Abstract
Microbial ecology provides insights into the ecological and evolutionary dynamics of microbial communities underpinning every ecosystem on Earth. Microbial communities can now be ...investigated in unprecedented detail, although there is still a wealth of open questions to be tackled. Here we identify 50 research questions of fundamental importance to the science or application of microbial ecology, with the intention of summarising the field and bringing focus to new research avenues. Questions are categorised into seven themes: host–microbiome interactions; health and infectious diseases; human health and food security; microbial ecology in a changing world; environmental processes; functional diversity; and evolutionary processes. Many questions recognise that microbes provide an extraordinary array of functional diversity that can be harnessed to solve real-world problems. Our limited knowledge of spatial and temporal variation in microbial diversity and function is also reflected, as is the need to integrate micro- and macro-ecological concepts, and knowledge derived from studies with humans and other diverse organisms. Although not exhaustive, the questions presented are intended to stimulate discussion and provide focus for researchers, funders and policy makers, informing the future research agenda in microbial ecology.
We identify research questions in the field of microbial ecology, with emerging themes that recognise vast microbial functions that could benefit humanity, and the need to integrate knowledge across organisms.
•Participants described a thin and overtly muscular body as the female body ideal.•Athleisure connotates adherence to “health” and “fitness,” akin to fitspiration.•A person’s body type determines ...their access to athleisure; larger = less access.•Wearing athleisure encourages adherence to the athleisure lifestyle and body ideal.•Participants experienced cognitive dissonance about athleisure and body standards.
Clothes play a ubiquitous, yet under-appreciated social role. In the context of body image, clothes may both reflect and facilitate wearers’ ideals and anxieties about their physical appearance. Athleisure, referring to athletic-inspired workout apparel that explicitly accentuates wearers’ physiques, is a hitherto unexamined clothing trend worth tens of billions of dollars annually (and growing) in the United States consumer market alone. We conducted the first qualitative examination of athleisure by interviewing 20 women who regularly wore athleisure. Four master themes emerged from the data: (1) the athleisure lifestyle, (2) the conditional nature of athleisure, (3) athleisure embodiment, and (4) athleisure-linked cognitive dissonance. Our results suggest that wearing athleisure communicates to others an adherence to the lifestyles depicted in fitspiration – a class of social media imagery that glorifies thin-fit bodies. Participants articulated that athleisure encouraged them to feel more confident and athletic; athleisure also emphasized the women’s physiques, and whether they aligned with the thin-fit ideal. Thus, the act of wearing athleisure motivated participants to engage in fitspiration-based activities. Given the (a) massive public demand for athleisure, and (b) industry projections for continued growth in athleisure spending, our findings compel additional research on the connections between clothing and body image.
Host-microbe interactions play crucial roles in marine ecosystems. However, we still have very little understanding of the mechanisms that govern these relationships, the evolutionary processes that ...shape them, and their ecological consequences. The holobiont concept is a renewed paradigm in biology that can help to describe and understand these complex systems. It posits that a host and its associated microbiota with which it interacts, form a holobiont, and have to be studied together as a coherent biological and functional unit to understand its biology, ecology, and evolution. Here we discuss critical concepts and opportunities in marine holobiont research and identify key challenges in the field. We highlight the potential economic, sociological, and environmental impacts of the holobiont concept in marine biological, evolutionary, and environmental sciences. Given the connectivity and the unexplored biodiversity specific to marine ecosystems, a deeper understanding of such complex systems requires further technological and conceptual advances, e.g., the development of controlled experimental model systems for holobionts from all major lineages and the modeling of (info)chemical-mediated interactions between organisms. Here we propose that one significant challenge is to bridge cross-disciplinary research on tractable model systems in order to address key ecological and evolutionary questions. This first step is crucial to decipher the main drivers of the dynamics and evolution of holobionts and to account for the holobiont concept in applied areas, such as the conservation, management, and exploitation of marine ecosystems and resources, where practical solutions to predict and mitigate the impact of human activities are more important than ever.
Post-COVID-19 condition (also known as long COVID) is an emerging chronic illness potentially affecting millions of people. We aimed to evaluate whether outpatient COVID-19 treatment with metformin, ...ivermectin, or fluvoxamine soon after SARS-CoV-2 infection could reduce the risk of long COVID.
We conducted a decentralised, randomised, quadruple-blind, parallel-group, phase 3 trial (COVID-OUT) at six sites in the USA. We included adults aged 30–85 years with overweight or obesity who had COVID-19 symptoms for fewer than 7 days and a documented SARS-CoV-2 positive PCR or antigen test within 3 days before enrolment. Participants were randomly assigned via 2 × 3 parallel factorial randomisation (1:1:1:1:1:1) to receive metformin plus ivermectin, metformin plus fluvoxamine, metformin plus placebo, ivermectin plus placebo, fluvoxamine plus placebo, or placebo plus placebo. Participants, investigators, care providers, and outcomes assessors were masked to study group assignment. The primary outcome was severe COVID-19 by day 14, and those data have been published previously. Because the trial was delivered remotely nationwide, the a priori primary sample was a modified intention-to-treat sample, meaning that participants who did not receive any dose of study treatment were excluded. Long COVID diagnosis by a medical provider was a prespecified, long-term secondary outcome. This trial is complete and is registered with ClinicalTrials.gov, NCT04510194.
Between Dec 30, 2020, and Jan 28, 2022, 6602 people were assessed for eligibility and 1431 were enrolled and randomly assigned. Of 1323 participants who received a dose of study treatment and were included in the modified intention-to-treat population, 1126 consented for long-term follow-up and completed at least one survey after the assessment for long COVID at day 180 (564 received metformin and 562 received matched placebo; a subset of participants in the metformin vs placebo trial were also randomly assigned to receive ivermectin or fluvoxamine). 1074 (95%) of 1126 participants completed at least 9 months of follow-up. 632 (56·1%) of 1126 participants were female and 494 (43·9%) were male; 44 (7·0%) of 632 women were pregnant. The median age was 45 years (IQR 37–54) and median BMI was 29·8 kg/m2 (IQR 27·0–34·2). Overall, 93 (8·3%) of 1126 participants reported receipt of a long COVID diagnosis by day 300. The cumulative incidence of long COVID by day 300 was 6·3% (95% CI 4·2–8·2) in participants who received metformin and 10·4% (7·8–12·9) in those who received identical metformin placebo (hazard ratio HR 0·59, 95% CI 0·39–0·89; p=0·012). The metformin beneficial effect was consistent across prespecified subgroups. When metformin was started within 3 days of symptom onset, the HR was 0·37 (95% CI 0·15–0·95). There was no effect on cumulative incidence of long COVID with ivermectin (HR 0·99, 95% CI 0·59–1·64) or fluvoxamine (1·36, 0·78–2·34) compared with placebo.
Outpatient treatment with metformin reduced long COVID incidence by about 41%, with an absolute reduction of 4·1%, compared with placebo. Metformin has clinical benefits when used as outpatient treatment for COVID-19 and is globally available, low-cost, and safe.
Parsemus Foundation; Rainwater Charitable Foundation; Fast Grants; UnitedHealth Group Foundation; National Institute of Diabetes, Digestive and Kidney Diseases; National Institutes of Health; and National Center for Advancing Translational Sciences.
The American Psychiatric Association recently included Internet gaming disorder (IGD) as a potential diagnosis, recommending that further study be conducted to help illuminate it more clearly. This ...paper is a summary of the review undertaken by the IGD Working Group as part of the 2015 National Academy of Sciences Sackler Colloquium on Digital Media and Developing Minds. By using measures based on or similar to the IGD definition, we found that prevalence rates range between ∼1% and 9%, depending on age, country, and other sample characteristics. The etiology of IGD is not well-understood at this time, although it appears that impulsiveness and high amounts of time gaming may be risk factors. Estimates for the length of time the disorder can last vary widely, but it is unclear why. Although the authors of several studies have demonstrated that IGD can be treated, no randomized controlled trials have yet been published, making any definitive statements about treatment impossible. IGD does, therefore, appear to be an area in which additional research is clearly needed. We discuss several of the critical questions that future research should address and provide recommendations for clinicians, policy makers, and educators on the basis of what we know at this time.
Cytochromes P450 (CYPs) catalyze various oxidative transformations in drug metabolism, xenobiotic degradation, and natural product biosynthesis. Here we report biochemical, structural, and ...theoretical studies of TxtC, an unusual bifunctional CYP involved in the biosynthesis of the EPA-approved herbicide thaxtomin A. TxtC was shown to hydroxylate two remote sites within the Phe residue of its diketopiperazine substrate thaxtomin D. The reactions follow a preferred order, with hydroxylation of the α-carbon preceding functionalization of the phenyl group. To illuminate the molecular basis for remote site functionalization, X-ray crystal structures of TxtC in complex with the substrate and monohydroxylated intermediate were determined. Electron density corresponding to a diatomic molecule (probably dioxygen) was sandwiched between the heme iron atom and Thr237 in the TxtC-intermediate structure, providing insight into the mechanism for conversion of the ferrous-dioxygen complex into the reactive ferryl intermediate. The substrate and monohydroxylated intermediate adopted similar conformations in the active site, with the π-face of the phenyl group positioned over the heme iron atom. Docking simulations reproduced this observation and identified a second, energetically similar but conformationally distinct binding mode in which the α-hydrogen of the Phe residue is positioned over the heme prosthetic group. Molecular dynamics simulations confirmed that the α-hydrogen is sufficiently close to the ferryl oxygen atom to be extracted by it and indicated that the two substrate conformations cannot readily interconvert in the active site. These results indicate that TxtC is able to hydroxylate two spatially remote sites by binding distinct conformations of the substrate and monohydroxylated intermediate.
Tree pathogens are a major threat to forest ecosystems. Conservation management strategies can exploit natural mechanisms of resistance, such as tree genotype and host‐associated microbial ...communities. However, fungal and bacterial communities are rarely looked at in the same framework, particularly in conjunction with host genotype. Here, we explore these relationships and their influence on ash dieback disease, caused by the pathogen Hymenoscyphus fraxineus, in European common ash trees.
We collected leaves from UK ash trees and used microsatellite markers to genotype trees, quantitative PCR to quantify H. fraxineus infection load and ITS and 16S rRNA amplicon sequencing to identify fungal and bacterial communities, respectively.
There was a significant association between H. fraxineus infection intensity and ash leaf fungal and bacterial community composition. Higher infection levels were positively correlated with fungal community alpha‐diversity, and a number of fungal and bacterial genera were significantly associated with infection presence and intensity. Under higher infection loads, leaf microbial networks were characterized by stronger associations between fewer members than those associated with lower infection levels. Together these results suggest that H. fraxineus disrupts stable endophyte communities after a particular infection threshold is reached, and may enable proliferation of opportunistic microbes. We identified three microbial genera associated with an absence of infection, potentially indicating an antagonistic relationship with H. fraxineus that could be utilized in the development of anti‐pathogen treatments.
Host genotype did not directly affect infection, but did significantly affect leaf fungal community composition. Thus, host genotype could have the potential to indirectly affect disease susceptibility through genotype × microbiome interactions, and should be considered when selectively breeding trees.
Synthesis. We show that the diversity, composition and network structure of ash leaf microbial communities are associated with the severity of infection from ash dieback disease, with evidence of disease‐induced dysbiosis. We also show that host genotype influences leaf fungal community composition, but does not directly influence tree infection. These findings help to elucidate relationships between host genetics, the microbiome and a tree pathogen, highlighting potential resistance mechanisms and possible co‐infection concerns that could inform ash tree management.
We show that the diversity, composition and network structure of ash leaf microbial communities are associated with the severity of infection from ash dieback disease, with evidence of disease‐induced dysbiosis. We also show that host genotype influences leaf fungal community composition, but does not directly influence tree infection. These findings help to elucidate relationships between host genetics, the microbiome and a tree pathogen, highlighting potential resistance mechanisms and possible co‐infection concerns that could inform ash tree management.
Marine sponges are hosts to large, diverse communities of microorganisms. These microbiomes are distinct among sponge species and from seawater bacterial communities, indicating a key role of host ...identity in shaping its resident microbial community. However, the factors governing intraspecific microbiome variability are underexplored and may shed light on the evolutionary and ecological relationships between host and microbiome.
Here, we examined the influence of genetic variation and geographic location on the composition of the Ircinia campana microbiome.
We developed new microsatellite markers to genotype I. campana from two locations in the Florida Keys, USA, and characterized their microbiomes using V4 16S rRNA amplicon sequencing.
We show that microbial community composition and diversity is influenced by host genotype, with more genetically similar sponges hosting more similar microbial communities. We also found that although I. campana was not genetically differentiated between sites, microbiome composition differed by location.
Our results demonstrate that both host genetics and geography influence the composition of the sponge microbiome. Host genotypic influence on microbiome composition may be due to stable vertical transmission of the microbial community from parent to offspring, making microbiomes more similar by descent. Alternatively, sponge genotypic variation may reflect variation in functional traits that influence the acquisition of environmental microbes. This study reveals drivers of microbiome variation within and among locations, and shows the importance of intraspecific variability in mediating eco‐evolutionary dynamics of host‐associated microbiomes.
For the first time, the authors show that intraspecific genetic variation affects microbiome composition in a marine sponge (Ircinia campana), with positive correlations observed between genetic and microbiome similarity. This has significant implications for our understanding of the ecological and evolutionary relationships between host and microbiome in this important model system.
Amphibian populations worldwide are at risk of extinction from infectious diseases, including chytridiomycosis caused by the fungal pathogen Batrachochytrium dendrobatidis (Bd). Amphibian cutaneous ...microbiomes interact with Bd and can confer protective benefits to the host. The composition of the microbiome itself is influenced by many environment- and host-related factors. However, little is known about the interacting effects of host population structure, genetic variation and developmental stage on microbiome composition and Bd prevalence across multiple sites. Here we explore these questions in Amietia hymenopus, a disease-affected frog in southern Africa. We use microsatellite genotyping and 16S amplicon sequencing to show that the microbiome associated with tadpole mouthparts is structured spatially, and is influenced by host genotype and developmental stage. We observed strong genetic structure in host populations based on rivers and geographic distances, but this did not correspond to spatial patterns in microbiome composition. These results indicate that demographic and host genetic factors affect microbiome composition within sites, but different factors are responsible for host population structure and microbiome structure at the between-site level. Our results help to elucidate complex within- and among- population drivers of microbiome structure in amphibian populations. That there is a genetic basis to microbiome composition in amphibians could help to inform amphibian conservation efforts against infectious diseases.
1. Altered global climates in the 21st century pose serious threats for biological systems and practical actions are needed to mount a response for species at risk. 2. We identify management actions ...from across the world and from diverse disciplines that are applicable to minimizing loss of amphibian biodiversity under climate change. Actions were grouped under three thematic areas of intervention: (i) installation of microclimate and microhabitat refuges; (ii) enhancement and restoration of breeding sites; and (iii) manipulation of hydroperiod or water levels at breeding sites. 3. Synthesis and applications. There are currently few meaningful management actions that will tangibly impact the pervasive threat of climate change on amphibians. A host of potentially useful but poorly tested actions could be incorporated into local or regional management plans, programmes and activities for amphibians. Examples include: installation of irrigation sprayers to manipulate water potentials at breeding sites; retention or supplementation of natural and artificial shelters (e.g. logs, cover boards) to reduce desiccation and thermal stress; manipulation of canopy cover over ponds to reduce water temperature; and, creation of hydrologoically diverse wetland habitats capable of supporting larval development under variable rainfall regimes. We encourage researchers and managers to design, test and scale up new initiatives to respond to this emerging crisis.
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