Sepideh Pakpour

The intestinal mucus network, primarily composed of O -glycosylated MUC2 mucin polymers, is essential for protecting the gastrointestinal tract from microbial threats. Sialic acid (Sia), a terminal monosaccharide on complex O -glycans, plays a key role in maintaining mucus integrity and is frequently modified by Casd1-dependent O -acetylation ( O Ac). Despite its prevalence, the biological significance of sialic acid O Ac ( O Ac-Sia) modifications in human and murine mucus remains unclear. We hypothesized that O Ac-Sia variants on mucus interact with the microbiota and are required for optimal mucus barrier function and host-microbe homeostasis in the colon. To test this, we profiled O Ac-Sia on human and mouse MUC2 in situ using viral-derived probes with bacterial FISH and confocal microscopy; generated intestinal epithelial cell (IEC)-specific Casd1 null mice (IEC Casd1 ^-/- ); performed sialylomic and O -glycomic HPLC-MS analyses; assessed microbial communities by 16S rRNA sequencing with quantitative microbial profiling (QMP); and evaluated disease susceptibility using DSS colitis and Citrobacter rodentium infection models. Results revealed that both human and murine mucins are extensively O -acetylated and interact with the microbiota, suggesting biological relevance. IEC Casd1 ^-/- mice were viable and displayed a complete loss of mucin O Ac-Sia, indicating Casd1 is the sole contributor to O Ac-status. Unexpectedly, mucus function was intact in IEC Casd1 ^-/- mice, with no difference in structure or quality vs. WT co-housed littermates.16S rRNA analysis showed a modest but significant sex-specific reduction of microbial loads in male IEC Casd1 ^-/- mice, and a clear trend toward reduced Turicibacter spp. vs. WT mice in both male and females, without impacting overall short-chain fatty acid (SCFA) production. DSS treatment led to more severe and extensive tissue damage in IEC Casd1 ^-/- mice. C. rodentium infection led to increased damage in the cecum and distal colon of IEC Casd1 ^-/- mice without affecting pathogen load, suggesting that O Ac-Sia status has a role in tolerance defense. These findings establish intestinal epithelial Sia O -acetylation as a component dispensable for mucus and host-microbe homeostasis at baseline, but important in limiting damage to mucosal inflammatory insults.

Airborne cellulosic fibers (CFs) and microplastics (MPs) are emerging pollutants with potential environmental and health implications. This study presents an active sampling‐based characterization of airborne CFs and MPs in Western Canada, focusing on a university campus in Kelowna. Sampling was conducted from September 2021 to October 2022, on three separate days each month, using a BioSampler operated at 12.5 L/min, across one outdoor site and three indoor locations (cafeteria, gym laundry, and manufacturing shop). Outdoor environments exhibited higher concentrations of both total particles (CFs and MPs combined, 31.4 ± 46.9 particles/m ³ ) and MPs (5.67 ± 8.82 MPs/m ³ ) compared to indoor air (13.7 ± 12.1 particles/m ³ and 2.89 ± 4.72 MPs/m ³ ). CFs dominated total particle counts, while MPs were predominantly fragments and fibers, suggesting differential sources and fragmentation processes. Polymer identification using μ ‐FTIR spectroscopy revealed that polyester and polyamide were most prevalent across all locations, likely reflecting contributions from synthetic textiles and clothing, which are known sources of airborne MPs. Smaller contributions from other polymer types suggest the presence of additional location‐specific sources. Seasonal variations were also observed, with indoor MP concentrations peaking in summer, likely influenced by regional wildfires and the associated increase in indoor activities. Higher levels were additionally observed in winter at locations with increased fabric handling and material processing. These findings highlight the pervasive nature of airborne particles, even in smaller cities with localized sources. This study underscores the importance of targeted mitigation strategies and further research to understand the implications of chronic exposure to these pollutants on environmental and human health.

Background: The escalating accumulation of micro- and nanoplastics (MNPs) in the environment has raised significant concerns regarding their neurotoxic potential in vertebrates. This critical review synthesizes evidence from 234 original research articles across aquatic and terrestrial models, as well as in vitro systems, to evaluate the impacts of MNPs on the brain. Main body: Emerging data suggest that MNPs may reach the brain via olfactory translocation or by penetrating the blood–brain barrier, potentially facilitated by biomolecular corona formation. However, distribution kinetics, long-term retention, and true internal exposure levels remain unresolved. We highlight that neurotoxic outcomes, such as oxidative stress, cholinergic dysfunction, neurotransmitter imbalances, and neuronal apoptosis, vary widely depending on particle size, shape, polymer type, exposure concentration, and host species. Nevertheless, inconsistencies across models and experimental conditions, such as mismatches between oxidative stress markers and behavioral effects or lack of dose-response relationships, hinder mechanistic clarity and translational relevance to human health. Notably, most current studies employ spherical polystyrene particles at supraphysiological concentrations, limiting ecological and clinical extrapolation. Interactions with microbial biofilms and host microbiota are largely unexplored, despite their probable role in modulating neurotoxicity via the gut–brain axis. Moreover, most studies rely on analytical methods validated only for microplastic detection, while robust, standardized approaches for identifying nanoplastics in environmental and biological matrices remain lacking. These gaps hinder accurate exposure quantification, obscure tissue-specific accumulation patterns, and complicate human health risk estimation. Conclusion: To advance the field, we recommend comprehensive physicochemical characterization of MNPs, adoption of environmentally relevant exposure scenarios, inclusion of diverse polymer types and shapes, and mechanistic integration through multi-omics and adverse outcome pathway frameworks. Addressing these challenges through harmonized methodologies and interdisciplinary collaboration is essential for developing predictive models of MNP-induced neurotoxicity and informing human health risk assessments. Graphical

Influenza claims over 290,000 lives annually, and the annual flu season remains a major public health challenge. Within the domain of health-focused architectural design, indoor daylight emerges as a potential shield against microbial threats. Yet, a significant gap in our understanding remains: the effect of indoor daylight on viruses. To bridge this knowledge gap, we used a living lab setup to investigate the impact of modulated indoor daylight on the stability of genomic material and persistence of infectivity of enveloped influenza A and B viruses, along with the non-enveloped bacteriophage MS2 on an environmental surface of glass. Indoor daylight modulation showed capacity for viral inactivation with differential activity depending on spectrum, intensity, and duration of exposure. Intensity was the most impactful, significantly reducing the infectivity of influenza A virus and both the infectivity and amount of recoverable genomic material of influenza B virus following 8 h of exposure. Even at low-intensity light, comparable to light passing through traditional blinds, spectrum-modulated, blue-enriched light significantly reduced the infectivity of influenza A and B within 8 h. Moreover, for all viruses, the infectivity declined before the stability of genomic material, suggesting a mechanism of photoinactivation via the disruption of viral proteins involved in infection. This research emphasizes the paramount importance of considering daylighting conditions as a strategic approach to control infectious disease transmission in built environments. Our findings not only underscore this significance but also offer innovative pathways to transform indoor spaces into safer, healthier environments for everyone. IMPORTANCE: This study examined the interplay between indoor daylighting and viruses, specifically influenza A, influenza B, and MS2 bacteriophage in a simulated indoor environment on a surface material of glass. It demonstrated that indoor daylight modulation was able to inactivate influenza A and B following 8 h of exposure at high-intensity and low-intensity blue-enriched light; however, the stability of genomic material of influenza A was unaffected until at least 24 h of exposure. These results, which focus on differences between stability of genomic material and infectivity, provide deeper insight into viral photoinactivation mechanisms, and the use of a living-lab setup lays the foundation for a framework for healthy building design using indoor daylight modulation for infection control.

Introduction: Fecal microbiota transplantation (FMT) is highly effective in preventing Clostridioides difficile recurrence by restoring gut microbiota composition and function. However, the impact of recent antibiotic use, a key exclusion criterion for stool donors, on gut microbiota recovery is poorly understood.Methods: We investigated microbial recovery dynamics following antibiotic use in three long-term stool donors from Canada and Finland. Using longitudinal stool sampling, metagenomic sequencing, and qPCR, we assessed changes in bacterial diversity, community composition, microbial functions, the gut phageome, and the risk of transmitting antibiotic-resistant genes (ARGs).Results: Antibiotics caused lasting disruption to bacterial communities, significantly reducing important taxa like Bifidobacterium bifidum, Blautia wexlerae, Akkermansia muciniphila, Eubacterium sp. CAG 180, and Eubacterium hallii, with effects persisting for months. Functional analyses revealed alterations in housekeeping genes critical for energy production and biosynthesis, with no direct links to key health-related pathways. Antibiotics also disrupted viral populations, decreasing diversity and increasing crAssphage abundance, reflecting disrupted host-bacteriophage dynamics. No significant increase in clinically important ARGs was detected.Discussion: These findings highlight the unpredictable and complex recovery of gut microbiota post-antibiotics. Individualized suspension periods in donor programs, guided by metagenomic analyses, are recommended to optimize FMT outcomes in various indications by considering antibiotic spectrum, duration, and host-specific factors.

Fecal microbiota transplantation (FMT) is the most effective therapy for preventing recurrent Clostridioides difficile infection (rCDI). However, the impact of FMT formulations and storage conditions on bacterial viability, community structure, functionality, and clinical efficacy remains under-investigated. We studied the effect of different storage conditions on the bacterial viability (live/dead staining and cell sorting), community structure (16S rDNA analysis), and metabolic functionality (fermentation) of frozen and lyophilized FMT formulations. The clinical success rates of rCDI patients were correlated retrospectively with FMT formulations, storage durations, and host factors using the Edmonton FMT program database. Bacterial viability remained at 10–20% across various storage conditions and formulations and was comparable to that of fresh FMT. Live and dead bacterial fractions in both frozen and lyophilized FMT preparations exhibited distinct community structures. Storage durations, but not temperatures, negatively affected bacterial diversity. More short-chain fatty acids were found in the metabolomic profiling of in vitro fermentation products using lyophilized than frozen FMT. Clinical success rates in 537 rCDI patients receiving a single dose of FMT were not significantly different among the three formulations. However, longer storage durations and advanced recipient age negatively impacted clinical efficacy. Together, our findings suggest that FMT formulations and storage durations should be considered when establishing guidelines for product shelf life for optimal treatment outcomes.

Fecal microbiota transplantation (FMT) is the most effective therapy for preventing recurrent Clostridioides difficile infection (rCDI). However, the impact of FMT formulations and storage conditions on bacterial viability, community structure, functionality, and clinical efficacy remains under-investigated. We studied the effect of different storage conditions on bacterial viability (live/dead staining and cell sorting), community structure (16S rDNA analysis), and metabolic functionality (fermentation) of frozen and lyophilized FMT formulations. Clinical success rates of rCDI patients were correlated retrospectively with FMT formulations, storage durations, and host factors using the Edmonton FMT program database. Bacterial viability remained at 10%–20% across various storage conditions and formulations and was comparable to that of fresh FMT. Live and dead bacterial fractions in both frozen and lyophilized FMT preparations exhibited distinct community structures. Storage durations, but not temperatures, negatively affected bacterial diversity. More short chain fatty acids were found in metabolomic profiling of in vitro fermentation products using lyophilized than frozen FMT. Clinical success rates in 537 rCDI patients receiving a single dose of FMT were not significantly different among the three formulations. However, longer storage durations and advanced recipient age negatively impacted clinical efficacy. Together, our findings suggest that FMT formulations and storage durations should be considered when establishing guidelines for product shelf life for optimal treatment outcomes.

Objective: Improving the hospital environment and developing novel disinfection strategies are critical for infection control in healthcare settings. In this study, we explored the effects of electrochromic (EC) windows on indoor and patient microbiome in an inpatient hospital. Patient and setting: Hematology-Oncology patients at the University of Vermont Medical Center Methods: We conducted a prospective study in ten occupied patient rooms. Five of the patient rooms had active EC windows that tint dynamically to control for heat and glare, and the other five rooms had deactivated EC windows that simulated traditional windows and blinds. Samples were collected one day before patient admission as baseline and on the 1st, 3rd, and 5th day of the patient stay. Total bacterial abundance and bacterial community structure were determined through quantitative PCR and 16s rRNA Illumina MiSeq sequencing, respectively. Results: Patient rooms with active EC windows had significantly lower light intensity and temperature than traditional patient rooms with blinds. The absolute bacterial abundance and diversities on windows were significantly lower in rooms with EC windows and the bacterial composition changed after one day EC window activation. Compared to baseline, relative abundance of the Staphylococcus genus was significantly lower on EC window surface during the five-day experiment. In contrast, the air microbiome was more diverse in rooms with EC windows. Conclusion: Active electrochromic (EC) windows in patient rooms result in lower light intensity and temperature, reduced bacterial abundance and diversities on window surfaces, and a more diverse air microbiome, informing future healthcare design.