The gut microbiome is increasingly recognized as a key modulator of cancer immunotherapy efficacy. Given that diet is one of the most important determinants of the gut microbiome composition and function, nutritional strategies have emerged as promising tools to modulate anti-tumor immune responses. Here, we demonstrate that dietary supplementation with inulin reduces tumor growth and enhances αPD-1 efficacy in mice. These effects were associated with increased frequencies of intra-tumoral CD8⁺ and CD4⁺ T cells, particularly CCR9⁺CXCR3⁺ subsets, and enrichment of beneficial taxa such as Akkermansia and Lachnospiraceae, alongside elevated short-chain fatty acids (SCFA) levels. Among the SCFA, butyrate alone recapitulated the anti-tumor effect of inulin and had an additive effect when combined with αPD-1 therapy in a CD8⁺ T cell-dependent manner. Butyrate exerted its anti-tumor effects by transcriptional changes in CD8⁺ T cells involving activation of proliferation, trafficking, and metabolic pathways. In a cohort of 117 non-small cell lung cancer (NSCLC) patients amenable to immunotherapy, the median dietary fiber intake was lower than previously published studies but correlated with enrichment of Faecalibacterium praunitzii and metabolic pathways related to sucrose degradation and tryptophan biosynthesis. Collectively, our findings highlight the therapeutic potential of targeting diet-microbiome-immune system interactions to improve cancer immunotherapy outcomes.
Journal of the International Society of Sports NutritionKrzysztof Durkalec-Michalski, Michał Murawa, Michal Steffl, Tomasz Podgórski, Jakub Adamczewski, Małgorzata Marchelek-Myśliwiec, Tereza Jandova, Michal Vagner,…
BACKGROUND: β-hydroxy-β-methylbutyrate (HMB) supplementation may support aerobic capacity and isometric strength. Its utility has been studied mainly for 3 g HMB·day-1. Therefore, new and personalized HMB supplementation protocols should be verified. This parallel randomized placebo(PLA)-controlled triple-blind study was designed to evaluate the effects of liquid HMB free acid supplementation during customary training/lifestyle or combined with high-intensity functional training (HIFT) on aerobic fitness, physical capacity, and isometric strength indices following an incremental cycling test (ICT) in trained (TR) and untrained (UTR) males. METHODS: Fifty-three TR (29.1 ± 7.7 years; body mass (BM): 84.8 ± 10.0 kg; FFM: 71.2 ± 8.9 kg) and 37 UTR participants (32.3 ± 7.6 years; BM: 90.1 ± 16.5 kg; FFM: 68.4 ± 10.3 kg) completed two 3-weeks periods, including: 1) supplementation period (SUP)-ingesting 90 mg·kgFFM -1·day-1 of either HMB or PLA and performing usual training (TR) or lifestyle (UTR), and 2) HMB/PLA ingestion combined with the additional HIFT stimuli (2 units per week; SUP + EX). TR_HMB, TR_PLA, UTR_HMB, UTR_PLA groups were analyzed. Testing visits were performed at baseline (T BAS ), and after the SUP (T SUP ) and the SUP + EX (T SUP+EX ). The following evaluations were performed: BM and body composition, ICT, and maximal voluntary isometric contraction (MVIC) of the lower limb. A general linear model was conducted to examine the main effects and interaction of treatment (supplementation) (HMB/PLA), training status (TS; TR/UTR), and baseline values (BAS) over repeated measurements (T BAS , T SUP , T SUP+EX ). The following interactions were tested: visit × treatment; visit × TS; visit × treatment × TS; and visit × treatment × TS × BAS. One-way ANOVA or Kruskal-Wallis ANOVA (non-normal distribution) were conducted to examine differences in the degree of absolute changes (ΔT SUP -T BAS , ΔT SUP+EX -T SUP , ΔT SUP+EX -T BAS ) in the measured indices between studied subgroups. RESULTS: Increases (T SUP+EX -T BAS ) in VO2MAX (p = 0.024), time to the anaerobic threshold (AT; p < 0.001), VO2AT (p = 0.001), power output at the AT (p < 0.001), heart rate at the AT (p < 0.001), time to the respiratory compensation point (RCP; p < 0.001), VO2RCP (p < 0.001), power output at the RCP (p < 0.001) were higher in TR_HMB vs. TR_PLA. Simultaneously, in UTR, greater increases in TimeRCP (p = 0.001) and PowerRCP (p = 0.002) occurred with HMB supplementation compared to PLA. MVIC indices did not change due to the treatment. CONCLUSIONS: Supplementation of high HMB dose combined with HIFT increases aerobic fitness and capacity, especially RCP and AT indices. HMB supplementation combined with HIFT evoked significant favorable changes in a greater number of the evaluated aerobic fitness and capacity indices in trained compared to untrained individuals. Thus, untrained individuals probably need greater exercise stimuli (>2 HIFT units per week) and a longer intervention period to obtained greater benefits. These findings suggest that incorporating liquid HMB supplementation at a dose of 90 mg·kgFFM -1·day-1 alongside HIFT is an effective strategy to enhance aerobic fitness and capacity in trained individuals, while further research including longer intervention periods and greater training stimuli is needed to determine the optimal supplementation protocol for untrained individuals.
Gut microbesBerengère Benoit, Pierre Letourneau, Vincent Verdier, Angélique Viney, Cécile Barnel, Karim Chikh, Oriane Vitalis, Audrey Jalabert, Sandra Wagner, Manolo Laiol…
Low-protein diets (LPD) are recommended in chronic kidney disease (CKD) to reduce disease progression. However, their clinical efficacy and safety are debated due to the risk of protein-energy wasting. A deeper mechanistic understanding is therefore required. Herein, the metabolic effects of LPD in both murine models and a randomized controlled trial in nondiabetic CKD patients were investigated, focusing on glucose homeostasis, plasmatic uremic toxin (UTs) levels, gut microbiota remodeling, and endocrine adaptations. In both experimental and clinical settings, LPD improved glucose tolerance and significantly decreased circulating levels of gut-derived UTs while reducing body weight (-33% weight gain in mice and a decrease in body mass index of ~-0.5 kg/m2 in humans). These metabolic improvements were associated with alterations in gut microbiota composition and function, including the downregulation of microbial pathways involved in aromatic amino acid biosynthesis. In both mice and patients, LPD triggered a significant hepatic induction of fibroblast growth factor 21 (FGF21), an endocrine regulator of amino acid deficiency (+2.9-fold in human and 28-fold in mice) FGF21 levels correlated negatively with lean mass and positively with fat mass and glycemic control, supporting a dual role in metabolic adaptation and catabolic signaling. To mitigate the adverse nutritional effects of LPD, we administered Lactiplantibacillus plantarum WJL (LpWJL), a probiotic previously found to enhance growth of under nutritional stress in CKD mice. LpWJL restored circulating amino acid levels, suppressed FGF21 induction (-26%) and stress-related biosynthetic responses, and preserved body weight (+247% weight gain) and composition, without impairing the benefits of LPD on kidney and metabolic parameters. The present findings identify UTs and FGF21 as crucial factors of the metabolic response to LPD, and support microbiota-targeted strategies, such as LpWJL supplementation, to enhance LPD efficacy. Clinical trials are, however, required to confirm their relevance in CKD management.
Gut microbesMengXuan Du, Wenzhao Wang, Min-Zhi Jiang, Xin-Wei Sun, Lei Sun, Chang Liu, Shuang-Jiang Liu
Next-generation probiotics derived from gut commensals show promise for metabolic disease intervention, yet effective anti-obesity strains remain limited. Here, we demonstrate that oral administration of Christensenella massiliensis markedly alleviates obesity and metabolic dysfunction in high-fat diet-induced obese mice. Treatment reduced food intake, improved glucose tolerance and insulin sensitivity, lowered blood glucose and lipid levels, and attenuated hepatic steatosis and adipose accumulation. C. massiliensis increased the levels of plasma GLP-1 and ileal GLP-1 receptor expression while decreasing ghrelin level, suggesting modulation of gut hormone regulation. C. massiliensis also suppressed systemic and colonic inflammation, accompanied by upregulation of metabolic homeostasis-related genes (ppara, pparg, ucp2). Targeted and quantitative metabolomics identified altered gut metabolic profiles, particularly reduced kynurenine levels. In vitro assays further showed that C. massiliensis converted kynurenine into kynurenic acid, and its lysate reversed kynurenine-induced lipid accumulation, inflammation, and PPARγ suppression in hepatocytes, providing mechanistic support for the observed in vivo metabolic benefits. These findings support C. massiliensis as a promising next-generation probiotic for obesity management.
Clostridioides difficile infection (CDI) is a major cause of antibiotic-associated diarrhea, with frequent recurrences closely linked to antibiotic-induced dysbiosis of the gut microbiota and bile acid metabolism. Parabacteroides distasonis, a potential probiotic capable of converting primary to secondary bile acids, has shown therapeutic promise in several metabolic and inflammatory diseases. This study evaluated the preventive and therapeutic effects of P. distasonis against CDI and explored the underlying mechanisms. We characterized the probiotic properties of four P. distasonis strains and investigated the inhibitory activity of strain 1190003 against C. difficile, as well as its protective and therapeutic efficacy in mouse models. Gut microbiota structure and bile acid metabolic profiles were analyzed by integrating 16S rRNA gene sequencing and metabolomics. The four P. distasonis strains exhibited strong acid and bile salt tolerance as well as auto-aggregation ability. Supernatants from P. distasonis co-cultured with cholic acid (4 mM and 8 mM) significantly inhibited C. difficile growth, toxin expression and spore formation, with deoxycholic acid identified as the key inhibitory metabolite. Both live P. distasonis and its culture supernatant alleviated disease severity in CDI mouse models and ameliorated gut microbiota dysbiosis. Notably, the relative abundance of Parabacteroides goldsteinii was increased following supernatant treatment. Furthermore, intervention with either live P. distasonis or its supernatant elevated the level of hyodeoxycholic acid. In summary, P. distasonis acts as a potential probiotic that alleviates CDI by ameliorating gut microbiota dysbiosis and remodeling bile acid metabolism. These findings provide experimental evidence for its use as a microbiota-based therapeutic strategy.
Journal of the International Society of Sports NutritionXuebing Bai, Tailong Xu
BACKGROUND: Creatine (Cr) and β-alanine (BA) are among the most studied ergogenic supplements, acting on distinct physiological pathways-Cr facilitates phosphocreatine resynthesis and rapid ATP turnover, while BA elevates intramuscular carnosine to enhance acid-base buffering. Although both compounds improve high-intensity performance independently, the ergogenic potential of their combined use remains uncertain. OBJECTIVE: To systematically evaluate and compare the isolated and combined effects of Cr and BA supplementation on aerobic and anaerobic performance indices using a network meta-analytic approach. METHODS: Following PRISMA guidelines, a comprehensive search of PubMed, Scopus, and Web of Science (to August 2025) identified randomized controlled trials (RCTs) examining Cr, BA, or Cr + BA supplementation (≥2 weeks) in healthy adult athletes. Fifty-two RCTs (PEDro ≥ 6) met the inclusion criteria. Standardized mean differences (SMD) and 95% confidence intervals (CI) were computed within random effects models. Performance outcomes included sprint, jump, agility, upper- and lower-body muscular endurance (UME, LME), and repeated-sprint ability (RSA). RESULTS: Cr supplementation significantly improved sprint performance (SMD = -0.64; p = 0.04), jump performance (SMD = 0.33; p = 0.002), RSA (SMD = -0.78; p = 0.01), and UME (SMD = 0.43; p = 0.01) versus placebo, with P scores ≥ 0.90 across these domains. In contrast, BA supplementation produced non-significant or context-specific effects, and combined Cr + BA showed no synergistic benefits. Agility and LME outcomes remained unaffected (p > 0.05). Heterogeneity ranged from low to moderate (I2 = 0-73%), with no global inconsistency or substantive publication bias. CONCLUSION: Evidence indicates Cr supplementation alone yields the most consistent improvements in high-intensity and anaerobic performance by enhancing phosphocreatine recovery and neuromuscular output. BA's buffering advantage appears task-specific and insufficient to augment Cr's ergogenic efficacy. Co-supplementation of Cr and BA offers no additional advantage beyond Cr monotherapy. Standardized, long-term, multi-arm RCTs are warranted to further clarify potential interactive mechanisms and sex or sport-specific responses.
Gut microbesTroels Holger Vaaben, Ditte Olsen Lützhøft, Karl Alex Hedin, Linda Ahonen, Ruben Vazquez-Uribe, Morten Otto Alexander Sommer
The gut microbiome shapes cancer progression and treatment responses, yet scalable microbiome-targeted interventions remain limited. We screened commercial probiotics for activation of the host aryl hydrocarbon receptor (AhR) and identified the yeast Saccharomyces boulardii as a consistent AhR activator. In an immunocompetent syngeneic colorectal cancer model, daily oral gavage of S. boulardii slowed growth of established subcutaneous tumors without detectable tumor colonization. Integrated profiling of the gut microbiome, circulating metabolites, cytokines, and tumor transcriptomes revealed a coordinated systemic response. S. boulardii increased microbial diversity and functionally rebalanced the gut microbiota, enriching taxa with lower genome-encoded biosynthetic autonomy. These changes were accompanied by elevated plasma levels of several indole metabolites, including the AhR agonists 5-hydroxyindole-3-acetic acid (5-HIAA) and indole-3-propionic acid (IPA). Targeted LC-MS/MS showed that S. boulardii can produce 5-HIAA under culture conditions, whereas IPA was not detected, suggesting that increased plasma levels of these metabolites may arise through a combination of probiotic activity and broader microbiome-associated processes. Circulating IL-17A and CTLA-4 were reduced, and tumors exhibited downregulation of programs linked to invasion, inflammation, and KRAS signaling. Multi-omics integration showed strong covariation across microbial, metabolic, immune signaling, and tumor compartments, highlighting coordinated cross-compartment responses during S. boulardii-associated tumor suppression.
Microbiological researchXiaowei He, Kemin Mao, Kaige Peng, Jinrong Zhao, Xianghong Wang, Jie Gao, Yaxin Sang
To systematically evaluate the potential fermentation and probiotic-related properties of E. durans B21 isolated from kefir, this study integrated whole-genome sequencing, comparative genomics, genome-scale metabolic model (GEM) reconstruction, and in vitro phenotypic assays to comprehensively analyze its genetic characteristics, metabolic potential, safety, and probiotic-related functions. The results showed that E. durans B21 possesses a 3.14 Mb circular chromosome and three plasmids, with a total of 2935 predicted coding genes. The genome encodes 91 carbohydrate-active enzymes (CAZymes) and multiple lactose metabolism-related genes, indicating strong carbohydrate utilization potential. Comparative genomic analysis revealed high genomic similarity between B21 and the potential probiotic strain E. durans A8-1, and 27 probiotic-related functional genes were identified in B21. Additionally, the reconstructed GEM achieved a MEMOTE score of 86.7%. Flux balance analysis predicted that the strain could produce acetaldehyde and other flavor-related metabolites through lactose metabolism, which was experimentally validated by in vitro assays showing an acetaldehyde yield of 0.2137 mM in M17 medium. In vitro functional assays demonstrated that the strain exhibited certain tolerance to simulated intestinal fluid and bile salts, along with strong auto-aggregation and biofilm formation abilities. Nevertheless, multiple antimicrobial resistance-associated genes and several virulence-related factors were also identified in the genome, suggesting that its safety still requires further evaluation through antimicrobial resistance transferability analysis and animal experiments. Overall, E. durans B21 exhibits fermentation-associated and probiotic-related traits and may serve as a potential functional fermentation strain for further investigation.
Early-life nutritional overfeeding is increasingly recognized as a critical driver of metabolic programming and long-term obesity risk. This study investigated the protective effects and underlying mechanisms of Bifidobacterium animalis DPU-MWFBA, designated as FBA-40, against early-life overfeeding-induced obesity and metabolic dysfunction. An early overfeeding mouse model was established by small-litter rearing, followed by a two-week oral intervention with FBA-40. FBA-40 significantly attenuated excessive body weight gain and adiposity, improved glucose tolerance and insulin sensitivity, and alleviated dyslipidemia, systemic inflammation, and hepatic dysfunction. Histological analyses showed that FBA-40 reduced hepatic lipid accumulation and improved liver morphology. In addition, colonic histology and immunohistochemistry demonstrated that FBA-40 preserved intestinal barrier integrity by increasing ZO-1 and Occludin expression while suppressing TNF-α-associated inflammatory activation. Gut microbiota analysis revealed that FBA-40 restored microbial richness and diversity and reshaped gut microbial composition toward a more metabolically favorable profile. Hepatic transcriptomic analysis further showed that FBA-40 reprogrammed lipid metabolism-, oxidative stress-, and inflammation-related pathways, particularly PPAR signaling, linoleic acid metabolism, cholesterol metabolism, bile secretion, and arachidonic acid metabolism. qRT-PCR and estern blot validation confirmed that FBA-40 suppressed lipogenesis-related targets, including Scd1, Acaca, Lpin1, and SCD1, while restoring PPARα/EHHADH-associated fatty acid β-oxidation and GPX1-mediated antioxidant defense. Collectively, these findings demonstrate that FBA-40 alleviates early-life overfeeding-induced metabolic dysfunction by coordinating gut microbial remodeling, intestinal barrier protection, and hepatic lipid metabolic reprogramming. This study provides mechanistic evidence supporting FBA-40 as a promising early-life probiotic candidate for preventing obesity and associated metabolic disorders.
Pharmaceutical biologyNadeem Akhtar, Joanne Barnes, Paula Gardiner, Bill J Gurley, Richard Ko, Igor Koturbash, Deval Patel, Richard B van Breemen, Amy L Roe
BACKGROUND: The United States Pharmacopeia (USP) Dietary Supplement Admission Evaluation and Labeling Expert Committee (DSAEL EC) routinely monitors safety‑related literature for dietary ingredients covered by USP monographs. Following multiple reports of hepatotoxicity associated with turmeric- or curcuminoid-containing products, the DSAEL EC conducted a comprehensive evaluation. OBJECTIVE: To assess the safety of turmeric and curcuminoids and determine whether cautionary labeling should be added to the USP monographs for these ingredients. METHODS: Following USP Guidelines, the DSAEL EC reviewed safety and toxicological information. RESULTS AND DISCUSSION: Hepatotoxicity has been observed with high-dose turmeric rhizome powder or extract in a few rodent toxicology studies. Numerous clinical trials involving turmeric- or curcuminoid-containing supplements have not reported organ toxicity or serious adverse events. Published case reports of clinically apparent liver injury often involve concomitant medications or supplements. Reported hepatotoxicity typically occurs after 1 to 4 months of use and generally resolves upon discontinuation; cases of acute liver failure have been reported albeit rarely. Proposed mechanisms include idiosyncratic, immune-mediated injury, and emerging evidence suggests possible genetic susceptibility. CONCLUSIONS: The USP DSAEL EC recommends adding the following cautionary statement to its turmeric and curcuminoids monographs: Liver problems have been reported very rarely in people taking supplements containing turmeric and/or curcuminoids. Consult your health-care practitioner before using this product if you have a history of liver problems. Stop using this product if you develop symptoms such as abdominal pain, dark urine, or jaundice (yellowing of the skin or eyes), and seek medical advice.
Journal of the International Society of Sports NutritionBarbara Strasser, Johannes Burtscher, Jesus Álvarez-Herms, Martin Kopp, Benjamin Pageaux, Martin Burtscher
BACKGROUND: Exercise tolerance is a pivotal factor in determining athletic competitive success, as well as mobility and quality of life in elderly individuals and those afflicted by chronic ailments. Since tolerance to endurance exercise is closely related to the perception of effort, any measure that influences this perception may also impact endurance performance. METHODS: The aim of this brief review was to evaluate how dietary interventions can improve endurance performance by reducing perceived effort. We contextualize our review within theoretical frameworks that consider effort perception to be a key regulator of endurance performance. Next, we integrate evidence on the ergogenic effects of various dietary interventions with existing knowledge on the perception of effort. RESULTS: Dietary interventions may enhance endurance performance by improving motor command transmission, slowing fatigue development and related compensatory increase in motor command, and/or modifying the activity of brain networks involved in effort perception and fatigue. Beta-alanine, caffeine or carbohydrate mouth rinsing are examples of evidence-based ergogenic aids. The impact on endurance performance is achieved through their potential to overcome cardiorespiratory and metabolic limitations or through modulation of the central nervous system. Other dietary supplements, such as branched-chain amino acids, citrulline, taurine, and probiotics, may indirectly impact performance by influencing tolerance to physical exertion. CONCLUSION: While current evidence supports a key role for dietary interventions on endurance performance by influencing individuals' perceived effort, more research is needed to determine the optimal doses and precise formulations for different sports, in order to employ a personalized strategy.
Gut microbesPeter Suenaert, Anneleen Segers, Leen Rymenans, Hélène Devroye, Janne Marie Moll, Patrice D Cani, Willem M de Vos
Pasteurized Akkermansia muciniphila MucT was found to improve barrier function in preclinical models and a proof-of-concept study in obese and prediabetic adults. Here, we describe the results of a double-blind placebo-controlled multicenter (Ireland and Germany) trial in 142 adults with metabolic syndrome, with or without prediabetes. The primary endpoint of whole-body insulin sensitivity (Matsuda index) did not differ after 4-months of daily administration of capsules containing 30 billion cells of pasteurized A. muciniphila MucT compared to placebo in the intention-to-treat subjects. Subsequent exploratory analyses showed that 3-months intake of pasteurized A. muciniphila MucT already improved HOMA-based hepatic insulin sensitivity in prediabetic (12%; p = 0.05) and 63-y-or-older-age subgroups (p = 0.05) while increasing post-OGTT excursion of the insulinotropic hormone glucagon-like peptide 1 (GLP-1) over placebo (p < 0.01). Further analysis of the gut microbiota by deep metagenomic analysis showed minor effects of the intervention but revealed that the baseline microbial composition differed from that in matched healthy adults. We found that participants with low baseline Akkermansia gene counts experienced significant health improvements and GLP-1 excursion after 3-months of treatment with pasteurized A. muciniphila MucT over the placebo. These benefits included improved insulin sensitivity (as shown by Matsuda and HOMA-S indices) and GLP-1 excursion (post-OGTT) (p < 0.05), reductions in body weight (p = 0.06) and decreased trunk fat (p < 0.05). In conclusion, daily supplementation with pasteurized A. muciniphila MucT has the potential to improve health markers in overweight or obese normo- or dysglycemic adults with the most significant improvements in subjects with low baseline intestinal Akkermansia levels, who are apparently truly in need of this intervention. Clinical trial registration no.: NCT05114018 clinicaltrials.gov.
Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and GynaecologyPedro Belchín Fernández, Virginia Calvente, Maria Jose Gómez Roso, Eva González Expósito, Ana Silván Bueno, Maya Aparicio Fluge, Daniel Ordoñez Pérez
BACKGROUND: PCOS is frequently associated with metabolic disturbances, including a high prevalence of insulin resistance and compensatory hyperinsulinemia, which can impair reproductive outcomes. Previous evidence indicates that combining myo-inositol and D-chiro-inositol in a specific 3.6:1 ratio may support ovarian physiology and reproductive performance in women with PCOS. This study aimed to evaluate whether taking a 3.6:1 MYO:DCI inositol-based supplement enriched with antioxidants for at least 1 month prior to controlled ovarian stimulation could improve IVF-ICSI outcomes. METHODS: A retrospective observational cohort study was conducted, including 92 women diagnosed with PCOS according to the Rotterdam criteria. Patients were allocated to 2 groups: those who used the MYO:DCI 3.6:1 antioxidant-containing supplement (Group 1) and those who followed conventional supplementation (Group 2). Outcomes assessed included ovarian response, fertilization rates, blastocyst development and pregnancy results. RESULTS: The number of retrieved oocytes (21.5 in Group 1 vs. 20.7 in Group 2; p = 0.56) and the metaphase II oocyte rate (72.06% in Group 1 vs. 71.23% in Group 2; p = 0.68) were comparable between both groups. Notably, Group 1 achieved higher fertilization rates (77.66% vs. 71.61%; p = 0.0314) and a lower proportion of cycles without at least one good-quality blastocyst to transfer (4.35% vs. 17.39%; p = 0.0450). In addition, both clinical and ongoing pregnancy rates were significantly improved in the supplemented group (54.39% vs. 42.65%; p = 0.0203; 45.61% vs. 36.76%; p = 0.0033). CONCLUSION: This observational pilot study suggests that a pre-treatment with 3.6:1 MYO:DCI ratio and antioxidant-based supplement taken for at least 1 month prior to ovarian stimulation may improve oocyte quality and increase pregnancy rates. These findings, while promising, require confirmation in larger prospective trials.
Global health actionNaiyuan Liang, Cheng Huang, Qiang Pan
BACKGROUND: Maternal folic acid supplementation is a cornerstone of public health for preventing neural tube defects (NTDs), yet its long-term impact on child development remains underexplored. OBJECTIVE: This study evaluates the long-term cognitive and mental health associations of maternal folic acid supplementation by utilising China's 2009 Folic Acid Supplementation Programme for rural women as a quasi-experimental framework. METHODS: We analysed 1,953 children aged 10-15 years from the 2020 China Family Panel Studies. Using provincial NTD prevalence in 2009 from the Maternal and Child Health Surveillance system as a proxy for intervention intensity, we employed difference-in-differences models to estimate associations, adjusting for demographic and parental covariates. RESULTS: Maternal folic acid supplementation was significantly associated with improved outcomes among girls: higher memory scores (β [95% CI], 0.232 [0.069, 0.394]), enhanced numerical reasoning skills (5.234, [2.188, 8.279]), lower Center for Epidemiological Studies Depression Scale score (-0.523 [-0.933, -0.113]), and reduced likelihood of depressive symptoms (-0.024 [-0.048, -0.001]). No comparable associations were observed in the boys. Although cognitive associations were observed across socioeconomic status (SES) groups among girls, the mental health associations were concentrated among girls from higher-SES families. Results were robust to adjustment for covariates. CONCLUSIONS: This study highlights sex-specific, long-term associations of maternal folic acid supplementation but reveals that socioeconomic disparities may constrain mental health gains. Thus, universal nutrition interventions alone may be insufficient to bridge health equity gaps. The findings should be interpreted within the broader nutritional ecology and alongside concurrent macro-social changes that shape child development outcomes.
Microorganisms with health-promoting potential often experience substantial losses in viability and function due to stresses encountered during manufacturing and gastrointestinal transit. In this study, we investigate whether biofilm can be leveraged to enhance microbial resilience and functional performance. Using Bacillus subtilis as a model biofilm-forming bacterium, we examined strains with defined biofilm phenotypes: a biofilm-deficient mutant (tasA eps), a biofilm-overproducing mutant (sinR), and an isogenic wild-type control. These strains were evaluated across multiple functional benchmarks, including survival in simulated gastric and bile juices, thermotolerance, and intestinal bacterial colonization in the Caenorhabditis elegans model. Commercially available strains Lactobacillus rhamnosus GG and Saccharomyces boulardii were included as reference comparators. The biofilm-overproducing B. subtilis sinR strain demonstrated markedly enhanced survival under simulated gastrointestinal conditions and showed increased colonization within the C. elegans intestine. In contrast, the biofilm-deficient tasA eps mutant exhibited severe sensitivity to gastric stress and reduced the intestinal bacterial load. Furthermore, we demonstrate that cell-free B. subtilis biofilm can function as an effective bioencapsulation matrix. When used to encapsulate multiple probiotic strains, the biofilm matrix significantly improved their survival under acidic gastric conditions by neutralizing the environmental pH, indicating its broad potential for probiotic formulations and targeted gastrointestinal delivery. Overall, biofilms are traditionally studied for their roles in infection and antimicrobial resistance; however, their protective and adaptive traits may be repurposed for beneficial use. As an example of this concept, our findings show that B. subtilis biofilms enhance multiple functional and technological traits and highlight biofilm-based strategies as a promising platform for improving beneficial microbial robustness and the delivery of live biotherapeutics.
White brined cheeses can provide a suitable environment for the persistence of spore-forming bacteria such as Clostridioides difficile. This study examined the behaviour of C. difficile during the controlled manufacture and 90-day ripening of laboratory-scale white brined cheeses and assessed the inhibitory effects of two probiotic combinations. After pasteurization, C. difficile spores were inoculated into designated batches, while two formulations previously shown to suppress the pathogen in vitro (commercial probiotic + isolate 43; YF-L901 + isolate 33) were added to separate groups. Physicochemical and microbiological parameters were monitored throughout ripening. Six experimental white-brined cheese groups were produced, consisting of rennet-only control cheeses with and without Clostridioides difficile inoculation, as well as probiotic-containing cheeses prepared with two different culture combinations under both inoculated and non-inoculated conditions. In the rennet-only batch containing C. difficile, counts decreased from 6.54 to 5.00 log CFU/g by day 90. C. difficile counts declined from 5.61 to 4.20 log CFU/g in cheeses containing the commercial probiotic + isolate 43, and from 5.54 to 4.38 log CFU/g in those with YF-L901 + isolate 33. Probiotic-supplemented cheeses also showed stronger lactic acid bacteria development, confirming successful colonisation of the cheese matrix. Although typical ripening changes in pH, moisture and salt were observed, these factors alone did not account for the reductions in C. difficile. Overall, probiotic-containing cheeses exhibited a more pronounced decline in C. difficile than the non-probiotic control. These results indicate that inhibition may be influenced not only by acidification but also by broader microbial interactions associated with the added cultures.
Food research international (Ottawa, Ont.)Huimin Zhang, Ting Liu, Qiang Meng, Ke Ren, Yibo Yuan, Jing Tian, Yane Luo, Tianli Yue
Intestinal barrier dysfunction is a core pathological feature of inflammatory bowel disease (IBD). Postbiotics have emerged as promising alternatives to probiotics due to their superior stability and safety. C. glutamicum is an industrial microorganism being Generally Recognized as Safe (GRAS); however, the efficacy and mechanism of its lysate in repairing the intestinal barrier remain largely unexplored. In this study, a dextran sulfate sodium (DSS)-induced colitis mouse model and a lipopolysaccharide (LPS)-induced Caco-2 cell inflammatory barrier model were employed to evaluate the barrier-restorative effects of lysate of C. glutamicum (CG-LS). The effects of CG-LS on cell viability, barrier integrity, inflammatory responses, oxidative stress, and cell cycle progression were systematically investigated as well as its bioactive components. In vivo experiments confirmed that oral administration of live C. glutamicum (108 CFU) attenuated DSS-induced colitis. Remarkably, in vitro studies revealed for the first time that CG-LS (107 CFU/mL) exhibited superior barrier-restorative effects compared to its live counterpart, with a 72.1% reduction in IL-6 and a 3.2-fold increase in IL-10 expression. CG-LS also restored tight junction protein expression (ZO-1 and Occludin-1 by 3.1- and 2.8-fold, respectively), alleviated oxidative stress (ROS reduced by 38.8%), and reversed LPS-induced G0/G1 cell cycle arrest (from 77.0% to 62.3%). Mechanistically, CG-LS specifically activated the FOXO pathway, orchestrating downstream gene networks involved in antioxidant defense, cell cycle progression, and barrier assembly. Furthermore, L-arginine was identified as the key bioactive component in CG-LS. These findings support the development of CG-LS or L-arginine-based functional foods or dietary supplements for intestinal barrier-related disorders.
Food research international (Ottawa, Ont.)Brenda Alessandra Munhoz, Carla Gabrieli Angelo, Nicole Catarine Silva, Vitória Cheli de Sousa, Aline de Souza Lopes, Débora Parra Baptista
High-protein fermented milks are promising vehicles for delivering probiotics and bioactive compounds, contributing to health promotion, particularly in the context of healthy aging. This study evaluated the effect of fermenting dairy formulations with different protein profiles using Lacticaseibacillus rhamnosus, with a focus on bioactive potential and peptide bioaccessibility. Milk was supplemented with calcium caseinate (CC) or whey protein isolate (WPI) to obtain distinct protein profiles. Fermented and non-fermented formulations were submitted to in vitro gastrointestinal digestion under older adults' conditions, followed by the assessment of probiotic viability, bacterial growth-promoting effect, angiotensin-converting enzyme (ACE) inhibitory activity, and peptide bioaccessibility. L. rhamnosus remained highly viable after intestinal digestion (7.27 log CFU/mL). Fermentation also exerted a positive effect on L. rhamnosus growth-promoting potential, particularly in the WPI-supplemented formulation. Furthermore, formulations containing WPI exhibited greater ACE inhibition. The peptide profile revealed sequences derived from caseins, especially the β-casein fraction, including peptides previously described as bioactive. Overall, these findings highlight the combined role of fermentation by L. rhamnosus and protein profile in modulating the bioactive potential of high-protein fermented milks. The results also support their potential as multifunctional matrices capable of delivering bioaccessible peptides with biological relevance, contributing to the development of products aimed at promoting health during aging.
Food research international (Ottawa, Ont.)Shuyi Zhou, Qunyan Fan, Yujie Fang, Yunxia Zhu, Xuncai Liu, Na Zhang, Guansheng Ma
Edible bird's nest (EBN) is a traditional functional food in Asia, with reported antioxidant and metabolic regulatory properties in preclinical studies, but evidence from controlled human studies describing its metabolic effects remains limited. This study aimed to characterize the serum metabolomic response to dietary EBN supplementation in healthy adults. In a 12-week randomized, double-blind, placebo-controlled trial, 109 healthy women were randomly assigned to placebo, low-dose EBN (3.5 g/day), or high-dose EBN (7.0 g/day). Untargeted serum metabolomics was conducted at baseline and during follow-up to assess metabolic changes associated with EBN intake. EBN intake was associated with time- and dose-dependent alterations in serum metabolomic profiles, with separation from the placebo group emerging by Week 4 and further separation observed at Week 8, followed by attenuation at Week 12. The metabolic response was primarily characterized by changes in amino acid- and lipid-related metabolites, including reduced circulating branched-chain amino acids and increased levels of phosphatidylcholine (PC 18:0) and nordihydroguaiaretic acid. Pathway analysis indicated coordinated modulation of branched-chain amino acid metabolism, glycerophospholipid metabolism, and pentose phosphate pathway-related redox processes, whereas pathway-level changes in the placebo group were limited. These findings provide human-based metabolomic evidence supporting EBN as a functional food with potential dose-dependent metabolic effects. Further studies are warranted to assess these responses across populations and intake durations, and to clarify optimal intake levels and their physiological relevance.
Brown milk beverages have garnered widespread attention due to their unique flavor and potential as a functional matrix for probiotic delivery. This study aimed to identify Lacticaseibacillus paracasei strains suitable for fermenting brown milk beverages by combining artificial intelligence-driven predictive screening with experimental validation and metabolomic analysis. Using the iProbiotics platform, 27 L. paracasei strains underwent initial screening, yielding seven candidates for further evaluation. These trains were systematically evaluated for gastrointestinal tolerance and bile salt tolerance, fermentation performance, storage stability, and metabolic profiles. Strains PC724 and PC646 demonstrated superior probiotic and technological properties, outperforming the commercial control strain LC-01 in acidification capacity, viable cell counts, and textural attributes. Over 35 days of refrigerated storage, both strains maintained high viability (>108 CFU/mL) and stable metabolic activity, confirming remarkable storage stability. Non-targeted metabolomics revealed sustained enrichment of carbohydrate metabolism, amino acid metabolism, and global metabolic regulation in PC724 and PC646. These metabolic signatures likely underpin their robust stress tolerance long-term survival. Collectively, integrating artificial intelligence prediction with metabolomic profiling provides a scalable strategy for identifying industrially viable probiotic candidates, offering a valuable framework for developing functional fermented milk beverages.