Food & Function

The postprandial effects of a novel food-grade extracted salmon polar lipids (SPL) supplement against platelet-activating factor (PAF) and thrombin-induced platelet aggregation in a human pilot study was evaluated. This study was double-blinded, crossover, and placebo controlled in design. Five healthy volunteers completed 4 h time-course trials on 5 separate days. Blood was drawn at baseline before subjects consumed a standardized breakfast with one of the following treatments: a low-dose (0.25 g) or a high-dose (0.5 g) of SPL encapsulated within a stomach resistant capsule (LDSR and HDSR respectively) or a non-resistant capsule (LDSNR and HDSNR, respectively), or placebo capsules containing food-grade glycerin (0.5 g; Placebo). Blood was analyzed at 1 h intervals for 4 h. Among the treatments tested, the high-dose non-resistant capsule (HDSNR) produced the clearest postprandial effects, inducing significant increases in EC50 (reduced platelet sensitivity) for PAF at 2-3 h and for thrombin at 3-4 h post-ingestion. Smaller or delayed effects were observed with the high-dose resistant capsule (HDSR), while low-dose formulations produced minimal changes. Postprandial plasma glucose, lipid profile (TC, HDL-C, LDL-C, TG), fibrinogen, prothrombin time, and activated partial thromboplastin time remained unaffected across all trials. This pilot study provides the first in vivo indication that SPL supplementation may modestly attenuate platelet responsiveness to both PAF and thrombin without altering standard haemostatic or metabolic biomarkers. Larger controlled studies are warranted to confirm these preliminary findings and define optimal dosing and formulation strategies.

Previous study demonstrated 150 mg{middle dot}kg-1 glycerol monolaurate (GML) consumption induced gut microbiota dysbiosis and metabolic syndrome (MetS) in low-fat diet fed mice. However, little is known about the dose-effect of dietary GML modulating the gut microbiome alterations and its impacts on the induction of MetS in low-fat diet. Dietary GML-induced effects on MetS and gut microbiota alterations were investigated, combined with antibiotics-treated germ-free experiment and specific gut microbiota transplantation. Our results demonstrated that high-dose (500 mg{middle dot}kg-1) GML alleviated MetS by significantly decreasing the body weight, weight gain, food intake, fat droplet size and percentage of abdominal fat, serum triglycerides (TG), LDL, LPS, TNF- and atherogenic index, compared to the medium-dose (150 mg{middle dot}kg-1) GML. Importantly, high-dose GML significantly increased Lactobacillus reuteri compared to the medium-dose GML. Co-occurrence network analysis revealed Lactobacillus reuteri was positively associated with the metabolic improvement of high-dose GML. Notably, antibiotics-treated germ-free experiment and Lactobacillus reuteri transplantation demonstrated that altered gut microbiota was necessary and sufficient for GML-induced distinct effects on metabolic syndrome. Our results indicate that GML impacts gut microbiome inducing distinct effects on metabolic syndrome, thereby calling for reassessing the safe dosage of GML and other non-specific antibacterial food additives. IMPORTANCEGrowing evidence indicate that the broad use of food emulsifying agents may lead to increase the societal incidence of obesity/ MetS and other chronic inflammatory diseases. GML is widely and regularly consumed as a generally safe food emulsifier and as a potent antimicrobial agent in commonly foods such as meat products, cereals and soft beverage by the general public. Our results indicate that GML impacts gut microbiome inducing distinct effects on metabolic syndrome. Our study provides important and timely evidence supporting the emerging concept that non-specific antibacterial food additives have two-sided effect on gut microbiota contributing to the uncertainties for the incidence of obesity/metabolic syndrome and other chronic inflammatory diseases.

Flavonoids, plant-derived compounds, are broadly categorized into glycoside (sugar-bonded) and aglycone (sugar-removed) forms and are predominantly found as glycosides in nature. Rutin, a glycoside, is a widely recognized flavonoid with significant potential as an anti-obesity agent. However, its low bioavailability in the body presents challenges in obesity treatment. We aimed to enhance the bioavailability and anti-obesity effect of rutin through microbial involvement. Lactiplantibacillus plantarum HAC03, one of the candidates, demonstrated the ability to hydrolyze rutin into isoquercetin and quercetin in vitro. In a diet-induced obesity mouse model, the combination of rutin and the L. plantarum strain resulted in significant weight loss, reduced adipocyte size and lowered obesity-related biomarkers in the blood, decreased fat-synthesis related gene expression, and increased fatty acid {beta}-oxidation related gene expression compared to other test groups. This includes groups treated with rutin or quercetin alone or in combination with a different species from the same Lactobacillus genus, known for its anti-obesity effect but lacking the ability to hydrolyze rutin. This synergistic combination also alleviated insulin resistance and reduced fat in the liver. Gut microbiota analysis revealed localization of L. plantarum in the ileum and beneficial changes in disrupted microbiota in the intestine. These findings provide insights into underlying mechanisms causing the synergistic effect and suggest a novel combination that is as safe as microbial monotherapies with L. plantarum or L. rhamnosus but more effective in anti-obesity treatment.

IntroductionFiber intake is the most common nutritional inadequacy in the Western diet, with most adults consuming less than half of the recommended intake with only 5% of adults meeting the RDI. A novel, short-chain beta-glucan derived from oats (scOat Fiber), with improved solubility, low viscosity and enhanced palatability, compared to conventional oat fibers, was investigated for its benefits as a source of fiber supplementation. MethodsA 14-day pilot study evaluated the gastrointestinal tolerance and functional benefits of scOat Fiber in 63 healthy adults randomized to receive 5, 10 or 20 g daily doses. The primary outcome, gastrointestinal tolerability, was assessed using the Gastrointestinal Symptom Rating Scale (GSRS). Secondary outcome included glycemic response during rice challenges, measured via continuous glucose monitoring (CGM). CGM was also used to explore overall glucose dynamics. Additional exploratory outcomes (mood, energy, appetite and sleep) were assessed via validated questionnaires. ResultsscOat Fiber was exceptionally well tolerated across all doses, with no increase in GSRS scores, which remained in the low to mild range. Significant reductions in total GSRS scores were observed, with benefits evident after just one week at 5 g/day and maintained over time at both 5 and 10 g/day groups. Evaluation of GSRS sub-categories revealed that the 5 g/day and 10 g/day dose groups experienced significant reductions in abdominal pain symptoms. Both dose groups also demonstrated a significant decrease in constipation at the end of the study. Postprandial glucose responses were attenuated following product use, with a significant reduction in peak glucose during rice challenges after 2 weeks in the 20 g/day group. Both 10 and 20 g/day doses were associated with significant improvement in glycemic metrics during the study, including reductions in glucose mean, all glycemic excursions, and an increase in time-in-range. Exploratory analysis suggested that scOat Fiber may improve mental health and concentration in participants with elevated baseline symptoms. ConclusionsDespite the lack of a placebo control and short duration, the dose-dependent nature of the results supports the potential of scOat Fiber as a well-tolerated and functional source of fiber with benefits including glycemic control, digestive health and mental health (NCT06739941)

This study focused on the development of functional dairy products fortified with bioactive peptides derived from Lactobacillus rhamnosus C25-fermented sheep milk and their evaluation during storage. Microencapsulated peptides were incorporated into flavoured milk and srikhand, and their antimicrobial, antioxidant, and sensory properties were monitored over refrigerated storage. Flavoured milk supplemented with free peptides exhibited strong antimicrobial activity, while encapsulated peptides provided a controlled and sustained release, maintaining functionality over six days. In srikhand, both plain and mango-flavoured formulations demonstrated enhanced biofunctional properties, with encapsulated peptides showing gradual peptide release, higher antioxidant activity, and better preservation of sensory quality over 15 days. Sheep milk used for fermentation showed good microbial quality, supporting safe peptide production. Fermentation yielded peptide fractions (<3, <5, and <10 kDa), which were analyzed using RP-HPLC and LC-MS/MS, identifying over 3,100 peptides. In silico screening predicted 34 peptides with antimicrobial potential, including cationic and amphipathic -helical peptides primarily derived from {beta}-casein and {kappa}-casein. Functional assays demonstrated potent antimicrobial activity against Gram-positive and Gram-negative pathogens, particularly in the 5-10 kDa fractions. Antioxidant activity was highest in the 5 kDa retentate, indicating that medium-sized peptides contributed most to radical scavenging. Microencapsulation using sodium alginate improved peptide stability and controlled release, mitigating bitterness and preserving product acceptability. Overall, the study highlights the potential of L. rhamnosus C25-fermented sheep milk peptides as natural bioactive ingredients for functional dairy products with enhanced shelf life, antimicrobial efficacy, and antioxidant capacity. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=135 SRC="FIGDIR/small/673363v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@1c368bdorg.highwire.dtl.DTLVardef@118db8org.highwire.dtl.DTLVardef@6f4addorg.highwire.dtl.DTLVardef@9c2ddc_HPS_FORMAT_FIGEXP M_FIG C_FIG

Outcomes from the COSMOS trial have reinforced the notion of flavanols as important plant-derived bioactives contributing to cardiovascular health. As discussions continue on whether specific dietary reference values for flavanols are warranted, it is possible that existing dietary guidelines emphasizing fruits and vegetables already yield sufficient flavanol intake levels. If this were the case, developing flavanol specific dietary reference values might be unnecessary. This study therefore aimed at assessing whether adherence to dietary recommendations for fruit and vegetable intake and overall diet quality achieves flavanol intake levels of 500 mg/day, the amount proven to mediate cardiovascular benefits in the COSMOS trial. Flavanol intake was objectively evaluated using two validated and complementary biomarkers, 5-(3{square},4{square}-dihydroxyphenyl)-{gamma}-valerolactone metabolites (gVLMB) and structurally related (-)-epicatechin metabolites (SREMB), in two geographically distinct studies: COSMOS (US; n=6,509) and EPIC-Norfolk (UK; n=24,154). The results showed that higher fruit and vegetable intakes and diet quality (assessed via the alternative healthy eating index-aHEI) were associated with increased flavanol intake in COSMOS. Nevertheless, fewer than 25% of participants meeting dietary guidelines achieved an estimated flavanol intake of [&ge;]500 mg/day. Similar findings were observed in EPIC-Norfolk as well as through flavanol intake simulations considering fruits and vegetables commonly consumed in the US diet. In conclusion, adherence to existing dietary guidelines does not yield flavanol intake levels comparable to those shown to provide cardiovascular benefits in COSMOS. Thus, specific dietary reference values for flavanols may still be necessary if aiming to increase the intake of these dietary compounds. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=101 SRC="FIGDIR/small/26346949v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@2966f5org.highwire.dtl.DTLVardef@269232org.highwire.dtl.DTLVardef@483edborg.highwire.dtl.DTLVardef@116a957_HPS_FORMAT_FIGEXP M_FIG C_FIG

Dietary choices and gut microbiota alterations are linked to the rising prevalence of cardiovascular diseases, including atherosclerosis. Fermented foods, recognized for their health benefits, are known for maintaining cardiovascular health, yet their impact on atherogenesis and associated gut microbiota changes is poorly understood. Here, we showed the restorative potential of long-term dietary supplementation with a traditional Indian fermented soybean, hawaijar, in mitigating atherogenic lesions formation and gut microbiota alteration induced by an atherogenic diet in C57BL/6 mice. The diet caused atherogenesis, characterized by increased inflammatory gene expression (IL-1{beta}, ICAM-1, CD4, FoxP3), elevated serum LPS endotoxin levels, and compromised gut health, indicated by increased permeability and decreased expression of tight junction and mucin-producing genes essential for gut barrier integrity (Ocln, Cldn-1, Cldn-4, Muc-2). Metagenomic analysis revealed diet-induced gut dysbiosis, evidenced by an elevated Firmicutes-to-Bacteroidetes ratio, reduced bacterial diversity, and a shift in bacterial composition, including a loss of beneficial Ligilactobacillus spp. while pathogenic Romboutsia spp., Escherichia spp., and Clostridium spp. emerged. Conversely, feeding hawaijar for sixteen weeks significantly improved atherogenesis, reducing atherosclerotic lesions, serum endotoxins, and inflammatory gene expression. It corrected dysbiosis, restoring gut microbiota to a healthy composition and enhancing gut barrier integrity by reducing permeability and increasing tight junction gene expression. Core beneficial bacteria such as Phocaeicola sartorii, Faecalibaculum rodentium, and Akkermansia muciniphila resurged, alongside the recovery of Muribaculum gordoncarteri and Duncaniella dubosii, which were lost in the atherogenic condition. Gut eubiosis upon fermented soybean supplementation was also linked with a predicted reduction in major metabolic pathways and a distinct increase in terpenoids and polyketide metabolism. The study highlights the importance of traditional fermented soybean in restoring gut microbiota diversity and gut health against dietary-induced dysbiosis, providing insights into its role in modulating atherogenesis in a gut microbiota-dependent manner. Highlights of findingsO_LIMetagenomics reveals changes in gut microbiota composition associated with diet-induced atherogenesis and consumption of traditional fermented soybean, hawaijar, in C57BL/6 mice. C_LIO_LIFermented soybean supplementation in atherogenic diet reduces atherogenic lesions, expression of genes associated with inflammatory response (IL-1{beta}, ICAM-1, CD4, and FoxP3), and serum LPS endotoxin level. C_LIO_LIFermented soybean consumption improves gut barrier integrity, indicated by decreased gut permeability and elevated expressions of tight junction genes (Ocln, Cldn-1, Cldn-4). C_LIO_LIDietary fermented soybean supplementation promotes eubiosis of atherogenic diet-induced dysbiotic microbiota with a profile characteristic of a normal diet. C_LIO_LIFive core microbiota members, including Ligilactobacillus spp., CAG-485 sp002493045 and others, are lost under atherogenic diet regime; however, only Muribaculum gordoncarteri and Duncaniella dubosii are restored with fermented soybean supplementation. C_LIO_LIEubiosis of diet-induced dysbiotic microbiota upon fermented soybean supplementation is associated with a predicted reduction in major metabolic pathways and a distinct increase in terpenoids and polyketide metabolism. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=197 SRC="FIGDIR/small/649253v1_ufig1.gif" ALT="Figure 1"> View larger version (79K): org.highwire.dtl.DTLVardef@77bf59org.highwire.dtl.DTLVardef@1b38d1forg.highwire.dtl.DTLVardef@f62a97org.highwire.dtl.DTLVardef@1665035_HPS_FORMAT_FIGEXP M_FIG C_FIG

AimsDysbiosis is an important factor that leads to metabolic disorders by disrupting energy balance and insulin sensitivity. A decrease in Akkermansia muciniphila is a phenotype of obesity-induced dysbiosis. Although interventions to increase A. muciniphila are expected to improve glucose metabolism, the underlying mechanism has not been fully understood. MethodsIsoxanthohumol (IX), a prenylated flavonoid found in beer hops was administered to high fat diet-fed mice. We analyzed glucose metabolism, gene expression profiles and histology of liver, epididymal adipose tissue and colon. Lipase activity, fecal lipid profiles and plasma metabolomic analysis were assessed. Fecal 16s rRNA sequencing was obtained and selected bacterial species were used for in vitro studies. Fecal microbiota transplantation and monocolonization were conducted to antibiotic-treated or germ-free (GF) mice. ResultsThe administration of IX lowered weight gain, decreased steatohepatitis and improved glucose metabolism. Mechanistically, IX inhibited pancreatic lipase activity and lipid absorption by decreasing the expression of the fatty acid transporter CD36 in the small intestine, which was confirmed by increased lipid excretion in feces. IX administration improved the gut barrier function and reduced metabolic endotoxemia. In contrast, the effects of IX were nullified by antibiotics. As revealed using 16S rRNA sequencing, the microbial community structure changed with a significant increase in the abundance of A. muciniphila in the IX-treated group. An anaerobic chamber study showed that IX selectively promoted the growth of A. muciniphila while exhibiting antimicrobial activity against some Bacteroides and Clostridium species. To further explore the direct effect of A. muciniphila on lipid and glucose metabolism, we monocolonized either A. muciniphila or Bacteroides thetaiotaomicron to GF mice. A. muciniphila monocolonization decreased CD36 expression in the jejunum and improved glucose metabolism, with decreased levels of multiple classes of fatty acids determined using plasma metabolomic analysis. ConclusionOur study confirmed a direct role of A. muciniphila in energy metabolism, which was induced by microbial actions of IX. These highlight new treatment strategies for preventing metabolic syndrome by boosting the gut microbiota with food components.

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.

Functional oligosaccharides, such as galacto-oligosaccharides (GOS), are valued for modulating gut microbiota and promoting health. This study aimed to produce a high-purity GOS ingredient (ALPINA GOS) via nanofiltration/diafiltration and assess its prebiotic efficacy using an in vitro fermentation model. GOS-rich syrup was obtained from transgalactosylation of lactose in concentrated whey permeate (30% lactose) and processed by diafiltration/nanofiltration to reduce monosaccharides and enrich oligosaccharide content. Carbohydrate composition was analyzed by HPAEC-PAD. Prebiotic activity was evaluated using a MicroColon model with fecal inocula from healthy adults, measuring pH, short-chain fatty acids (SCFAs), and microbiota shifts. Membrane processing increased oligosaccharides from 55.5% to 70.2% (dry basis) and reduced monosaccharides from 25.2% to 5.1%. ALPINA GOS induced a dose-dependent pH reduction and significantly enhanced lactate and acetate production, with stronger effects at 10 mg/mL. Microbiota profiling showed increased abundance of beneficial bacteria, especially Bifidobacterium, versus control. The findings confirm that GOS can be sustainably produced from whey permeate and exhibits potent prebiotic activity, supporting its application in functional foods aimed at gut health.

Mounting evidence supports the potential of dietary bioactive compounds to reduce chronic disease risk. Recently, the biological activity of N-trans-caffeoyltyramine (NCT) and N-trans-feruloyltyramine (NFT) has been hypothesized to drive regulation of gut permeability,but the impact of these components on the human gut microbiome composition has not been studied. The aim of this work is to determine whether purified NCT and NFT, or a hemp hull product containing NCT and NFT (Brightseed(R) Bio Gut Fiber), can impact the gut microbiome using an in vitro fermentation assay. To address this question, we treated three fecal inocula, representative of the human gut microbiome, with Bio Gut Fiber and NCT/NFT and evaluated their respective impact against starch and methylcellulose as controls. We found strong changes exerted by Bio Gut Fiber and NCT/NFT on the gut microbiome relative to starch and methylcellulose, with distinct responses across all microbial communities. Among communities treated with Bio Gut Fiber, we saw increased community productivity and increased community diversity. Further, to determine whether changes found in gut microbiome profiles were dose-dependent, we tested different concentrations of NCT/NFT and found a dose-dependent impact on the resulting microbial compositions. Through this work, we provide novel insight into the potential of bioactive components to shape the gut microbiome, highlighting the potential for plant-derived bioactives to improve the human gut microbiome and host health.

Black rice oligosaccharides (BO) were extracted with 80% aqueous ethanol (v/v) and purified by charcoal-celite chromatography followed by dialysis using a 500 Da molecular weight cut-off (MWCO) membrane, yielding an oligosaccharide fraction with a degree of polymerisation (DP) between three and eight (DP3-DP8; 2.87 {+/-} 0.29% w/w). MALDI-TOF MS showed sodium adduct ions from m/z 527 to 1330, and GC-MS analysis of hydrolysed samples identified glucose and galactose as the major monomers, while ketosyl residues were detected in the intact fraction by selective staining and are most plausibly attributed to fructosyl units based on cereal origin and DP distribution. BO showed high resistance to simulated salivary, gastric, and pancreatic digestion (only 2.08 {+/-} 0.51%, 0.34 {+/-} 0.03%, and 4.29 {+/-} 0.73% hydrolysis, respectively) with approximately 93% remaining carbohydrate available for fermentation. All Lactobacillus strains showed positive prebiotic activity scores, with the highest response observed for Lactobacillus rhamnosus (1.165 {+/-} 0.255) and Lactobacillus plantarum (0.980 {+/-} 0.163). Fermentation produced metabolically relevant short-chain fatty acids (SCFA), mainly acetate (34.82 {+/-} 2.08 mM), as well as strain-dependent propionate and butyrate levels. BO greatly promoted probiotic biofilm formation, with biomass reaching 391.33 {+/-} 26.08% and viable cell counts of 9.01 {+/-} 0.70 log CFU/mL relative to the control. Collectively, the results indicate that BO represents a digestion-resistant, hexose-based oligosaccharide series that is selectively utilised by probiotic lactobacilli, promotes SCFA production and enhances biofilm development. To our knowledge, this work is the first to combine structural profiling with in vitro functional evaluation of a purified, low-DP oligosaccharide fraction obtained from black rice. HighlightsO_LIPurified oligosaccharides (DP3-DP8) were obtained from black rice using charcoal-celite chromatography followed by dialysis. C_LIO_LIStructural analysis confirmed that the oligosaccharides were hexose-based and composed mainly of glucose and galactose. C_LIO_LIBlack rice oligosaccharides exhibited higher resistance to simulated gastric and intestinal digestion compared with starch. C_LIO_LIPositive prebiotic activity scores were observed due to selective utilisation by probiotic Lactobacillus strains. C_LIO_LIFermentation of black rice oligosaccharides significantly increased short-chain fatty acid production. C_LIO_LIPurified oligosaccharides enhanced probiotic biofilm formation, indicating improved colonisation potential. C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=179 SRC="FIGDIR/small/705216v1_ufig1.gif" ALT="Figure 1"> View larger version (43K): org.highwire.dtl.DTLVardef@9a5915org.highwire.dtl.DTLVardef@14eac7aorg.highwire.dtl.DTLVardef@1db8baorg.highwire.dtl.DTLVardef@14ad50a_HPS_FORMAT_FIGEXP M_FIG C_FIG

Inadequate dietary fiber intake and excess added sugar intake are dietary factors attributed to the rise in obesity, type 2 diabetes, and associated cardiometabolic diseases. Until recently, consumers had limited options for finding similar tasting, yet highly approachable, solutions to meet intake recommendations for added sugars and dietary fiber. Modern sodas with lower sugar and supplemented with prebiotic fiber may serve as functionally beneficial alternatives to traditional sugar-sweetened beverages. The primary objective was to compare the acute effects of a prebiotic soda, (PREB: 3g sugar, 6g dietary fiber) versus traditional soda (SODA: 39g sugar, no dietary fiber), with or without a meal, on postprandial glucose in generally healthy adults. Thirty middle- aged men and women [19 F, 11 M; (mean {+/-} standard deviation) 46.5 {+/-} 10.4 y; 29.5 {+/-} 2.6 kg/m2] consumed their assigned study product during the traditional lunch time in a free-living setting on 4-consecutive test days in a crossover design, counterbalanced by test sequence. Continuous glucose monitoring for blood glucose dynamics, visual analog scales for perceived hunger and alertness, and dietary logs for second meal behavior were all measured throughout the intervention. Glucose incremental area under the curve (iAUC) [mean difference (95% confidence interval); - 837 mg/min/dL (-1250, 188), p=0.032; -1690 mg/min/dL (-2790, -909), p<0.001; with and without meal, respectively] and maximum glucose concentration (Cmax) [-9 mg/dL (-27, 0), p=0.018; -36 mg/dL (-50, -22), p<0.001; with and without meal, respectively] were lower with PREB compared to SODA. PREB did not affect second meal timing nor energy intake compared to SODA. Perceived hunger or alertness were not altered by beverage type. In conclusion, a prebiotic soda is a favorable alternative to traditional soda formulations for managing postprandial blood glucose levels and maximal glucose excursion in generally healthy adults with overweight or obesity.

BackgroundIn vitro studies show that goat milk proteins form less compact coagulates in the stomach compared to cow milk proteins, which may facilitate gastric digestion and amino acid (AA) absorption. However, this has not been confirmed in vivo in humans. ObjectiveTo examine gastric digestion and changes in AA concentrations after cow milk-derived (cow MC) and goat milk-derived casein (goat MC) ingestion. MethodsIn this single-blind randomized cross-over study 18 men (age 23 {+/-} 1.6 years, BMI 23 {+/-} 1.6 kg/m2) consumed 300 ml of a drink containing 30 g of cow MC or goat MC. Participants underwent gastric MRI scans at baseline and every 10 minutes up to 60 minutes postprandially. Blood was drawn at baseline and up to 4 hours postprandially. In addition, participants verbally rated their appetite after each MRI measurement. Primary outcomes were gastric emptying and AA concentrations. Secondary outcome was gastric coagulation as inferred by image texture metrics. ResultsGastric emptying half-time was 80 {+/-} 25 minutes for goat and 85 {+/-} 24 minutes for cow MC (p = 0.395). In line with this, gastric emptying of the drinks over time was similar (MD 0.77 ml, 95% CI [-6.9, 8.5], p=0.845). Serum essential AA (MD -110 {micro}mol/L, 95% CI [-162, -58]) was higher over time for cow MC (p<0.001). The image texture metric contrast was lower for cow MC (MD 0.010, 95% CI [0.001, 0.020], p=0.036). ConclusionCow MC and goat MC have different coagulating properties, as inferred by AA concentrations and supported by image texture analysis. This did not influence overall gastric emptying or the emptying of the liquid and coagulated fractions, which were similar. This warrants further in vivo research on casein coagulation in the food matrix to help determine the optimal use for cow and goat milk and their protein fractions. Financial support: the study was funded by Ausnutria Dairy Corporation Ltd. Clinical trial registry number: NL8137 (Netherlands Trial Registry), accessible through https://trialsearch.who.int/Trial2.aspx?TrialID=NL-OMON28580

Alcoholic liver disease (ALD) is a major health burden linked to oxidative stress, gut dysbiosis, and disrupted hepatic metabolism. While Lactiplantibacillus plantarum (L. plantarum) has shown potential in alleviating ALD, the specific mechanisms and bioactive components remain unclear. This study investigated the hepatoprotective effects of L. plantarum fermentation liquid (PFL) and its key metabolite, 3,4-hydroxyphenyl lactic acid (HPLA), against alcohol-induced liver injury. Using acute and chronic alcohol intoxication mouse models, we demonstrated that PFL significantly reduced mortality, attenuated hepatocyte damage, and restored alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activities. UHPLC-QTOF-MS/MS analysis identified HPLA as the primary active component in PFL, exhibiting potent antioxidant properties. In vitro and in vivo experiments revealed that HPLA mitigated oxidative stress by enhancing superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, reducing malondialdehyde (MDA) levels, and suppressing lipid accumulation. Mechanistically, network pharmacology and molecular validation highlighted that HPLA alleviated hepatic injury by modulating the EGFR/PPAR- signaling axis, thereby counteracting alcohol-induced oxidative stress and lipid metabolism disorders. These findings elucidate a novel "gut-liver" axis mechanism mediated by HPLA, offering a theoretical foundation for the clinical application of L. plantarum and its metabolites in ALD management. ImportanceNumerous animal studies and clinical trials have demonstrated the effectiveness of probiotics in treating alcoholic liver disease. In this study, we primarily created a mouse model for both acute and chronic alcoholism and discovered that Lactiplantibacillus plantarum fermentation solution significantly decreased the inflammatory response and oxidative stress caused by alcohol. Its key metabolite, 3,4-hydroxyphenyl lactic acid (HPLA), exhibited strong antioxidant properties, helping to reduce oxidative stress by preventing lipid accumulation. This research offers insights into how probiotic interventions can mitigate alcoholic liver damage, enhancing our understanding of the protective effects of Lactiplantibacillus plantarum and emphasizing the potential of its metabolite, HPLA, as a targeted treatment for alcoholic liver disease.

Diets low in diverse fibre-rich plant foods are a major factor in the rise of chronic diseases globally. The BIOME study (NCT06231706) was a 6-week, parallel design randomised controlled trial in 399 healthy adults in the UK, investigating a simple dietary intervention containing 30+ whole-food ingredients high in plant polyphenolic compounds, fibre and micronutrients. Participants were randomised to the primary intervention (prebiotic blend; 30g/d) or control (bread croutons; 28g/d; isocaloric functional equivalent) or a daily probiotic (L. rhamnosus). The primary outcome was change in favourable and unfavourable microbiome species compared to control, secondary outcomes included changes in blood metabolites, gut symptoms, stool output, anthropometric measures, subjective hunger, sleep, energy and mood. A crossover test meal challenge sub-study was conducted in 34 participants, investigating postprandial glucose responses, subjective hunger, satiety and mood. In the 349 male and female participants (mean age 50yrs) included in the analysis (intention-to-treat), self-reported adherence was high (> 98% for all treatments). Following the prebiotic blend, significant improvements were seen in the change and ranking of favourable and unfavourable species as well as beta diversity (weighted-UniFrac measure), but not in the control or probiotic group. There were significantly greater improvements in self reported indigestion, constipation, heartburn, flatulence and energy, following the prebiotic vs control, and hunger following the prebiotic vs probiotic. Addition of the prebiotic to a high carbohydrate test meal challenge resulted in significant improvements in subjective hunger, fullness, and energy (3h incremental area under the curve). No other significant differences between groups were observed. This prebiotic blend is a simple dietary strategy that benefits gut microbiome composition, gut symptoms and self-reported energy and hunger. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=131 SRC="FIGDIR/small/24309816v1_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@1b26c20org.highwire.dtl.DTLVardef@d8dd09org.highwire.dtl.DTLVardef@1978cc5org.highwire.dtl.DTLVardef@9ae6a3_HPS_FORMAT_FIGEXP M_FIG C_FIG

Isomalto/malto-polysaccharides (IMMPs) are a novel type of soluble dietary fibres with a prebiotic potential promoting growth of beneficial microbes in the gut. However, the mode of action of IMMPs remains unknown. Previous studies on IMMPs showed an increase in total bacteria, especially lactobacilli, and higher production of short chain fatty acids (SCFA) when IMMPs were fed to rats or used during in vitro fermentation. Here we investigated with metatranscriptomics how IMMPs with different amounts of -(1[-&gt;]6) glycosidic linkages affected microbial function during incubation with human faecal inoculum. We showed that active microbial community dynamics during fermentation varied depending on the type of IMMP used and that the observed changes were reflected in the community gene expression profiles. Based on metatranscriptome analysis, members of Bacteroides, Lactobacillus and Bifidobacterium were the predominant degraders of IMMPs, and the increased gene expression in these bacteria correlated with high amounts of -(1[-&gt;]6) glycosidic linkages. We also noted an increase in relative abundance of these bacteria and an activation of pathways involved in SCFA synthesis. Our findings could provide a baseline for more targeted approaches in designing prebiotics for specific bacteria and to achieve more controlled modulation of microbial activity towards desired health outcomes.

Emerging evidence suggests that low-grade systemic inflammation plays a key role in altering brain activity, behaviour, and affect. Modulation of the gut microbiota using prebiotic fibre offers a potential therapeutic tool to regulate inflammation, mediated via the production of short-chain fatty acids (SCFAs). However, the impact of prebiotic consumption on affective symptoms, and the possible contribution from inflammation, gut symptoms, and the gut microbiome, is currently underexamined. In this 12-week study, the effects of a diverse prebiotic blend on inflammation, gut microbiota profiles, and affective symptoms in a population with Metabolic Syndrome (MetS) was examined. Sixty patients meeting the criteria for MetS were randomised into a treatment group (n = 40), receiving 10g per day of a diverse prebiotic blend and healthy eating advice and a control group (n = 20), receiving healthy eating advice only. Our results showed a significant reduction in C-reactive protein (CRP), alongside improvements in self-reported affective scores in the treatment compared to the control group. While there were no differences in relative abundance between groups at week 12, there was a significant increase from baseline to week 12 in Bifidobacterium and Parabacteroides in the treatment group, both of which are recognised as SCFA producers. Multivariate regression analyses further revealed that changes in affective scores were positively associated with both gastrointestinal symptoms and CRP. Together, this study provides preliminary support for the use of a diverse prebiotic blend for mood, stress, and anxiety.

The increasing popularity of plant-based meat alternatives (PBMAs) has triggered a contentious debate about their impact on gut health in comparison to traditional animal-based meats. This study investigates the digestibility and bioavailability of a beef patty, a commercial PBMA, and a homemade pea protein-based patty by examining their influence on gut microbial metabolism. Fecal samples from five different donors were utilized to replicate colonic fermentation in vitro, with samples collected at various time points (0, 6, 12, 24, 32, and 48 hours). A rapid biochemical profiling, comparing red meat and meat analogs in terms of traditional biomarkers of gut health (ammonia, phenols, indoles, pH, and short-chain fatty acids), was conducted. Additionally, an untargeted metabolomics workflow specially designed for time-series studies, utilizing ultra-high performance liquid chromatography hyphenated to a quadrupole time-of-flight mass spectrometer (UPLC-QTOF MS), was implemented to assess differences in terms of protein-related gut microbial metabolites (GMMs). The findings of this approach revealed notable differences in the production of intestinal inflammation markers, metabolites related to the carnitine pathways, and GMMs with signaling functions in the intestinal tract during the fermentation of animal- and plant-based burgers.

The coronavirus disease 2019 (COVID-19) pandemic has caused worldwide health issues. Although several vaccines have been developed, it is still difficult to prevent and reduce the inflammation caused by the infection. Studies have shown that there are correlations between the gut environment and severity of symptoms caused by SARS-CoV-2 infection. Several gut metabolites produced by the gut microbiota such as SCFAs and the secondary bile acid UDCA are reported to improve the survival rate of the host after viral infection in an animal model through modulation of the host immune system. Therefore, in this study, we attempted to use the prebiotic dietary fiber PHGG to modulate the gut microbiome and intestinal metabolites for improvement of host survival rate after SARS-CoV-2 infection in a Syrian hamster model. We were able to show that PHGG significantly improved the host survival rate and body weight reduction. Analysis of the gut microbiome, serum, and intestinal metabolites revealed that PHGG significantly increased the concentrations of several intestinal SCFAs, fecal secondary bile acids, and serum secondary bile acids. Furthermore, several microbial species and metabolites identified in this study are consistent with reports in humans. Taken together, our data suggest that PHGG is a candidate prebiotic food for reducing the morbidity of COVID-19.