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-log2 fold increase in Lactobacillaceae (p = 0.023) and a 2.4-log2 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. ### Competing Interest Statement The authors have declared no competing interest. Channel 7 Children's Research Foundation, https://ror.org/0592vaq06, 21-16816523 Hospital Research Foundation, https://ror.org/043ae3f44, 2022-CF-EMCR-004-25314

Semaglutide (SEM) is a glucagon-like peptide-1 (GLP-1) receptor agonist formulated for oral delivery with the absorption enhancer salcaprozate sodium (SNAC). Although oral SEM achieves 0.4-1% bioavailability through gastric epithelial uptake, gastrointestinal (GI) adverse events remain a major cause of therapy discontinuation. This study examined the effects of SEM (0.74 mg/kg/day), SNAC (22 mg/kg/day), and combined SEM-SNAC (1:33 w/w) treatments on microbiota and metabolic function, in healthy Sprague Dawley rats over 21 days. Whilst microbial α-diversity remained stable, SNAC significantly altered β-diversity (PERMANOVA, p < 0.05) and depleted primary fermenters in Muribaculaceae (-62%) and Bacteroidaceae (-77%) compared to the control group. These compositional changes correlated with reduced predicted saccharolytic enzyme abundance and fecal butyrate concentrations (-77% SNAC, -75% SEM-SNAC). Plasma cytokine analysis showed elevated tumor necrosis factor-α (TNF-α, 70%) and suppressed brain-derived neurotrophic factor (BDNF, 85%), consistent with changes in circulating inflammatory and neurotrophic markers from SNAC monotherapy. SNAC-treated animals also exhibited increased liver weight and reduced caecum mass, occurring alongside microbiota compositional changes and altered fermentation-associated markers. Spearman correlations linked Muribaculaceae and Bacteroidaceae loss with decreased saccharolytic enzyme abundance, lower SCFA levels, and increased TNF-α. While these findings are associative and require mechanistic validation, they indicate that chronic SNAC exposure is linked to concurrent microbial, metabolic, and inflammatory marker changes in healthy rats, highlighting the potential need for alternative, microbiota-safe strategies for oral peptide delivery.

Due in part to adsorption of apolipoprotein E (ApoE) and subsequent receptor-mediated uptake by hepatocytes, lipid nanoparticles (LNPs) have a propensity to accumulate within the liver. The mechanistic contribution of PEGylation to this phenomenon has yet to be fully elucidated. Using fluorescence quenching, circular dichroism spectroscopy, molecular dynamics simulations, and in vivo bioluminescence imaging, we investigated how PEGylation influences ApoE interactions with DC-Chol-based nanoparticles. Association studies revealed that non-PEGylated formulations bound ApoE ∼ 1.7-fold more strongly than particles with surface PEG moieties, quantified by Stern-Volmer constants of 0.083 vs. 0.048 μM-1, respectively. Circular dichroism measurements demonstrated a greater structural perturbation to ApoE upon binding to non-PEGylated particles (80% helical loss) versus PEGylated LNPs (24-48% helical loss). Molecular dynamics simulations showed that PEG-2000 creates a dynamic steric barrier that reduces direct protein-lipid contact formation by 2.9-fold and decreases the tendency of ApoE to remain closely associated with the nanoparticle surface. Correspondingly, biodistribution studies in mice showed rapid hepatic accumulation of non-PEGylated nanoparticles within 24 h, whereas PEGylated formulations exhibited delayed liver accumulation that became prominent at 48 h. Together, these findings indicate that PEGylation reduces ApoE association primarily through steric exclusion and highlight PEGylation as a useful strategy for modulating nanoparticle biodistribution.

INTRODUCTION:Nutraceuticals have garnered increasing scientific and commercial interest for their potential roles in health promotion, disease prevention and adjunctive disease management. However, the complex physicochemical and biological environment of the gastrointestinal (GI) tract presents formidable barriers to their effective oral delivery, contributing to a persistent gap between preclinical promise and clinical efficacy. A mechanistic understanding of GI physiology, nutraceutical-specific delivery challenges and available formulation strategies is therefore essential to advance the field. AREAS COVERED:Preclinical and clinical studies exploring the oral delivery of nutraceuticals were identified through targeted PubMed, Scopus and Web of Science searches to examine the GI tract as a dynamic delivery environment. Nutraceuticals are classified according to their primary delivery challenges, including lipophilicity, chemical and enzymatic lability and requirements for colon-targeted or microbiome-directed delivery. Formulation strategies are reviewed mechanistically, with particular attention to lipid-based systems, polymeric nanoparticles, hydrogel and hybrid biomaterials and colon-targeted delivery platforms. EXPERT OPINION:Advancing nutraceutical science requires moving toward a formulation-driven approach to overcome the biological barriers faced by oral delivery. There is a critical need for regulatory oversight to ensure that marketed claims are backed by scientific evidence relating to nutraceutical pharmacokinetics, pharmacodynamics and safety evaluations.

In situ forming implants (ISFIs) have gained considerable attention over the past decade as minimally invasive long-acting injectable systems for localised and sustained drug delivery. N-Methyl-2-pyrrolidone (NMP) remains the most commonly used solvent for ISFIs; however, concerns regarding its environmental toxicity and teratogenicity have driven the search for alternatives. Therefore, in this study, we investigated bio-derived and bio-renewable solvents - dimethyl isosorbide (DMI) and γ-valerolactone (GVL) - as potential substitutes for NMP. ISFI formulations were individually prepared with each solvent and poly(lactic-co-glycolic acid) (PLGA; L/G 1:1, 10 kDa) at polymer concentrations of 20, 30, and 40% w/w, and containing 1% w/w eosin Y dye as a model hydrophilic drug. ISFIs were subsequently evaluated for their rheological behaviour, injectability, implant morphology, and dye and solvent release. Rheological analyses revealed solvent-dependent differences, with GVL exhibiting flow behaviour comparable to NMP, while DMI showed significantly higher viscosity. These trends translated into injectability performance. Post-injection, NMP- and DMI-based ISFIs formed spherical implants, whereas GVL-based ISFIs produced collapsed and irregular structures. Moreover, in vitro release studies of eosin Y showed that GVL-based ISFIs significantly reduced burst release while exhibiting overall faster release kinetics, which was attributed to rapid polymer solidification and collapsed implant morphology that shortened diffusion path lengths. A two-stage model was developed to fit the release profiles and determine the average diffusion coefficients (D), allowing a quantitative comparison of the different formulations. To compare the performance of the solvents in vivo in rats, ISFI formulations were prepared containing testosterone (2.5% w/w) as a clinically relevant hydrophobic drug. Testosterone release from DMI- and GVL-based ISFIs was comparable to NMP, although NMP formulations resulted in lower overall plasma concentrations. This study highlights the potential of DMI and GVL as alternative solvents for ISFIs, with comparable performance to the traditionally used NMP.

The gut microbiome plays a critical role in host lipid metabolism, yet its influence on the intraluminal processes governing dietary lipid digestion, particularly lipase-mediated hydrolysis at oil-water interfaces, remains poorly understood. In this study, we combined in vivo microbiome modulation in rats with an ex vivo lipolysis model to examine how microbial perturbations affect intestinal lipid digestion. Rats were pretreated for 14 days with either broad-spectrum antibiotics or a prebiotic to induce distinct microbial profiles. Small intestinal luminal contents were collected from the jejunum and used to monitor the ex vivo digestion of coconut oil and olive oil, representing dietary lipids with varying triglyceride chain lengths. Microbial diversity was positively associated with both the rate and extent of lipid digestion. Notably, the prebiotic group showed a 3-4-fold increase in fatty acid release compared to the antibiotic group after 60 min of digestion (p < 0.0001). Physicochemical analyses indicated that prebiotic treatment enhanced emulsification efficiency, increasing the interfacial surface area available for lipase adsorption by up to 250%. Biomolecular profiling revealed marked changes in the intestinal lipidome and proteome, together with changes in endogenous bile acid and carbohydrate concentrations suggesting that microbial modulation of the luminal milieu plays a critical role in lipid emulsification and bioaccessibility. Together, these findings demonstrate that microbiome composition directly impacts the physicochemical environment of the small intestine and shapes lipid digestion outcomes, highlighting the potential of microbiome-targeted strategies to enhance digestive efficiency and metabolic health.

Nanomedicines promise to transform oncology by improving pharmacokinetics, enhancing tumor targeting, and reducing systemic toxicities relative to conventional chemotherapies. However, clinical outcomes remain inconsistent, with marked inter-patient variability in biodistribution and therapeutic response. This variability is thought to arise from heterogeneity in "bio-nano" interactions, yet the upstream drivers of these interactions are poorly defined. We propose that the gut microbiota is a clinically relevant regulator of nanomedicine behavior, given its established influence on host immunity, metabolism, and proteome composition - all key determinants of bio-nano interactions. To test this, rats underwent a 14-day microbiota modulation using a prebiotic, broad-spectrum antibiotics, or control treatment. PEGylated liposomes were then intravenously administered to assess the impact of microbiota composition on (i) protein corona formation, (ii) nanoparticle biodistribution, and (iii) in vitro anti-cancer efficacy of doxorubicin-loaded liposomes following exposure to plasma from each group. Microbiota modulation produced distinct protein coronas, characterized by increased protein adsorption and unique proteomic profiles enriched in complement factors, apolipoproteins, and immunoglobulins. These corona differences were associated with altered biodistribution profiles, affecting both the magnitude and organ-level partitioning of nanoparticle-associated signal. Antibiotic treatment increased total systemic signal consistent with altered retention and/or clearance, whereas prebiotic supplementation was associated with reduced overall signal and decreased proportional partitioning into mononuclear phagocyte system organs, with a corresponding shift in distribution balance toward peripheral tissues including the heart, kidney, and brain. Notably, the prebiotic-derived corona markedly enhanced liposomal uptake and cytotoxicity in A549 and ES-2 cancer cells, linking protein adsorption and corona composition with bio-nano cellular interactions. Collectively, these findings provide experimental evidence that microbiota modulation influences nanoparticle behavior by altering bio-nano interactions, revealing an emerging "gut-nano axis" as a potentially controllable source of nanomedicine variability.

Metabolic dysregulation is strongly associated with excessive dietary lipid absorption and gut microbiota imbalances under high-fat diet (HFD) conditions. This study evaluates a spray-dried inulin-montmorillonite (INU-MMT) hybrid designed to simultaneously restrict intestinal lipid digestion and modulate gut microbiota composition. In simulated intestinal digestion, INU-MMT maintained the strong lipid-inhibitory effect of montmorillonite, reducing free fatty acid release by 2.8-fold compared to HFD conditions, while exhibiting improved dispersion stability attributed to INU's ability to reduce clay platelet aggregation. In a 21-day HFD-fed rat model, INU-MMT supplementation (1 g/kg/day) attenuated cumulative weight gain by 4.7% compared to the HFD control, exceeding reductions with INU (2.0%) and MMT (1.5%) alone. 16S rRNA gene sequencing of fecal samples revealed improved gut microbial diversity (Simpson's index, p = 0.0161) and uniquely enriched health-associated taxa including Akkermansiaceae (2.5-fold), Eggerthellaceae (7.7-fold), Ruminococcaceae (3.5-fold), and Peptostreptococcaceae (8-fold). Beta diversity analysis highlighted that INU-MMT induced a distinct microbial composition from INU, suggesting the complimentary effects of the hybrid promote a more widespread microbial change than prebiotic alone. 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, consistent with the observed in vitro lipolysis suppression. These findings demonstrate that the INU-MMT hybrid preserves MMT's restriction of lipid digestion while delivering INU's prebiotic benefits, producing additive effects in diet-induced weight gain and microbiota modulation. The multifunctional nature of this spray-dried hybrid highlights its potential as a dietary strategy for metabolic dysregulation.

Background/Objectives: The growing prevalence of obesity necessitates innovative gut-targeted material strategies to modulate diet-associated metabolic dysfunction. This study investigates a spray-dried konjac glucomannan-montmorillonite (KGM-MMT) hybrid designed to integrate fermentable polysaccharide properties with luminal lipid-adsorptive clay functions within a single micro-engineered formulation. Methods: In HFD-fed mice treated for 42 days with 2% w/w KGM-MMT, cumulative body weight gain was attenuated by 7.6%, with an AUC of 5094 ± 52.95, compared to 5513 ± 81.35 in HFD controls (p < 0.0001). Results: Serum IL-6 concentrations were reduced by 97% (p = 0.0002), while blood glucose decreased by 46% (p < 0.0001); these effects were greater than those observed with MMT (24%, p = 0.0271) and KGM (16%, ns). Gut microbiota profiling demonstrated a significant 6.2-log2-fold increase in Lactobacillaceae (p = 0.023) and a 2.4-log2-fold increase in Enterococcaceae (p = 0.015) following KGM-MMT treatment. Functional shifts inferred from 16S rRNA gene-based prediction indicated a 1.9-fold increase in short-chain fatty acid-related pathways and a 5.4-fold increase in bile acid deconjugation pathways. Conclusions: Although the KGM-MMT hybrid did not consistently outperform its individual components across all endpoints, it consolidated complementary KGM- and MMT-associated effects within a single dosage form. These findings support spray-dried KGM-MMT as a gut-targeted biomaterial strategy that integrates multiple luminal and microbiota-associated functions within a single formulation. Future studies should define dose-response relationships, validate microbiota-derived functional predictions using higher-resolution approaches, and assess durability and safety under longer-term exposure.

Orlistat is an established pharmacotherapy for metabolic syndrome (MetS); however, its clinical utility is constrained by gastrointestinal adverse effects and gut microbiota disruption. This study evaluates hybrid inulin (INU)-bentonite (BEN) microparticles (InuClay) as a microbiota-protective adjunct to orlistat therapy. In vitro lipolysis under biorelevant fasted-state conditions demonstrated that InuClay significantly reduced free fatty acid liberation relative to untreated controls and INU alone (p < 0.01). In a 21-day high-fat diet rat model of MetS, InuClay and orlistat monotherapies reduced cumulative weight gain by 4.5% and 5.7%, respectively. Co-administration achieved a 7.7% reduction that was significantly greater than either monotherapy alone. Combination therapy also produced the greatest reduction in fasting blood glucose (27%) exceeding both InuClay monotherapy (12%) and orlistat monotherapy (16%). At the microbiota level InuClay co-administration prevented orlistat-induced Proteobacteria expansion (2.5-fold reduction versus orlistat alone) while selectively enriching butyrate-producing taxa including Lachnospiraceae (1.42-fold) and Blautia (11.8-fold) without significantly altering alpha diversity. Circulating markers of cellular injury were substantially lower with combination therapy, with lactate dehydrogenase decreased by 63% and aspartate aminotransferase by 23% versus controls. These reductions were absent with orlistat monotherapy. Collectively these findings establish InuClay as a dual-action adjunct that enhances orlistat efficacy while attenuating dysbiotic shifts and systemic markers of tissue stress. This approach represents a promising strategy for improving translational outcomes in lipase inhibitor-based MetS management.

Background: Lipid nanoparticles (LNPs) and polyethyleneimine (PEI) have independently been used for DNA complexation and delivery. However, non-ideal gene delivery efficiency and toxicity have hindered their clinical translation. We developed DNA-PEI-LNPs as a strategy to overcome these limitations and enhance DNA delivery and transgene expression. Methods: Three microfluidic mixing protocols were evaluated: (i) LNPs without PEI, (ii) a single-step process incorporating PEI in the organic phase, and (iii) a two-step process with DNA pre-complexed with PEI before LNP incorporation. The influence of DNA/PEI ratios (1:1, 1:2, 1:3) and DNA/lipid ratios (1:10, 1:40) on particle properties and delivery efficiency was examined. Results: In luciferase formulations, higher DNA/lipid ratios (1:40) produced smaller particles (136 nm vs. 188 nm) with improved cellular uptake (77% vs. 50%). The two-step method with higher DNA/PEI ratios improved transfection efficiency, with LNP-Luc/PEI 1:3 (40) achieving ~1.9 × 106 relative light units (RLU) in luciferase expression. In green fluorescent protein (GFP) studies, LNP-GFP/PEI 1:3 (40) showed ~23.8% GFP-positive cells, nearly twofold higher than LNP-GFP (40) at ~12.6%. Conclusions: These results demonstrate the capability of microfluidic-prepared DNA-PEI-LNPs to improve DNA delivery and transgene expression through optimized formulation strategies and selection of appropriate preparation methods.

Self-expandable metal stents (SEMS) represent the gold standard for the clinical management of malignant obstructions in the gastrointestinal tract. Gastrointestinal stent blockage (restenosis) caused by tumour growth is a common problem. The incorporation of anticancer drugs into SEMS for localised delivery could potentially address restenosis, although further studies are required to better understand the influence of the stent structure in combination with different drug-eluting polymer formulations and chemotherapeutics. Therefore, in this work, we investigated for the first time the suitability of a polyurethane-silicone (PUS) elastomer for the controlled encapsulation and release of 5-fluorouracil (5FU) from membrane-covered oesophageal stents (OS) and bare enteral colonic stents (CS). The stents were coated with a bilayer structure consisting of a 5FU-loaded (7.0% w/w) PUS basecoat and poly(ethylene-co-vinyl acetate) (PEVA) diffusion regulating topcoat. Physicochemical characterisation of the coatings revealed that 5FU is uniformly distributed and semi-crystalline in the PUS layer, and that 5FU did not leach into the topcoat during coating. Interestingly, drug release from the coated stents revealed a significant difference, with 5FU release from CS plateauing after similar to 12 d, while a much more gradual release was observed with the OS over 150 d. Imaging revealed that defects in the coatings due to the underlying stent structure are likely contributors to these differences. The coated stents were found to be stable to gamma sterilisation and in accelerated stability tests. In vitro cytotoxicity, cell cycle and apoptosis assays revealed that 5FU released from the stents had comparable anticancer efficacy to free 5FU against human colon carcinoma cells. This research demonstrates the potential of polymer-coated SEMS for controlled drug-release and highlights the importance of the underlying stent structure on performance.

Decreased saliva production due to salivary gland damage can result in difficulty speaking and swallowing, significantly reducing quality of life for head and neck cancer patients receiving radiotherapy. It is therefore imperative that treatment options are available to mitigate the effects of these debilitating side effects. D-limonene, a naturally occurring terpene, has shown protective effects on saliva production during radiotherapy treatment of mice, however the lipophilic nature of the molecule has necessitated a high oral dose to facilitate sufficient absorption. In this study, lipid-based drug delivery systems have been utilised to formulate D-limonene in order to reduce undesirable gastrointestinal side effects and increase solubility for enhanced absorption. Lipid-based formulations produced up to 180-fold increased solubility over pure D-limonene, coupled with enhanced storage stability and protection against oxidation. Furthermore, pharmacokinetic evaluation of optimised lipid-based formulations in Sprague Dawley rats displayed up to a 51.25-fold increase in bioavailability relative to pure oral D-limonene. Finally, elevated levels of lipid-formulated D-limonene were localised within the submandibular salivary glands, indicating potential for local action on saliva production. Overall, the administration of D-limonene utilising lipid-based formulations shows significant promise for advancing prevention and treatment strategies for xerostomia.

Lung cancer remains one of the leading causes of cancer-related mortality worldwide, highlighting the urgent need for more effective therapeutic strategies. Nanomedicine offers a promising avenue to improve treatment outcomes by enabling localised drug delivery within the lungs. Drawing inspiration from the recent success of mRNA lipid nanoparticles, we developed a novel class of polymeric-lipid nanoparticles (P-LNPs) designed to encapsulate RB-012, an anticancer compound that inhibits 14-3-3 protein function but is rapidly cleared from systemic circulation due to its cationic and amphiphilic properties. RB-012 was co-assembled with the anionic polymer polyacrylic acid (PAA) and various combinations of cholesterol, pegylated, and charged helper lipids to form stable P-LNPs that significantly impeded in vitro premature drug release. This approach resulted in >30-fold increase in bioavailability following intravenous administration (2 mg/kg) to Sprague-Dawley rats. Varying the helper lipid composition, through the inclusion of 16-32 mol% of the cationic lipid, DOTAP, yielded a > 50-fold increase in pulmonary drug exposure compared to unformulated RB-012. These biodistribution enhancements were linked to altered protein corona profiles on the nanoparticle surface, with P-LNPs formulated with DOTAP increasing the degree of protein corona adsorption in a concentration-dependent manner, compared to P-LNPs prepared with the anionic helper lipid, DOPE. In vitro and in ovo assays confirmed that the P-LNPs significantly improved the anti-tumour efficacy of RB-012, supporting their potential as a targeted therapeutic platform for lung cancer treatment.

Background/Objectives: Lipid-based formulations are widely used to enhance the oral bioavailability of poorly water-soluble drugs. However, for weakly basic drugs with higher solubility under acidic conditions, precipitation and recrystallisation after gastric emptying can compromise a formulation’s ability to maintain the drug in a solubilised, absorbable state. To address this, we evaluated an enteric coating strategy to preserve the biopharmaceutical performance of a silica-solidified lipid-based formulation. Methods and Results: The model weakly basic BCS Class IV drug, abiraterone acetate, was loaded into a lipid-based formulation and solidified using mesoporous silica nanoparticles. In an in vitro lipolysis model, introducing the formulation only after the onset of the intestinal phase led to lower precipitation and over 50% greater drug presence in the aqueous phase compared to a two-stage gastric–intestinal digestion. In an in vivo pharmacokinetic study in Sprague Dawley rats, the silica–lipid formulation (6 mg/kg), delivered in gelatine minicapsules enteric-coated with Eudragit L100-55, resulted in a 2.6-fold higher systemic exposure compared to the non-coated formulation (p < 0.0001). Conclusions: These findings support the use of enteric coating for lipid-based formulations and silica nanoparticles containing weakly basic drugs as a strategy to maintain formulation integrity until reaching the small intestine.

The gastrointestinal microbiota has received increasing recognition as a key mediator of neurological conditions with neuroinflammatory features, through its production of the bioactive metabolites, short-chain fatty acids (SCFAs). Although neuroinflammation is a hallmark shared by the neuropsychological complications of chemotherapy (including cognitive impairment, fatigue and depression), the use of microbial-based therapeutics has not previously been studied in this setting. Therefore, we aimed to investigate the effect of a high fibre diet known to modulate the microbiota, and its associated metabolome, on neuroinflammation caused by the common chemotherapeutic agent 5-fluorouracil (5-FU). Twenty-four female C57Bl/6 mice were treated with 5-FU (400 mg/kg, intraperitoneal, i.p.) or vehicle control, with or without a high fibre diet (constituting amylose starch; 4.7 % crude fibre content), given one week prior to 5-FU and until study completion (16 days after 5-FU). Faecal pellets were collected longitudinally for 16S rRNA gene sequencing and terminal SCFA concentrations of the caecal contents were quantified using gas chromatography-mass spectrometry (GC-MS). Neuroinflammation was determined by immunofluorescent analysis of astrocyte density (GFAP). The high fibre diet significantly altered gut microbiota composition, increasing the abundance of Bacteroidaceae and Akkermansiaceae (p < 0.0001 and p = 0.0179) whilst increasing the production of propionate (p = 0.0097). In the context of 5-FU, the diet reduced GFAP expression in the CA1 region of the hippocampus (p < 0.0001) as well as the midbrain (p = 0.0216). Astrocyte density negatively correlated with propionate concentrations and the abundance of Bacteroidaceae and Akkermansiaceae, suggesting a relationship between neuroinflammatory and gastrointestinal markers in this model. This study provides the first evidence of the neuroprotective effects of fibre via dietary intake in alleviating the neuroimmune changes seen in response to systemically administered 5-FU, indicating that the microbiota-gut-brain axis is a targetable mediator to reduce the neurotoxic effects of chemotherapy treatment.

Obesity, a global epidemic, leads to metabolic dysregulation and systemic inflammation. Recently, therapies targeting the gut microbiome have garnered attention for metabolic health regulation. This study evaluates the potential of inulin-coated medium-chain triglyceride (InuMCT) microcapsules in rats with diet-induced obesity (DIO). Inulin prebiotic fibers have been shown to promote the gut microbiome, while the digestion products of medium chain triglycerides (MCTs), free fatty acids, and mono-/diglycerides, can attenuate pro-inflammatory outcomes. It is hypothesized that encapsulating MCTs within inulin via spray drying creates a solid dosage form that can exert multifunctional effects in ameliorating inflammation in DIO. Inulin and InuMCT treatments not only reduce DIO weight gain but also improve metabolic markers in high-fat diet (HFD) fed rats. Specifically, inulin attenuates the reduction of high-density lipoprotein (HDL) by 55% and lowers glucose levels by 21%. Meanwhile, InuMCT increases HDL by 23% and reduces glucose levels by 15%. Furthermore, inulin decreases serum proinflammatory tumor necrosis factor-alpha (TNF-alpha) by 35%, while InuMCT further reduces TNF-alpha to normal diet levels within 21 days. These results highlight InuMCT's superior efficacy, offering a promising strategy for combating obesity and related metabolic diseases. Spray-dried Inulin-medium chain triglyceride (InuMCT) microcapsules are innovative hybrid systems that enhance gut microbiota diversity, reduce weight gain, and improve HDL and glucose markers in diet-induced obese rats. Additionally, InuMCT lowers pro-inflammatory TNF-alpha to normal diet levels, suggesting its potential as a therapeutic strategy for obesity and other metabolic diseases. image