Biology subjects

Pakpour, S.

Publications and source records attributed to Pakpour, S..

4 recordsLinked to original sources

bioRxiv2026

Intestinal epithelial Casd1 influences mucus sialic acid O-acetylation and tissue damage susceptibility toward large-intestinal mucosal insults.

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 (OAc). Despite its prevalence, the biological significance of sialic acid OAc (OAc-Sia) modifications in human and murine mucus remains unclear. We hypothesized that OAc-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 OAc-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 OAc-Sia, indicating Casd1 is the sole contributor to OAc-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 OAc-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.

cell biology↗

bioRxiv2024

The transition from a non-westernized to westernized gut microbiome in Indian-Immigrants and Indo-Canadians is associated with dietary acculturation

Indian immigration to westernized countries has recently surged, increasing their risk of Inflammatory Bowel Disease (IBD) post-migration. While crucial for understanding IBD risk, the gut microbiome remains understudied in Indians. This cross-sectional study examines the gut microbiomes of Indians residing in India, Indo-Immigrants, and Indo-Canadians in comparison to Euro-Canadian and Euro-Immigrant controls to understand the impact of westernization on their gut. Stool samples for 16S rRNA and shotgun sequencing assessed microbial taxa and functional profiles, complemented by dietary and demographic data to evaluate lifestyle patterns. Results revealed distinct microbiotas in Indians and Indo-Immigrants compared to control groups, with high abundances of Prevotella spp. and CAZymes reflecting their high complex carbohydrate diet. Indo-Canadians exhibited a transitional microbiome towards westernization, mirroring increasing dietary acculturation. Considering 44% of Canadians are first- and second-generation immigrants and the global adoption of westernized practices, future research should investigate the health implications of such microbiome transitions in immigrant populations and newly industrialized nations.

microbiology↗

bioRxiv2022

The effect of indoor daylight spectrum and intensity on viability of indoor pathogens on different surface materials

Built environments play a key role in the transmission of infectious diseases. Ventilation rates, air temperature and humidity affect airborne transmission while cleaning protocols, material properties and light exposure can influence viability of pathogens on surfaces. We investigated how indoor daylight intensity and spectrum through electrochromic (EC) windows can impact the growth rate and viability of indoor pathogens on different surface materials (polyvinyl chloride (PVC) fabric, polystyrene (PS), and glass) compared to traditional blinds. Our results showed that tinted EC windows let in higher energy, shorter wavelength daylight than those with clear window and blind. The growth rates of pathogenic bacteria and fungi were significantly lower in spaces with EC windows compared to blinds: nearly 100% growth rate reduction was observed when EC windows were in their clear state followed by 41-100% reduction in bacterial growth rate and 26-42% reduction in fungal growth rate when EC windows were in their darkest tint. Moreover, bacterial viabilities were significantly lower on PVC fabric when they were exposed to indoor light at EC-tinted window. These findings are deemed fundamental to the design of healthy modern buildings, especially those that encompass sick and vulnerable individuals. PO_SCPLOWRACTICALC_SCPLOW IO_SCPLOWMPLICATIONSC_SCPLOWO_LILight is an important factor that influences occupant health. C_LIO_LIHealthcare Associated Infections (HAI) bring substantial costs on the healthcare systems hence new disinfection methods are always needed to minimize fomites especially with the increasing antibiotic resistance. C_LIO_LIWe found that indoor light modulated by the EC smart windows can significantly reduce the growth rate and viability of pathogenic bacteria and fungi, which is mainly due to the high energy blue light spectrum at wavelength of 400-500nm. C_LIO_LIPathogenic fungi are found to be more affected by the indoor light intensity, while indoor bacteria on surfaces are more susceptible to the light spectrums. C_LIO_LIThese results also demonstrate the promising potential of indoor daylight exposure as an alternative for fomite disinfection strategy and expand the benefits of EC window as part of healthy building design in the future. C_LI

microbiology↗

bioRxiv2020

Fecal microbiota transplantation efficacy for Clostridium difficile infection: A trans-kingdom battle between donor and recipient gut microbiomes

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 Clostridium difficile infections (rCDI) and other dysbiosis-related conditions. In a single cohort 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 methods, our results suggested that the FMT outcome is not only dependent on the ecological structure of the recipients, but also the interactions between the donor and recipient microbiomes, both at the taxonomical and functional levels. Importantly, we observed that the presence of specific bacteria in donors (Clostridiodes spp., Desulfovibrio spp., Odoribacter spp. and Oscillibacter spp.) and the absence of specific fungi (Yarrowia spp.) and bacteria (Wigglesworthia spp.) in recipients prior to FMT could accurately predict FMT success. Our results also suggested a series of interlocked mechanisms for FMT success, including the repair of the disturbed gut microbial ecosystem by transient colonization of nexus species followed by secondary succession of bile acid metabolizers, sporulators, and short chain fatty acid producers. Therefore, a better understanding of such mechanisms can be fundamental key elements to develop adaptive, personalized microbial-based strategies for the restoration of the gut ecosystem. ImportanceThere have been a number of studies focusing on understanding the underlying mechanisms in FMT treatment, which can accordingly be used for the optimization of future treatments. However, the current scientific lens has mainly had a uni-kingdom major focus on bacteria, leading to the proposition of the existence of FMT "super-donors". On the contrary, our preliminary study here suggests that FMT is not necessarily a one stool fits all approach and that donor-recipient cross-kingdom microbiota interactions, along with their short-term fluctuations in the gut, bring profound implications in FMT success. The results also conceptualize a series of interlocked mechanisms for FMT success, including first repairing the disturbed gut microbial ecosystem by transient species, followed by secondary succession of indigenous or exogenous bile acid metabolizers, sporulators, and short chain fatty acid producers.

microbiology↗