Racial and ethnic differences in diagnosis age and blood biomarkers in a pediatric inflammatory bowel disease cohort.

OBJECTIVE: Prompt diagnosis of pediatric-onset inflammatory bowel disease (IBD) is crucial for preventing a complicated disease course; however, it is not well understood how social determinants of health might affect pediatric IBD diagnosis. This study examined differences in diagnosis age, biomarkers of disease severity, and anthropometrics with sociodemographic factors in a pediatric IBD cohort. METHODS: Pediatric IBD patients (n = 114) and their parents/caregivers were enrolled from the Children's of Alabama Pediatric IBD Clinic in Birmingham, Alabama. Primary analyses examined associations of child race and ethnicity, parental income, parental education, single-parent household status, insurance type, and distance to a tertiary pediatric gastroenterology referral center with diagnosis age. Secondary analyses examined differences in biomarker levels, height, and body mass index at the time of diagnosis. RESULTS: Racial and ethnic minority children were diagnosed at an older age compared to Non-Hispanic White children (14.4 ± 0.40 vs. 11.7 ± 0.38 years; p < 0.001), and this trend was robust to adjustment with other sociodemographic variables. Parental attainment of a college education attenuated the link between minority race and ethnicity and the likelihood of older age at diagnosis, while other sociodemographic variables had no moderating effect. Racial and ethnic minority children were 5.7 times more likely to have clinically elevated erythrocyte sedimentation rate at diagnosis compared to Non-Hispanic White children (p = .024). CONCLUSIONS: These results suggest that child race and ethnicity may exert a primary effect on the age at diagnosis with pediatric-onset IBD. This study highlights the need for further research on racial and ethnic disparities to promote health equity in pediatric-onset IBD.

Associations between dietary habits, socio-demographics and gut microbial composition in adolescents.

The relationship between dietary habits and microbiota composition during adolescence has not been well examined. This is a crucial knowledge gap to fill considering that diet-microbiota interactions influence neurodevelopment, immune system maturation and metabolic regulation. This study examined the associations between diet and the gut microbiota in a school-based sample of 136 adolescents (Mage = 12·1 years; age range 11-13 years; 48 % female; 47 % Black, 38 % non-Hispanic White, 15 % Hispanic or other minorities) from urban, suburban and rural areas in the Southeast USA. Adolescents completed the Rapid Eating Assessment for Participants and provided stool samples for 16S ribosomal RNA gene sequencing. Parents reported their child and family socio-demographic characteristics. The associations between diet and socio-demographics with gut microbiota diversity and abundance were analysed using multivariable regression models. Child race and ethnicity, sex, socio-economic status and geographic locale contributed to variation within microbiota composition (ß-diversity). Greater consumption of processed meat was associated with a lower microbial α-diversity after adjusting for socio-demographic variables. Multi-adjusted models showed that frequent consumption of nutrient-poor, energy-dense foods (e.g. sugar-sweetened beverages, fried foods, sweets) was negatively associated with abundances of genera in the family Lachnospiraceae (Anaerostipes, Fusicatenibacter and Roseburia), which are thought to play a beneficial role in host health through their production of short-chain fatty acids (SCFAs). These results provide new insights into the complex relationships among socio-demographic factors, diet and gut microbiota during adolescence. Adolescence may represent a critical window of opportunity to promote healthy eating practices that shape a homoeostatic gut microbiota with life-long benefits.

Twenty-year record of white pox disease in the Florida Keys: importance of environmental risk factors as drivers of coral health.

Declining coral populations worldwide place a special premium on identifying risks and drivers that precipitate these declines. Understanding the relationship between disease outbreaks and their drivers can help to anticipate when the risk of a disease pandemic is high. Populations of the iconic branching Caribbean elkhorn coral Acropora palmata have collapsed in recent decades, in part due to white pox disease (WPX). To assess the role that biotic and abiotic factors play in modulating coral disease, we present a predictive model for WPX in A. palmata using 20 yr of disease surveys from the Florida Keys plus environmental information collected simultaneously in situ and via satellite. We found that colony size was the most influential predictor for WPX occurrence, with larger colonies being at higher risk. Water quality parameters of dissolved oxygen saturation, total organic carbon, dissolved inorganic nitrogen, and salinity were implicated in WPX likelihood. Both low and high wind speeds were identified as important environmental drivers of WPX. While high temperature has been identified as an important cause of coral mortality in both bleaching and disease scenarios, our model indicates that the relative influence of HotSpot (positive summertime temperature anomaly) was low and actually inversely related to WPX risk. The predictive model developed here can contribute to enabling targeted strategic management actions and disease surveillance, enabling managers to treat the disease or mitigate disease drivers, thereby suppressing the disease and supporting the persistence of corals in an era of myriad threats.

Adverse childhood experiences are associated with vascular changes in adolescents that are risk factors for future cardiovascular disease.

BACKGROUND: Adverse childhood experiences (ACEs), such as abuse, neglect, and household dysfunction, are associated with a higher risk of cardiovascular disease (CVD) and indicators of future CVD risk in adulthood, such as greater vascular stiffness. The impact of ACEs in adolescence is unclear, and understanding how ACEs relate to blood pressure (BP) and vascular function during early life is key for the development of prevention strategies to reduce CVD risk. We hypothesized that exposure to ACEs would be associated with changes in central hemodynamics such as increased vascular stiffness and higher BP during adolescence. METHODS: This pilot study enrolled 86 adolescents recruited from the Children's of Alabama. A validated ACE questionnaire was employed, and ACEs were modeled both as a continuous variable and a categorical variable (ACE ≥ 1 vs. ACE = 0). The primary outcomes used are considered to be indicators of future cardio-renal disease risk: aortic augmentation index normalized to 75 bpm (Alx75, a surrogate for vascular stiffness), carotid-femoral PWV (m/s), and ambulatory BP patterns. RESULTS: Adolescents with ACE ≥ 1 had significantly higher Alx75 (ACE: 5.2% ± 2.2 compared to no ACE: - 1.4% ± 3.0; p = 0.043). PWV only reflected this trend when adjustments were made for the body mass index. Adolescents with ACEs showed no differences in ambulatory BP patterns during the 24-h, wake, or sleep periods compared to adolescents with no ACEs. CONCLUSIONS: ACEs were associated with higher AIx75 in adolescence, which is a risk factor for future CVD. Adolescence could present an opportunity for early detections/interventions to mitigate adverse cardiovascular outcomes in adulthood. A higher resolution version of the Graphical abstract is available as Supplementary information.

Influence of Aging, Macronutrient Composition and Time-Restricted Feeding on the Fischer344 x Brown Norway Rat Gut Microbiota.

Both ketogenic diets (KD) and time-restricted feeding (TRF) regimens have the ability to influence several parameters of physical health, including gut microbiome composition and circulating cytokine concentration. Moreover, both of these dietary interventions prevent common impairments associated with the aging process. However, significantly altering macronutrient intake, which is required for a KD, may be unappealing to individuals and decrease compliance to dietary treatments. In contrast to a KD, TRF allows individuals to continue eating the foods they are used to, and only requires a change in the time of day at which they eat. Therefore, we investigated both a KD and a diet with a more Western-like macronutrient profile in the context of TRF, and compared both diets to animals allowed access to standard chow ad libitum in young adult and aged rats. While limited effects on cytokine levels were observed, both methods of microbiome analysis (16S sequencing and metagenomics) indicate that TRF and KDs significantly altered the gut microbiome in aged rats. These changes were largely dependent on changes to feeding paradigm (TRF vs. ad libitum) alone regardless of macronutrient content for many gut microbiota, but there were also macronutrient-specific changes. Specifically, functional analysis indicates significant differences in several pathways, including those involved in the tricarboxylic acid (TCA) cycle, carbohydrate metabolism and neurodegenerative disease. These data indicate that age- and disease-related gut dysbiosis may be ameliorated through the use of TRF with both standard diets and KDs.

ICOS ligand and IL-10 synergize to promote host-microbiota mutualism.

Genome-wide association studies have identified ICOSLG, which encodes the inducible costimulator ligand (ICOSLG or ICOSL) as a susceptibility locus for inflammatory bowel disease. ICOSL has been implicated in the enhancement of pattern recognition receptor signaling in dendritic cells, induction of IL-10 production by CD4 T cells, and the generation of high-affinity antibodies to specific antigens-all of which can potentially explain its involvement in gastrointestinal inflammation. Here, we show that murine ICOSL deficiency results in significant enrichment of IL-10-producing CD4 T cells particularly in the proximal large intestine. Transient depletion of IL-10-producing cells from adult ICOSL-deficient mice induced severe colonic inflammation that was prevented when mice were first treated with metronidazole. ICOSL-deficient mice displayed reduced IgA and IgG antibodies in the colon mucus and impaired serum antibody recognition of microbial antigens, including flagellins derived from mucus-associated bacteria of the Lachnospiraceae family. Confirming the synergy between ICOSL and IL-10, ICOSL deficiency coupled with CD4-specific deletion of the Il10 gene resulted in juvenile onset colitis that was impeded when pups were fostered by ICOSL-sufficient dams. In this setting, we found that both maternally acquired and host-derived antibodies contribute to the life anti-commensal antibody repertoire that mediates this protection in early life. Collectively, our findings reveal a partnership between ICOSL-dependent anti-commensal antibodies and IL-10 in adaptive immune regulation of the microbiota in the large intestine. Furthermore, we identify ICOSL deficiency as an effective platform for exploring the functions of anti-commensal antibodies in host-microbiota mutualism.

Early life stress in mice alters gut microbiota independent of maternal microbiota inheritance.

Exposure to early life stress (ELS) is associated with a greater risk of chronic disease development including depression and cardiovascular disease. Altered gut microbiota has been linked to both depression and cardiovascular disease in mice and humans. Rodent models of early life neglect are used to characterize the mechanistic links between early life stress (ELS) and the risk of disease later in life. However, little is understood about ELS exposure and the gut microbiota in the young mice and the influence of the maternal inheritance of the gut microbiota. We used a mouse model of ELS, maternal separation with early weaning (MSEW), and normally reared mice to determine whether the neonate microbiota is altered, and if so, are the differences attributable to changes in dam microbiota that are then transmitted to their offspring. Individual amplicon sequence variants (ASVs) displayed differential abundance in the microbiota of MSEW compared with normally reared pups at postnatal day (PD) 28. Additionally, ELS exposure reduced the alpha diversity and altered microbial community composition at PD28. The composition, levels of alpha diversity, and abundance of individual ASVs in the microbiota of dams were similar from MSEW or normally reared cohorts. Thus, the observed shifts in the abundance of individual bacterial ASVs in the neonates and young pups are likely driven by endogenous effects of MSEW in the offspring host and are not due to inherited differences from the dam. This knowledge suggests that exposure to ELS has a direct effect on microbial factors on the risk of chronic disease development.

The sad weekend: A perilous North American tradition.

Obesity is a global concern and affects millions of Americans who consume poor-quality diets. Diets directly affect the gut microbiota, which can have subsequent effects on inflammation and contribute to other chronic states. Previously we have shown that a Standard American Diet (SAD) increased immune cell activation and prolonged recovery and that a beneficial diet could reduce these negative effects. Here, male and female mice were given access to regular chow (REG), SAD, our Anti-Inflammatory Diet (AID) or a combination of SAD and AID. This latter group was modeled on the commonplace dietary pattern of healthy eating during the week (AID: Monday-Friday) and relaxed eating patterns on the weekend (SAD: Saturday-Sunday). After 14 weeks of diet consumption and an inflammatory injury, we found that the SAD prolonged and the AID promoted recovery. However, recovery was significantly delayed in those mice consuming the AID-SAD, regardless of weekly healthy diet access. In addition, fecal samples taken during the study revealed dramatic differences in microbial community composition, relative abundance of abundant bacterial phyla and alpha diversity. These data confirm the impact of diet on gut microbiota and suggest a relation between abundance of specific bacterial taxa and susceptibility to prolonged recovery from injury.

Abundance and Multilocus Sequence Analysis of Vibrio Bacteria Associated with Diseased Elkhorn Coral (Acropora palmata) of the Florida Keys.

The critically endangered elkhorn coral (Acropora palmata) is affected by white pox disease (WPX) throughout the Florida Reef Tract and wider Caribbean. The bacterium Serratia marcescens was previously identified as one etiologic agent of WPX but is no longer consistently detected in contemporary outbreaks. It is now believed that multiple etiologic agents cause WPX; however, to date, no other potential pathogens have been thoroughly investigated. This study examined the association of Vibrio bacteria with WPX occurrence from August 2012 to 2014 at Looe Key Reef in the Florida Keys, USA. The concentration of cultivable Vibrio was consistently greater in WPX samples than in healthy samples. The abundance of Vibrio bacteria relative to total bacteria was four times higher in samples from WPX lesions than in adjacent apparently healthy regions of diseased corals based on quantitative PCR (qPCR). Multilocus sequence analysis (MLSA) was used to assess the diversity of 69 Vibrio isolates collected from diseased and apparently healthy A. palmata colonies and the surrounding seawater. Vibrio species with known pathogenicity to corals were detected in both apparently healthy and diseased samples. While the causative agent(s) of contemporary WPX outbreaks remains elusive, our results suggest that Vibrio spp. may be part of a nonspecific heterotrophic bacterial bloom rather than acting as primary pathogens. This study highlights the need for highly resolved temporal sampling in situ to further elucidate the role of Vibrio during WPX onset and progression.IMPORTANCE Coral diseases are increasing worldwide and are now considered a major contributor to coral reef decline. In particular, the Caribbean has been noted as a coral disease hot spot, owing to the dramatic loss of framework-building acroporid corals due to tissue loss diseases. The pathogenesis of contemporary white pox disease (WPX) outbreaks in Acropora palmata remains poorly understood. This study investigates the association of Vibrio bacteria with WPX.

Saharan dust nutrients promote Vibrio bloom formation in marine surface waters.

Vibrio is a ubiquitous genus of marine bacteria, typically comprising a small fraction of the total microbial community in surface waters, but capable of becoming a dominant taxon in response to poorly characterized factors. Iron (Fe), often restricted by limited bioavailability and low external supply, is an essential micronutrient that can limit Vibrio growth. Vibrio species have robust metabolic capabilities and an array of Fe-acquisition mechanisms, and are able to respond rapidly to nutrient influx, yet Vibrio response to environmental pulses of Fe remains uncharacterized. Here we examined the population growth of Vibrio after natural and simulated pulses of atmospherically transported Saharan dust, an important and episodic source of Fe to tropical marine waters. As a model for opportunistic bacterial heterotrophs, we demonstrated that Vibrio proliferate in response to a broad range of dust-Fe additions at rapid timescales. Within 24 h of exposure, strains of Vibrio cholerae and Vibrio alginolyticus were able to directly use Saharan dust-Fe to support rapid growth. These findings were also confirmed with in situ field studies; arrival of Saharan dust in the Caribbean and subtropical Atlantic coincided with high levels of dissolved Fe, followed by up to a 30-fold increase of culturable Vibrio over background levels within 24 h. The relative abundance of Vibrio increased from ∼1 to ∼20% of the total microbial community. This study, to our knowledge, is the first to describe Vibrio response to Saharan dust nutrients, having implications at the intersection of marine ecology, Fe biogeochemistry, and both human and environmental health.

Shifting white pox aetiologies affecting Acropora palmata in the Florida Keys, 1994-2014.

We propose 'the moving target hypothesis' to describe the aetiology of a contemporary coral disease that differs from that of its historical disease state. Hitting the target with coral disease aetiology is a complex pursuit that requires understanding of host and environment, and may lack a single pathogen solution. White pox disease (WPX) affects the Caribbean coral Acropora palmata. Acroporid serratiosis is a form of WPX for which the bacterial pathogen (Serratia marcescens) has been established. We used long-term (1994-2014) photographic monitoring to evaluate historical and contemporary epizootiology and aetiology of WPX affecting A. palmata at eight reefs in the Florida Keys. Ranges of WPX prevalence over time (0-71.4%) were comparable for the duration of the 20-year study. Whole colony mortality and disease severity were high in historical (1994-2004), and low in contemporary (2008-2014), outbreaks of WPX. Acroporid serratiosis was diagnosed for some historical (1999, 2003) and contemporary (2012, 2013) outbreaks, but this form of WPX was not confirmed for all WPX cases. Our results serve as a context for considering aetiology as a moving target for WPX and other coral diseases for which pathogens are established and/or candidate pathogens are identified. Coral aetiology investigations completed to date suggest that changes in pathogen, host and/or environment alter the disease state and complicate diagnosis.

Spatial Homogeneity of Bacterial Communities Associated with the Surface Mucus Layer of the Reef-Building Coral Acropora palmata.

Coral surface mucus layer (SML) microbiota are critical components of the coral holobiont and play important roles in nutrient cycling and defense against pathogens. We sequenced 16S rRNA amplicons to examine the structure of the SML microbiome within and between colonies of the threatened Caribbean reef-building coral Acropora palmata in the Florida Keys. Samples were taken from three spatially distinct colony regions--uppermost (high irradiance), underside (low irradiance), and the colony base--representing microhabitats that vary in irradiance and water flow. Phylogenetic diversity (PD) values of coral SML bacteria communities were greater than surrounding seawater and lower than adjacent sediment. Bacterial diversity and community composition was consistent among the three microhabitats. Cyanobacteria, Bacteroidetes, Alphaproteobacteria, and Proteobacteria, respectively were the most abundant phyla represented in the samples. This is the first time spatial variability of the surface mucus layer of A. palmata has been studied. Homogeneity in the microbiome of A. palmata contrasts with SML heterogeneity found in other Caribbean corals. These findings suggest that, during non-stressful conditions, host regulation of SML microbiota may override diverse physiochemical influences induced by the topographical complexity of A. palmata. Documenting the spatial distribution of SML microbes is essential to understanding the functional roles these microorganisms play in coral health and adaptability to environmental perturbations.

Perioperative blood product administration and thromboembolic events in patients with treated polycythemia vera: a case-control study.

BACKGROUND: Patients with polycythemia vera (PV) have historically been considered to be at high risk for perioperative hemorrhagic and thromboembolic complications. However, no recent studies have compared these outcomes between treated PV patients and patients without PV undergoing similar procedures. STUDY DESIGN AND METHODS: Patients with PV who underwent surgery with anesthesia from June 1, 2006, to May 31, 2011, were randomly matched (sex, age, type of surgical procedure, surgical year) at a ratio of 1:4 with control patients without PV. Conditional logistic regression analysis adjusting for surgical duration, preoperative hemoglobin, platelet count, and cardiovascular disease was used to assess the association between PV and blood product transfusions, thromboembolism, and other major cardiovascular and pulmonary complications. RESULTS: Fifty-six PV patients who underwent 79 surgeries were matched with 312 controls. During hospitalization, 35 (44.3%) and 82 (25.9%) PV and control patients, respectively, were transfused with blood products. PV patients were at increased risk for transfusion intraoperatively (odds ratio [OR], 4.35; 95% confidence interval [CI], 1.79-10.57; p = 0.001) and during hospitalization (OR, 4.35; 95% CI, 1.84-10.31; p < 0.001). The likelihood of thromboembolic complications and/or other major complications did not differ between the two study groups (thromboembolic-OR 1.53, 95% CI 0.39-6.02, p = 0.540; other major complications-OR 2.15, 95% CI 0.93-4.96, p = 0.073). CONCLUSIONS: Medically managed PV patients had an increased likelihood of receiving blood products perioperatively. Given the low number of observed thromboembolic events, we cannot make definitive conclusions regarding the association between PV and thromboembolism.