Food & Function

Traditional Mongolian fermented foods have been extensively utilized for dietary regulation and the promotion of gastrointestinal health. However, spontaneous fermentation remains inherently unpredictable, leading to significant variations in microbial community dynamics, metabolite accumulation, and the consistency and quality of the final product. Drawing on the traditional preparation of Mongolian acidic foods, this study established a controlled production strategy for whole-wheat probiotic fermented soup (WWPFS) by combining enzymatic pretreatment with probiotic-directed fermentation. Physicochemical characterization, 16S rRNA gene-based microbial community profiling, LC-MS/MS-based untargeted metabolomics, safety evaluation, and an Escherichia coli-induced gut microbiota dysbiosis model were employed to optimize and comprehensively characterize the fermentation process of WWPFS. The optimized process established a reproducible fermentation system consistently dominated by Lactobacillus and Bacillus across independent fermentation batches. Compared with traditional spontaneous fermentation, probiotic-directed fermentation remodeled the physicochemical properties of the whole-wheat matrix, including carbon, nitrogen, phosphorus, sulfur, and mineral composition, and facilitated the accumulation of putatively annotated LC-MS/MS features, including DL-lactate, 1,4-D-xylobiose, diacetyl, and phenyllactic-acid-related features derivatives. Acute oral and 28-day repeated-dose toxicity evaluations showed no treatment-related adverse effects within the tested dose range and study duration. In the Escherichia coli-induced gut microbiota dysbiosis mouse model, microbial richness, diversity, and community structure differed among the experimental groups, and both low- and high-dose WWPFS groups showed significant shifts in overall gut microbial community composition relative to the model group after multiple-testing correction, together with directional recovery of selected model-responsive bacterial genera. Cross-system integration identified coordinated response patterns between fermentation-derived metabolite features and model-responsive gut bacterial taxa, supporting a potential metabolite-microbiota link in WWPFS-mediated gut microbiota modulation. In summary, probiotic-directed fermentation improved the controllability of the traditional Mongolian fermented food production process, reshaped its metabolic profile, and enhanced its potential to modulate the gut microbiota. These findings provide experimental evidence supporting the modernization of traditional Mongolian fermented foods and the development of probiotic-based functional foods.

Background: Dietary fiber comprises a heterogeneous group of compounds with distinct physicochemical properties and biological effects. As such, functional outcomes observed for one fiber cannot be generalized to others. Some fermentable fibers, such as arabinoxylan, may exert biologically selective effects across multiple physiological domains, highlighting the need to evaluate individual ingredients for their domain-specific activity in controlled human studies. Methods: In this randomized, double-blind, parallel, 3-arm, placebo-controlled trial, healthy, overweight adults were assigned to consume one of two low doses of an arabinoxylan dietary fiber (3.5g or 5g) or placebo over the intervention period. Self-reported appetite sensations were assessed as the primary outcome using validated visual analogue scales. Secondary and exploratory endpoints included lipid parameters, gastrointestinal outcomes, mood-related measures, and gut microbiota composition and fermentation-derived metabolites. Analyses were conducted in the full analysis set and a high-compliance population to assess responses under sustained intake conditions, as per the intended dosing regimen. Results: The primary endpoint of appetite sensations did not differ between either arabinoxylan group and placebo. In contrast, evidence of microbial fermentation and selective microbiota engagement was observed. These responses occurred alongside consistent and favorable changes in lipid parameters under conditions of sustained intake, including reductions in low-density lipoprotein cholesterol and triglycerides. Additional outcomes, including gastrointestinal symptoms and mood, demonstrated domain-specific responses. Conclusion: This study demonstrates that supplementation with low doses of arabinoxylan dietary fiber elicit biologically selective, domain-specific effects across metabolic, microbial, gastrointestinal, and behavioral outcomes, particularly under conditions of sustained intake. These responses occurred independently of changes in appetite sensation, indicating that functional effects were not mediated through appetite-related pathways. Collectively, the findings highlight the ingredient's biological versatility and contextual responsiveness across physiological systems, and suggest its prebiotic potential through alignment with ISAPP's definition of a prebiotic, supporting further investigation of specific mechanistic pathways. Clinical trial registration: https://clinicaltrials.gov/study/NCT06884449, identifier: NCT06884449

BackgroundObesity is a complex multifactorial disease associated with chronic low grade inflammation, gut microbiota dysbiosis, and impaired gut-brain communication. Oligomeric procyanidins from grape seed extracts (GSE) are promising prebiotic candidates, capable of modulating host metabolism through interactions with the gut microbiota. MethodsC57Bl/6J male mice were rendered obese by feeding them a high fat, high sucrose diet and were orally administered GSE at a dose of 1or 2 g/kg/day for 12 weeks. We assessed body weight, adiposity, glucose tolerance, insulin sensitivity, circulating hormones, brain homeostasis markers, colonic and liver gene expression, 16S rRNA gene sequencing of the gut microbiota profiles, and untargeted cecal metabolomics. ResultsGSE reduced body weight gain, visceral adiposity, adipocyte hypertrophy, and improved oral glucose tolerance and insulin sensitivity. It normalized circulating lipid and glucose levels and lowered fasting insulin and leptin while increasing endogenous GLP-1. Hepatic gene expression analysis revealed a dose-dependent restoration of antioxidant defenses (SOD, CAT) and lipogenic transcription factors (SREBP, ChREBP). In the colon, GSE attenuated pro-inflammatory IL6 cytokine expression and strikingly upregulated GLP-1 and GLP-1 receptor expression. Microbiota analysis revealed a profound, dose-dependent remodeling of gut microbiota composition and diversity, with an expansion of health-associated taxa, such as Akkermansia muciniphila. Brain analyses revealed restoration of NAA and BDNF levels together with markers consistent with improved mitochondrial function. Cecal metabolomics revealed normalization of secondary bile acid metabolism, restoration of arginine bioavailability, and reduction in the accumulation of L-DOPA and spermidine. ConclusionsAn oligomeric procyanidin-rich grape seed extract acts as a multitarget prebiotic that alleviates diet-induced obesity and is associated with coordinated restoration of gut microbiota composition, GLP-1 signaling, and gut-brain and gut-liver communication pathways. Convergent dose-dependent effects on Akkermansia muciniphila abundance, GLP-1, NAA, and BDNF identify key mechanisms underlying its metabolic benefits.

Marine macroalgae are valuable sources of bioactive compounds. In this study, we thus investigated the chemical composition and biological activity of an extract from the green seaweed Ulva lacinulata, composed of small bioactive compounds. Comprehensive compositional analyses and high-resolution mass spectrometry revealed its diverse molecular profile composed in particular of peptides/amino acid derivatives, saccharides, low-chain fatty diacids, oxylipins and minerals. Its anti-inflammatory activity was assessed after 6 h pre-treatment in LPS-stimulated cultured RAW 264.7 macrophages, showing that it significantly and dose-dependently reduced the expression and/or secretion of pro-inflammatory cytokines such as TNF-alpha; and IL-6, and targeted the NF-kB signaling cascade. It modulated the SIRT1-AMPK signaling axis and increased the LC3-II/LC3-I ratio, supporting the activation of a controlled autophagic response. This work highlighted the potential of this marine-derived extract as a safe and effective functional ingredient for the development of functional food and/or dietary supplements targeting chronic low-grade inflammation.

Nisin is a promising antimicrobial peptide widely used in food preservation due to its efficacy against Gram-positive spoilage and pathogenic bacteria. Although Nisin is increasingly applied in the food sector, the biopeptide suffers from instability within food matrixes and can rapidly lose its antimicrobial potential following interaction with food biomolecules. Thus, it is necessary to investigate approaches that can be employed to extend the stability and activity of Nisin. Hence, the aim of this study was to develop and characterise a chitosan-alginate polyelectrolyte microencapsulation system capable of enhancing Nisin stability while retaining antimicrobial activity. The microencapsulation of Nisin was achieved by pre-gelation of alginate using calcium chloride and subsequent direct electrostatic interaction between cationic Nisin and chitosan with pre-gelled anionic alginate at pH 5.0. Following microcapsule formation, physicochemical and structural characterisation was performed using Zeta potential determination and measurement of the polydispersity index (PDI) via dynamic light scattering. SEM micrographs were used to confirm morphology, while Fourier-transform infrared (FTIR) spectroscopy and high-performance liquid chromatography (HPLC) were utilised to assess chemical integrity and functional group preservation of encapsulated Nisin. Following this, stable microcapsules with diameters ranging from 150-200 nm and smooth surface morphology were obtained. Microcapsule formation was strongly influenced by formulation parameters, particularly pH, calcium ion concentration, and chitosan content, with deviations from optimal acidic conditions (< pH 5.0) resulting in aggregation, increased polydispersity, and reduced encapsulation efficiency. The microcapsules were monodispersed (PDI {approx} 0.30) and electrostatically stable, exhibiting a Zeta potential of approximately +36 mV. These microcapsules remained stable over a prolonged storage period of 21 days under refrigerated conditions while retaining antimicrobial activity against Bacillus cereus. Encapsulation efficiency reached approximately 65%, confirming effective retention of Nisin within the polymer matrix. Overall, the findings demonstrate that chitosan-alginate ionic gelation is a non-denaturing and effective encapsulation strategy for extending the functional stability of Nisin. These microcapsules show strong potential as natural antimicrobial delivery systems for food and beverage applications, particularly in acidic food matrices, with implications for improved food safety and shelf-life extension.

Background: The U.S. Food and Nutrient Database for Dietary Studies (FNDDS) is updated across NHANES dietary cycles and is central to U.S. nutrition surveillance. However, multi-cycle food-code-level changes in nutrient composition have not been comprehensively characterized across the full WWEIA nutrient panel. Objective: To characterize ten-year temporal patterns in nutrient composition across five FNDDS cycles, evaluate pandemic-period food-code compositional stability, and distinguish exploratory mean-level signals from distributional heterogeneity that may reflect reformulation, database coverage, or food-code definition changes. Methods: We analyzed five consecutive FNDDS biennial releases: 2013-14, 2015-16, 2017-18, 2019-20, and 2021-23. Nutrient values were extracted from the public FNDDS/FoodData Central release files and standardized to per-100-g food-code-level records. Cycle midpoints, 2013.5, 2015.5, 2017.5, 2019.5, and 2022.0, served as the independent variable in an exploratory ordinary least squares (OLS) regression. Mann-Kendall testing assessed monotonic rank trends, Welch's ANOVA assessed food-code-level distributional heterogeneity, and pairwise Welch comparisons with Cohen's d summarized pre-pandemic, pandemic-period, and post-pandemic differences. Equivalence testing using TOST with +/-10% bounds was restricted to the 2019-20 versus 2021-23 stability comparison. OLS sensitivity analyses were repeated after excluding the structurally atypical 2017-18 cycle. Results: Sixty-three nutrients were analyzed. Eight nutrients showed nominal OLS trends, p < 0.05, but none remained significant after Bonferroni correction. Mann-Kendall testing identified two nominal monotonic signals, and none after adjustment. Welch's ANOVA detected cycle-level distributional differences for 61 of 63 nutrients at nominal p < 0.05 and 57 of 63 after adjustment. Pairwise pandemic-period analyses showed many adjusted differences when the pre-pandemic baseline was compared with 2019-20 or 2021-23, but standardized effects were small, with all absolute Cohen's d values < 0.20. No nutrient differed after adjustment between 2019-20 and 2021-23, and 39 of 48 primary analytes met +/-10% TOST equivalence criteria for that comparison. Slope estimates were directionally stable after excluding 2017-18, but nominal significance status remained sensitive to the short time series. Conclusions: FNDDS food composition varied across cycles, but there was no clear decade-long linear trend for most nutrients. The main signal was a possible increase in total PUFA and linoleic acid, which may reflect changes in fat quality. The 2021-23 cycle was very similar to 2019-20, suggesting no major post-pandemic shift in the foods represented. These findings should be interpreted as food-database signals, not as direct estimates of what people consumed.

Previous research has shown that mammalian fatty acids (FAs) can influence antibiotic tolerance of Staphylococcus aureus, yet many of these studies overlook the sources of these FAs, which are primarily esterified into glycero- and phospholipids, and the impact S. aureus lipase activity has on host lipids. Here we attempt to gain insight into the complex interplay between the S. aureus lipidome and its environment using culture media supplemented tissue-specific phospholipid mixtures. Phospholipid profiles of heart, liver, and brain-derived lipids revealed distinct distributions of headgroup and fatty acyl tail structures within the phospholipids. Following the growth of S. aureus in lipid-enriched broth, PG species containing mono- and poly-unsaturated acyl tails were detected with abundances that correlated strongly with the FA profile of the tissue extract. We found that S. aureus cultured with liver-derived lipid extract, which yielded the most unsaturated PGs, promoted growth in high concentrations of the membrane-targeting antimicrobial daptomycin. To explore the influence of lipase activity on the extracellular lipids, comparative analysis of fresh versus spent media revealed that the lipase-mediated degradation of complex phospholipid mixtures was influenced by both head group structure and acyl tail linkage. Concurrently, the spent media contained elevated levels of mono- and polyunsaturated lysophospholipids that were predominantly of the 2-acyl form rather than the 1-acyl form observed in the fresh media. Together, these results demonstrate the extent to which the lipase activity of S. aureus remodels both its own lipidome as well as the structures of the phospholipids in the surrounding environment. IMPORTANCES. aureus releases a secreted glycerol ester hydrolase, Geh, into the extracellular environment, which enables the bacterium to generate free FA from glycerolipids, phospholipids, and cholesterol esters that are present in surrounding tissue of an infection. The liberated FAs can be incorporated into the phospholipids of S. aureus, thereby altering its membrane physiology with mono- and poly-unsaturated FAs it cannot otherwise synthesize. Simultaneously, the action of Geh on lipids in the host environment leads to higher levels of bioactive lysophospholipids that participate in mammalian signaling pathways. This work reveals the preferences of S. aureus Geh across phospholipids with different head group and acyl tail structures found within tissue-derived lipid extracts, as well as the fate of the liberated FAs within the staphylococcal membrane lipids. The impacts of these processes on both the host and bacterium have implications for the immune response to and antibiotic treatment of S. aureus infections.

Background: Sugar sweetened beverages (SSBs), artificially sweetened beverages (ASBs), and fruit and vegetable juices are consumed worldwide, yet their associations with cancer remain unclear. Methods: Within World Cancer Research Fund International's Global Cancer Update Programme (CUP Global), we conducted a systematic review by searching PubMed and Embase until September 2024 for cohort studies of SSBs, ASBs, and juices and cancer risk. Meta-analyses were conducted to calculate the relative risks (RRs) and 95% CIs per 1 serving/day (355 mL for SSBs/ASBs; 177 mL for juices). Evidence was graded by the CUP Global Expert Panel. The CUP Global standard protocol was registered at: https://osf.io/7utbm/. Findings: We identified 158 publications from 51 cohorts. Evidence supported a judgment of a probable causal association of SSBs, including carbonated SSBs, with pancreatic cancer incidence (RR 1.09 [95% CI 1.01-1.16]; I2=8%, n=18 studies), and of SSBs with colorectal cancer incidence (RR 1.07 [95% CI 1.00-1.14]; I2=41%, n=13). Limited suggestive evidence supported positive associations of SSBs with ovarian (RR 1.61 [95%CI 1.03-2.53]; I2=0%, n=2), endometrial (RR 1.21 [95%CI 1.03-1.42]; I2=0%, n=3), and postmenopausal breast cancer (RR 1.05 [95%CI 1.00-1.10] ; I2=0%, n=6), and of carbonated ASBs with leukaemia (RR 1.29 [95%CI 1.01-1.64]; I2=0%, n=2). Evidence supported a judgment of a probable causal association of orange juice with melanoma (RR 1.21 [95%CI 1.08-1.34]; I2=0%, n=4), and skin basal (RR 1.12 [95%CI 1.06-1.17]; I2=46%, n=2) and squamous cell carcinoma (RR 1.13 [95%CI 1.04-1.24]; I2=0%, n=2). An interactive evidence platform is available at: Soft Drinks and Cancer Risk - CUP Global Evidence Platform. Interpretation: This review provides evidence supporting probable causal associations of SSBs with pancreatic and colorectal cancers, and of orange juice with skin cancers, with additional suggestive evidence for SSBs with other obesity-related cancers, extending concerns about sugary drink consumption beyond cardiometabolic health to cancer risk. Funding: World Cancer Research Fund network of charities (American Institute for Cancer Research; World Cancer Research Fund; Wereld Kanker Onderzoek Fonds).

Lactoferrin is a multifunctional iron-binding glycoprotein that supports intestinal barrier function, immune regulation, and a favorable gut microbial environment. However, the contribution of gut microbial biotransformation to its gastrointestinal activity remains poorly understood. We investigated whether effera(R), a precision fermentation-derived recombinant human lactoferrin, supports intestinal barrier function through microbiome-mediated mechanisms. effera(R) underwent simulated upper gastrointestinal digestion followed by ex vivo colonic fermentation using the validated SIFR(R) technology pipeline, which employs bioreactors that are inoculated with fecal microbiota from six healthy adult donors. Microbial activity was evaluated by measuring short-chain fatty acid (SCFA) production, bacterial cell density, and microbiome composition. effera(R) produced dose-dependent increases in the production of SCFAs and bacterial cell density demonstrating enhanced microbial metabolic activity. These metabolic changes were accompanied by shifts in key microbial groups within Bacillota_A and Bacteroidota. Intact effera(R) and cell-free post-colonic fermentation-derived products were evaluated in a Caco-2/THP-1 epithelial-immune co-culture model under basal and lipopolysaccharide-challenged conditions. Whereas intact protein did not significantly improve epithelial barrier integrity, effera(R)s post-colonic fermentation-derived products significantly enhanced transepithelial electrical resistance (TEER) under basal conditions and produced an even stronger barrier-protective response following LPS challenge. Across matched doses, effera(R) consistently generated greater TEER responses than bovine lactoferrin. Improved barrier function was accompanied by increased expression of tight-junction-associated targets ZO-1 and occludin and reduced secretion of CXCL-10 and IL-8. Together, these findings demonstrate that microbial biotransformation enhances the biological activity of effera(R), linking increased microbial metabolism with improved epithelial barrier integrity and modulation of inflammatory signaling. This integrated study provides a strong mechanistic foundation for the use of human lactoferrin in adult gut-health applications and offers valuable guidance for future adult clinical studies and infant-relevant investigations.

During household storage, expressed human milk can develop odor and flavor changes that trigger infant refusal and lead caregivers to discard their saved milk supply. We show that typical refrigeration and freezing conditions disrupt the milk fat globule membrane (MFGM), exposing milk lipids to lipases that catalyze hydrolysis and oxidation. A pectin-based formulation (PBF) maintains MFGM integrity during storage and following lipase challenge, suppressing production of glycerol, free fatty acid, and oxylipin byproducts without broadly affecting milk macronutrients, the proteome, and culturable microbial burden. Across an independent cohort of lactating individuals, lipase activity varied but tracked with maternal milk lipase gene expression, implicating endogenous lipolysis in stored-milk deterioration. In a blinded olfactory panel, PBF-treated, lipase-challenged milk smelled more like fresh milk than untreated controls. Together, these findings show that stabilizing the MFGM can protect stored human milk from lipase-driven deterioration, preserve sensory quality, and support use for infant feeding.

Biopreservatives including nisin and its derivatives are becoming more desirable in the food processing industry because of the growing demand for naturally preserved and minimally processed foods free from artificial preservatives. However, ensuring microbiological safety while meeting these consumer preferences remains a major challenge. This has necessitated the continuous investigation of potential new antimicrobial agents produced by naturally occurring microorganisms. Hence, this study explored the synthesis, characterisation, and optimisation of a bacteriocinogenic lactic acid bacterium and its antimicrobial product, possibly novel bacteriocin (Nisin 2A) from Lactococcus lactis isolated from commercial brined cheese. The isolation was achieved by screening for wild-type bacteriocin-producing lactic acid bacteria from dairy products using MRS media. Screening was performed using antagonism assays, yielding five producer organisms. Of these, the isolate whose metabolites exhibited the most potent antimicrobial activity was identified as Lactococcus lactis, which synthesised an active antimicrobial peptide designated as Nisin 2A, with a molecular mass of approximately 3.3 kDa as determined by UHPLC-MS and SDS-PAGE. Production of Nisin 2A was scaled up through fed-batch fermentation of Lactococcus lactis in modified MRS broth following process optimisation using a Plackett-Burman experimental design and purified by ammonium sulphate precipitation and solid-phase extraction (SPE). Furthermore, the antimicrobial potential of the bacteriocin was evaluated by the agar well diffusion assay and quantified using the tube dilution method. The purified peptide demonstrated broad-spectrum antimicrobial activity, particularly against the test Gram-positive bacteria Bacillus cereus and retained its bioactivity across a wide pH range (3-9) and high thermal conditions (up to 100 {degrees}C). Furthermore, it had high sensitivity to proteolytic enzymes (Proteinase K and Trypsin). Notably, the peptide was thermostable and retained up to 90% of its initial activity after thermal treatment and maintained consistent inhibitory performance after extended storage. These findings highlight the potential application of Nisin 2A as a natural biopreservative in food systems.

Bacterial biofilms exhibit enhanced resistance to antibiotics compared to planktonic bacteria, though the mechanisms underlying this tolerance remain incompletely understood. Evidence suggests biofilm-associated bacteria maintain active lipid metabolism despite reduced metabolic rates, making lipid-targeting strategies potentially effective. We investigated isopropyl lipid ether amines (LEAs), computationally designed to bind phospholipase A2, as novel antibiotics targeting biofilm bacteria through lipid metabolism disruption. LEAs consist of variable-length alkyl chain analogs of natural fatty acids connected via ether linkages to cationic head groups. Using methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa in collagen microplate assays, minimal inhibitory concentration studies, and ex vivo porcine biofilm models, we systematically compared LEAs against their fatty acid analogs to isolate the contribution of the lipid and amine moieties. Palmitic acid analog LEA-160 and oleic acid analog LEA-181 achieved MIC and reduced microplate biofilm colony forming units (CFU) against MRSA, while short lipid chain octanoic acid analog LEA-80 reduced Pseudomonas biofilms, with no effect for natural fatty acids. This demonstrates that the cationic amine group provides essential antibacterial function beyond the alkyl chain contribution. Comprehensive lipidomics analysis using LC-IMS-MS/MS revealed that LEA treatment induces significant alterations in MRSA lipid profiles, supporting a mechanism involving disruption of bacterial membrane lipid metabolism. Structure-activity relationships confirmed that both the lipid chain and cationic moieties are necessary for LEA antibacterial efficacy, with metabolic effects distinct from their natural fatty acid analogs. These findings establish LEAs as a mechanistically distinct antibiotic class targeting bacterial lipid metabolism pathways critical for biofilm survival.

Child-targeted marketing on packaged foods can shape children's food preferences and parents' purchasing decisions, yet many products with child-targeted marketing are ultra-processed foods (UPFs) and contain cosmetic additives such as food colorings, which have raised concerns about adverse effects on children's health and behavior. This mixed-methods study examined the prevalence of food colorings in child-directed UPFs and explored parents' perceptions and knowledge of these additives in beverages commonly consumed by children. Quantitative data were obtained from the Mintel Global New Products Database to identify child-directed products launched in Brazil between 2018 and 2021, measured as having at least one child-targeted marketing strategy in the food package, and whether they contained food colorings. Qualitative data came from seven focus groups with parents of children aged 2-5 and 6-11 years in Brazil, alongside a brief survey assessing participants' ability to identify food colorings on product labels. Among 5,078 UPFs launched during the study period, 23.0% contained child-targeted marketing, and 40.3% of these had food colorings. The highest prevalence was observed in carbonated beverages, candies, and ice creams, in which more than half of products contained food colorings. Parents generally understood that food colorings are used to make products more attractive to children and associated them with potential health risks, but reported difficulties avoiding them. These findings highlight the widespread presence of food colorings in child-targeted UPFs in Brazil and underscore the need for stronger regulatory measures to restrict the use of food colorings and improve labelling on food packages.

Consumption of ultra-processed foods is rising globally and has been implicated in inflammation and metabolic dysfunction, yet the impact of specific food additives on the human gut microbiota remains poorly understood. Using dietary data from the Food & You study (approximately 1000 participants in Switzerland), we identified 257 unique additives from 4,119 unique packaged products to quantify each participant's daily additive exposure. Higher exposure to a combination of high intensity sweeteners and sugar polyols, commonly found in low calorie products, was independently associated with reduced gut microbial Shannon diversity (beta = -0.39, p < 0.001), after adjustment for demographics, diet quality, BMI and bowel movement frequency. At a broader level, total additive exposure and fast food consumption were each negatively associated with gut microbial diversity; however, additive exposure remained independently associated and also specifically attenuated the diversity benefits of vegetable rich diets. Furthermore, microbial log ratio signatures linked to additive exposure showed strong negative correlations with Shannon diversity, including emulsifiers and thickeners (r = -0.66) and preservatives and antioxidants (r = -0.56). Integrating additive exposure with healthy dietary components such as HEI, fruits, or vegetables strengthened associations with gut microbial diversity; for example, vegetable linked correlations with Shannon diversity increased from r = 0.52 to r = 0.65 when contrasted against preservative-antioxidant exposure. Concordantly, microbial signatures associated with the sweeteners and sugar polyols additive combination showed depletion of fiber associated commensal taxa, and enrichment of pathways involved in polyol and aromatic compound metabolism. Notably, these associations emerged despite packaged foods representing only approximately 15% of logged dietary intake, underscoring the sensitivity of gut microbial diversity to limited exposure, and demonstrating that without integrating additive and processed-food metrics, one of the largest effect-size phenomena in human gut microbiota diversity would remain undetected.

Abstract Background and Objective: To investigate the efficacy of a new, proprietary high-resistance potato starch as a prebiotic in comparison to inulin and a control. Methods: In this prospective study, an intervention of 9 g of resistant potato starch (RPS, Potatodaat), inulin, or accessible corn starch was given to participants with mild to moderate indigestion for 30 days. Short chain fatty acid (SCFA) levels, changes to the gut microbiome, and changes in clinical symptoms of indigestion were assessed as primary outcomes. Results: Subjects in the RPS (n = 22), inulin (n = 23), and accessible corn starch (n = 22) groups demonstrated similarity in age, sex, and baseline parameters. At 30 days, the groups experienced 21.1%, 6.29%, and 9.15% increases in stool butyrate, respectively. Clinical symptoms like indigestion and flatulence showed greater improvement with the use of RPS compared to the other two groups. Conclusion: Consumption of high resistance potato starch helps improve stool SCFA levels along with clinical symptoms related to digestion, showing its better prebiotic potential as compared to inulin and accessible corn starch. The new high-resistance potato starch can be considered an effective replacement for inulin.

BackgroundEmerging evidence suggests that PFAS can cross blood-brain barrier and lead to neurotoxicity. Recent evidence also suggest that PFAS can bioaccumulate in gut microbiota resident in the gut. However, how gut microbes influence PFAS-driven reorganization of metabolic homeostasis in the brain is poorly understood. MethodsTo address this gap, we investigated how gut microbiota influences brain metabolomic and lipidomic responses to PFAS exposure. Specific pathogen-free (SPF) and germ-free (GF) mice were fed an obesogenic diet for 8 weeks to promote metabolic disturbance. After 1 week of acclimation, half received control water and half received water containing a PFAS mixture (PFHxS, GenX, PFOA, PFOS, and FTOH mixture). Plasma and brain samples (cortex, subcortex, cerebellum, olfactory bulb, and brainstem) were collected after 8 weeks. Untargeted analyses were performed for lipidomic, metabolomic and PFAS using high resolution liquid chromatography tandem mass spectrometry (LC-MS/MS). Data was processed using MassCube with open-sources libraries. ResultsPFHxS, GenX, PFOA, PFOS, PFDA, and PFDS were detected in plasma. PFHxS, PFOA, PFOS, and PFDS were detected across all five brain regions, with PFOS as the predominant brain-enriched species. Pathway analysis identified nicotinate and nicotinamide metabolism as the most consistently PFAS-altered pathway in both SPF and GF mice. PFAS exposure induced region-specific metabolic remodeling, with gut microbiota differentially modulating responses in the cortex, cerebellum, and brainstem, whereas the olfactory bulb showed a largely microbiota-independent response. In addition to local effects within individual brain regions, plasma-brain analysis suggested systemic metabolic responses across tissues, with association strength varying by brain region and microbiome status. Gut microbiota also shaped PFAS-induced lipid dysregulation in the brain, and methylnicotinamide and delta-valerobetaine were among the most responsive metabolites. ConclusionThis study is the first to demonstrate that resident microbiota impact PFAS-associated metabolic remodeling across the gut-plasma-brain axis. HighlightsO_LIPFAS-induced metabolic remodeling in the brain is modified by gut microbiota. C_LIO_LIPFAS exposure alters nicotinate and nicotinamide metabolism throughout the brain. C_LIO_LIPFAS-induced brain metabolic responses are region specific and microbiota dependent. C_LIO_LIPlasma-brain analysis suggests potential systemic metabolic disruption by PFAS. C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=104 SRC="FIGDIR/small/743341v1_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@15301deorg.highwire.dtl.DTLVardef@9fac0aorg.highwire.dtl.DTLVardef@d7f0f4org.highwire.dtl.DTLVardef@10c29c2_HPS_FORMAT_FIGEXP M_FIG C_FIG

Background. Obesity is a modifiable risk factor for osteoarthritis and may contribute to pain, functional impairment, inflammation, and cartilage degradation. Resveratrol has potential anti-inflammatory and chondroprotective effects, but its efficacy as an adjunct to dietary intervention remains unclear. Objective. This study evaluated whether resveratrol supplementation provides additional benefits when combined with a low-calorie diet in postmenopausal women with obesity and knee osteoarthritis. Methods. A total of 97 postmenopausal women with obesity and knee osteoarthritis were included in this randomized controlled clinical study. Participants received either a 10-day low-calorie diet alone or the same diet combined with 150 mg/day trans-resveratrol. Anthropometric parameters, body composition, biochemical markers, pain intensity, functional status, and urinary CTX-II were assessed at baseline and follow-up. Results. Both interventions were associated with reductions in body weight, BMI, waist and hip circumferences, fat mass, glucose, HOMA-IR, lipid parameters, hsCRP, VAS, WOMAC, LAI, and urinary CTX-II. Compared with diet alone, resveratrol supplementation did not provide additional benefits for anthropometric parameters, glucose metabolism, lipid profile, or WOMAC score. However, the resveratrol group showed a greater reduction in hsCRP and urinary CTX-II. The obesity class did not modify the treatment effect. Conclusion. A short-term low-calorie diet improved metabolic, inflammatory, and osteoarthritis-related parameters in postmenopausal women with obesity and knee osteoarthritis. The addition of resveratrol did not enhance weight loss or improve most metabolic outcomes but was associated with greater reductions in hsCRP and urinary CTX-II. These findings suggest a potential anti-inflammatory and cartilage-related effect of resveratrol, which requires confirmation in longer randomized trials.

BackgroundGroup B coxsackieviruses (CVBs) are involved in triggering type 1 diabetes. Free bifidobacterial lipoproteins (BLps) prevent CVBs cell infection. Our objective is to isolate free BLps potentially released by bifidobacteria in breastmilk and document their bioavailability. MethodsBifidobacterium breve and B. longum were quantified by qPCR in samples donated to the hospitals biobank (DHM) within two weeks following delivery. BLps were captured onto CV B4, analyzed by SDS-PAGE and competitive ELISA. BLps transport through Caco-2 monolayers was monitored after DHM contact. Titration of anti-CV B IgA was carried out by ELISA. ResultsAmong the 90 enrolled donors, seven were excluded, 68 donated a unique sample and 15 donated multiple specimens (2 to 12). B. breve and B.longum were detected in 93.0 % and 32.8% unique DHM samples, respectively. The two species showed unstable counts in the multiple donation group. Although at highly variable amounts, BLps were readily detected. Free B.longum Lps were found in absence of B.longum itself. The BLps crossed the cell layer within 4h still binding CV B4. ConclusionDHM contained BLps able to cross a cell layer mimicking the intestine still retaining their capacity to bind CV B. It suggested a possible newborns systemic protection against CV B4 infection that needs further investigation. ImpactO_LIOur study provided the first observation of anti-coxsackievirus B free bifidobacterial lipoproteins (BLps) in donor human milk (DHM) samples, complementing the anti-CV B IgA pool. C_LIO_LITheir isolation independently of the bifidobacteria themselves pointed towards an extramammary source. C_LIO_LIDHM BLps were transferred without losing their antiviral potential across the human intestinal epithelial monolayer at a concentration compatible with neonate intake in the first week following birth. C_LIO_LIThe study highlighted that breastmilk encompasses a broader anti-viral repertoire, opening new perspectives to combat enterovirus. C_LI

Background: Almost 1 in 2 adults in the US has obesity, with women facing the highest prevalence of severe obesity. Emerging evidence shows that the gut microbiome and its metabolites play a key role in metabolic regulation, acting as signals in active metabolic tissues such as adipose and skeletal muscle, thereby contributing to the deterioration of cardiometabolic health in individuals with obesity. Recent findings suggest that functional characteristics of the gut microbiome, rather than compositional changes alone, may partially explain why some individuals experience greater metabolic benefits from exercise than others. We designed a pilot trial to assess the acute response to an exercise bout across distinct obesity phenotypes and to identify microbial signatures associated with lifestyle interventions. Methods: We proposed a pilot trial in which 40 young adults (21 to 40 years old) with distinct exercise (< 150 minutes per week or > 4 hours per week) and body compositions (body mass index [BMI] 18.5 to 24.99 or > 30 kg/m2) would undergo an acute exercise bout. The outcomes of this pilot trial are as follows: (1) Examine the effects of a 30-minute bout of moderate-intensity aerobic exercise (60 to 70% heart rate reserve) on the abundance and functional activity of short-chain fatty acid (SCFA)-producing gut bacteria across different obesity phenotypes in women; (2) Assess the acute effects of the same exercise bout on SCFA concentrations in stool and circulating plasma metabolomic profiles. Discussion: The results of this pilot study will inform the feasibility of a larger trial to establish the gut-synthesized

Kakadu plum (Terminalia ferdinandiana), an Australian native fruit, is among the richest known dietary sources of vitamin C and hydrolysable tannins, yet its capacity to protect the intestinal epithelium against oxidative stress remains largely unexplored. This study optimised the extraction of bioactive compounds from freeze-dried Kakadu plum powder and evaluated their antioxidant activity using both chemical and cellular antioxidant in vitro assay. Phenolic compounds were extracted using three solvents (water, 80% ethanol, and 80% methanol) combined with shaking, ultrasound, or microwave assistance. Solvent, rather than processing technique, was the dominant determinant of antioxidant capacity: ethanol and methanol maximised total phenolic content, total flavonoid content, and DPPH radical-scavenging activity, whereas water extracts showed the highest ferric-reducing antioxidant power. Twenty-four phenolic compounds identified by HPLC-ESI-QTOF-MS/MS were mapped by network pharmacology to nine core oxidative-stress targets, and cross-species molecular docking predicted conserved binding of key phenolics to canine orthologs of PTGS2 and MMP2. In an H2O2-induced oxidative-stress in vitro cell model using canine small intestinal epithelial cells, both water (less than 25 ug/mL) and ethanol (less than 250 ug/mL) extracts significantly suppressed intracellular reactive oxygen species (ROS) in a dose-dependent manner, with the ethanol extract effective across a wider concentration range. This work demonstrated that Kakadu plum extract could be a promising natural, multi-target antioxidant ingredient for canine intestinal health, and provided a reference for future in vivo research.