Coronary artery disease (CAD) is the most common health problem worldwide and remains the leading cause of morbidity and mortality. Over the past decade, it has become clear that the inhabitants of our gut, the gut microbiota, play a vital role in human metabolism, immunity, and reactions to diseases, including CAD. Although correlations have been shown between CAD and the gut microbiota, demonstration of potential causal relationships is much more complex and challenging. In this review, we will discuss the potential direct and indirect causal roots between gut microbiota and CAD development via microbial metabolites and interaction with the immune system. Uncovering the causal relationship of gut microbiota and CAD development can lead to novel microbiome-based preventative and therapeutic interventions. However, an interdisciplinary approach is required to shed light on gut bacterial-mediated mechanisms (e.g., using advanced nanomedicine technologies and incorporation of demographic factors such as age, sex, and ethnicity) to enable efficacious and high-precision preventative and therapeutic strategies for CAD. Key points The causal relationship between gut microbiota and CAD development has yet to be confirmed. It is imperative to understand the potential direct and indirect causal roots between gut microbiota and CAD development via microbial metabolites and interaction with the immune system. Dynamic elements including our diet and demographic factors such as age, sex, and ethnicity can also affect our gut microbiota and CAD development and complicate this matter. Interdisciplinary approaches are required to shed light on the factors involved in the modulation of gut microbiota and its association with CAD development. Elucidating the system-level multifaceted web of factors involved in microbiome-mediated mechanisms and human health and disease can guide novel preventative and therapeutic interventions for CAD.
Colon mucus segregates the intestinal microbiota from host tissues, but how it organizes to function throughout the colon is unclear. In mice, we found that colon mucus consists of two distinct O-glycosylated entities of Muc2: a major form produced by the proximal colon, which encapsulates the fecal material including the microbiota, and a minor form derived from the distal colon, which adheres to the major form. The microbiota directs its own encapsulation by inducing Muc2 production from proximal colon goblet cells. In turn, O-glycans on proximal colon–derived Muc2 modulate the structure and function of the microbiota as well as transcription in the colon mucosa. Our work shows how proximal colon control of mucin production is an important element in the regulation of host-microbiota symbiosis.
The development and application of bio-sourced composites have been gaining wide attention, yet their deterioration due to the growth of ubiquitous microorganisms during storage/manufacturing/in-service phases is still not fully understood for optimum material selection and design purposes. In this study, samples of non-woven flax fibers, hemp fibers, and mats made of co-mingled randomly-oriented flax or hemp fiber (50%) and polypropylene fiber (50%) were subjected to 28 days of exposure to (i) no water-no fungi, (ii) water only and (iii) water along with the Chaetomium globosum fungus. Biocomposite samples were measured for weight loss over time, to observe the rate of fungal growth and the respiration of cellulose components in the fibers. Tensile testing was conducted to measure mechanical properties of the composite samples under different configurations. Scanning electron microscopy was employed to visualize fungal hyphal growth on the natural fibers, as well as to observe the fracture planes and failure modes of the biocomposite samples. Results showed that fungal growth significantly affects the dry mass as well as the tensile elastic modulus of the tested natural fiber mats and composites, and the effect depends on both the type and the length scale of fibers, as well as the exposure condition and time.
Fundamental restoration ecology and community ecology theories can help us better understand the underlying mechanisms of fecal microbiota transplantation (FMT) and to better design future microbial therapeutics for recurrent Clostridioides difficile infections (rCDI) and other dysbiosis-related conditions. In this study, stool samples were collected from donors and rCDI patients one week prior to FMT (pre-FMT), as well as from patients one week following FMT (post-FMT). Using metagenomic sequencing and machine learning, our results suggested that FMT outcome is not only dependent on the ecological structure of the recipients, but also the interactions between the donor and recipient microbiomes at the taxonomical and functional levels. We observed that the presence of specific bacteria in donors (Clostridioides spp., Desulfovibrio spp., Odoribacter spp. and Oscillibacter spp.) and the absence of fungi (Yarrowia spp.) and bacteria (Wigglesworthia spp.) in recipients prior to FMT could predict FMT success. Our results also suggested a series of interlocked mechanisms for FMT success, including the repair of the disturbed gut ecosystem by transient colonization of nexus species followed by secondary succession of bile acid metabolizers, sporulators, and short chain fatty acid producers.
COVID-19 is a major pandemic facing the world today, which has implications on current microbiome-based treatments such as fecal microbiota transplantation (FMT) used for recurrent Clostridioides difficile infections. The bidirectional relationship between the inhabitants of our gut, the gut microbiota, and COVID-19 pathogenesis, as well as the underlying mechanism involved, must be elucidated in order to increase FMT safety and efficacy. In this perspective, we discuss the crucial cross-talk between the gut microbiota and the lungs, known as the gut–lung axis, during COVID-19 infection, as well as the putative effect of these microorganisms and their functional activity (i.e., short chain fatty acids and bile acids) on FMT treatment. In addition, we highlight the urgent need to investigate the possible impact of COVID-19 on FMT safety and efficacy, as well as instilling stringent screening protocols of donors and recipients during COVID-19 and post-COVID-19 pandemic to produce a cohesive and optimized FMT treatment plan across all centers and in all countries across the globe.
The new era in the design of modern healthy buildings necessitates multidisciplinary research efforts that link principles of engineering and material sciences with those of building biology, in order to better comprehend and apply underlying interactions among design criteria. As part of this effort, there have been an array of studies in relation to the effects of building characteristics on indoor microbiota and their propensity to cause health issues. Despite the abundance of scientific inquiries, limited studies have been dedicated to concomitantly link these effects to the deterioration of ‘structural integrity’ in the building materials. This study focuses on the observed biodeteriorative capabilities of indoor fungi upon the ubiquitous gypsum board material as a function of building age and room functionality within a university campus. We observed that the fungal growth significantly affected the physical (weight loss) and mechanical (tensile strength) properties of moisture-exposed gypsum board samples; in some cases, tensile strength and weight decreased by more than 80%. Such intertwined associations between the biodeterioration of building material properties due to viable indoor fungi, and as a function of building characteristics, would suggest a critical need towards multi-criteria design and optimization of next-generation healthy buildings. Next to structural integrity measures, with a better understanding of what factors and environmental conditions trigger fungal growth in built environment materials, we can also optimize the design of indoor living spaces, cleaning strategies, as well as emergency management measures during probable events such as flooding or water damage.
Background The gel-forming O-glycoprotein Mucin-2 (MUC2) is a key mediator of host-microbe homeostasis in part by forming a barrier to segregate inflammatory microbes from distal colon tissues. While animal models have provided insights into how Muc2 functions, relatively few studies have explored human MUC2. This is due to difficulty in accessing primary MUC2 which has been traditionally seen as firmly adherent to tissues and thus attainable mainly through invasive approaches (e.g. surgery, biopsies, etc), or via transformed cell lines (e.g. LS174T). This highlights a need to find alternative sources of MUC2. Purpose The purpose of this study is to develop a non-invasive method to analyze human MUC2 from healthy persons and determine if this can be applied to disease states. Recent studies have shown a significant portion of MUC2 is bound to feces (Bergstrom and Shan et al, 2020). We therefore reasoned this fecal MUC2 was accessible for both purification and structural and functional characterization. Method We purified MUC2 from feces via established extraction methods used for tissues. The mucins were resolved by composite urea agarose polyacrylamide gel electrophoresis (UreaAgPAGE) and analyzed by in-gel staining with Alcian Blue (AB), or Western blot for lectins and MUC2. Mucins were subjected to both proteomics to confirm enrichment of MUC2; and O-glycomics via non-reductive ammonia-catalyzed β-elimination followed by capillary electrophoresis (CE) and mass spectrometry in parallel with Type III porcine gastric mucin (PGM) O-glycans for comparison. Purified O-glycans were tested functionally via microbial growth assays with Bacteroides spp, and the ability to be metabolized into short-chain fatty acids (SCFA). Mucus barrier function was also visualized directly on Carnoy's-fixed paraffin-embedded (CFPE) fecal sections followed by dual staining for bacteria by FISH, and MUC2 and/or lectins. Result(s) Confocal imaging of CFPE fecal sections revealed a microbiota-encapsulating barrier layer of varying thickness among various healthy human subjects. UreaAgPAGE showed high molecular weight bands (~1 – 2 MDa) by AB staining. Proteomics and western analysis confirmed MUC2 enrichment in fecal mucin preparations. Western analysis via a lectin panel showed human MUC2 bound several lectins but was notably lacking in signal for Sambucus nigra lectin (SNA; α2,6-linked sialic acid) or Ulex europaeus agglutinin I (UEA1; α1,2-linked fucose). O-glycomics revealed extensive sialylation, moderate sulfation, and very little fucosylation vs. PGM. Functionally, the glycans supported growth of Bacteroides thetaiotaomicron as well as B.theta-dependent SCFA production in vitro. Pilot studies with human Ulcerative Colitis (UC) showed intact MUC2 with a differential O-glycosylation profile by glycan "fingerprinting" via CE. Conclusion(s) These studies highlight a new way to access primary human MUC2 for downstream functional analyses and pave the way for characterizing MUC2 dysfunction in diseases including IBD. Disclosure of Interest None Declared A71 SIGNIFICANT RACIAL/ETHNIC DIFFERENCES EXIST IN THE RECEIPT OF IBD-RELATED SURGERY A SYSTEMATIC REVIEW AND META-ANALYSIS T. Chhibba*, P. Tandon, N. Natt, G. Brar, G. Malhi, G. Nguyen Background Patients with inflammatory bowel disease (IBD) may require surgical intervention for management of their disease. There is a rising incidence of IBD in racial and ethnic minorities but studies regarding healthcare utilization patterns in these populations have yielded variable results. Purpose We aimed to examine the differences in surgical rates of ethnic and racial groups compared to White patients with IBD. Method Electronic databases were searched through December 20, 2021. Studies that compared ulcerative colitis (UC) or Crohn’s disease (CD) surgery rates between different racial/ethnic groups were included. Both pediatric and adult studies were included. Pooled event rates were generated and p-value < 0.05 was considered statistically significant in generating odds ratios (OR) with 95% confidence interval (CI). We also compared differences in disease location, phenotype, and IBD-medication exposure amongst different groups included. Result(s) Forty-one studies stratified rates of IBD-related surgeries by race or ethnicity (n=1,094,693 patients). Black patients were less likely to undergo IBD-related surgeries compared to White patients (pooled OR 0.70, 95% CI, 0.55-0.89, I2=87.0%). Black patients were also less likely compared to White patients to undergo an emergent colectomy with an incidence rate ratio of 0.43 (95% CI, 0.32-0.58). Furthermore, Hispanic patients were less likely to undergo a CD-related surgery (pooled OR 0.57, 95% CI, 0.48-0.68, I2=0%) compared to White patients. Finally, Asian patients had no significant difference in likelihood of CD-related and UC-related surgeries compared to White patients. Black patients were more likely to have perianal disease (pooled OR 1.40, 95% CI, 1.06-1.86), I2=58.2%) but otherwise disease characteristics and phenotypes were similar across all populations compared to Caucasians. Conclusion(s) Black and Hispanic patients with IBD are less likely to have surgery, including emergent surgery, for IBD compared to White patients with IBD, despite similar disease phenotype characteristics. Disparities in access to care may be contributory toward these findings and efforts should be made to provide equitable care to all persons living with IBD, regardless of race and ethnicity. Please acknowledge all funding agencies by checking the applicable boxes below Other Please indicate your source of funding below: Nil Disclosure of Interest None Declared
Detection of viable viruses in the air is critical in order to determine the level of risk associated with the airborne diffusion of viruses. Different methods have been developed for the isolation, purification, and detection of viable airborne viruses, but they require an extensive processing time and often present limitations including low physical efficiency (i.e., the amount of collected viruses), low biological efficiency (i.e., the number of viable viruses), or a combination of all. To mitigate such limitations, we have employed an efficient technique based on the magnetic levitation (Maglev) technique with a paramagnetic solution and successfully identified distinct variations in levitation and density characteristics among bacteria (Escherichia coli), phages (MS2), and human viruses (SARS-CoV-2 and influenza H1N1). Notably, the Maglev approach enabled a significant enrichment of viable airborne viruses in air samples. Furthermore, the enriched viruses obtained through Maglev exhibited high purity, rendering them suitable for direct utilization in subsequent analyses such as reverse transcription-polymerase chain reaction (RT-PCR) or colorimetric assays. The system is portable, easy to use, and cost-efficient and can potentially provide proactive surveillance data for monitoring future outbreaks of airborne infectious diseases and allow for the induction of various preventative and mitigative measures.
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