Search

Asthma and obesity are both complex conditions characterized by chronic inflammation, and obesity-related severe asthma has been associated with differences in the microbiome. However, whether the airway microbiome and microbiota-immune response relationships differ between obese persons with or without non-severe asthma is unestablished.To compare the airway microbiome and microbiota-immune mediator relationships between obese and non-obese subjects, with and without mild-moderate asthma.We performed cross-sectional analyses of the airway (induced sputum) microbiome and cytokine profiles from blood and sputum, employing 16S rRNA gene and ITS region sequencing to profile bacteria and fungi, and multiplex immunoassays. Analysis tools included QIIME2, linear discriminant analysis effect size (LEfSe), Piphillin, and SParse InversE Covariance Estimation for Ecological Association Inference (SPIEC-EASI).Obesity, irrespective of asthma status, was associated with significant differences in sputum bacterial community structure and composition (unweighted Unifrac PERMANOVA, p=0.02), including a higher relative abundance of Prevotella, Gemella, and Streptococcus species. Among asthmatic subjects, additional differences in sputum bacterial composition and fungal richness were identified between obese and non-obese individuals. Correlation network analyses demonstrated differences between obese and non-obese asthma in relationships between cytokine mediators, and these together with specific airway bacteria, involving blood PAI-1, sputum IL1-β, GM-CSF, IL-8, TNF-α, and several Prevotella species.Obesity itself is associated with an altered sputum microbiome, which further differs in those with mild-moderate asthma. The distinct differences in airway microbiota and immune marker relationships in obese asthma suggest potential involvement of airway microbes that may impact mechanisms or outcomes of obese asthma.

The human microbiota has been established as a key regulator of host health, in large part owing to its constant interaction with and impact on host immunity. A range of environmental exposures spanning from the prenatal period through adulthood are known to affect the composition and molecular productivity of microbiomes across mucosal and dermal tissues with short- and long-term consequences for host immune function. Here we review recent findings in the field that provide insights into how microbial-immune interactions promote and sustain immune dysfunction associated with allergy and asthma. We consider both early life microbiome perturbation and the molecular underpinnings of immune dysfunction associated with subsequent allergy and asthma development in childhood, as well as microbiome features that relate to phenotypic attributes of allergy and asthma in older patients with established disease.

This report presents the proceedings from a workshop titled "Microbiome, Metabolism and Immunoregulation of Asthma" that was held virtually May 13 and 14, 2021. The workshop was jointly sponsored by the American Thoracic Society (Assembly on Allergy, Immunology, and Inflammation) and the National Institute of Allergy and Infectious Diseases. It convened an interdisciplinary group of experts with backgrounds in asthma immunology, microbiome science, metabolomics, computational biology, and translational pulmonary research. The main purpose was to identify key scientific gaps and needs to further advance research on microbial and metabolic mechanisms that may contribute to variable immune responses and disease heterogeneity in asthma. Discussions were structured around several topics, including 1) immune and microbial mechanisms of asthma pathogenesis in murine models, 2) the role of microbes in pediatric asthma exacerbations, 3) dysregulated metabolic pathways in asthma associated with obesity, 4) metabolism effects on macrophage function in adipose tissue and the lungs, 5) computational approaches to dissect microbiome-metabolite links, and 6) potential confounders of microbiome-disease associations in human studies. This report summarizes the major points of discussion, which included identification of specific knowledge gaps, challenges, and suggested directions for future research. These include questions surrounding mechanisms by which microbiota and metabolites shape host health versus an allergic or asthmatic state; direct and indirect influences of other biological factors, exposures, and comorbidities on these interactions; and ongoing technical and analytical gaps for clinical translation.

Inhaled corticosteroids are widely prescribed for many respiratory diseases, including asthma and COPD. While they benefit many patients, corticosteroids can also have negative effects.

Many speculated that the faculty job market would be severely impacted by the COVID-19 pandemic, potentially for years. Our examination of faculty job postings from 2018 to 2021 found that while they decreased in 2020, the market recovered in 2021. We also surveyed how the pandemic affected the perceptions, behaviors, and outcomes of individuals on the faculty job market in 2019–20 and 2020–21. Approximately 10% of the faculty job offers made to 2019–20 survey respondents were reported as rescinded. Respondents also reported altering their application documents in response to the pandemic as well as delaying or even abandoning their faculty job search. Thus, while the faculty job market may have recovered, the effect of the pandemic on postdoctoral career choices may have future implications.One-Sentence SummaryThe COVID-19 pandemic resulted in changes of perceptions and behaviors of individuals on the faculty job market.

Inflammatory bowel diseases (IBDs) including colitis are intestinal disorders characterized by chronic inflammation, barrier dysfunction and dysbiosis. Specific forms of vitamin E have been shown to attenuate colitis, but the mechanisms are not fully understood. The objective of this study is to examine the impact of α-tocopherol (αT) and γ-tocopherol-rich tocopherols (γTmT) on gut inflammation, barrier integrity and microbiota in dextran sulfate sodium (DSS)-induced colitis in mice. We observe that αT and γTmT mitigated DSS-caused fecal bleeding, diarrhea and elevation of IL-6. These vitamin E forms inhibited colitis-induced loss of the tight junction protein occludin, and attenuated colitis-caused elevation of LPS-binding protein in the plasma, a surrogate marker of intestinal barrier dysfunction, suggesting protection of gut barrier integrity. Consistently, αT and γT mitigated TNF-α/IFN-γ-induced impairment of trans-epithelial electrical resistance in human intestinal epithelial Caco-2 cell monolayer. Using 16S rRNA gene sequencing of fecal DNA, we observe that DSS reduced gut microbial evenness and separated microbial composition from healthy controls. In colitis-induced mice, γTmT but not αT separated gut microbial composition from controls, and attenuated DSS-caused depletion of Roseburia, which contains butyrate producing bacteria and is decreased in IBD patients. Canonical correspondence analysis also supports that γTmT favorably altered gut microbial community. In contrast, neither αT nor γTmT affected gut microbes in healthy animals. These results provide evidence supporting protective effects of αT and γT on intestinal barrier function and that γTmT caused favorable changes of the gut microbiota in colitis-induced mice.

PURPOSE OF REVIEW: Asthma is a heterogeneous condition shaped not only by genetics but also host conditioning by environmental factors. Recognizing the ecological context of microbe-immune interactions across environments and body sites is a necessary step towards better understanding how human microbiota influence or drive the pathogenesis and pathophysiology of asthma in its various presentations. RECENT FINDINGS: There is increasing evidence of a critical role for microbiota in asthma pathogenesis and outcomes across various body compartments, including the upper and lower airways and gut. We discuss recent studies from this area including: 1) development of a method to quantify microbial farm-effect in non-farm environments, 2) relationships between environmental microbial exposures and asthma prevalence across different geographies, 3) microbiome-mediated responses to ozone, and 4) microbiome-immune interactions within and across body compartments. Beyond bacteria, recent reports of asthma-associated differences in archaea and fungal organisms also are highlighted. SUMMARY: Collective evidence warrants application of an ecological framework to advance mechanistic insights into microbiota-immune interactions in asthma. This is necessary to achieve goals of developing successful therapeutic interventions targeting modification of microbiomes.

This article proposes ways to improve inclusion and training in microbiome science and advocates for resource expansion to improve scientific capacity across institutions and countries. Specifically, we urge mentors, collaborators, and decision-makers to commit to inclusive and accessible research and training that improves the quality of microbiome science and begins to rectify long-standing inequities imposed by wealth disparities and racism that stall scientific progress.

Humans are inextricably linked to each other and our natural world, and microorganisms lie at the nexus of those interactions. Microorganisms form genetically flexible, taxonomically diverse, and biochemically rich communities, i.e., microbiomes that are integral to the health and development of macroorganisms, societies, and ecosystems. Yet engagement with beneficial microbiomes is dictated by access to public resources, such as nutritious food, clean water and air, safe shelter, social interactions, and effective medicine. In this way, microbiomes have sociopolitical contexts that must be considered. The Microbes and Social Equity (MSE) Working Group connects microbiology with social equity research, education, policy, and practice to understand the interplay of microorganisms, individuals, societies, and ecosystems. Here, we outline opportunities for integrating microbiology and social equity work through broadening education and training; diversifying research topics, methods, and perspectives; and advocating for evidence-based public policy that supports sustainable, equitable, and microbial wealth for all.

Objective To synthesize evidence on the role of microbiota in asthma pathogenesis, phenotype, and treatment outcomes, and to provide perspective on future research directions and challenges. Data Sources Studies identified from a PubMed search, including all or some of the terms “asthma,” “microbiome,” “microbiota,” “gut,” “airway,” “respiratory,” “lung,” “viral,” and “fungal”. Study Selections Studies included and referenced based on the authors' opinion of the study design and methods, value of the research questions, and the relevance of the results to the objective of the article. Results Many studies have demonstrated an important role for intestinal or upper airway microbiota in mediating the pathogenesis of childhood asthma. Fewer but robust studies have implicated a role for lower respiratory tract microbiota in adult asthma phenotype, including effects of treatments. Bacterial and fungal members of the respiratory microbiota are associated with and may drive specific molecular phenotypes of asthma in adults. Conclusion Current evidence supports the role of human microbiota changes in shaping asthma risk, pathogenesis, and clinical presentation. Further understanding of how microbiota functionally mediate these aspects in clinically relevant contexts will require better integration of advanced scientific tools, analytic methods, and well-designed clinical studies. These efforts should be pursued with a systems-level perspective of the complex interactions between human hosts and their microbiomes, and the impact on these interactions of changes in environmental and lifestyle factors across the lifespan.

The Microbes and Social Equity working group was formed in 2020 to foster conversations on research, education, and policy related to how microorganisms connect to personal, societal, and environmental health, and to provide space and guidance for action. In 2021, we designed our first virtual symposium to convene researchers already working in these areas for more guided discussions. The symposium organizing team had never planned a research event of this scale or style, and this perspective piece details that process and our reflections. The goals were to (1) convene interdisciplinary audiences around topics involving microbiomes and health, (2) stimulate conversation around a selected list of paramount research topics, and (3) leverage the disciplinary and professional diversity of the group to create meaningful agendas and actionable items for attendees to continue to engage with after the meeting. Sixteen co-written documents were created during the symposium which contained ideas and resources, or identified barriers and solutions to creating equity in ways which would promote beneficial microbial interactions. The most remarked-upon aspect was the working time in the breakout rooms built into the schedule. MSE members agreed that in future symposia, providing interactive workshops, training, or collaborative working time would provide useful content, a novel conference activity, and allow attendees to accomplish other work-oriented goals simultaneously.

Exploratory Science Center, Merck & Co , Inc , Cambridge, Massachusetts, United States of America Affiliation: Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, United States of America ORCID logo http://orcid org/0000-0003-3140-537X Patrick D Schloss * E-mail: pschloss@umich edu Affiliation: Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, United States of America ORCID logo http://orcid org/0000-0002-6935-4275 Introduction For most biologists, the ability to generate data has outpaced the ability to analyze those data In addition to building upon material from traditional coursework and staying current on the literature, Journal Clubs help strengthen skills in critical thinking, communication, and integrating the literature [11] Because most Journal Clubs occur on a regular schedule, they are effective by virtue of repeated practice With this model in mind, over the past four years we have experimented with creating a Code Club model with the goal of improving reproducible data analysis skills in a laboratory environment [ ]presenters were reluctant to offer to present again

Oscillations are ubiquitous features of brain dynamics that undergo task-related changes in synchrony, power, and frequency. The impact of those changes on target networks is poorly understood. In this work, we used a biophysically detailed model of prefrontal cortex (PFC) to explore the effects of varying the spike rate, synchrony, and waveform of strong oscillatory inputs on the behavior of cortical networks driven by them. Interacting populations of excitatory and inhibitory neurons with strong feedback inhibition are inhibition-based network oscillators that exhibit resonance (i.e., larger responses to preferred input frequencies). We quantified network responses in terms of mean firing rates and the population frequency of network oscillation; and characterized their behavior in terms of the natural response to asynchronous input and the resonant response to oscillatory inputs. We show that strong feedback inhibition causes the PFC to generate internal (natural) oscillations in the beta/gamma frequency range (>15 Hz) and to maximize principal cell spiking in response to external oscillations at slightly higher frequencies. Importantly, we found that the fastest oscillation frequency that can be relayed by the network maximizes local inhibition and is equal to a frequency even higher than that which maximizes the firing rate of excitatory cells; we call this phenomenon population frequency resonance. This form of resonance is shown to determine the optimal driving frequency for suppressing responses to asynchronous activity. Lastly, we demonstrate that the natural and resonant frequencies can be tuned by changes in neuronal excitability, the duration of feedback inhibition, and dynamic properties of the input. Our results predict that PFC networks are tuned for generating and selectively responding to beta- and gamma-rhythmic signals due to the natural and resonant properties of inhibition-based oscillators. They also suggest strategies for optimizing transcranial stimulation and using oscillatory networks in neuromorphic engineering. Author Summary The prefrontal cortex (PFC) flexibly encodes task-relevant representations and outputs biases to mediate higher cognitive functions. The relevant neural ensembles undergo task-related changes in oscillatory dynamics at beta- and gamma frequencies. Using a computational model of the PFC network, we show that strong feedback inhibition causes the PFC to generate internal oscillations and to prefer external oscillations at similar frequencies. The precise frequencies that are generated and preferred can be flexibly tuned by varying the synchrony and strength of input network activity, the level of background excitation, and neuromodulation of intrinsic ion currents. We also show that the peak output frequency in response to external oscillations, which depends on the synchrony and strength of the input as well as the strong inhibitory feedback, is faster than the internally generated frequency, and that this difference enables exclusive response to oscillatory inputs. These properties enable changes in oscillatory dynamics to govern the selective processing and gating of task-relevant signals in service of cognitive control.

Many postdoctoral researchers apply for faculty positions knowing relatively little about the hiring process or what is needed to secure a job offer. To address this lack of knowledge about the hiring process we conducted a survey of applicants for faculty positions: the survey ran between May 2018 and May 2019, and received 317 responses. We analyzed the responses to explore the interplay between various scholarly metrics and hiring outcomes. We concluded that, above a certain threshold, the benchmarks traditionally used to measure research success – including funding, number of publications or journals published in – were unable to completely differentiate applicants with and without job offers. Respondents also reported that the hiring process was unnecessarily stressful, time-consuming, and lacking in feedback, irrespective of outcome. Our findings suggest that there is considerable scope to improve the transparency of the hiring process.

Applying for a faculty position is a critical phase of many postdoctoral careers, but most postdoctoral researchers in STEM fields enter the academic job market with little knowledge of the process and expectations. A lack of data has made it difficult for applicants to assess their qualifications relative to the general applicant pool and for institutions to develop effective hiring policies. We analyzed responses to a survey of faculty job applicants between May 2018 and May 2019. We establish various background scholarly metrics for a typical faculty applicant and present an analysis of the interplay between those metrics and hiring outcomes. Traditional benchmarks of a positive research track record above a certain threshold of qualifications were unable to completely differentiate applicants with and without offers. Our findings suggest that there is no single clear path to a faculty job offer and that metrics such as career transition awards and publications in high impact factor journals were neither necessary nor sufficient for landing a faculty position. The applicants perceived the process as unnecessarily stressful, time-consuming, and largely lacking in feedback, irrespective of a successful outcome. Our findings emphasize the need to improve the transparency of the faculty job application process. In addition, we hope these and future data will help empower trainees to enter the academic job market with clearer expectations and improved confidence.

Crohn's Disease and Ulcerative Colitis are chronic, inflammatory conditions of the digestive tract, collectively known as Inflammatory Bowel Disease (IBD). The combined influence of lifestyle factors, genetics, and the gut microbiome contribute to IBD pathogenesis. Studies of the gut microbiome have shown significant differences in its composition between healthy individuals and those with IBD. Due to the high inter-individual microbiome variation seen in humans, mouse models of IBD are often used to investigate potential IBD mechanisms and their interplay between host, microbial, and environmental factors. While fecal samples are the predominant material used for microbial community analysis, they may not be the ideal sample to use for analysis of the microbiome of mice with experimental colitis, such as that induced by 2, 4, 6 trinitrobenzesulfonic acid (TNBS). As TNBS is administered intrarectally to induce colitis and inflammation is confined to the colon in this model, we hypothesized that the microbiome of the colonic mucus would most closely correlate with TNBS colitis severity. Based on our previous research, we also hypothesized that sex would be associated with both disease severity and microbial differences in mice with chronic TNBS colitis. We examined and compared the fecal, cecal content, and colonic mucus microbiota of 8-week old male and female C57BL/6J wild-type mice prior to and after the induction of TNBS colitis via 16S rRNA gene sequencing. We found that the colonic mucus microbiome was more closely correlated with disease severity than were alterations in the fecal and cecal microbiomes. We also found that the microbiomes of the feces, cecum, and mucus were distinct, but found no significant differences that were associated with sex in either compartment. Our findings highlight the importance of sampling colonic mucus in TNBS-induced colitis. Moreover, consideration of the differential impact of sex on the microbiome across mouse strains may be critical for the appropriate application of TNBS colitis models and robust comparisons across studies in the future.

To synthesize evidence on the role of microbiota in asthma pathogenesis, phenotype, and treatment outcomes, and to provide perspective on future research directions and challenges.Studies identified from a PubMed search, including all or some of the terms "asthma," "microbiome," "microbiota," "gut," "airway," "respiratory," "lung," "viral," and "fungal".Studies included and referenced based on the authors' opinion of the study design and methods, value of the research questions, and the relevance of the results to the objective of the article.Many studies have demonstrated an important role for intestinal or upper airway microbiota in mediating the pathogenesis of childhood asthma. Fewer but robust studies have implicated a role for lower respiratory tract microbiota in adult asthma phenotype, including effects of treatments. Bacterial and fungal members of the respiratory microbiota are associated with and may drive specific molecular phenotypes of asthma in adults.Current evidence supports the role of human microbiota changes in shaping asthma risk, pathogenesis, and clinical presentation. Further understanding of how microbiota functionally mediate these aspects in clinically relevant contexts will require better integration of advanced scientific tools, analytic methods, and well-designed clinical studies. These efforts should be pursued with a systems-level perspective of the complex interactions between human hosts and their microbiomes, and the impact on these interactions of changes in environmental and lifestyle factors across the lifespan.

Mouse models are often used to determine the interactions between the microbiota and inflammatory processes and overcome the confounding effect of the naturally high inter-individual variation of the gut microbiota in humans. However, the microbiomes of mice are also variable and data detailing the degree to which factors like mouse sex and age contribute to mouse gut microbiota variation is limited. Our objective was to determine the impact sex and age have on the mouse gut microbiota and the severity of acute 2, 4, 6-trinitrobenzenesulfonic acid (TNBS) induced colitis. We used Illumina sequencing of 16S rRNA genes to characterize the fecal microbiota of B6.129S wild-type (WT) mice and mice lacking tumor necrosis factor (Tnf-/-) before and after acute TNBS colitis. There were differences between the fecal microbiota of male and female WT mice as well as Tnf-/- mice, both pre-and post-colitis. Male WT mice had more severe colitis than female WT mice and Tnf-/- mice of both sexes. We also identified microbial taxa differences between 4-5 and 6-7-week old WT and Tnf-/- mice both pre-and post-colitis. Here we provide evidence that the mouse fecal microbiome is shaped, in part, by sex, age and TNF production and that these effects correlate with the degree of animals' colitis.

Inflammatory Bowel Disease (IBD) consists of Ulcerative Colitis and Crohn's Disease (CD). The etiology remains unclear; however tumor necrosis factor (TNF) is known to promote the inflammation seen...

Inflammatory bowel disease (IBD) is associated with prolonged, excess secretions of Tumor Necrosis Factor (TNF). Many patients with IBD have successful management of IBD symptoms by blocking TNF secretion or signaling. However, some patients are non-responsive to this therapy, eventually become refractory to therapy, or may develop harmful side-effects [corrected]. Alterations in the microbiota that are associated with the lack of TNF could be a contributing cause of this therapeutic insufficiency seen in some patients. Here we use wildtype (WT) and mice lacking Tnf (Tnf-/-) in an acute TNBS colitis model to investigate the role of TNF in colitis and how its presence or absence affects the colonic microbiota. As expected, Tnf-/- had less severe inflammation than WT mice. Microbiome analysis revealed significant Tnf dependent-differences in alpha and beta diversity. There were also notable differences in many species that were also primarily Tnf dependent. Taken together, our data indicates that TNF contributes significantly to the inflammation and microbiotal alterations in that occur in IBD.