Food & Function

This study investigated the effects of Lactiplantibacillus plantarum VB165, a probiotic strain with intrinsic -glucosidase inhibitor (AGI) activity, on metabolic disorders in high-fat diet (HFD)-induced insulin-resistant (IR) mice. Male C57BL/6 mice were divided into four groups: normal control diet (NCD), NCD supplemented with VB165, HFD, and HFD supplemented with VB165. After 16 weeks, VB165 supplementation significantly attenuated HFD-induced weight gain and reduced epididymal and inguinal white adipose tissue indices. VB165 also improved glucose intolerance and insulin resistance (IR), as demonstrated by oral glucose tolerance tests (OGTT) and insulin tolerance tests (ITT), and lowered fasting blood glucose, fasting insulin, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) levels. Additionally, it ameliorated dyslipidemia by reducing serum total cholesterol, triglycerides, and low-density lipoprotein cholesterol (LDL-C), while alleviating hepatic steatosis and adipocyte hypertrophy. Mechanistically, VB165 enhanced intestinal barrier function by upregulating tight junction proteins (ZO-1 and Occludin), reduced systemic inflammation by lowering LPS, IL-6, and IL-1{beta}. Gut microbiota analysis revealed that VB165 modulated community composition, suppressing HFD-enriched genera (e.g., Ileibacterium and Coriobacteriaceae_UCG_002) and promoting beneficial taxa (e.g., Faecalibaculum and Oscillibacter). These findings demonstrate that L. plantarum VB165 improves HFD-induced metabolic disorders via multi-target mechanisms, highlighting its potential as a probiotic intervention for IR and related metabolic diseases.

Steroidal alkaloids may be responsible for some of the health benefits of a tomato rich diet, but little is known about their metabolic fate after consumption. The objective of this study was to elucidate the pharmacokinetic parameters of plasma steroidal alkaloids and to define their bioavailability and metabolism following a single tomato containing meal. Healthy subjects (n = 11, 6M/5F) consumed 505 g of tomato juice following a two-week tomato washout and blood plasma were collected post-prandially at 11 time points over 12-hours. Plasma steroidal alkaloids were analyzed using UHPLC-MS. The fractional absorption of steroidal alkaloids was 11.8 {+/-} 7% and over 99% of the absorbed dose were present as metabolized products. The maximum concentration of total plasma steroidal alkaloids in subjects was 406.5 {+/-} 377.0 nmol/L occurring at 6 hours after consumption, with an AUC0-12hr of 2529.0 {+/-} 1644.8 nmol*h/L. Liver S9 enzymatic synthesis of steroidal alkaloid metabolites including trihydroxy-tomatidine and sulfonated dihydroxy-tomatidine improved confidence in compound identification. This study reports the first pharmacokinetic data for tomato steroidal alkaloids, demonstrating moderate absorption and extensive metabolism after tomato juice consumption. These data provide context for future studies investigating the potential role that these compounds may play in human health.

Todays canola quality rapeseed press cake (RPC) is a protein-rich co-product with potential as human food, but its application is limited due to antinutritional compounds and bitter taste. It remains, however, unknown how introduction of raw RPC to a food matrix affects sensory perception and which metabolites drive the sensation. Here, raw RPC from whole or dehulled seeds was introduced into snack bars at 0%, 7%, 14%, and 21%, and sensory responses were correlated to selected known RPC-derived bitter compounds. A trained panel evaluated 13 RPC-characteristic sensory attributes, and the bitter compounds sinapic acid, kaempferol 3-O-(2'''-O-sinapoyl-{beta}-sophoroside) (KSS), KSS-hexose, selected bitter glucosinolates, and goitrin were quantified using targeted LC-MS/MS. Most dose-dependent sensory responses increased up to 14% RPC and then plateaued, whereas astringent mouthfeel increased almost linearly across the full dose range. Dehulling intensified several odor- and flavor-related attributes but did not increase bitterness or protein content in the final product. Principal component analysis linked bitterness and astringency positively with KSS, KSS-hexose, and goitrin. Dose-over-threshold analysis further showed that goitrin, but not progoitrin, reached concentrations relevant for bitterness perception. Together, the results demonstrate that raw RPC contributes distinct dose-dependent sensory attributes and that metabolite transformations in the food matrix shape final sensory profiles. These findings provide a basis for developing RPC-containing foods and for breeding rapeseed lines with improved sensory characteristics. HIGHLIGHTSO_LIThis study presents the first sensory panel assessment of rapeseed press cake (RPC)-containing in food products (snack bars) made from whole and dehulled seeds. C_LIO_LI13 RPC-characteristic sensory attributes are identified. C_LIO_LISensory profiles of the tasted snack bars differed significantly, influenced by the dosage of RPC and by the dehulling treatment. Bitterness and astringency are positively correlated with the RPC dosage. C_LIO_LIGoitrin, kaempferol 3-O-(2'''-O-sinapoyl-{beta}-sophoroside) (KSS) and sinapic acid are RPC-derived bitter compounds that correlate with bitter taste of RPC-containing snack bars. C_LIO_LIApproximately 90% of glucosinolates introduced with the RPC are not detected in the snack bars, and goitrin levels in snack bars accounts for only [~]10% of introduced progoitrin. C_LIO_LIGoitrin is - for the first time - reported to contribute to the perceived bitterness of an RPC-containing food product. C_LI

Reported avocado dietary fiber (DF) content and composition are inconsistently reported, particularly during ripening. Thus, this study aimed to characterize the amount and type of DF in Hass avocados and evaluate DF changes during ripening. Unripe (day 0), ripe (day 5), and overripe (day 12) Hass avocados were freeze-dried and defatted. DF was analyzed using non-starch polysaccharide (NSP) enzymatic-chemical methods. Per 100g of as-is avocado, unripe contained 3.96g total DF, ripe 3.68g, and overripe 3.26g. In ripe avocados, DF comprised 43% soluble (SDF) and 57% insoluble dietary fiber (IDF). SDF consisted primarily of rhamnogalacturonan-1 and arabinan pectins, while IDF was predominantly cellulose (32%), hemicelluloses (23%), and lignin (2%). Total DF decreased with ripening, with pectin undergoing solubilization and depolymerization, while cellulose and hemicelluloses remained stable. These findings are important as dietary fibers differentially influence intestinal microbial fermentation and health benefits.

Vitamin B2 (riboflavin) is a key redox cofactor that may modulate gut microbial ecology, yet conventional supplements are absorbed proximally and have limited colonic exposure. We evaluated whether colon-targeted riboflavin alters microbiome composition, function and network structure as well as host biomarkers in healthy older adults. In a randomized, double-blind, placebo-controlled, parallel-group clinical trial (N=348; 50-70 years), participants received colon-targeted riboflavin (1.4, 10, or 75 mg/day) or placebo for 12 weeks. The primary endpoint was the change in fecal microbial composition, while secondary endpoints encompassed microbiome function, host health biomarkers, and clinical outcomes. Shotgun metagenomics and fecal/blood biomarkers were assessed at baseline, week 4, and week 12. Although no significant changes were observed between groups in overall community-wide diversity metrics (alpha and beta diversity), colon-delivered riboflavin significantly altered the relative abundance of several microbial taxa compared with placebo. The most pronounced effects on microbiome composition, function, and network structure were observed with the 10 mg dose at week 12, reflected by within-group increases in alpha diversity, the largest rise in total species counts, higher HACK index values indicating greater community resilience, and distinct shifts in KEGG module abundance, including enhanced potential for riboflavin biosynthesis. Supplementation with 75 mg riboflavin led to higher fecal butyrate concentrations at week 4 versus placebo, while the lowest dose (1.4 mg) significantly reduced the dysbiosis index within groups and modestly improved network structure across groups. All three doses (1.4, 10, and 75 mg) influenced keystone species abundance. No between-group differences were observed for gastrointestinal symptoms, quality-of-life measures, fecal pH, high-sensitivity C-reactive protein (hs-CRP), calprotectin, or soluble CD14, except for an increase in plasma riboflavin concentrations at 75 mg after 12 weeks, indicating colonic absorption. The product was safe and well-tolerated across all doses. These findings indicate that colon-targeted riboflavin can act as a functional modulator of the human gut microbiome, with the most consistent effects observed at 10 mg and additional dose-specific effects at 1.4 mg and 75 mg. Future studies are warranted to establish related health benefits, either as a standalone intervention or in combination with classical pre-, pro-, or postbiotics, particularly in target populations such as individuals with IBS, stress, mild cognitive decline, or early metabolic or inflammatory alterations.

Background/ObjectivesGlucagon-Like Peptide-1 (GLP-1) is a key incretin hormone that regulates glucose homeostasis and energy metabolism. Impaired GLP-1 signaling contributes to the development of obesity, metabolic syndrome, and type 2 diabetes. Emerging evidence indicates that gut microbiota-derived components can influence GLP-1 secretion, highlighting the therapeutic potential of microbial modulators. Akkermansia muciniphila, a next-generation probiotic associated with improved metabolic health, remains underexplored for its capacity to stimulate GLP-1 release. This study aimed to investigate the GLP-1- stimulatory effects of live and pasteurized (dead) A. muciniphila strains in human enteroendocrine cells. MethodsHuman enteroendocrine L-cells (NCI-H716) were treated with varying doses of live and dead A. muciniphila from Vidya Herbss proprietary VHAKM strain and a commercially available marketed strain (dead form). Following incubation, GLP-1 levels were quantified from culture supernatants using enzyme-linked immunosorbent assay (ELISA). Comparative analyses assessed differences in GLP-1 secretion between strains and treatment forms. ResultsBoth live and pasteurized VHAKM strains significantly increased GLP-1 secretion compared to untreated controls. The live VHAKM strain exhibited higher GLP-1 stimulatory activity than its pasteurized counterpart and the marketed strain. The results suggest a strain-specific and viability-dependent modulation of GLP-1 secretion in human L-cells. ConclusionsThis study demonstrates that A. muciniphila VHAKM enhances GLP-1 secretion in a strain- and form-dependent manner, with live cells showing superior efficacy. These findings provide foundational insights for developing microbiome-targeted interventions to boost endogenous GLP-1 levels and improve metabolic health outcomes.

Frailty is an age-related syndrome characterized by biological dysfunction and reduced physiological reserve in response to stressors. Its prevalence is increasing with population aging, resulting in a substantial health burden due to adverse outcomes on health, such as cardiovascular disease and mortality. Ultra-processed foods (UPFs), defined as industrial formulations made primarily from processed ingredients, have received increasing attention due to their potential role in the development and progression of frailty. This systematic review and meta-analysis examined the association between ultra-processed food intake and the risk of frailty in older adults. This study systematically searched for all relevant studies published up to January 2026. Ten observational studies involving 105327 participants, comprising 6 prospective and 4 cross-sectional studies, were included in the systematic review, of which 6 were eligible for meta-analysis. Random-effects models were employed to estimate pooled effect sizes and 95% confidence intervals (95% CIs). Meta-analysis showed that higher consumption of UPFs was significantly associated with an increased risk of frailty (pooled OR = 1.43, 95% CI = [1.02-2.005], p = 0.041). Narrative synthesis further supported a positive association between UPF intake and frailty or related outcomes. Our findings suggest that a higher consumption of ultra-processed foods may contribute to frailty risk, potentially through inflammatory pathways. However, given the high heterogeneity, results should be interpreted with caution. Overall, our findings suggest that reducing UPF consumption may be a promising target for public health strategies to prevent frailty in ageing populations.

The modern Western diet (MWD) provides high linoleic acid (LA) exposure, typically contributing 6-9% of total caloric intake. These high LA levels have fueled a longstanding debate regarding whether this dietary pattern confers benefit or risk. Importantly, LA intake is disproportionately elevated among lower socioeconomic populations due to greater reliance on industrial seed oils and ultra-processed foods. Despite decades of research, controlled dietary intervention studies directly evaluating the biological consequences of varying LA exposure remain limited. The current randomized, double-blind intervention compared the effects of a 12-week Low LA diet (2.5% energy) versus a High LA diet (10.0% energy) in healthy adults. Primary outcomes included plasma highly unsaturated fatty acid (HUFA) concentrations and ex vivo zymosan-stimulated whole-blood oxylipin generation. Fifty- two participants completed the intervention. High LA exposure resulted in a marked reduction in plasma n-3 eicosapentaenoic acid (EPA) concentrations compared with the LowLA arm. In contrast, levels of arachidonic acid (ARA), dihomo-gamma-linolenic acid (DGLA) and docosahexaenoic acid (DHA) did not differ by dietary LA exposure. Analysis of oxylipin species revealed that levels of EPA-derived relative to ARA-derived mediators were significantly reduced in the High LA arm. These findings reveal that higher dietary LA selectively suppresses EPA pools and EPA-derived oxylipins without altering ARA, shifting the lipid mediator balance toward a more n-6-dominant profile.

1.Fermentable fibres such as inulin can support metabolic health but may exacerbate gastrointestinal symptoms in individuals with irritable bowel syndrome (IBS) due to rapid fermentation and gas production. The gel-forming fibre psyllium improves IBS symptoms, although the underlying mechanisms remain unclear. We hypothesised that fibre gelation alters fermentation by modulating microbial access to substrates. To test this, we compared psyllium with methylcellulose, a chemically modified, gel-forming fibre, to determine the effects of gelation on inulin fermentation. Inulin alone or combined with psyllium or methylcellulose was fermented for 48 hrs in a colonic fermentation model inoculated with healthy human faeces. Gas production, metabolite profiles, microbial community composition and microbial localisation within fibre gels were assessed. Bioactivity of fermentation products was evaluated in STC-1 cells. Psyllium co-fermentation significantly accelerated fermentation and enhanced production of metabolites, while methylcellulose had minimal effects. Psyllium maintained higher diversity and enriched polysaccharide-degrading taxa including Bacteroides and Phoecaeicola species, which were strongly associated with metabolic activity. Bacterial penetration into the psyllium matrix was observed but not into methylcellulose. Fermentation products from psyllium but not methylcellulose stimulated GLP-1 and 5-HT secretion in STC-1 cells. These findings demonstrate that delayed-onset fermentable gel-forming fibres enhance microbial access to entrapped substrates, driving metabolic and hormonal responses.

The gut microbiome is a key regulator of metabolic homeostasis and contributes to obesity progression through effects on immune signaling, gut barrier integrity, and systemic inflammation. Microbiome-targeted strategies are therefore being explored as complementary approaches to conventional weight-loss therapies. Here, we investigated the probiotic yeast Saccharomyces boulardii in a murine model of diet-induced obesity (DIO) using an integrated multi-omics framework combining metabolic phenotyping, gut microbiome profiling, cecal metabolomics, colonic transcriptomics, and portal cytokine analysis. S. boulardii reduced food intake, attenuated weight gain, and increased energy expenditure without major changes in circulating metabolic hormone levels. Microbial diversity remained largely preserved, but selective enrichment of Bacteroidales lineages, including Muribaculaceae, was observed alongside functional remodeling of microbial pathways. Cecal metabolomics revealed increased B-vitamins, betaine, and GABA, with reduced stress-associated metabolites. Colonic transcriptomics showed attenuation of TNF/NF-{kappa}B signaling and enrichment of interferon and epithelial programs, while portal cytokine profiling indicated reduced inflammatory chemokines with trends toward increased IL-17A and IL-22. Integrated multi-omics analysis identified coordinated host-microbe interactions across metabolic, transcriptional, and immune layers. Collectively, these findings demonstrate that S. boulardii modulates the gut-immune-metabolic axis in obesity, supporting microbiome-based interventions as potential adjunct strategies targeting metabolic inflammation.

Introduction. Ultra-processed foods (UPFs), defined as foods in group 4 of the NOVA classification system, are a key contributor to chronic disease in the United States. Front-of-package warning labels ('warnings') offer a promising strategy to help Americans reduce consumption of UPFs. Requiring warning labels on UPFs could help reduce consumption of these foods. However, the effects of UPF warnings are largely unknown. The impact of warning labels on UPFs among Latino adults was examined. Study design. Online randomized trial. Setting/participants. 4,107 Latino adults (49% limited English proficiency) in the US. Intervention. Participants viewed one of three labels: control labels displaying barcodes; identity warnings stating 'WARNING: Ultra-processed food'; or health warnings stating 'WARNING: Consuming ultra-processed food and drinks can cause weight gain, which increases the risk of obesity and type 2 diabetes'. Main outcome measures. Participants viewed four UPF products displaying their randomly assigned labels. Participants indicated whether the product was UPF (primary outcome) and rated perceived healthfulness of the product, intentions to purchase the product, and perceived message effectiveness (secondary outcomes). Results. Identity warnings (70% correct) and health warnings (67% correct) both led to higher correct identification of UPF compared to control labels (54%, p<.001), with the identity warning having a larger impact than the health warning (p=.007). Compared to the control label, the identity warning and health warning both elicited higher perceived message effectiveness and lower perceptions of healthfulness and purchase intentions (p<.001 for all outcomes) with no significant differences between UPF labels. The impact of the health warning label (vs. the control label) on correct identification of UPF was greater for participants with high education (p=0.012) compared to those with low education, and participants with limited English proficiency (p=0.001). Conclusions: UPF warnings may help consumers identify UPFs and influence product perceptions and intentions.

BackgroundDiet is central to cardiovascular disease (CVD) prevention, yet free-living studies rarely capture what people eat at home or how closely they follow an assigned diet due to limitations in self-reporting. Short-term inpatient feeding studies, with all meals provided and supervised intake, allow direct assessment of the physiological effects of dietary patterns. Objectivesi) To compare the short-term effects of a UK-National Institute for Health and Care Excellence (NICE) aligned diet versus a Western-style diet on CVD risk factors, metabolic phenotypes and microbiome; ii) To evaluate whether urinary metabolic phenotyping can objectively classify dietary adherence in adults with increased CVD risk. MethodsIn a controlled inpatient randomized crossover trial, 18 adults at elevated CVD risk completed two 72 h isocaloric diets: NICE-compliant and Western-style. Repeated-measures MCCV-PLS-DA assessed NMR fasting serum and 24 h urine metabolomic phenotypes. Univariate analyses examined CVD markers, urinary metabolites, serum SCFAs, and gut microbial richness and -diversity. ResultsDiet modulated CVD risk markers, with the NICE compliant diet lowering systolic blood pressure and atherogenic lipid parameters, whereas the Western-style diet increased these measures (all q < 0.05). The Western-style diet reduced microbial richness and tended towards lower -diversity. Urinary metabolic phenotyping identified 27 discriminatory metabolites between the diets reflecting food intake. Most diet-linked metabolites diverged from baseline within 24 h; microbiome derived metabolites demonstrated early and sustained divergence across 72 h. The urinary MCCV-PLS-DA model extended from a previously published framework in healthy adults, robustly classified dietary adherence (Q2Y=0.96), and correctly predicted allocated dietary intervention at earlier timepoints (24-48 h). ConclusionsUrinary metabolic phenotyping offers a sensitive and non-invasive tool for objectively assessing dietary intake. Short-term adherence to contrasting dietary patterns produced rapid, diet-specific metabolic and microbial effect in individuals at elevated CVD risk and differentially impacted cardiovascular risk profiles. This trial was registered at the ISRCTN registry (https://www.isrctn.com/ISRCTN44705179).

Dietary patterns worldwide have shifted toward increased consumption of ultraprocessed foods (UPFs), which has been linked to higher disease burden. One mechanism proposed to impact both their consumption and contribution to metabolic disease is altered post-ingestive metabolic response in comparison to nutritionally similar foods. Here, we recruited 57 healthy-weight 18-45-year-old adults to examine the effects of food processing on postprandial metabolism and brain response. Despite nutritional matching, UPF meals evoked a greater insulinemic and energetic response with attenuated carbohydrate oxidation relative to non-UPF meals. Next, between-condition differences in peak carbohydrate oxidation were associated with mesolimbic and superior temporal gyrus activation in response to food cues. Finally, although food value did not differ between conditions, brain responses correlated with food valuation were positive for non-UPF but negative for UPF in visual cortex and striatum. These findings demonstrate that food processing influences post-ingestive metabolism in a way that could help explain long term health effects and differences in food reward through mechanisms beyond calories and macronutrient composition alone.

Abstract Objective: Frailty is an important concern in old age. Inflammation can cause frailty. Anti-inflammatory food supplements can play a role in slowing down frailty processes and consequences. This study explored the views of people (aged 50-89 years) on the need to develop a frailty supplement, preferences for its form and how older people could be encouraged to use such a supplement. Design: We conducted semi-structured qualitative interviews and used a framework method to analyse the data. Participants: 30 participants from a city in the UK. Setting: These participants were recruited from social housing, care homes, foodbanks and the wider population. Participants were from diverse ethnic, gender and age backgrounds. Results: Participants identified a strong need for the development of a food-based supplement for frailty. They expressed excitement for the supplement and viewed it as something which they would be happy to integrate in their daily food routine. In terms of preferences, our participants wanted to have multiple options, however, a biscuit-based supplement was preferred by most. The participants preferences were mainly based on taste of the supplement, its effectiveness, convenience in use and affordability. Muslim participants in the sample said they would be happy to use this supplement if it was developed using Halal ingredients. In terms of creating awareness and encouraging people to use the proposed supplement, participants suggested a variety of marketing methods. These included: word of mouth, face to face sessions with older adults, social media, especially YouTube and advertising on TV. Conclusion: The participants were generally open to the idea of a food-based supplement and felt that it could easily fit with their existing food practices and lifestyles. Keywords: older adults, frailty, food supplement, co-creation, healthy ageing

Structured AbstractO_ST_ABSINTRODUCTIONC_ST_ABSAdults with Down syndrome (DS) have a higher risk of developing Alzheimers disease (AD). As gut microbiota (GM) alterations have been reported in AD, we investigated their association with cognitive decline and plasma AD biomarkers in DS. METHODSFecal and plasma samples were collected from 58 adults with DS (21-75 years) and 30 euploid controls (CTRL; 25-83 years). GM was profiled using 16S rRNA sequencing. Major Neurocognitive Disorder (NcD) was diagnosed according to DSM-5 criteria. Plasma levels of p-Tau181, NfL, and GFAP were measured using the Simoa platform. RESULTSCompared with CTRL, DS showed significant changes in UBA1819 and Intestinibacter genera, previously reported to be associated with mild cognitive impairment. Furthermore, DS with NcD were characterized by a reduced abundance of Roseburia genus, which was also negatively associated with plasma levels of AD biomarkers. CONCLUSIONAdults with DS display AD-associated changes in GM partially resembling those previously reported in euploid AD patients

Background and AimFecal microbiota transplantation (FMT) in Alcohol-related liver disease (ALD) has shown therapeutic potential, with variable efficacy and unclear mechanism. Because dietary protein influences gut microbiota composition, we hypothesized that donor dietary preconditioning could enhance FMT efficacy. We therefore examined in a murine ALD model if high-protein donor diet improves FMT outcome. MethodsALD was induced in C57BL/6N mice using a Lieber-DeCarli ethanol diet combined with thioacetamide administration for 12 weeks. FMT was performed using stool from diet-modulated donors, and recovery was assessed on day7 post-FMT. Multi-omics analysis using 16s rRNA and mass spectroscopy was performed for Gut microbiota composition, plasma- and stool-metabolome, and hepatic proteomes. Multi-omics outcomes were validated in ALD animal and Huh7 hepatocytes. ResultsBoth protein-based FMTs improved ALD recovery; Veg-FMT demonstrated superior efficacy, significantly reducing hepatic injury (AST 1.2-fold, p=0.002; bilirubin 1.2-fold, p=0.03; steatosis 1.7-fold,p=0.01) and restoring gut barrier integrity (occludin 1.5-fold,p=0.04; mucin 2 2.2-fold, p=002; and plasma endotoxin 1.7-fold, p=0.02). A significant 2-fold increase was observed in Lachnospiraceae NK4A136, Coriobacteriaceae UCG-002, and short-chain fatty acids, particularly caproic acid. Functional validation confirmed that caproic acid promoted hepatic fatty acid {beta}-oxidation through PPAR-dependent mechanisms, reducing triglyceride accumulation and lipogenesis in both cellular and animal models. ConclusionDonor preconditioning with a plant-protein enriched diet enhances FMT efficacy in ALD by gut microbiota modulation with increased metabolites like caproic acid. These findings highlight a microbiota-metabolite-host axis through which diet-modulated FMT improves hepatic lipid metabolism and injury, and identifies a pathway via which FMT imparts its effect. SignificanceThis study identifies a mechanistic basis for improving fecal microbiota transplantation (FMT) efficacy in alcohol-related liver disease (ALD) by demonstrating that dietary preconditioning of donor microbiota improves therapeutic outcomes. We show that plant protein-modulated donor microbiota supplements abstinence-associated recovery through increased production of the microbial metabolite caproic acid, which promotes hepatic fatty acid {beta}-oxidation via PPAR signaling. These findings highlight donor dietary conditioning and microbiota-derived metabolites, rather than microbial composition alone, as important determinants of FMT efficacy. The results suggest that microbial metabolites such as caproic acid may represent potential therapeutic targets or biomarkers to enhance and standardize microbiota-based interventions in ALD. Although the current work is based on a murine model, the identified microbiota-metabolite-host metabolic axis provides a framework for future translational studies aimed at optimizing FMT strategies in liver disease.

The genetically authenticated Finnish hop genotype LUKE 2541 obtained from wild was evaluated for antibacterial, anti-inflammatory, and anticancer activities. Water extracts from hop cones inhibited the Gram-positive bacteria Staphylococcus aureus and Bacillus cereus, with MIC values of 0.094- 0.188mg/mL, whereas Gram-negative strains showed limited sensitivity. In LPS-primed THP-1 cells, both IPA and IPA-Control extracts reduced reactive oxygen species formation in a dose-dependent manner, exhibiting similar IC50 values (50.41{micro}g/mL and 35.41{micro}g/mL). This hop genotype also displayed clear tissue- and solvent-dependent antiproliferative effects in human cancer cell lines. Bioactivity was strongly enriched in hop cones and predominantly associated with non-polar extracts, particularly hexane and dichloromethane fractions, which produced marked, dose-dependent reductions in cell viability. In contrast, aqueous and methanolic extracts were largely inactive, underscoring the critical importance of extraction chemistry and tissue selection. Sensitivity varied among cancer cell lines, with colorectal cells generally more responsive and leukemia cells less affected, highlighting cell-specific susceptibility. Further research is needed to elucidate underlying mechanisms, determine selectivity toward non-malignant cells, and identify the active compounds responsible for all in all investigated effects.

Multidrug resistant (MDR) bacterial wound infections are an increasing clinical challenge and require alternatives to conventional antibiotics. Although antimicrobial proteins offer promise, their therapeutic use is limited by poor stability, proteolytic degradation, reduced activity under physiological conditions, and potential toxicity. This work reports pH-sensitive lipid nanocarriers composed of granulysin (GNLY) and oleic acid (OA) for antimicrobial delivery to infected tissues. At neutral pH, GNLY is retained within OA-based nanocarriers and protected from proteolytic degradation. At pH 5.0, such as in infected wounds, the carriers undergo structural reorganization and release GNLY, restoring antimicrobial activity. OAGNLY (32 {micro}g/mL) achieved >3-log reductions in Staphylococcus aureus and Escherichia coli within 1 hour, and up to 4-log reductions in Pseudomonas aeruginosa and Acinetobacter baumannii, at physiological salt concentrations where free GNLY was largely inactive. Minimum inhibitory concentrations were 16 {micro}g/mL for MRSA and 32 {micro}g/mL for colistin-resistant E. coli. Ultrastructural analysis using transmission electron microscopy revealed disruptions of bacterial membranes and intracellular structures following OAGNLY treatment. In a murine surgical wound infection model, topical application of OAGNLY for 4 hours reduced bacterial burden by >5 logs and significantly decreased inflammation, as confirmed by histological analysis. In parallel, OAGNLY demonstrated minimal cytotoxicity to mammalian cells at active concentrations. These findings identify OAGNLY nanocarriers as a promising platform for pH-responsive delivery of GNLY and highlight their potential application for treating MDR skin and soft tissue infections..

Enteroaggregative Escherichia coli (EAEC) is a leading cause of persistent diarrhea in children in low- and middle-income countries, and the emergence of multidrug-resistant (MDR) strains necessitates non-antibiotic therapeutic strategies. This study evaluates Lactobacillus johnsonii, previously characterized by our group, as a probiotic candidate against a clinically confirmed MDR EAEC isolate resistant to ampicillin, ciprofloxacin, azithromycin, amoxicillin, and gentamicin. L. johnsonii demonstrated robust gastrointestinal resilience, high cell surface hydrophobicity, phenol tolerance, and rapid autoaggregation reaching 80.4 {+/-} 2.3% by 4 hours, collectively supporting mucosal colonization potential. In antimicrobial assays, L. johnsonii produced zones of inhibition against MDR EAEC substantially exceeding those of gentamicin, reduced viable biofilm-associated EAEC by over 80%, and displaced pre-adhered EAEC from HCT-116 intestinal epithelial cells in a time-dependent manner. L. johnsonii also attenuated MDR EAEC-induced gas production and reduced nitric oxide levels by 67.7% in infected RAW 264.7 macrophages, suggesting immunomodulatory activity. Nutrient competition did not appear to contribute to EAEC suppression under tested conditions, indicating inhibition is predominantly secretome-dependent. Fractionation of the L. johnsonii cell-free supernatant by fast protein liquid chromatography yielded five fractions below 75 kDa; fractions S5 and S6 exhibited sustained bactericidal activity at 6 hours. Gram staining confirmed that both fractions reduced viable EAEC cell numbers, with S6 producing a greater reduction than S5, indicating quantitatively distinct bactericidal potencies. These in vitro findings support the potential of L. johnsonii as a biotherapeutic candidate for antibiotic-resistant enteric infections. In vivo validation and chemical characterization of active fractions remain important next steps.

Natural products, especially polyphenol-rich medicinal plants, are increasingly investigated as multitarget therapeutics in both human and veterinary medicine for angiogenic regenerative properties and for inflammation based-diseases. Recent developments in natural product formulation, notably microencapsulation, have been shown to improve the stability, bioavailability, and controlled release of bioactive compounds. The integration of complementary in vitro and in vivo models is critical for evaluating both efficacy and translational potential. In this context, the present study assessed the phytochemical composition and biological activity of a microencapsulated Ecuadorian Vaccinium floribundum extract (VFM), using a combination of in vitro and in vivo approaches. VFM biochemical characterization identified 15 compounds, including flavonoids, procyanidins, dihydrochalcones, and phenolic acids, with chlorogenic acid and quercetin as the most abundant metabolites. Anthocyanins ideain and petunidin were also detected, confirming a rich bioactive profile. Primary porcine thoracic aortic endothelial cells (pAECs) were treated with VFM to assess cell viability and angiogenic potential and challenged with bacterial lipopolysaccharide (LPS) in the presence or absence of the extract. Anti-inflammatory effects were further evaluated in vivo using a carrageenan-induced mouse paw edema model. VFM enhanced endothelial cell viability, promoted capillary-like network and modulated early angiogenic signaling pathways. It mitigated LPS-induced endothelial dysfunction by reducing pro-inflammatory cytokines and oxidative stress markers. In vivo, paw edema assays confirmed its anti-inflammatory efficacy, with microencapsulation likely sustaining bioactive release. These findings support the traditional use of Vaccinium floribundum and highlight its potential for developing nutraceutical formulations targeting vascular and inflammatory disorders.