Biology subjects

Wardill, H. R.

Publications and source records attributed to Wardill, H. R..

4 recordsLinked to original sources

bioRxiv2026

Gut-immune signaling drives blood-brain barrier damage in pediatric allogeneic stem cell transplant

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a life-saving therapy for children with high-risk hematological diseases. However, allo-HSCT also confers the risk of long-term neurocognitive dysfunction, particularly in pediatric recipients, and the mechanisms underlying this remain poorly understood. While gastrointestinal toxicities and immune responses following allo-HSCT have been well characterized, their contribution to central nervous system toxicities is unknown. Here, using clinical biomarker analysis, we show evidence of blood-brain barrier (BBB) dysfunction in pediatric allo-HSCT, associated with IL-6 signaling and reduced levels of brain-derived neurotrophic factor. Pre-transplant gastrointestinal mucosal barrier injury was associated with post-transplant BBB leakage, implicating disrupted gut-brain-axis signaling. In vitro, gut damage-associated immune activation induced apoptosis and remodeling of brain microvascular endothelial cells (BMECs), with surviving cells exhibiting tight junction disruption and cytoskeletal reorganization. Plasma from allo-HSCT recipients similarly induced BMEC apoptosis. Notably, both immune signaling- and patient plasma-induced BMEC apoptosis were prevented by IL-6 inhibition or supplementation with the gut microbiota-derived metabolite propionate. Together, these findings identify immune signaling as a correlate of BBB damage clinically and a causative driver in vitro in pediatric allo-HSCT.

neuroscience↗

bioRxiv2026

OpusTaxa: A Unified Workflow for Taxonomic Profiling, Assembly, and Functional Analysis of Shotgun Metagenomes

Shotgun metagenomics has become a cornerstone of microbiome research, yet the complexity of existing workflows remains a major barrier for life scientists without dedicated bioinformatics support. Manual database setup, detailed sample sheet preparation, and management of software dependencies can make routine analysis difficult and time-consuming. Cross-study comparisons are further hampered by inconsistent processing pipelines, database versions, and profiling strategies, limiting reproducibility and the potential for large-scale meta-analyses. We present OpusTaxa, an open-source Snakemake workflow that provides end-to-end processing of short paired-end shotgun metagenomic data with minimal configuration. Users provide either FASTQ files or Sequence Read Archive accessions; OpusTaxa automatically downloads required databases, performs quality control, removes host reads, and executes taxonomic profiling, metagenome assembly, and functional analysis. All analysis modules can be independently toggled, and per-sample outputs are automatically merged into harmonised, cross-sample tables ready for downstream exploration. Across two public datasets, we demonstrate how OpusTaxa can be used to compare consistency across complementary taxonomic profilers and to estimate microbial load in addition to standard metagenomic workflows. AvailabilityOpusTaxa is freely available at https://github.com/yenkaiC/OpusTaxa. Documentation, test data, and example configurations are included in the repository.

bioinformatics↗

bioRxiv2026

Micro-engineered Konjac Glucomannan-Montmorillonite Hybrids as Multifunctional Biomaterials for Addressing Diet-Induced Obesity in Mice

The growing prevalence of obesity necessitates innovative treatments. This study investigates a spray-dried konjac glucomannan-montmorillonite (KGM-MMT) hybrid designed to combine the fermentable, satiety-promoting effects of KGM with the lipid-binding and anti-inflammatory properties of MMT. In HFD-fed mice treated for 42 days with 2% w/w KGM-MMT, body weight gain was reduced by 7.6%, with an AUC of 5094[{+/-}[52.95, compared to 5513[{+/-}[81.35 in HFD controls (p < 0.0001). Serum IL-6 concentrations were reduced by 97% (p = 0.0002), while blood glucose decreased by 46% (p < 0.0001), outperforming reductions seen with MMT (24%, p = 0.0271) and KGM (16%, ns). Gut microbiota profiling demonstrated a significant 6.2-log[ fold increase in Lactobacillaceae (p = 0.023) and a 2.4-log[ fold increase in Enterococcaceae (p = 0.015) with KGM-MMT treatment. Predicted functional shifts revealed a 1.9-fold increase in short-chain fatty acid synthesis pathways and a 5.4-fold increase in bile acid deconjugation. Although the KGM-MMT hybrid did not consistently outperform its individual components in all measurements within the current study, it generally consolidated their metabolic benefits within a single dosage form. These findings support the utility of spray-dried KGM-MMT as a gut-targeted dietary strategy with additive effects on metabolic health. Future studies should explore underlying mechanisms and dosage effects of the hybrid formulation. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=110 SRC="FIGDIR/small/701163v1_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@738445org.highwire.dtl.DTLVardef@1f0d465org.highwire.dtl.DTLVardef@86e5aorg.highwire.dtl.DTLVardef@184fba8_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LISpray-dried KGM-MMT reduced HFD-induced weight gain by 7.6% in obese mice C_LIO_LISerum IL-6 and glucose levels decreased by 97% and 46%, respectively C_LIO_LI6.2-log[J and 2.4-log[J increases in Lactobacillaceae & Enterococcaceae relative abundance C_LIO_LIBile acid deconjugation and SCFA pathways increased 5.4- and 1.9-fold C_LIO_LIKGM-MMT microparticles offer additive gut-targeted benefits in metabolic disease C_LI

bioengineering↗

bioRxiv2019

TLR4 mediates Il-6 production in irinotecan induced mucositis

IntroductionIrinotecan is a first line chemotherapeutic agent for colorectal carcinoma and well known for debilitating diarrhoea caused by mucositis. Tlr4, a pattern recognition receptor, has been implicated in irinotecan -induced mucositis due to its activation of downstream inflammatory pathways and interaction with luminal microbes. Tlr4 deletion has been reported to attenuate mucosal injury in preclinical models of mucositis, hypothesised to occur by blockade of Il-6 production. As such, the current study aimed to determine the relationship between Tlr4 and Il-6 in the context of irinotecan induced mucositis.\n\nMaterials and methodsArchived ileum and colon tissues from BALB/c wild type (WT) and Tlr4 -/-billy (Tlr4 KO) female mice were used throughout the study. Mice had received single dose of irinotecan (i.p. 270 mg/kg) or vehicle and sacrificed at 6 and 72 hours. Il-6 mRNA and protein expression was determined by qPCR and immunofluorescence, respectively. Data was analysed by Kruskal-Wallis test (qPCR delta CT values) and one-way analysis of variance (ANOVA) (immunofluorescence % area stained).\n\nResultsIl-6 protein expression was significantly reduced in Tlr4 KO mice as compared to WT mice at 6 h in ileum and colon. mRNA expression was not significantly different between groups.\n\nConclusionThese findings support the hypothesis that Tlr4 deletion protects from irinotecan-induced mucositis by ameliorating Il-6 production. The effect appears to be post-transcriptionally mediated, although further research is required to determine if it is via a direct or indirect mechanism. In the future, Il-6 may be targeted therapeutically to ameliorate symptoms of mucositis.

physiology↗