Serum short chain fatty acids mediate hippocampal BDNF and correlate with decreasing neuroinflammation following high pectin fiber diet in mice

IntroductionDietary components, such as prebiotic fiber, are known to impact brain chemistry via the gut-brain axis. In particular, short chain fatty acids (SCFAs) generated from excessive soluble fiber consumption are thought to impact neuroimmune signaling and brain function through increased production of neurotropic factors. Given reports that high dietary fiber intake is associated with increased mental health and improved quality of life scores, we set out to identify whether changes in SCFA levels as a result of a high soluble fiber diet mediate hippocampal neuroinflammation and brain derived neurotrophic factor (BDNF) in mice.MethodsAdult male and female C57BL/6 mice were fed a 1-month high pectin fiber or cellulose-based control diet. Following 1 month of excessive pectin consumption, serum SCFAs were measured using gas chromatography–mass spectrometry (GC-MS) and hippocampal cytokines and BDNF were assessed via multiplex magnetic bead immunoassay.ResultsPectin-based fiber diet increased circulating acetic acid in both sexes, with no effect on propionic or butyric acid. In the hippocampus, a high fiber diet decreased TNFa, IL-1ß, IL-6, and IFNγ and increased BDNF levels. Furthermore, increased SCFA levels were inversely correlated with neuroinflammation in the hippocampus, with acetic acid revealed as a strong mediator of increased BDNF production.ConclusionCollectively, these findings highlight the beneficial effects of fiber-induced molecular changes in a brain region known to influence mood- and cognition-related behaviors. Dietary composition should be considered when developing mental health management plans for men and women with an emphasis on increasing soluble fiber intake

Pacific Portraits: The People Behind the Scenes at Pacific University (Volume Three)

There\u27s a saying that if you build a fire on a hill, all sorts of interesting people will climb that hill to meet you, to hear your story or to tell one, or both. In these pages, the students brought the fire to a variety of locations on and off campus to meet interesting characters, staff some of us see on a daily basis but hardly know a thing about. We invite you to peer into these fires, once again, and gaze at the vivid lives of members of our Pacific community to hear a good story, and perhaps, inspire your own.https://commons.pacificu.edu/beetree/1008/thumbnail.jp

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

Forouzanfar MH, Afshin A, Alexander LT, et al. Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. LANCET. 2016;388(10053):1659-1724.Background The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors-the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57.8% (95% CI 56.6-58.8) of global deaths and 41.2% (39.8-42.8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211.8 million [192.7 million to 231.1 million] global DALYs), smoking (148.6 million [134.2 million to 163.1 million]), high fasting plasma glucose (143.1 million [125.1 million to 163.5 million]), high BMI (120.1 million [83.8 million to 158.4 million]), childhood undernutrition (113.3 million [103.9 million to 123.4 million]), ambient particulate matter (103.1 million [90.8 million to 115.1 million]), high total cholesterol (88.7 million [74.6 million to 105.7 million]), household air pollution (85.6 million [66.7 million to 106.1 million]), alcohol use (85.0 million [77.2 million to 93.0 million]), and diets high in sodium (83.0 million [49.3 million to 127.5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Copyright (C) The Author(s). Published by Elsevier Ltd

Data_Sheet_1_Serum short chain fatty acids mediate hippocampal BDNF and correlate with decreasing neuroinflammation following high pectin fiber diet in mice.docx

IntroductionDietary components, such as prebiotic fiber, are known to impact brain chemistry via the gut-brain axis. In particular, short chain fatty acids (SCFAs) generated from excessive soluble fiber consumption are thought to impact neuroimmune signaling and brain function through increased production of neurotropic factors. Given reports that high dietary fiber intake is associated with increased mental health and improved quality of life scores, we set out to identify whether changes in SCFA levels as a result of a high soluble fiber diet mediate hippocampal neuroinflammation and brain derived neurotrophic factor (BDNF) in mice.MethodsAdult male and female C57BL/6 mice were fed a 1-month high pectin fiber or cellulose-based control diet. Following 1 month of excessive pectin consumption, serum SCFAs were measured using gas chromatography–mass spectrometry (GC-MS) and hippocampal cytokines and BDNF were assessed via multiplex magnetic bead immunoassay.ResultsPectin-based fiber diet increased circulating acetic acid in both sexes, with no effect on propionic or butyric acid. In the hippocampus, a high fiber diet decreased TNFa, IL-1ß, IL-6, and IFNγ and increased BDNF levels. Furthermore, increased SCFA levels were inversely correlated with neuroinflammation in the hippocampus, with acetic acid revealed as a strong mediator of increased BDNF production.ConclusionCollectively, these findings highlight the beneficial effects of fiber-induced molecular changes in a brain region known to influence mood- and cognition-related behaviors. Dietary composition should be considered when developing mental health management plans for men and women with an emphasis on increasing soluble fiber intake.</p

Image_1_Serum short chain fatty acids mediate hippocampal BDNF and correlate with decreasing neuroinflammation following high pectin fiber diet in mice.JPEG

IntroductionDietary components, such as prebiotic fiber, are known to impact brain chemistry via the gut-brain axis. In particular, short chain fatty acids (SCFAs) generated from excessive soluble fiber consumption are thought to impact neuroimmune signaling and brain function through increased production of neurotropic factors. Given reports that high dietary fiber intake is associated with increased mental health and improved quality of life scores, we set out to identify whether changes in SCFA levels as a result of a high soluble fiber diet mediate hippocampal neuroinflammation and brain derived neurotrophic factor (BDNF) in mice.MethodsAdult male and female C57BL/6 mice were fed a 1-month high pectin fiber or cellulose-based control diet. Following 1 month of excessive pectin consumption, serum SCFAs were measured using gas chromatography–mass spectrometry (GC-MS) and hippocampal cytokines and BDNF were assessed via multiplex magnetic bead immunoassay.ResultsPectin-based fiber diet increased circulating acetic acid in both sexes, with no effect on propionic or butyric acid. In the hippocampus, a high fiber diet decreased TNFa, IL-1ß, IL-6, and IFNγ and increased BDNF levels. Furthermore, increased SCFA levels were inversely correlated with neuroinflammation in the hippocampus, with acetic acid revealed as a strong mediator of increased BDNF production.ConclusionCollectively, these findings highlight the beneficial effects of fiber-induced molecular changes in a brain region known to influence mood- and cognition-related behaviors. Dietary composition should be considered when developing mental health management plans for men and women with an emphasis on increasing soluble fiber intake.</p