Biomarkers of Intestinal Permeability are Associated with Inflammation in Metabolically Healthy Obesity, but not Normal-Weight Obesity.

Systemic inflammation is reported in normal-weight obesity (NWO) and metabolically healthy obesity (MHO), which may be linked to their increased cardiovascular disease (CVD) risk. Yet, drivers of this inflammation remain unclear. We characterized factors known to influence inflammatory status (i.e., intestinal permeability, adipose tissue, diet quality, microbiota) - and their relationships with measured inflammation - in NWO and MHO, healthy controls (CON) and metabolically unhealthy obesity (MUO; N=80; n=20/group). Serum indicators of intestinal permeability and inflammation were assessed using ELISA and/or multiplex. Total, visceral, and percent body fat were measured with dual-energy X-ray absorptiometry (DXA). Fecal microbiota composition was assessed via 16S rRNA sequencing (n=9-10/group). For C-reactive protein (CRP), MUO > NWO > CON (p<0.0001). In MHO, CRP was intermediate - and similar to - both MUO and NWO. Lipopolysaccharide binding protein (LBP) and the ratio of LBP to soluble CD14 (sCD14) were higher in MHO and MUO versus CON/NWO (p's<0.0001). Across correlation and regression analyses, LBP consistently displayed the strongest relationships with CRP in the entire sample (r=0.78;ß = 0.57;p's<0.0001) and in MHO (r=0.74;p<0.01), but not NWO (r=0.37;p = 0.11). Shannon index was higher in CON compared to MUO (p<0.05) and inversely correlated with CRP in the full sample (r=-0.37;p<0.05). These data are consistent with the notion that intestinal permeability is associated with low-grade inflammation in MHO, which could be implicated in this population's reported CVD risk.

The gut-brain axis in individuals with alcohol use disorder: An exploratory study of associations among clinical symptoms, brain morphometry, and the gut microbiome.

BACKGROUND: Alcohol use disorder (AUD) is commonly associated with distressing psychological symptoms. Pathologic changes associated with AUD have been described in both the gut microbiome and brain, but the mechanisms underlying gut-brain signaling in individuals with AUD are unknown. This study examined associations among the gut microbiome, brain morphometry, and clinical symptoms in treatment-seeking individuals with AUD. METHODS: We performed a secondary analysis of data collected during inpatient treatment for AUD in subjects who provided gut microbiome samples and had structural brain magnetic resonance imaging (MRI; n = 16). Shotgun metagenomics sequencing was performed, and the morphometry of brain regions of interest was calculated. Clinical symptom severity was quantified using validated instruments. Gut-brain modules (GBMs) used to infer neuroactive signaling potential from the gut microbiome were generated in addition to microbiome features (e.g., alpha diversity and bacterial taxa abundance). Bivariate correlations were performed between MRI and clinical features, microbiome and clinical features, and MRI and microbiome features. RESULTS: Amygdala volume was significantly associated with alpha diversity and the abundance of several bacteria including taxa classified to Blautia, Ruminococcus, Bacteroides, and Phocaeicola. There were moderate associations between amygdala volume and GBMs, including butyrate synthesis I, glutamate synthesis I, and GABA synthesis I & II, but these relationships were not significant after false discovery rate (FDR) correction. Other bacterial taxa with shared associations to MRI features and clinical symptoms included Escherichia coli and Prevotella copri. CONCLUSIONS: We identified gut microbiome features associated with MRI morphometry and AUD-associated symptom severity. Given the small sample size and bivariate associations performed, these results require confirmation in larger samples and controls to provide meaningful clinical inferences. Nevertheless, these results will inform targeted future research on the role of the gut microbiome in gut-brain communication and how signaling may be altered in patients with AUD.

Examining the relationship between the oral microbiome, alcohol intake and alcohol-comorbid neuropsychological disorders: protocol for a scoping review.

INTRODUCTION: Heavy alcohol use and alcohol use disorder (AUD) continues to rise as a public health problem and increases the risk for disease. Elevated rates of anxiety, depression, sleep disruption and stress are associated with alcohol use. Symptoms may progress to diagnosed neurophysiological conditions and increase risk for relapse if abstinence is attempted. Research on mechanisms connecting the gastrointestinal microbiome to neuropsychological disorders through the gut-brain axis is well-established. Less is known how the oral microbiome and oral microbial-associated biomarkers may signal to the brain. Therefore, a synthesis of research studying relationships between alcohol intake, alcohol-associated neurophysiological symptoms and the oral microbiome is needed to understand the state of the current science. In this paper, we outline our protocol to collect, evaluate and synthesise research focused on associations between alcohol intake and AUD-related neuropsychological disorders with the oral microbiome. METHODS AND ANALYSIS: The search strategy was developed and will be executed in collaboration with a medical research librarian. Studies will be screened by two independent investigators according to the aim of the scoping review, along with the outlined exclusion and inclusion criteria. After screening, data will be extracted and synthesised from the included papers according to predefined demographic, clinical and microbiome methodology metrics. ETHICS AND DISSEMINATION: A scoping review of primary sources is needed to synthesise the data on relationships between alcohol use, neuropsychological conditions associated with AUD and the oral microbiome. The proposed scoping review is based on the data from publicly available databases and does not require ethical approval. We expect the results of this synthesis will identify gaps in the growing literature and highlight potential mechanisms linking the oral-brain axis to addiction and other associated neuropsychological conditions. The study findings and results will be disseminated through journals and conferences related to psychology, neuroscience, dentistry and the microbiome.

Mock community taxonomic classification performance of publicly available shotgun metagenomics pipelines.

Shotgun metagenomic sequencing comprehensively samples the DNA of a microbial sample. Choosing the best bioinformatics processing package can be daunting due to the wide variety of tools available. Here, we assessed publicly available shotgun metagenomics processing packages/pipelines including bioBakery, Just a Microbiology System (JAMS), Whole metaGenome Sequence Assembly V2 (WGSA2), and Woltka using 19 publicly available mock community samples and a set of five constructed pathogenic gut microbiome samples. Also included is a workflow for labelling bacterial scientific names with NCBI taxonomy identifiers for better resolution in assessing results. The Aitchison distance, a sensitivity metric, and total False Positive Relative Abundance were used for accuracy assessments for all pipelines and mock samples. Overall, bioBakery4 performed the best with most of the accuracy metrics, while JAMS and WGSA2, had the highest sensitivities. Furthermore, bioBakery is commonly used and only requires a basic knowledge of command line usage. This work provides an unbiased assessment of shotgun metagenomics packages and presents results assessing the performance of the packages using mock community sequence data.

An Integrative Literature Review of Heart Rate Variability Measures to Determine Autonomic Nervous System Responsiveness Using Pharmacological Manipulation.

BACKGROUND: Heart rate variability (HRV) is defined as the difference in the timing of intervals between successive heartbeats and is used as a surrogate measure to the responsiveness of the autonomic nervous system. A review and synthesis of HRV as an indicator of autonomic nervous system responsiveness to pharmacologic stimulation/blockade of sympathetic and/or parasympathetic nervous system branches have not been completed. PURPOSE: The aim of this integrative review is to synthesize research examining pharmacological modulation of the autonomic nervous system and the response of time domain, frequency domain, and nonlinear measures of HRV. CONCLUSIONS: Sympathetic nervous system blockade resulted in a consistent decrease in the standard deviation of normal-normal interval metric across studies. Stimulation of the parasympathetic nervous system was associated with an increase in several time, frequency, and nonlinear HRV indices, whereas blockade of the parasympathetic nervous system led to a decrease in similar indices. CLINICAL IMPLICATIONS: Recommendations to improve the reproducibility of future HRV research are provided for standardization of recording, analysis, and metric decisions and more thorough reporting of HRV indices in published studies. Alterations in autonomic nervous system input to the cardiovascular system are associated with an increased risk for adverse patient outcomes and increased mortality; therefore, understanding the influence of pharmacologic autonomic nervous system modulation on HRV indices and important considerations for reproducible HRV research design will inform future translational research on cardiovascular risk reduction.

Geographic social vulnerability is associated with the alpha diversity of the human microbiome.

IMPORTANCE: As a risk factor for conditions related to the microbiome, understanding the role of SVI on microbiome diversity may assist in identifying public health implications for microbiome research. Here we found, using a sub-sample of the Human Microbiome Project phase 1 cohort, that SVI was linked to microbiome diversity across body sites and that SVI may influence race/ethnicity-based differences in diversity. Our findings, build on the current knowledge regarding the role of human geography in microbiome research, suggest that measures of geographic social vulnerability be considered as additional contextual factors when exploring microbiome alpha diversity.

Exploring physical and biological manifestations of burnout and post-traumatic stress disorder symptoms in healthcare workers: a scoping review protocol.

INTRODUCTION: The COVID-19 pandemic has strained the mental and physical well-being of healthcare workers (HCW). Increased work-related stress and limited resources have increased symptoms of anxiety, depression, insomnia and post-traumatic stress disorder (PTSD) in this population. Stress-related disorders have been strongly associated with long-term consequences, including cardiometabolic disorders, endocrine disorders and premature mortality. This scoping review aims to explore available literature on burnout, PTSD, and other mental health-associated symptoms in HCW to synthesise relationships with physiological and biological biomarkers that may be associated with increased risk of disease, creating an opportunity to summarise current biomarker knowledge and identify gaps in this literature. METHODS AND ANALYSIS: This scoping review uses the Arksey and O'Malley six-step scoping review methodology framework. The research team will select appropriate primary sources using a search strategy developed in collaboration with a health sciences librarian. Three reviewers will initially screen the title and abstracts obtained from the literature searches, and two reviewers will conduct independent reviews of full-text studies for inclusion. The research team will be reviewing literature focusing on which burnout and/or PTSD-associated physiological and biological biomarkers have been studied, the methodologies used to study them and the correlations between the biomarkers and HCW experiencing burnout/PTSD. Data extraction forms will be completed by two reviewers for included studies and will guide literature synthesis and analysis to determine common themes. ETHICS AND DISSEMINATION: This review does not require ethical approval. We expect results from this scoping review to identify gaps in the literature and encourage future research regarding improving biological and physiological biomarker research in HCW. Preliminary results and general themes will be communicated back to stakeholders. Results will be disseminated through peer-reviewed publications, policy briefs and conferences as well as presented to stakeholders to an effort to invest in HCW mental and physical health.

Administration of Bifidobacterium animalis subsp. lactis strain BB-12® in healthy children: characterization, functional composition, and metabolism of the gut microbiome.

Introduction: The consumption of probiotics may influence children's gut microbiome and metabolome, which may reflect shifts in gut microbial diversity composition and metabolism. These potential changes might have a beneficial impact on health. However, there is a lack of evidence investigating the effect of probiotics on the gut microbiome and metabolome of children. We aimed to examine the potential impact of a two (Streptococcus thermophilus and Lactobacillus delbrueckii; S2) vs. three (S2 + Bifidobacterium animalis subsp. lactis strain BB-12) strain-supplemented yogurt. Methods: Included in this study were 59 participants, aged one to five years old, recruited to phase I of a double-blinded, randomized controlled trial. Fecal samples were collected at baseline, after the intervention, and at twenty days post-intervention discontinuation, and untargeted metabolomics and shotgun metagenomics were performed. Results: Shotgun metagenomics and metabolomic analyses showed no global changes in either intervention group's gut microbiome alpha or beta diversity indices, except for a lower microbial diversity in the S2 + BB12 group at Day 30. The relative abundance of the two and three intervention bacteria increased in the S2 and S2 + BB12 groups, respectively, from Day 0 to Day 10. In the S2 + BB12 group, the abundance of several fecal metabolites increased at Day 10, including alanine, glycine, lysine, phenylalanine, serine, and valine. These fecal metabolite changes did not occur in the S2 group. Discussion: In conclusion, there were were no significant differences in the global metagenomic or metabolomic profiles between healthy children receiving two (S2) vs. three (S2 + BB12) probiotic strains for 10 days. Nevertheless, we observed a significant increase (Day 0 to Day 10) in the relative abundance of the two and three probiotics administered in the S2 and S2 + BB12 groups, respectively, indicating the intervention had a measurable impact on the bacteria of interest in the gut microbiome. Future research using longer probiotic intervention durations and in children at risk for gastrointestinal disorders may elucidate if functional metabolite changes confer a protective gastrointestinal effect.

Exploring Physical and Biological Manifestations of Burnout and Post-Traumatic Stress Disorder Symptoms in Healthcare Workers: A Scoping Review Protocol.

Introduction: The COVID-19 pandemic has strained the mental and physical well-being of healthcare workers (HCW). Increased work-related stress and limited resources has increased symptoms of anxiety, depression, insomnia, and post-traumatic stress disorder (PTSD) in this population. Stress-related disorders have been strongly associated with long-term consequences including cardiometabolic disorders, endocrine disorders and premature mortality. This scoping review aims to explore available literature on burnout, PTSD, and other mental health-associated symptoms in HCW to synthesize relationships with physiological and biological biomarkers that may be associated with increased risk of disease, creating an opportunity to summarize current biomarker knowledge and identify gaps in this literature. Methods and Analysis: This scoping review uses the Arksey and O'Malley six-step scoping review methodology framework. The research team will select appropriate primary sources using a search strategy developed in collaboration with a health sciences librarian. Three reviewers will initially screen the title and abstracts obtained from the literature searches, and two reviewers will conduct independent reviews of full-text studies for inclusion. The research team will be reviewing literature focusing on which burnout and/or PTSD-associated physiological and biological biomarkers have been studied, the methodologies used to study them and the correlations between the biomarkers and HCW experiencing burnout/PTSD. Data extraction forms will be completed by two reviewers for included studies and will guide literature synthesis and analysis to determine common themes. Ethics and Dissemination: This review does not require ethical approval. We expect results from this scoping review to identify gaps in the literature and encourage future research regarding improving biologic and physiologic biomarker research in HCW. Preliminary results and general themes will be communicated back to stakeholders. Results will be disseminated through peer-reviewed publications, policy briefs, and conferences, as well as presented to stakeholders to an effort to invest in HCW mental and physical health. Strengths and Limitations of This Study: This will be the first scoping review to assess the current understanding of the biologic and physiological impact of burnout on healthcare workers. The target population is restricted to healthcare workers; however, identified research gaps may be used to guide future studies in other high-burnout occupations and industries.This scoping review will be guided by the Arksey and O'Malley six-step methodological framework and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Review checklist.Both peer reviewed manuscript and pre-prints/abstracts will be evaluated, but studies that have not been peer reviewed will be notated in the summary table. Conference abstracts are excluded.Preliminary and final themes and results identified by this scoping review will be communicated to stakeholders, including hospital staff and HCW, to ensure agreement with our interpretation and to convey knowledge gained with our population of interest.This review will advance the field's current understanding of mechanisms connecting the burnout and pathogenic stress to biologic and physiologic outcomes in healthcare workers and provide researchers with gaps in the literature to inform opportunities for future research.

Neighbourhood environment as a risk factor for adverse health outcomes through association with the microbiome: protocol for a scoping review.

INTRODUCTION: The connection of the microbiome to human health intersects with the physical environment of humans. Each microbiome location can be influenced by environmental conditions that relate to specific geographical locations, which in turn are influenced by social determinants of health such as a neighbourhood. The objective of this scoping review is to explore the current evidence on the relationships between microbiome and neighbourhood to explain microbiome-related health outcomes. METHODS AND ANALYSIS: Arksey and O'Malley's literature review framework will be employed throughout the process, as well as Page, et al's 2020 Preferred Reporting Items for Systematic Review and Meta-Analysis updated workflow to process search results. The literature search will be completed using PubMed/Medline (NLM), Embase (Elsevier), Web of Science, Core Collection (Clarivate Analytics), Scopus (Elsevier), medRxiv preprint server and Open Science Framework server. The search will be conducted using a list of pre-identified Medical Subject Headings (MeSH) terms relating to neighbourhood, microbiome and individual characteristics. There will be no date or language restrictions used in the search. In order to be included in the study, a piece must include an evaluation of the relationship between microbiome diversity and neighbourhood (including at least one measurement of the neighbourhood and at least one human microbiome site). Excluded from the review will be those works that do not include all of these measures, literature reviews based on secondary sources and postmortem populations with no report of premortem health factors. The review itself will be an iterative process completed by two reviewers, with a third individual identified to break ties. Documents will be undergoing a risk assessment of bias in order for the authors to comment on the quality of the literature in this area. Finally, results will be discussed with identified stakeholders, including individuals connected to neighbourhoods facing structural inequity and experts in the topics of study through a community advisory board, for their feedback and knowledge transfer. ETHICS AND DISSEMINATION: This review does not require ethical approval. Results of this search will be disseminated through peer-reviewed publications. Furthermore, this work is completed in conjunction with a community advisory board so as to ensure dissemination to multiple stakeholders.

A Comparison of Hypothesis-Driven and Data-Driven Research: A Case Study in Multimodal Data Science in Gut-Brain Axis Research.

Data science, bioinformatics, and machine learning are the advent and progression of the fourth paradigm of exploratory science. The need for human-supported algorithms to capture patterns in big data is at the center of personalized healthcare and directly related to translational research. This paper argues that hypothesis-driven and data-driven research work together to inform the research process. At the core of these approaches are theoretical underpinnings that drive progress in the field. Here, we present several exemplars of research on the gut-brain axis that outline the innate values and challenges of these approaches. As nurses are trained to integrate multiple body systems to inform holistic human health promotion and disease prevention, nurses and nurse scientists serve an important role as mediators between this advancing technology and the patients. At the center of person-knowing, nurses need to be aware of the data revolution and use their unique skills to supplement the data science cycle from data to knowledge to insight.

Administration of Bifidobacterium animalis subsp. lactis Strain BB-12 ® in Healthy Children: Characterization, Functional Composition, and Metabolism of the Gut Microbiome.

The consumption of probiotics may influence children's gut microbiome and metabolome, which may reflect shifts in gut microbial diversity composition and metabolism. These potential changes might have a beneficial impact on health. However, there is a lack of evidence investigating the effect of probiotics on the gut microbiome and metabolome of children. We aimed to examine the potential impact of a two ( Streptococcus thermophilus and Lactobacillus delbrueckii ; S2) vs . three (S2 + Bifidobacterium animalis subsp. lactis strain BB-12) strain-supplemented yogurt. Included in this study were 59 participants, aged one to five years old, recruited to phase I of a double-blinded, randomized controlled trial. Fecal samples were collected at baseline, after the intervention, and at twenty days post-intervention discontinuation, and untargeted metabolomics and shotgun metagenomics were performed. Shotgun metagenomics and metabolomic analyses showed no global changes in either intervention group's gut microbiome alpha or beta diversity indices. The relative abundance of the two and three intervention bacteria increased in the S2 and S2 + BB12 groups, respectively, from Day 0 to Day 10 . In the S2+BB12 group, the abundance of several fecal metabolites was reduced at Day 10 , including alanine, glycine, lysine, phenylalanine, serine, and valine. These fecal metabolite changes did not occur in the S2 group. Future research using longer probiotic intervention durations and in children at risk for gastrointestinal disorders may elucidate if functional metabolite changes confer a protective gastrointestinal effect.

Multi-amplicon microbiome data analysis pipelines for mixed orientation sequences using QIIME2: Assessing reference database, variable region and pre-processing bias in classification of mock bacterial community samples.

Microbiome research relies on next-generation sequencing and on downstream data analysis workflows. Several manufacturers have introduced multi-amplicon kits for microbiome characterization, improving speciation, but present unique challenges for analysis. The goal of this methodology study was to develop two analysis pipelines specific to mixed-orientation reads from multi-hypervariable (V) region amplicons. A secondary aim was to assess agreement with expected abundance, considering database and variable region. Mock community sequence data (n = 41) generated using the Ion16S™ Metagenomics Kit and Ion Torrent Sequencing Platform were analyzed using two workflows. Amplicons from V2, V3, V4, V6-7, V8 and V9 were deconvoluted using a specialized plugin based on CutPrimers. A separate workflow using Cutadapt is also presented. Three reference databases (Ribosomal Database Project, Greengenes and Silva) were used for taxonomic assignment. Bray-Curtis, Euclidean and Jensen-Shannon distance measures were used to evaluate overall annotation consistency, and specific taxon agreement was determined by calculating the ratio of observed to expected relative abundance. Reads that mapped to regions V2-V9 varied for both CutPrimers and Cutadapt-based methods. Within the CutPrimers-based pipeline, V3 amplicons had the best agreement with the expected distribution, tested using global distance measures, while V9 amplicons had the worst agreement. Accurate taxonomic annotation varied by genus-level taxon and V region analyzed. For the first time, we present a microbiome analysis pipeline that employs a specialized plugin to allow microbiome researchers to separate multi-amplicon data from the Ion16S Metagenomics Kit into V-specific reads. We also present an additional analysis workflow, modified for Ion Torrent mixed orientation reads. Overall, the global agreement of amplicons with the expected mock community abundances differed across V regions and reference databases. Benchmarking data should be referenced when planning a microbiome study to consider these biases related to sequencing and data analysis for multi-amplicon sequencing kits.

The role of the oral microbiome in smoking-related cardiovascular risk: a review of the literature exploring mechanisms and pathways.

Cardiovascular disease is a leading cause of morbidity and mortality. Oral health is associated with smoking and cardiovascular outcomes, but there are gaps in knowledge of many mechanisms connecting smoking to cardiovascular risk. Therefore, the aim of this review is to synthesize literature on smoking and the oral microbiome, and smoking and cardiovascular risk/disease, respectively. A secondary aim is to identify common associations between the oral microbiome and cardiovascular risk/disease to smoking, respectively, to identify potential shared oral microbiome-associated mechanisms. We identified several oral bacteria across varying studies that were associated with smoking. Atopobium, Gemella, Megasphaera, Mycoplasma, Porphyromonas, Prevotella, Rothia, Treponema, and Veillonella were increased, while Bergeyella, Haemophilus, Lautropia, and Neisseria were decreased in the oral microbiome of smokers versus non-smokers. Several bacteria that were increased in the oral microbiome of smokers were also positively associated with cardiovascular outcomes including Porphyromonas, Prevotella, Treponema, and Veillonella. We review possible mechanisms that may link the oral microbiome to smoking and cardiovascular risk including inflammation, modulation of amino acids and lipids, and nitric oxide modulation. Our hope is this review will inform future research targeting the microbiome and smoking-related cardiovascular disease so possible microbial targets for cardiovascular risk reduction can be identified.

Sleep, time, and space-fatigue and performance deficits in pilots, commercial truck drivers, and astronauts.

Sleep is essential for preventing fatigue in occupations that require sustained vigilance. We conducted a scoping review to synthesize knowledge about sleep, fatigue, and performance in pilots, commercial truck drivers, and astronauts. We found 28 studies where researchers objectively or subjectively measured sleep, fatigue, and performance. The research included laboratory-based (simulator) and field-based studies (i.e. real-world missions and a variety of shift-work schedules). Most researchers used actigraphy to measure sleep, and they found that ~6 hrs of sleep was common. The research also demonstrated how sleep duration and quality were negatively affected by schedule irregularity, early-morning start times, and high-risk missions (e.g. extravehicular activities in space). Collectively, the data demonstrated how shorter sleep durations, short off-duty time, and early-morning start times were associated with slower reaction times, more lapses in attention, and premature responses on psychomotor vigilance tests. Considering that few studies included polysomnography and circadian rhythm biomarkers, there remains limited knowledge about the effects of sleep microstructure and circadian rhythm alterations on performance abilities in these occupations. Future neurobiological and mechanistic discoveries will be important for enhancing vigilance, health, and safety for people working in the skies, on the roads, and in space. This paper is part of the David F. Dinges Festschrift Collection. This collection is sponsored by Pulsar Informatics and the Department of Psychiatry in the Perelman School of Medicine at the University of Pennsylvania.

Validation of PiezoSleep Scoring Against EEG/EMG Sleep Scoring in Rats.

Introduction: Current methods of sleep research in rodents involve invasive surgical procedures of EEG and EMG electrodes implantation. Recently, a new method of measuring sleep, PiezoSleep, has been validated against implanted electrodes in mice and rats. PiezoSleep uses a piezoelectric film transducer to detect the rodent's movements and respiration and employs an algorithm to automatically score sleep. Here, we validate PiezoSleep scoring versus EEG/EMG implanted electrodes sleep scoring in rats. Methods: Adult male Brown Norway and Wistar Kyoto rats were implanted with bilateral stainless-steel screws into the skull for EEG recording and bilateral wire electrodes into the nuchal muscles for EMG assessment. In Brown Norway rats, the EEG/EMG electrode leads were soldered to a miniature connector plug and fixed to the skull. In Wistar Kyoto rats, the EEG/EMG leads were tunneled subcutaneously to a telemetry transmitter implanted in the flank. Rats were allowed to recover from surgery for one week. Brown Norway rats were placed in PiezoSleep cages, and had their headsets connected to cable for recording EEG/EMG signals, which were then manually scored by a human scorer in 10-sec epochs. Wistar Kyoto rats were placed in PiezoSleep cages, and EEG/EMG signals were recorded using a telemetry system (DSI). Sleep was scored automatically in 4-sec epochs using NeuroScore software. PiezoSleep software recorded and scored sleep in the rats. Results: Rats implanted with corded EEG/EMG headsets had 85.6% concurrence of sleep-wake scoring with PiezoSleep. Rats implanted with EEG/EMG telemetry had 80.8% concurrence sleep-wake scoring with PiezoSleep. Sensitivity and specificity rates were similar between the EEG/EMG recording systems. Total sleep time and hourly sleep times did not differ in all three systems. However, automatic sleep detection by NeuroScore classified more sleep during the light period compared to the PiezoSleep. Conclusion: We showed that PiezoSleep system can be a reliable alternative to both automatic and visual EEG/EMG- based sleep-wake scoring in rat.

Examining the Relationships Between Sleep Physiology and the Gut Microbiome in Preclinical and Translational Research: Protocol for a Scoping Review.

BACKGROUND: Sleep is an instrumental behavioral state with evidence supporting its active role in brain function, metabolism, immune function, and cardiovascular systems. Research supports that there are pathways underlying the bidirectional communication between the brain and gastrointestinal system, also known as the "gut-brain axis." Primary research examining sleep and gut microbiome relationships continues to increase. Although current data include both preclinical and clinical research, gut microbiome results are reported through a wide range of metrics (alpha diversity, beta diversity, and bacterial compositional changes), which makes cross-study comparison challenging. Therefore, a synthesis of the research examining sleep and gut microbiome relationships is necessary to understand the state of the science and address gaps in the literature for future research. OBJECTIVE: In this paper, we outline a scoping review protocol to evaluate and synthesize preclinical and clinical primary research focused on the associations between sleep and the gut microbiome. METHODS: The search strategy was facilitated through a medical research librarian and involved electronic databases including PubMed/MEDLINE, Embase, Scopus, Web of Science, CENTRAL trials database, BIOSIS Citation Index, and the Zoological Record. Gray literature sources including medRxiv and bioRxiv preprint servers were also searched. Studies were screened according to the aims and exclusion and inclusion criteria of the protocol. After screening, data will be extracted and synthesized from the included studies according to predefined sleep and microbiome methodology metrics. RESULTS: The search strategy yielded 4622 references that were imported for study screening, and source screening was completed in May 2022 by 2 independent investigators, resulting in a total of 93 sources for data extraction and synthesis. The data synthesis table is expected to be completed by August 2022, and the results will be disseminated through paper submission by December 2022 and presented at conferences related to neuroscience, sleep physiology, bioinformatics, and the microbiome. CONCLUSIONS: A scoping review of preclinical and clinical research is needed to synthesize the growing data focused on the relationships between sleep and the gut microbiome. We expect the results of this synthesis will identify gaps in the literature and highlight pathways linking the gut-brain axis and sleep physiology to stimulate future research questions. TRIAL REGISTRATION: Open Science Framework 69TBR; https://osf.io/69tbr. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/38605.

The Neuro-Endo-Microbio-Ome Study: A Pilot Study of Neurobiological Alterations Pre- Versus Post-Bariatric Surgery.

BACKGROUND: Plausible phenotype mechanisms following bariatric surgery include changes in neural and gastrointestinal physiology. This pilot study aims to investigate individual and combined neurologic, gut microbiome, and plasma hormone changes pre- versus post-vertical sleeve gastrectomy (VSG), Roux-en-Y gastric bypass (RYGB), and medical weight loss (MWL). We hypothesized post-weight loss phenotype would be associated with changes in central reward system brain connectivity, differences in postprandial gut hormone responses, and increased gut microbiome diversity. METHODS: Subjects included participants undergoing VSG, n = 7; RYGB, n = 9; and MWL, n = 6. Ghrelin, glucagon-like peptide-1, peptide-YY, gut microbiome, and resting state functional magnetic resonance imaging (rsfMRI; using fractional amplitude of low-frequency fluctuations [fALFF]) were measured pre- and post-intervention in fasting and fed states. We explored phenotype characterization using clustering on gut hormone, microbiome, and rsfMRI datasets and a combined analysis. RESULTS: We observed more widespread fALFF differences post-bariatric surgery versus post-MWL. Decreased post-prandial fALFF was seen in food reward regions post-RYGB. The highest number of microbial taxa that increased post-intervention occurred in the RYGB group, followed by VSG and MWL. The combined hormone, microbiome, and MRI dataset most accurately clustered samples into pre- versus post-VSG phenotypes followed by RYGB subjects. CONCLUSION: The data suggest surgical weight loss (VSG and RYGB) has a bigger impact on brain and gut function versus MWL and leads to lesser post-prandial activation of food-related neural circuits. VSG subjects had the greatest phenotype differences in interactions of microbiome, rsfMRI, and gut hormone features, followed by RYGB and MWL. These results will inform future prospective research studying gut-brain changes post-bariatric surgery.

Comparing Published Gut Microbiome Taxonomic Data Across Multinational Studies.

BACKGROUND: Nurse researchers are well poised to study the connection of the microbiome to health and disease. Evaluating published microbiome results can assist with study design and hypothesis generation. OBJECTIVES: This article aims to present and define important analysis considerations in microbiome study planning and to identify genera shared across studies despite methodological differences. This methods article will highlight a workflow that the nurse scientist can use to combine and evaluate taxonomy tables for microbiome study or research proposal planning. METHODS: We compiled taxonomy tables from 13 published gut microbiome studies that had used Ion Torrent sequencing technology. We searched for studies that had amplified multiple hypervariable (V) regions of the 16S rRNA gene when sequencing the bacteria from healthy gut samples. RESULTS: We obtained 15 taxonomy tables from the 13 studies, comprised of samples from four continents and eight V regions. Methodology among studies was highly variable, including differences in V regions amplified, geographic location, and population demographics. Nevertheless, of the 354 total genera identified from the 15 data sets, 25 were shared in all V regions and the four continents. When relative abundance differences across the V regions were compared, Dorea and Roseburia were statistically different. Taxonomy tables from Asian subjects had increased average abundances of Prevotella and lowered abundances of Bacteroides compared with the European, North American, and South American study subjects. DISCUSSION: Evaluating taxonomy tables from previously published literature is essential for study planning. The genera found from different V regions and continents highlight geography and V region as important variables to consider in microbiome study design. The 25 shared genera across the various studies may represent genera commonly found in healthy gut microbiomes. Understanding the factors that may affect the results from a variety of microbiome studies will allow nurse scientists to plan research proposals in an informed manner. This work presents a valuable framework for future cross-study comparisons conducted across the globe.