Biology subjects

Joyce, P.

Publications and source records attributed to Joyce, P..

4 recordsLinked to original sources

bioRxiv2026

Spray Dried Inulin-Montmorillonite Hybrids Alleviate High-Fat Diet-Induced Inflammatory and Metabolic Dysregulation in Rats

Obesity-related metabolic disorders are linked to excessive dietary lipid absorption and gut microbiota imbalances, particularly under high-fat diet (HFD) conditions. This study evaluates a spray-dried hybrid of inulin and montmorillonite (INU-MMT) designed to concurrently restrict intestinal lipid digestion and modulate the gut microbiota. Using an in vitro simulated intestinal lipolysis model, INU-MMT significantly reduced free fatty acid (FFA) release from medium-chain triglycerides by 4.0-fold compared to HFD conditions, outperforming INU and MMT individually. This superior inhibition is attributed to INUs ability to prevent MMT aggregation, resulting in smaller, more dispersed particles with enhanced lipid-binding capacity. In a 21-day in vivo study in HFD-fed rats, INU-MMT (1g/kg bodyweight/d) supplementation significantly attenuated cumulative weight gain by 4.7% compared to the HFD control, exceeding the effects of INU (2.0%) and MMT (1.5%) alone. 16S rRNA gene sequencing of fecal samples revealed improved gut microbial diversity (Simpsons index, p = 0.0161) and enrichment of health-associated taxa including Peptostreptococcaceae (8-fold), Ruminococcaceae (3.5-fold), Akkermansiaceae (2.5-fold), and Eggerthellaceae (7.7-fold). Beta diversity analysis highlighted that INU-MMT induced a distinct microbial composition from HFD and INU groups (PERMANOVA, adjusted p < 0.05), driven largely by MMT. Predictive metagenomic analysis using the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States 2 (PICRUSt2) software demonstrated a 98% reduction in microbial triacylglycerol lipase abundance, aligning with the observed in vitro lipolysis suppression results. These findings highlight the dual-mechanistic potential of INU-MMT in managing diet-induced obesity by targeting lipid digestion and imbalances within the gut microbiota. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=113 SRC="FIGDIR/small/701174v1_ufig1.gif" ALT="Figure 1"> View larger version (43K): org.highwire.dtl.DTLVardef@1d2c787org.highwire.dtl.DTLVardef@1298bacorg.highwire.dtl.DTLVardef@90da36org.highwire.dtl.DTLVardef@1e6271c_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LISpray-dried INU-MMT restricts FFA release 4-fold in intestinal conditions C_LIO_LIHybrid outperforms INU and MMT in reducing HFD-induced weight gain in rats C_LIO_LIPromotes beneficial microbiota shifts and key SCFA-producing taxa C_LIO_LISuppressed predicted microbial lipase levels by 98% with INU-MMT treatment C_LIO_LIINU-MMT offers a multi-mechanistic strategy for future metabolic disease therapies. C_LI

bioengineering↗

bioRxiv2024

Prebiotic Supplementation Modulates the Gut Microbiome for Improving Oral Antipsychotic Bioavailability

Atypical antipsychotics are crucial for the management of schizophrenia and bipolar disorder, yet they exhibit significant pharmacokinetic variability which leads to inconsistent therapeutic responses. This study investigates the hypothesis that gut microbiome composition critically influences the oral bioavailability of lurasidone, a poorly soluble weak base antipsychotic with pH-dependent solubility. To investigate this, male Sprague-Dawley rats underwent systematic gut microbiome manipulation through pretreatment with antibiotics or prebiotics (inulin) for 14 days prior to a single oral dose of lurasidone. Pharmacokinetic analysis of collected plasma samples revealed a significant 4.3-fold increase in lurasidone bioavailability following prebiotic pretreatment, compared to a control (no pretreatment) group. Conversely, lurasidone bioavailability was highly variable in rats with a depleted microbiome (i.e., antibiotic treatment group), with 80% of animals demonstrating lower bioavailability than the control group. Characterisation of gut microbiome composition and short-chain fatty acid (SCFA) concentrations demonstrated positive correlations between lurasidone bioavailability, microbial diversity, and SCFA levels, mediated by modulation of luminal pH. Elevated SCFA levels created a favourable environment for lurasidone solubilisation by lowering intestinal pH. These findings highlight the potential for optimising antipsychotic pharmacokinetics through personalised microbiome interventions. Furthermore, the correlation between SCFAs and lurasidone bioavailability suggests their potential as biomarkers for predicting inter-patient pharmacokinetic variability, particularly for poorly soluble weak bases. Thus, new avenues are opened for developing novel co-therapies and screening tools to enhance antipsychotic pharmacokinetic performance, potentially improving treatment outcomes for patients with schizophrenia and bipolar disorder. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=108 SRC="FIGDIR/small/604016v2_ufig1.gif" ALT="Figure 1"> View larger version (37K): org.highwire.dtl.DTLVardef@7dac6borg.highwire.dtl.DTLVardef@c2cf1corg.highwire.dtl.DTLVardef@1ab5460org.highwire.dtl.DTLVardef@130ab14_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗

bioRxiv2024

The atypical antipsychotic lurasidone positively modulates the gut microbiota in rats: A comparative study to olanzapine

Background and PurposeAntipsychotics like olanzapine are associated with significant metabolic dysfunction, attributable to gut microbiota dysbiosis. A recent notion that most psychotropics are detrimental to the gut microbiota has arisen from consistent findings of metabolic adverse effects. However, unlike olanzapine, the metabolic effects of lurasidone are conflicting, with most reports observing weight loss rather than gain. Thus, this study investigates the contrasting effects of olanzapine and lurasidone on the gut microbiota to explore the hypothesis of "gut neutrality" for lurasidone exposure. Experimental ApproachUsing a Sprague-Dawley rat model, the impact of olanzapine and lurasidone administration on the gut microbiota was explored. Faecal and blood samples were collected weekly over a 21-day period to analyse changes to the gut microbiota and related metabolic markers. Key ResultsLurasidone triggered no significant weight gain or metabolic alterations, instead positively modulating gut microbiota through increases in mean OTUs (+50 OTUs) and alpha diversity (+0.5 increase in Shannons index). This novel finding suggests an underlying mechanism for lurasidones metabolic inertia. In contrast, olanzapine triggered a statistically significant decrease in mean OTUs (-75 OTUs) and substantial compositional variation, suggesting a decrease in microbial richness. Microbiota alterations correlated with metabolic dysfunction, evidenced through a statistically significant 30% increase in weight gain, increase in pro-inflammatory cytokine expression, and increase in blood triglycerides and glycaemic levels. Conclusion and ImplicationsThe study challenges the notion that all antipsychotics disrupt the gut microbiota similarly and highlights the potential benefits of gut positive or neutral antipsychotics like lurasidone in managing metabolic side effects. Further research is warranted to validate these findings in humans to guide personalised pharmacological treatment regimens for schizophrenia. Bullet point summary- What is already known: O_LIOlanzapine induces weight gain by disrupting the gut microbiome. C_LIO_LIThe impact of lurasidone on the gut microbiome is unknown and weight gaining propensities unclear. C_LI - What this study adds: O_LILurasidone positively modulates gut microbiota through enhancement of microbial diversity and richness. C_LIO_LIPotential mechanisms underlying lurasidones weight and metabolic neutrality are elucidated. C_LI - Clinical significance: O_LIGut neutral antipsychotics like lurasidone could be favourable alternatives for patients unable to tolerate olanzapine. C_LIO_LIPersonalised treatment for schizophrenia considering individual sensitivities to metabolic effects is emphasised. C_LI

pharmacology and toxicology↗

bioRxiv2017

Selecting among three basic fitness landscape models: additive, multiplicative and stickbreaking

Fitness landscapes map genotypes to organismal fitness. Their topography depends on how mutational effects interact-epistasis-and is important for understanding evolutionary processes such as speciation, the rate of adaptation, the advantage of recombination, and predictability versus stochasticity of evolution. The growing amount of empirical data has made it possible to better test landscape models empirically. We argue that this endeavor will benefit from the development and use of meaningful null models against which to compare more complex models. Here we develop statistical and computational methods for fitting fitness data from mutation combinatorial networks to three simple models: additive, multiplicative and stickbreaking. We employ a Bayesian framework for doing model selection. Using simulations, we demonstrate that our methods work and we explore their statistical performance: bias, error, and the power to discriminate among models. We then illustrate our approach and its flexibility by analyzing several previously published datasets. An R-package that implements our methods is available in the CRAN repository under the name Stickbreaker.

evolutionary biology↗