 1718–1729, doi:10.1038/ajg.2015.357.

Description: Exploring associations between the gut microbiota and colonic inflammation and assessing sequential changes during exclusive enteral nutrition (EEN) may offer clues into the microbial origins of Crohn’s disease (CD). Fecal samples (n=117) were collected from 23 CD and 21 healthy children. From CD children fecal samples were collected before, during EEN, and when patients returned to their habitual diets. Microbiota composition and functional capacity were characterized using sequencing of the 16S rRNA gene and shotgun metagenomics. Microbial diversity was lower in CD than controls before EEN (P=0.006); differences were observed in 36 genera, 141 operational taxonomic units (OTUs), and 44 oligotypes. During EEN, the microbial diversity of CD children further decreased, and the community structure became even more dissimilar than that of controls. Every 10 days on EEN, 0.6 genus diversity equivalents were lost; 34 genera decreased and one increased during EEN. Fecal calprotectin correlated with 35 OTUs, 14 of which accounted for 78% of its variation. OTUs that correlated positively or negatively with calprotectin decreased during EEN. The microbiota of CD patients had a broader functional capacity than healthy controls, but diversity decreased with EEN. Genes involved in membrane transport, sulfur reduction, and nutrient biosynthesis differed between patients and controls. The abundance of genes involved in biotin (P=0.005) and thiamine biosynthesis decreased (P=0.017), whereas those involved in spermidine/putrescine biosynthesis (P=0.031), or the shikimate pathway (P=0.058), increased during EEN. Disease improvement following treatment with EEN is associated with extensive modulation of the gut microbiome.

Description: The IBD team at Royal Hospital for Children, Glasgow, is supported by the Catherine McEwan Foundation and the Yorkhill IBD fund.

Description: Fatty acid (FA) chemoreception in the oral cavity, known as fat taste, may trigger a satiety response that is homologous to FA chemoreception in the gastrointestinal tract. In addition, individuals with an impaired fat taste sensitivity are more likely to have an impaired satiety response. This study aimed to assess the effect of an FA mouth rinse on self-reported appetite, and to determine if the effect is modified by fat taste sensitivity. Thirty-one participants (age, 32.0 ± 8.4 y; body mass index (BMI), 26.1 ± 8.1 kg/m2) were studied on four separate days to evaluate the effect of a 20 mM oleic acid (OA) mouth rinse (in duplicate) compared to a control (in duplicate) on self-reported appetite by using a visual analogue scale (VAS) every 30 min for three hours following a standardized low-fat breakfast. The area under the curve ratings for fullness were greater (p = 0.003), and those for hunger were lower (p = 0.002) following the OA rinse compared to the control. The effect of the OA rinse was greater in individuals who were hypersensitive to fat taste compared to moderately sensitive and hyposensitive individuals for fullness (p 〈 0.010) and hunger (p 〈 0.010) ratings. In summary, an OA mouth rinse decreases self-reported hunger and increases self-reported fullness, particularly in those who are more sensitive to fat taste. FA receptors in the oral cavity may be potential targets to regulate appetite.

Description: Early B lymphopoiesis in mammals is induced within the bone marrow (BM) microenvironment, but which cells constitute this niche is not known. Previous studies had shown that osteoblasts (OBs) support hematopoietic stem cell (HSC) proliferation and myeloid differentiation. We now find that purified primary murine OBs also support the differentiation of primitive hematopoietic stem cells through lymphoid commitment and subsequent differentiation to all stages of B-cell precursors and mature B cells. Lin−Sca-1+Rag-2− BM cell differentiation to B cells requires their attachment to OBs in vitro, and this developmental process is mediated via VCAM-1, SDF-1, and IL-7 signaling induced by parathyroid hormone (PTH). Addition of cytokines produced by nonosteoblastic stromal cells (c-Kit ligand, IL-6, and IL-3) shifted the cultures toward myelopoiesis. Confirming the role of OBs in B lymphopoiesis, we found that selective elimination of osteoblasts in Col2.3Δ-TK transgenic mice severely depleted pre-pro-B and pro-B cells from BM, preceding any decline in HSCs. Taken together, these results demonstrate that osteoblasts are both necessary and sufficient for murine B-cell commitment and maturation, and thereby constitute the cellular homolog of the avian bursa of Fabricius.

Description: Owing to the public health concern associated with the consumption of added sugar, the World Health Organization recommends cutting down sugar in processed foods. Furthermore, due to the growing concern of increased calorie intake from added sugar in sweetened dairy foods, the present review provides an overview of different types and functions of sugar, various sugar reduction strategies, and current trends in the use of sweeteners for sugar reduction in dairy food, taking flavoured milk as a central theme where possible to explore the aforementioned aspects. The strength and uniqueness of this review are that it brings together all the information on the available types of sugar and sugar reduction strategies and explores the current trends that could be applied for reducing sugar in dairy foods without much impact on consumer acceptance. Among different strategies for sugar reduction, the use of natural non-nutritive sweeteners (NNSs), has received much attention due to consumer demand for natural ingredients. Sweetness imparted by sugar can be replaced by natural NNSs, however, sugar provides more than just sweetness to flavoured milk. Sugar reduction involves multiple technical challenges to maintain the sensory properties of the product, as well as to maintain consumer acceptance. Because no single sugar has a sensory profile that matches sucrose, the use of two or more natural NNSs could be an option for food industries to reduce sugar using a holistic approach rather than a single sugar reduction strategy. Therefore, achieving even a small sugar reduction can significantly improve the diet and health of an individual.

Description: There is a paucity of pharmacokinetic (PK) data about hydroxyurea (HU) in persons with sickle cell anemia (SCA) and none in very young children. HU clearance is predominantly renal. The kidney may be damaged during infancy in SCA, but the first abnormality is usually hyperfiltration which may lead to enhanced HU clearance. Following a 15 mg/kg oral dose of commercially available HU capsules, PKs in 7 adults with SCA and normal renal function have been reported to be a mean±SD half-life (T1/2) of 3.14±0.9 hrs, a maximal concentration (Cmax) of 28.32±11.0 ug/mL, and an area under the curve (AUC) of 81.66±15.5 ug•hr/mL. The Phase II Study of HU in adults concluded that initial 2 hour clearance of HU was not associated with either the maximum tolerated dose or fetal hemoglobin response to treatment. However, the AUC did predict HU toxicity and, in another study, the need for dose adjustment in adults with SCA and renal insufficiency. BABY HUG is an NHLBI-NICHD sponsored Pediatric Phase III Clinical Trial designed to critically assess the efficacy of a novel liquid HU preparation in preventing organ damage in young children with SCA. Forty-five African-American infants, 12 to 18 months (mo) of age (mean 14.7 mo) were recruited without regard to disease severity to the just completed randomized, double-blind, placebo-controlled BABY HUG Feasibility and Safety Pilot Trial. First dose PKs were obtained 0, 1, 2, and 4 hours after oral administration of 20 mg/kg of HU in 22 consecutive patients (mean age 14.5 mo), coincident with measurement of glomerular filtration rate (GFR) by nuclear medicine DTPA clearance. An additional PK sample was obtained between 4 and 8 hours in 15 of the 22 (68%). Samples were frozen at −70°C, shipped, and assayed by high resolution gas chromatography with mass spectrometric detection (limit of detection 0.5 ug/mL). The T1/2 (2.36±0.99 hrs), Cmax (19.81±5.8 ug/mL; 0.26±0.8 uM/L), and AUC (68.82±11.5 ug•hr/mL) were somewhat lower in BABY HUG patients than in the small group of adults with SCA from the literature. There were no apparent relationships between PKs and baseline GFR measured by DTPA or calculated from the Schwartz equation. Younger patients ≤15 mo (n=15) had a trend toward a shorter T1/2 (2.1 vs 2.8 hours; p=0.118) and a lower predicted measurable HU concentration at 8 hours (1.2 vs 2.1 ug/mL; p=0.056) than those 16–18 mo (n=7). There were no age related differences in AUC (67.4 vs 71.8 ug•hr/mL; p=0.421) or Cmax (20.5 vs 18.2 ug/mL; p=0.409). PKs of this novel liquid preparation of HU in young children with SCA may be different than that of adults with the standard capsule formulation. The BABY HUG Trial will continue to refine the PK model by additional evaluations including samples from patients as young as 9 mo of age, the new lower age of eligibility for the open study currently accruing patients.

Description: The identification of bone marrow (BM) niches controlling many aspects of hematopoiesis is of great interest. It is believed that these niches provide the necessary signals to maintain primitive hematopoietic cells including hematopoietic stem cells (HSC). Downstream of HSC are programs for both myelopoiesis and lymphopoiesis, although little is known about the niches that support these processes. Accumulating data implicating osteoblasts (OB) as a component of the HSC niche suggest that these cells are able to regulate HSC properties, and that the HSC are located in direct contact with OB at the bone endosteum. However, the interpretation of these data is controversial, and others have suggested that endothelial cells dictate the structure and function of the HSC niche. In order to determine whether OB are a critical component of hematopoietic niches, we employed Col2.3ΔTK mice, a transgenic mouse strain bearing a fusion gene composed of the rat type I collagen promoter and HSV-thymidine kinase. This construct allows for selective depletion of OB following in vivo gancyclovir (GCV) treatment. Mice received 100 mg/kg GCV for a period of 8, 21, or 28 days. Following 8 days of GCV, OB were depleted from the BM as determined by a lack of staining for osteocalcin. Concommitant with the loss of OB, there was a decrease in total BM cellularity of approximately 50% that included reductions in both myeloid and B lymphoid cells. Among the B cell populations that were measured, pre-pro-B and pro-B cells were reduced to the greatest extent, 64% and 81%, respectively. Despite this marked reduction in B lymphopoiesis, number of Lin− Sca-1+ cKit+ cells (LSK), a population enriched for HSCs, was unchanged immediately following OB depletion. This loss of B cell precursors, occurring before any observable effects on HSC numbers, suggests that OB may directly support the proliferation and maturation of early B cell precursors. Although minimal changes in BM LSK were observed immediately after GCV, BM LSK were reduced after 21 and 28 days of GCV treatment, when their numbers decreased 40% and 88%, respectively. During this same period, however, spleen LSK increased by 165% and 300%, respectively. Assuming that femurs and tibiae constitute 25% of total murine BM, the total number of LSK lost from the BM after 21 and 28 days of GCV is approximately 1.42 and 3.12×10^5 cells, respectively. These values are remarkably consistent with the increase in splenic LSK at the same time points, 1.2 and 3.7×10^5 cells, respectively. These data indicate that loss of OB plays a pivotal role in the partitioning of LSK into and out of the BM. Given the finding that the shift in LSK is most pronounced 2–3 weeks after the loss of OB, these data raise the intriguing possibility that the partitioning of LSK from the BM to the spleen following OB deletion is not the result of increased emigration from the BM but, rather, due to a decreased ability of HSC to home back to the BM following daily limited physiological mobilization. For example, it is plausible that OB supply chemotactic signals that control the ability of HSC to home to the BM. In conclusion, in vivo depletion of OBs causes an immediate reduction in the number of B cell precursors with a delayed shift in LSK from the BM to the periphery, thus demonstrating that OB play a major role in BM HSC trafficking and B lymphopoiesis.

Description: Physical activity (PA) patterns track from childhood through to adulthood. The study aimed to determine the levels and correlates of sedentary time (ST), total PA (TPA), and moderate-to-vigorous PA (MVPA) in preschool-aged children. We conducted cross-sectional analyses of 1052 children aged three-to-four-years-old from six studies included in the International Children’s Accelerometry Database. Multilevel linear regression models adjusting for age, gender, season, minutes of wear time, and study clustering effects were used to estimate associations between age, gender, country, season, ethnicity, parental education, day of the week, time of sunrise, time of sunset, and hours of daylight and the daily minutes spent in ST, TPA, and MVPA. Across the UK, Switzerland, Belgium, and the USA, children in our analysis sample spent 490 min in ST per day and 30.0% and 21.2% of children did not engage in recommended daily TPA (≥180 min) and MVPA (≥60 min) guidelines. There was evidence for an association between all 10 potential correlates analyzed and at least one of the outcome variables; average daily minutes spent in ST, TPA and/or MVPA. These correlates can inform the design of public health interventions internationally to decrease ST and increase PA in preschoolers.