Biology subjects

Okyere, L.

Publications and source records attributed to Okyere, L..

6 recordsLinked to original sources

bioRxiv2026

Over-the-counter fiber supplementation associates with metabolic and microbial shifts in rectal mucosa

Fiber supplements are the first line of treatment for all patients with benign anorectal disease. In addition, fiber has been found to support gut microbiota and reduce inflammation; however, their integrated effect on the colonic mucosal environment is incompletely defined. We evaluated how mixed-fiber formulations may collectively shape the rectal mucosal environment through coordinated effects on microbiota composition, short-chain fatty acid (SCFA) handling, and host transcription. We evaluated multi-compartment responses to a 28-day mixed-fiber intervention in 37 participants with benign anorectal disease (~15 g/day; 7.5g psyllium husk, 8g wheat dextrin) and assessed the microbiota (16S rRNA), the metabolome (GC-MS and LC-MS), and transcriptome (subset n=10) before (PRE) and after (POST) supplementation. Changes in KEGG pathways were tested with gene set enrichment analysis (GSEA). Associations were tested by Spearman correlation, and microbiota-based prediction of SCFA responses by random-forest regression. Microbiota diversity was stable after the fiber intervention, however, 10 mucosal ASVs were differentially abundant including Parabacteroides and Lachnospiraceae NK4A136 group while SCFAs, propionate and isobutyrate, both decreased in rectal tissue and butyrate decreased in serum. To understand these shifts in the metabolome, we proceeded with the transcriptome where we identified 130 differentially expressed genes and enrichment of metabolic and SCFA-related pathways. Random forest regression captured a modest signal for serum butyrate. Taken together, short-term mixed-fiber supplementation produced selective rectal mucosal taxonomic shifts and enriched mucosal metabolic and SCFA-metabolism program despite reduced SCFA pools, suggesting that even brief over-the-counter fiber supplementation may reshape the mucosal metabolic environment.

microbiology↗

bioRxiv2026

Sex-stratified Gut Microbiome Disruption is Associated with Altered Hepatic Gene Expression during Acute Azoxystrobin Exposure

Azoxystrobin is a widely used fungicide that has been associated with to reproductive, neurological, and developmental defects. This chemical also disrupts gut microbial communities; however, if these perturbations contribute to the harms associated with exposure to azoxystrobin, this remains unclear. In this study, we investigated the effects of acute exposure to a series of concentrations (5-500 mg/kg) of azoxystrobin on the host and gut microbiota in zebrafish. Fecal amplicon and shotgun metagenomic sequencing was integrated with liver gene expression to quantify associations between microbiome disruption azoxystrobin toxicity in the host. Azoxystrobin exposure resulted in significant alteration in microbiome composition and functional potential in a dose- and sex-dependent manner. Microbial communities in exposed animals exhibited an increased abundance of xenobiotic metabolism pathways and decreased bacterial motility and lipopolysaccharide biosynthesis pathway metabolism. At the host level, histopathology identified increased biliary proliferation, most evident in medium- and high-dose fish. We also observed hepatic transcriptional changes consistent with a stress response, including altered redox-associated genes and reduced expression of lipid and small-molecule metabolic genes, with sex-stratified differences. Importantly, alterations in host transcriptional programming correlated with the compositional changes in exposed microbiota. Together, these results suggest concurrent impacts of azoxystrobin on gut microbiota and the liver implicate the microbiome as a potential contributor to changes in liver gene expression during exposure. ImportanceWidespread fungicide use contaminates ecosystems worldwide, but the biological pathways underlying their effects on humans and other animals are not well understood. Using zebrafish (Danio rerio), we found that short-term exposure to the fungicide azoxystrobin was associated with changes in the gut microbiome, liver gene activity, and liver changes. Exposure produced dose- and sex-dependent shifts in microbial communities, including changes in predicted microbial functions involved in chemical metabolism, bacterial motility and defense. Compositional changes in the microbiome correlated with gene-expression changes consistent with stress and altered metabolism in exposed fish, suggesting that exposure induced disruption may contribute to exposure impact to the host. These results highlight a potential role for the microbiome in mediation of the impacts of azoxystrobin on host physiology. As such microbial based interventions could be a viable strategy to mitigate exposure impacts on health.

microbiology↗

bioRxiv2025

Long Term Culture of Germ-Free Zebrafish Using Gamma-Irradiated Feeds

Host associated microbiota play essential roles in regulating digestion, nutrient acquisition, immunity, and xenobiotic metabolism. Disruption of these communities is linked to numerous diseases and health defects though causal mechanisms underpinning these associations remain unclear in most cases. Gnotobiotic zebrafish provide a scalable low-cost in vivo model that is increasingly used to resolve causality in host-microbiota interactions. However, reliance on live diets limits the use of gnotobiotic zebrafish to early life stages where body systems and microbial communities are incompletely developed. As a result, many important host-microbiota interactions may be unable to be studied in this model system. Here we tested a simple method for long-term husbandry of gnotobiotic zebrafish using gamma-irradiated chow diets and evaluated effects on growth, gene expression, and microbial community composition. In conventionally reared animals, gamma irradiated diets did not affect growth or survival and only modestly impacted microbial community composition and diversity. In contrast, gnotobiotic zebrafish maintained on sterile irradiated diets for 55 days post fertilization were smaller, weighed less, and exhibited aberrant genes expression profiles relative to controls. These genes were enriched for pathways, related to immune response, xenobiotic metabolism, organ development, liver function, and lipid metabolism, with many expression patterns linked to the abundance of specific microbial taxa. Together, these findings establish a practical protocol for long-term maintenance of gnotobiotic zebrafish and extend the utility of this model to study microbiome-dependent effects on host physiology, and development beyond early larval stages of life. IMPORTANCEWhile the gnotobiotic zebrafish have been a powerful model for interrogation of host-microbiota interactions, their use has been limited to early life stages due to complications of long-term husbandry. To address this limitation, we developed a simple protocol that enables rearing germ-free zebrafish well beyond larval stages. Germ free fish exhibit physiological and developmental defects that mirror those described in mammalian counterparts supporting a conserved role for microbiota in vertebrate development and physiology. Our protocol provides a method to investigate microbial influences on adaptive immunity, metabolism, and chronic disease processes in zebrafish not possible with current methodologies. Given the rapid and simple methods for gnotobiotic derivation and the large number of transgenic animal lines available for zebrafish we anticipate this model will accelerate mechanistic discovery of microbial impacts on host health.

microbiology↗

bioRxiv2025

Influence of Housing, Sex, and Sampling Location on Taxonomy and Function of Adult Zebrafish Microbiomes

The zebrafish (Danio rerio) has emerged as an important animal model for the study of host-microbiome interactions. However, information on how variation in experimental parameters contribute to microbiome structure and function in adult zebrafish is limited which complicates experimental design, interpretation of results, and may reduce reproducibility. Here we quantified the impact of two potential sources of microbiome variation - housing strategy and sampling location - on microbial diversity of adult zebrafish using 16S rRNA amplicon sequencing. Our findings indicate that housing strategy significantly impacts gut microbiome diversity in adult fish with the highest similarity between individuals co-housed on recirculating water systems. Microbiome acclimation after housing transfer took between 14- and 21-days. Significant variation in microbiome composition was also observed across sampling sites. As in humans, fecal and intestinal microbial communities were similar and varied by sex, however each body site sampled possessed a small site-specific microbial community signature. Consistently, imputed function of these communities showed that gene family diversity is also predicted to vary by body site particularly between gut and non-gut locations. Together our work demonstrates that housing, sex, and sampling strategy all significantly impact microbial community composition and highlight the need for community wide discussions on best practices and reporting standards for adult zebrafish microbiome studies.

microbiology↗

bioRxiv2024

Two Key Actinomycetota Taxa in the Human Gut Microbiota are Associated with Schistosoma mansoni Infection Burden

In this study, we sought to identify key microbial taxa associated with human gut dysbiosis during S. mansoni infection and whether the changes are linked to the intensity of helminth infection. Stool samples were obtained from 20 persons infected with schistosomiasis and an equal number of uninfected persons from an endemic rural community in Ghana. Infection intensity was scored as egg count per gram (EPG) using the Kato-Katz method. Positive stool samples were further stratified as low-moderate (<400 EPG, n=15) and high (>400 EPG, n=5) infection burden. The composition and diversity of the gut microbiota and potential microbial markers associated with S. mansoni infection intensity were determined from 16S rRNA amplicon sequence analyses. No difference in {beta}-diversity was observed between positives and negatives (PERMANOVA: R2= 0.012, p= 0.723), although there was an increased abundance of Bifidobacterium (p= 0.008) in infected stool samples compared to the negatives. Further analyses showed that Bifidobacterium (p= 0.003) and Collinsella (p= 0.029) were elevated considerably among the low-moderate infected samples, while the pathobiont Escherichia-Shigella was reduced (p= 0.0078). Our findings show that intestinal schistosomiasis results in human gut microbiota dysbiosis, which is only distinguished when the intensity of infection is considered, with two key Actinomycetota species assuming importance depending on the infection burden. Author SummaryThis study investigates the relationship between Schistosoma mansoni infections, a major cause of intestinal schistosomiasis, and the human gut microbiome. Using samples from an endemic region in Ghana, the research examines how infection intensity impacts gut bacteria. The findings reveal that certain beneficial bacteria, such as Bifidobacterium and Collinsella, become more abundant in cases of low to moderate infection, potentially maintaining immune regulation and gut health. However, these effects are not seen in high-infection instances, possibly due to the aggressive hallmarks of high-intensity helminth infections. Understanding these dynamics could be pivotal for developing microbiome-based interventions to improve treatment outcomes for schistosomiasis and similar parasitic infections. This study sheds light on the complex interplay between infectious parasites and gut microbes, emphasising the promise of microbiome research in enhancing public health efforts in areas where parasitic diseases persist.

genomics↗

bioRxiv2024

Portal bile acids and microbiota along the murine intestinal tract exhibit sex differences in physiology

Microbes in the intestine transform bile acids during transit, altering their functional and signaling capacities before absorption into the portal vein. Sex differences in the gut microbiota have been noted, but their consequence on bile acid composition is unclear. Here, we investigated the composition and imputed functional potential of microbes in the small and large intestine together with portal and systemic bile acids. Female and male mice exhibit distinct microbial diversity throughout the length of the intestine leading to dimorphism in genes related to bile acid transformation. Subsequently, we found that the total portal bile acid concentrations were doubled in female mice compared to males. Conversely, oxo-bile acids that are rare in systemic circulation represented almost 30 percent of the portal pool in the male mice. Oxo- and deconjugated-bile acids were absent in germ-free mice consistent with microbe-mediated bile acid transformation. More importantly, gnotobiotic mice do not show sex differences in portal bile acids. Taken together, we demonstrate that sex differences in gut microbiota cause dimorphism in bile acid levels within the enterohepatic loop. HighlightsO_LIMurine microbial diversity exhibits sex-specific patterns along the small intestinal tract and colon. C_LIO_LIDistinct gut microbial profiles confer differential abundance of secondary bile acid metabolism genes in male and female mice. C_LIO_LIPortal bile acid compositions mirror sex differences in microbe-mediated bile acid processing that are lost in germ free conditions. C_LI

physiology↗