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659 result(s) for "Williams, Brent"
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Gut microbiomes of wild great apes fluctuate seasonally in response to diet
The microbiome is essential for extraction of energy and nutrition from plant-based diets and may have facilitated primate adaptation to new dietary niches in response to rapid environmental shifts. Here we use 16S rRNA sequencing to characterize the microbiota of wild western lowland gorillas and sympatric central chimpanzees and demonstrate compositional divergence between the microbiotas of gorillas, chimpanzees, Old World monkeys, and modern humans. We show that gorilla and chimpanzee microbiomes fluctuate with seasonal rainfall patterns and frugivory. Metagenomic sequencing of gorilla microbiomes demonstrates distinctions in functional metabolic pathways, archaea, and dietary plants among enterotypes, suggesting that dietary seasonality dictates shifts in the microbiome and its capacity for microbial plant fiber digestion versus growth on mucus glycans. These data indicate that great ape microbiomes are malleable in response to dietary shifts, suggesting a role for microbiome plasticity in driving dietary flexibility, which may provide fundamental insights into the mechanisms by which diet has driven the evolution of human gut microbiomes. Microbiota composition fluctuates in response to changes in environmental and lifestyle factors. Here, Hicks et al. show that the faecal microbiota of wild gorillas and chimpanzees is temporally dynamic, with shifts that correlate with seasonal rainfall patterns and periods of high and low frugivory.
Impaired Carbohydrate Digestion and Transport and Mucosal Dysbiosis in the Intestines of Children with Autism and Gastrointestinal Disturbances
Gastrointestinal disturbances are commonly reported in children with autism, complicate clinical management, and may contribute to behavioral impairment. Reports of deficiencies in disaccharidase enzymatic activity and of beneficial responses to probiotic and dietary therapies led us to survey gene expression and the mucoepithelial microbiota in intestinal biopsies from children with autism and gastrointestinal disease and children with gastrointestinal disease alone. Ileal transcripts encoding disaccharidases and hexose transporters were deficient in children with autism, indicating impairment of the primary pathway for carbohydrate digestion and transport in enterocytes. Deficient expression of these enzymes and transporters was associated with expression of the intestinal transcription factor, CDX2. Metagenomic analysis of intestinal bacteria revealed compositional dysbiosis manifest as decreases in Bacteroidetes, increases in the ratio of Firmicutes to Bacteroidetes, and increases in Betaproteobacteria. Expression levels of disaccharidases and transporters were associated with the abundance of affected bacterial phylotypes. These results indicate a relationship between human intestinal gene expression and bacterial community structure and may provide insights into the pathophysiology of gastrointestinal disturbances in children with autism.
The clinical epidemiology of fatigue in newly diagnosed heart failure
Background Fatigue is a common and distressing but poorly understood symptom among patients with heart failure (HF). This study sought to evaluate the prevalence, predictors, and prognostic value of clinically documented fatigue in newly diagnosed HF patients from the community. Methods This retrospective cohort study consisted of 12,285 newly diagnosed HF patients receiving health care services through the Geisinger Health System, with passive data collection through electronic medical records (EMR). Incident HF, fatigue, and other study variables were derived from coded data within EMRs. A collection of 87 candidate predictors were evaluated to ascertain the strongest independent predictors of fatigue using logistic regression. Patients were followed for all-cause mortality for an average of 4.8 years. The associations between fatigue and 6-month, 12-month, and overall mortality were evaluated via Cox proportional hazards regression models. Results Clinically documented fatigue was found in 4827 (39%) newly diagnosed HF patients. Depression demonstrated the strongest association with fatigue. Fatigue was often part of a symptom cluster, as other HF symptoms including dyspnea, chest pain, edema, syncope, and palpitations were significant predictors of fatigue. Volume depletion, lower body mass index, and abnormal weight loss were also strong predictors of fatigue. Fatigue was not significantly associated with either 6-month (HR = 1.12, p  = 0.16) or overall mortality (HR = 1.00, p  = 0.89) in adjusted models. Conclusions Fatigue is a commonly documented symptom among newly diagnosed HF patients, and its origins may lie in both psychologic and physiologic factors. Though fatigue did provide a prognostic signal in the short-term, this was largely explained by physiologic confounders. Proper therapeutic remediation of fatigue in HF relies on identifying underlying factors.
Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome
Background Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by unexplained persistent fatigue, commonly accompanied by cognitive dysfunction, sleeping disturbances, orthostatic intolerance, fever, lymphadenopathy, and irritable bowel syndrome (IBS). The extent to which the gastrointestinal microbiome and peripheral inflammation are associated with ME/CFS remains unclear. We pursued rigorous clinical characterization, fecal bacterial metagenomics, and plasma immune molecule analyses in 50 ME/CFS patients and 50 healthy controls frequency-matched for age, sex, race/ethnicity, geographic site, and season of sampling. Results Topological analysis revealed associations between IBS co-morbidity, body mass index, fecal bacterial composition, and bacterial metabolic pathways but not plasma immune molecules. IBS co-morbidity was the strongest driving factor in the separation of topological networks based on bacterial profiles and metabolic pathways. Predictive selection models based on bacterial profiles supported findings from topological analyses indicating that ME/CFS subgroups, defined by IBS status, could be distinguished from control subjects with high predictive accuracy. Bacterial taxa predictive of ME/CFS patients with IBS were distinct from taxa associated with ME/CFS patients without IBS. Increased abundance of unclassified Alistipes and decreased Faecalibacterium emerged as the top biomarkers of ME/CFS with IBS; while increased unclassified Bacteroides abundance and decreased Bacteroides vulgatus were the top biomarkers of ME/CFS without IBS. Despite findings of differences in bacterial taxa and metabolic pathways defining ME/CFS subgroups, decreased metabolic pathways associated with unsaturated fatty acid biosynthesis and increased atrazine degradation pathways were independent of IBS co-morbidity. Increased vitamin B6 biosynthesis/salvage and pyrimidine ribonucleoside degradation were the top metabolic pathways in ME/CFS without IBS as well as in the total ME/CFS cohort. In ME/CFS subgroups, symptom severity measures including pain, fatigue, and reduced motivation were correlated with the abundance of distinct bacterial taxa and metabolic pathways. Conclusions Independent of IBS, ME/CFS is associated with dysbiosis and distinct bacterial metabolic disturbances that may influence disease severity. However, our findings indicate that dysbiotic features that are uniquely ME/CFS-associated may be masked by disturbances arising from the high prevalence of IBS co-morbidity in ME/CFS. These insights may enable more accurate diagnosis and lead to insights that inform the development of specific therapeutic strategies in ME/CFS subgroups.
SWOT Water Surface Elevation in Herbaceous Wetlands of Florida's Everglades
Observing water level variations in wetlands is important for tracking global water and carbon cycles. The Surface Water and Ocean Topography (SWOT) mission was launched to measure Earth's surface waters, but its performance in vegetated wetlands was unknown. Here, we present the first assessment of SWOT over herbaceous wetlands in Florida's Everglades. Comparison of SWOT water surface elevation (WSE) measurements against in situ water levels from 5 August 2023 to 30 March 2024, shows strong positive correlation (r > 0.99) and mean absolute error of 6.7 cm for WSEs averaged over 1 km2 regions. Water surface elevation errors within 10–60 km of the SWOT observation swath have similar precision and accuracy. SWOT's performance in large herbaceous wetlands is better than pre‐launch expectations for large open water bodies, which is unexpected. Our results suggest we can accurately track water level variations in many of Earth's large herbaceous wetlands globally. Additional evaluation is needed in shrubby and forested wetlands. Plain Language Summary Water levels are critical to the overall function of wetlands. Measuring water level changes, therefore, is important for wetland management and for tracking the global water and carbon cycles. The Surface Water and Ocean Topography (SWOT) satellite mission was launched to measure water levels of the Earth's surface waters, including wetlands. However, the satellite's performance in wetlands with vegetation is largely uncharacterized. In this study, we assess its performance in herbaceous wetlands, focusing on areas of Florida's Everglades. We compare the surface water level measurements acquired from SWOT against water levels measured using ground‐based gauges in the wetlands. Our results show that SWOT's measurements are highly accurate and very strongly correlated with on‐the‐ground measurements. SWOT's performance in grassy wetlands is even better than what was expected for large water bodies before the launch of the satellite. Since wetland function depends on water levels, this high accuracy from SWOT will improve our understanding of many global wetlands. Key Points We show the first water surface elevation results in wetlands from the SWOT satellite mission SWOT's water surface elevations are highly accurate in large herbaceous wetlands, achieving a 68th percentile error of 6.4 cm SWOT can accurately track seasonal water level variations of less than 20 cm in large graminoid wetlands
Insights into myalgic encephalomyelitis/chronic fatigue syndrome phenotypes through comprehensive metabolomics
The pathogenesis of ME/CFS, a disease characterized by fatigue, cognitive dysfunction, sleep disturbances, orthostatic intolerance, fever, irritable bowel syndrome (IBS), and lymphadenopathy, is poorly understood. We report biomarker discovery and topological analysis of plasma metabolomic, fecal bacterial metagenomic, and clinical data from 50 ME/CFS patients and 50 healthy controls. We confirm reports of altered plasma levels of choline, carnitine and complex lipid metabolites and demonstrate that patients with ME/CFS and IBS have increased plasma levels of ceramide. Integration of fecal metagenomic and plasma metabolomic data resulted in a stronger predictive model of ME/CFS (cross-validated AUC = 0.836) than either metagenomic (cross-validated AUC = 0.745) or metabolomic (cross-validated AUC = 0.820) analysis alone. Our findings may provide insights into the pathogenesis of ME/CFS and its subtypes and suggest pathways for the development of diagnostic and therapeutic strategies.
SWOT Captures Hydrologic Waves Traveling Down Rivers
High discharge events propagate down rivers as flow waves. River wave movements are described theoretically by routing equations or tracked using in‐situ gauge measurements of stage over time at a given location. However, the sparse distribution of gauges makes it challenging to show how stage evolves with along‐river distance as waves propagate downstream. Here we use novel measurements of water surface elevation from the Surface Water and Ocean Topography satellite to detect and analyze flow wave paths, presenting examples of the first direct observations of continuous downstream changes in river height at a given time within a flow wave. By removing long‐scale river elevation profiles, we develop “spatial hydrographs” as analogs to in‐situ time series and demonstrate their value for analyzing wave characteristics, including measuring length, estimating celerity, and partitioning event flow from baseflow. Our methods could be applied globally to study flow waves and their properties. Plain Language Summary Flow waves are very long waves (tens to thousands of kilometers) that travel down rivers corresponding to periods of high flow and are described by theory. Researchers have traditionally studied flow wave movement using measurements of river height and flow collected directly by stream gauges. These data show detailed changes in river height over time, but only at discrete locations in space. Satellite measurements, by contrast, can sample over a wide swath, but only at discrete times. We use data from the new Surface Water and Ocean Topography (SWOT) satellite, which collects fine‐scale measurements of global river heights, to develop snapshots of flow waves moving downstream. By converting these measurements to relative elevation changes, we find that SWOT data show the same patterns as gauge data. Just like gauge measurements, we demonstrate that SWOT measurements can be used to estimate the length of a flow wave, how fast it is traveling, and what percentage is contributed by groundwater versus surface runoff. Our methods could be used to identify and study flow waves around the world. Key Points Surface Water and Ocean Topography data show downstream changes in river height during a flow wave hydrologic event By removing the river's long profile, flow wave events are visualized as hydrograph‐like representations of stage over space Spatial flow wave observations can be used to measure event length, estimate wave celerity, and perform a hydrographic separation
Application of Novel PCR-Based Methods for Detection, Quantitation, and Phylogenetic Characterization of Sutterella Species in Intestinal Biopsy Samples from Children with Autism and Gastrointestinal Disturbances
Gastrointestinal disturbances are commonly reported in children with autism and may be associated with compositional changes in intestinal bacteria. In a previous report, we surveyed intestinal microbiota in ileal and cecal biopsy samples from children with autism and gastrointestinal dysfunction (AUT-GI) and children with only gastrointestinal dysfunction (Control-GI). Our results demonstrated the presence of members of the family Alcaligenaceae in some AUT-GI children, while no Control-GI children had Alcaligenaceae sequences. Here we demonstrate that increased levels of Alcaligenaceae in intestinal biopsy samples from AUT-GI children result from the presence of high levels of members of the genus Sutterella . We also report the first Sutterella -specific PCR assays for detecting, quantitating, and genotyping Sutterella species in biological and environmental samples. Sutterella 16S rRNA gene sequences were found in 12 of 23 AUT-GI children but in none of 9 Control-GI children. Phylogenetic analysis revealed a predominance of either Sutterella wadsworthensis or Sutterella stercoricanis in 11 of the individual Sutterella -positive AUT-GI patients; in one AUT-GI patient, Sutterella sequences were obtained that could not be given a species-level classification based on the 16S rRNA gene sequences of known Sutterella isolates. Western immunoblots revealed plasma IgG or IgM antibody reactivity to Sutterella wadsworthensis antigens in 11 AUT-GI patients, 8 of whom were also PCR positive, indicating the presence of an immune response to Sutterella in some children. IMPORTANCE Autism spectrum disorders affect ~1% of the population. Many children with autism have gastrointestinal (GI) disturbances that can complicate clinical management and contribute to behavioral problems. Understanding the molecular and microbial underpinnings of these GI issues is of paramount importance for elucidating pathogenesis, rendering diagnosis, and administering informed treatment. Here we describe an association between high levels of intestinal, mucoepithelial-associated Sutterella species and GI disturbances in children with autism. These findings elevate this little-recognized bacterium to the forefront by demonstrating that Sutterella is a major component of the microbiota in over half of children with autism and gastrointestinal dysfunction (AUT-GI) and is absent in children with only gastrointestinal dysfunction (Control-GI) evaluated in this study. Furthermore, these findings bring into question the role Sutterella plays in the human microbiota in health and disease. With the Sutterella -specific molecular assays described here, some of these questions can begin to be addressed. Autism spectrum disorders affect ~1% of the population. Many children with autism have gastrointestinal (GI) disturbances that can complicate clinical management and contribute to behavioral problems. Understanding the molecular and microbial underpinnings of these GI issues is of paramount importance for elucidating pathogenesis, rendering diagnosis, and administering informed treatment. Here we describe an association between high levels of intestinal, mucoepithelial-associated Sutterella species and GI disturbances in children with autism. These findings elevate this little-recognized bacterium to the forefront by demonstrating that Sutterella is a major component of the microbiota in over half of children with autism and gastrointestinal dysfunction (AUT-GI) and is absent in children with only gastrointestinal dysfunction (Control-GI) evaluated in this study. Furthermore, these findings bring into question the role Sutterella plays in the human microbiota in health and disease. With the Sutterella -specific molecular assays described here, some of these questions can begin to be addressed.