Jiahao Shao, Weilian Hung, Pingping Yin, Pan Huang, Wen Zhao, Leilei Yu, Fengwei Tian, Wei Chen, Jin Xu, Qixiao Zhai, Jun Li, Jianxin Zhao
{"title":"Efficacy of <i>Bifidobacterium animalis</i> subsp. <i>lactate</i> BL-99 in relieving functional constipation: a randomized placebo-controlled clinical trial.","authors":"Jiahao Shao, Weilian Hung, Pingping Yin, Pan Huang, Wen Zhao, Leilei Yu, Fengwei Tian, Wei Chen, Jin Xu, Qixiao Zhai, Jun Li, Jianxin Zhao","doi":"10.1039/d5fo03175c","DOIUrl":"10.1039/d5fo03175c","url":null,"abstract":"<p><p>Current therapies for functional constipation (FC) often exhibit limited long-term efficacy. Probiotics, particularly <i>Bifidobacterium animalis</i> subsp. <i>lactis</i> BL-99 (BL-99), may offer a novel approach to alleviate FC symptoms. This randomized, double-blind, placebo-controlled trial (No. WXSY-YXLL-AF/SC-11/01.0) enrolled 41 FC patients who completed the full 6-week study. Participants were randomly assigned to receive either BL-99 (1 × 10<sup>11</sup> colony-forming units per day) or placebo for 4 weeks in this population trial. After completing the 4-week intervention period, administration was discontinued and participants entered a 2-week observation following-up period for continued monitoring. Primary endpoint data collected after trial completion were the changes in the Patient Assessment of Constipation Symptoms (PAC-SYM, 12-item scale) score, evaluated on the first day (0 day), the 28th day (week 4), and the 42th day (week 6). Secondary outcomes included fecal metagenomic profiling to evaluate gut microbiota alterations. After 4 weeks of intervention, the BL-99 group demonstrated significant reductions in PAC-SYM scores compared to the placebo, particularly in domains of \"abdominal discomfort\" (<i>Δ</i> = 1.8 <i>vs.</i> 0.9, <i>p</i> = 0.007) and \"pain during defecation\" (<i>Δ</i> = 2.1 <i>vs.</i> 1.0, <i>p</i> = 0.003). These improvements persisted at the 2-week post-treatment follow-up (<i>p</i> < 0.05). Metagenomic analysis revealed that BL-99 enriched <i>Bifidobacterium</i> and <i>Faecalibacterium</i> while suppressing <i>Clostridium</i> species, shifting gut microbiota composition closer to that of the healthy controls. Functional annotation highlighted significant downregulation of infection-related pathways (<i>e.g.</i>, bacterial invasion and LPS biosynthesis) and metabolic disease-associated pathways (<i>e.g.</i>, insulin resistance) in the BL-99 group (<i>q</i> < 0.05). This trial suggests that 4-week BL-99 supplementation effectively alleviates FC symptoms, partially through microbiota modulation and metabolic pathway regulation. The sustained post-treatment effects warrant further investigation into its long-term benefits.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":"8691-8701"},"PeriodicalIF":6.3,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148987221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Fucoidan as an anti-inflammatory and immunomodulatory agent in humans: a systematic review of clinical evidence and translational potential.","authors":"Ensieh Sadat Anari, Tingwei Wang, Zhongxiang Fang, Pangzhen Zhang, Antonio Celentano","doi":"10.1039/d6fo01559j","DOIUrl":"https://doi.org/10.1039/d6fo01559j","url":null,"abstract":"<p><p><i>Purpose</i>: fucoidan is a sulphated polysaccharide from brown seaweeds, commonly used as a dietary supplement due to its proposed anti-inflammatory, immunomodulatory, and potential tumour-related properties. However, despite substantial preclinical evidence, its clinical effects in humans remain unclear. This systematic review aims to evaluate and synthesise current clinical evidence on the effects of fucoidan on inflammatory, immune, metabolic, and tumour-related outcomes in humans. <i>Methods</i>: a systematic literature search was conducted in PubMed, Scopus, and Web of Science in accordance with the PRISMA guidelines. Human interventional studies evaluating fucoidan supplementation and reporting clinically relevant outcomes were included. Eligible populations comprised healthy adults, individuals with metabolic or inflammatory conditions, and patients with cancer. Outcomes included immune function, inflammatory biomarkers, metabolic parameters, tumour-related outcomes, quality of life, and safety. Risk of bias was assessed using the OHAT tool. Due to heterogeneity in study design and outcomes, meta-analysis was not performed. <i>Results</i>: five clinical studies met the inclusion criteria, including three randomised controlled trials and two open-label studies involving patients with cancer, with intervention durations of 2 to 24 weeks. Fucoidan was consistently well-tolerated, with no serious adverse events reported. Individual controlled trials reported reductions in selected pro-inflammatory cytokines, sex-specific changes in NK cell activity, and changes in gut microbiota composition in individuals with metabolic risk. However, these findings were not consistently replicated across studies. Studies involving patients with cancer reported short-term reductions in inflammatory markers and stable quality-of-life (QOL) measures; however, tumour-related outcomes were inconclusive. <i>Conclusions</i>: current evidence suggests that fucoidan may exert modest anti-inflammatory and immunomodulatory effects under selected clinical conditions; however, the available evidence remains limited, heterogeneous, and inconsistent. Although oral fucoidan was generally well tolerated, the small number of studies, limited replication of findings, heterogeneity in study populations and fucoidan characteristics, and methodological limitations preclude definitive conclusions regarding clinical efficacy. Well-designed, adequately powered randomised controlled trials using well-characterised fucoidan and clinically meaningful outcomes are required to establish the clinical efficacy of fucoidan in humans.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":""},"PeriodicalIF":6.3,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149072896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yue Zheng, Haiming Zhuang, Lintao Dan, Yao Zhou, Bing Yan, Yao Zhang, Duowu Zou, Xinyu Wang, Jing Sun
{"title":"Resistant starch alleviates intestinal fibrosis involving an acetate-mediated HDAC2-H3K27ac axis in fibroblasts.","authors":"Yue Zheng, Haiming Zhuang, Lintao Dan, Yao Zhou, Bing Yan, Yao Zhang, Duowu Zou, Xinyu Wang, Jing Sun","doi":"10.1039/d6fo01179a","DOIUrl":"10.1039/d6fo01179a","url":null,"abstract":"<p><p>Dietary fibre-based interventions are of growing interest for the prevention and treatment of digestive diseases. In this study, we investigated the effect of resistant starch (RS) on intestinal fibrosis, a stricturing condition driven by excessive extracellular matrix (ECM) accumulation. RS was found to alleviate intestinal fibrosis in a dextran sulfate sodium (DSS)-induced chronic colitis mouse model, as evidenced by restored colon length, reduced ECM deposition (fibronectin and collagen I), and decreased levels of α-smooth muscle actin. Given that RS is fermented by the gut microbiota in the colon, metagenomic sequencing revealed that RS reshaped the composition of the gut microbiota and increased the abundance of beneficial gut bacteria, including <i>Bacteroides acidifaciens</i>, <i>Faecalibaculum rodentium</i>, and <i>Bifidobacterium pseudolongum</i>, which are known to enhance the production of short-chain fatty acids. Targeted metabolomic analysis further showed a marked increase in acetate levels, which was associated with reduced intestinal fibrosis. However, direct <i>in vivo</i> evidence that acetate is required for the anti-fibrotic effect of RS remains lacking. Using human (CCD-18Co) and primary mouse intestinal fibroblasts, the major ECM-producing cells that drive fibrosis progression, we demonstrated that acetate inhibited TGF-β-induced fibroblast activation by inhibiting histone deacetylase 2, thereby enhancing the acetylation level of histone H3 at lysine 27. Collectively, these results suggest a potential microbial-metabolic-epigenetic axis linking RS and acetate to fibrosis attenuation, which awaits causal validation <i>in vivo</i>. This axis holds promise as a therapeutic target for fibrotic diseases.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":"8215-8230"},"PeriodicalIF":6.3,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148823811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Haifei Yu, Zheng Xu, Mintao Tan, Yingmeng Li, Yang Zhan
{"title":"Postbiotics derived from <i>Lactobacillus acidophilus</i> exhibit prevention and treatment efficacy against rotavirus-induced diarrhea in neonatal mice.","authors":"Haifei Yu, Zheng Xu, Mintao Tan, Yingmeng Li, Yang Zhan","doi":"10.1039/d6fo01994c","DOIUrl":"10.1039/d6fo01994c","url":null,"abstract":"<p><p>Rotavirus (RV) is the leading cause of severe diarrhea in children under 5 years of age worldwide, and no specific clinical treatments are currently available. Developing a therapeutic agent that combines antiviral properties with the ability to repair the intestinal mucosa holds significant clinical value. In this study, a dual prevention and treatment intervention model was established using neonatal BALB/c mice to systematically investigate the protective effects and underlying mechanisms of Lacidophilin (LA) against RV-induced infectious diarrhea. The results showed that LA significantly alleviated diarrhea symptoms and reduced the loose stool rate and index in infected mice, with superior effects observed in the high-dose and preventive intervention groups. LA repaired RV-induced small intestinal pathological damage, reduced intestinal epithelial apoptosis, restored the expression of tight-junction proteins and mucosal protective factors, and decreased intestinal permeability. It not only inhibited RV replication <i>in vitro</i> and <i>in vivo</i> but also inhibited adenovirus and astrovirus replication <i>in vitro</i>. In addition, LA upregulated sIgA levels in serum and intestinal tissues, reshaped the imbalanced cytokine network, and restored protective Th1-type immunity. Multi-omics analyses revealed that LA regulated the intestinal microbial structure, reversed metabolic disorders, remodeled transcriptomic characteristics, and significantly enriched the PI3K-AKT, PPARγ and NF-κB signaling pathways in RV-infected mice. Molecular verification confirmed that LA repaired the intestinal epithelium by activating the pro-survival PI3K-AKT pathway, restoring normal PPARγ function and inhibiting NF-κB-mediated excessive inflammation. In conclusion, LA exerts a protective effect against RV-induced infectious diarrhea through multi-target synergistic actions of antiviral activity, intestinal barrier repair, immune response regulation, remodeling of the microbiota-metabolism-transcriptome network, and modulation of the PI3K-AKT/PPARγ/NF-κB signaling pathway, providing solid experimental evidence and theoretical support for its clinical translation and application.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":"8267-8287"},"PeriodicalIF":6.3,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148838563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Ethyl caffeate alleviates NAFLD by modulating JNK/IRS-1/AKT signaling and the gut microbiota.","authors":"Mengran Qi, Feini Qin, Ruoxuan Wang, Yanni Zhang, Xuanfeng Yue","doi":"10.1039/d6fo03689a","DOIUrl":"10.1039/d6fo03689a","url":null,"abstract":"<p><p>Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide, yet no specific pharmacotherapy has been approved. Ethyl caffeate (EC), a natural phenolic compound with anti-inflammatory and antioxidant properties, has been suggested as a potential hepatoprotective agent, but its efficacy against NAFLD remains unexplored. Here, we comprehensively evaluated the effects of EC on NAFLD using network pharmacology prediction, <i>in vivo</i> high-fat diet (HFD)-fed mouse models, <i>in vitro</i> oleic acid (OA)-induced HepG2 cells, as well as 16S rRNA gene sequencing and untargeted metabolomics of cecal contents. EC dose-dependently improved metabolic disturbances in HFD-fed mice and OA-induced HepG2 cells, as evidenced by reduced body weight gain, liver index, serum transaminases, and hepatic triglyceride/cholesterol levels, alongside enhanced glucose tolerance and insulin sensitivity. Mechanistically, EC alleviated insulin resistance and lipid accumulation by inhibiting the aberrant phosphorylation of JNK and IRS-1, thereby restoring AKT activation, and concurrently suppressing the expression of the lipogenic transcription factor SREBP-1c and the inflammatory cytokine TNF-α. In parallel, EC remodeled the gut microbiota by decreasing the Firmicutes/Bacteroidota ratio, specifically enriching the beneficial genus Akkermansia, and modulating cecal metabolite profiles, particularly affecting bile acid, fatty acid, and amino acid metabolism pathways. These findings suggest that EC ameliorates NAFLD potentially through dual direct (hepatic insulin signaling) and indirect (gut-liver axis) mechanisms, highlighting its potential as a promising natural candidate for NAFLD therapy.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":"8244-8266"},"PeriodicalIF":6.3,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148823790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xuan-Xuan Zhang, Xu Han, Jia-Jun Hang, Hui-Zhi Wang, He Han, Ji-Xiang Chen, Xin Fan, Jia-Hao Feng, Ying Wang
{"title":"Guaijaverin, a guava-derived flavonoid, attenuates high-fat diet-induced MASLD <i>via</i> regulating the gut microbiota-SCFA-ferroptosis axis.","authors":"Xuan-Xuan Zhang, Xu Han, Jia-Jun Hang, Hui-Zhi Wang, He Han, Ji-Xiang Chen, Xin Fan, Jia-Hao Feng, Ying Wang","doi":"10.1039/d6fo03414d","DOIUrl":"10.1039/d6fo03414d","url":null,"abstract":"<p><p>Guaijaverin (GUA), a guava-derived bioactive flavonoid, is a promising candidate for the development of functional foods targeting metabolic disorders. This study investigated the protective effects and underlying mechanisms of GUA against high-fat diet (HFD)-induced metabolic dysfunction-associated steatotic liver disease (MASLD), with particular emphasis on the gut-liver axis. Using an HFD-fed mouse model and free fatty acid (FFA)-stimulated AML12 hepatocytes, we integrated hepatic phenotypic evaluation, 16S rRNA sequencing, short-chain fatty acid (SCFA) quantification, antibiotic-mediated microbiota depletion, sodium butyrate supplementation, RSL3 rescue experiments, and hepatic transcriptomic analysis. GUA markedly alleviated hepatic steatosis, improved serum and hepatic lipid accumulation, and reduced liver injury. GUA also restored intestinal barrier integrity, reshaped gut microbiota composition, enriched SCFA-associated bacteria, and increased fecal SCFA levels. Antibiotic depletion attenuated the hepatoprotective effects of GUA, whereas butyrate supplementation partially restored these effects, supporting the involvement of gut microbiota-derived butyrate in GUA-mediated liver protection. Liver transcriptomic analysis further identified glutathione metabolism as a major pathway activated by GUA. Consistently, GUA restored redox homeostasis, reduced iron overload and lipid peroxidation, and maintained the GPX4-mediated anti-ferroptotic defense axis. These effects were weakened by microbiota depletion and partially rescued by butyrate supplementation. In AML12 hepatocytes, pharmacological induction of ferroptosis with RSL3 partially abolished the protective effects of GUA or sodium butyrate, further supporting ferroptosis inhibition as a functional downstream mechanism. Collectively, these findings indicated that GUA ameliorated HFD-induced MASLD, at least in part, through coordinated modulation of the gut microbiota-SCFA-ferroptosis axis, highlighting its potential as a guava-derived functional food ingredient for metabolic liver health.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":"8231-8243"},"PeriodicalIF":6.3,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148823834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhiwei Li, Yang Guo, Dandan Ma, Yong Cheng, Ebeydulla Rahman, Zhaojun Wang, Qiuming Chen, Maomao Zeng, Jie Chen, Guoping Liu, Zhiyong He
{"title":"From plate to pillow: the role of food-derived bioactive compounds in sleep modulation and the potential of glia-neuron crosstalk.","authors":"Zhiwei Li, Yang Guo, Dandan Ma, Yong Cheng, Ebeydulla Rahman, Zhaojun Wang, Qiuming Chen, Maomao Zeng, Jie Chen, Guoping Liu, Zhiyong He","doi":"10.1039/d6fo02383e","DOIUrl":"10.1039/d6fo02383e","url":null,"abstract":"<p><p>Sleep is a critical physiological process, yet the prevalence of sleep disorders is on the rise worldwide. Traditional pharmacological treatments often have limitations, prompting the search for alternative non-pharmacological interventions. Food-derived bioactive compounds (FBCs) have emerged as promising natural modulators for sleep improvement, offering vast potential for functional food development. This review systematically evaluates the nutritional significance of five major FBC categories: amino acids, polyphenols, fatty acids, bioactive peptides, and melatonin/indole derivatives. Furthermore, this review updates the mechanistic landscape by proposing a periphery-to-center axis that links peripheral signal perception (gut microbiota and peripheral circadian clocks), blood-brain barrier (BBB) translocation and/or BBB integrity modulation, and central integration through glia-neuron communication. Emerging evidence highlights that glial cells (astrocytes, microglia, and oligodendrocytes) are not passive support cells but active regulators of sleep homeostasis and circadian rhythms. FBCs may synchronize peripheral clocks, reinforce BBB tight junction function, and reprogram glial phenotypes to mitigate neuroinflammation and restore sleep architecture. It provides a solid scientific basis for developing safe, effective, and natural functional foods that promote sleep, offering novel insights into applying precision nutrition strategies to address sleep-related public health challenges.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":"7975-8001"},"PeriodicalIF":6.3,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148823840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Pearl mussel (<i>Hyriopsis cumingii</i>)-derived exosome-like nanovesicles promote osteogenesis and alleviate ovariectomy-induced bone loss in mice.","authors":"Yuanyuan Hu, Mengdan Hou, Shanwei Zhong, Shihong Zhong, Haoyu Zhang, Yiwen Xie, Beiwei Zhu","doi":"10.1039/d6fo02800d","DOIUrl":"10.1039/d6fo02800d","url":null,"abstract":"<p><p>Osteoporosis is the most common metabolic bone disease that has become a serious public health concern. Food-derived exosome-like nanovesicles have recently emerged as natural functional ingredients with diverse biological activities. In this study, mantle-derived exosome-like nanovesicles from pearl mussel (PMEs) were isolated and systematically characterized. PMEs exhibited a typical cup-shaped morphology with a major size peak at approximately 116.3 nm and were enriched in bioactive lipids, osteogenesis-related proteins, and mineral elements. PMEs were efficiently internalized by osteoblasts and significantly promoted osteogenic differentiation, as evidenced by increased alkaline phosphatase activity and mineralized nodule formation in MC3T3-E1 cells. Moreover, PMEs markedly upregulated osteogenesis-related genes (<i>Runx2</i>, <i>Osx</i>, <i>Ocn</i>, and <i>Opn</i>), and enhanced β-catenin expression and nuclear accumulation. PMEs also maintained structural stability during gastrointestinal digestion and reached bone tissue following oral administration. In ovariectomized mice, PMEs administration significantly improved bone mineral density and trabecular microarchitecture, increased serum PINP levels, and reduced TRAP 5b and IL-6 levels. In addition, no detectable systemic toxicity was observed in healthy mice following PMEs administration. Collectively, these findings identify PMEs as novel food-derived nanovesicles with osteoprotective activity, supporting their potential application as functional ingredients for bone health management.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":"8183-8196"},"PeriodicalIF":6.3,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148816875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Shilan Liang, Shiyun Peng, Yuxuan Zhao, Wenwen Liang, Jiafen Yu, Liya Zhang, Yong Cao, Qun Wang
{"title":"Rosmarinic acid alleviates colitis and repairs mucus barrier damage in a gut microbiota-dependent manner.","authors":"Shilan Liang, Shiyun Peng, Yuxuan Zhao, Wenwen Liang, Jiafen Yu, Liya Zhang, Yong Cao, Qun Wang","doi":"10.1039/d6fo03083a","DOIUrl":"10.1039/d6fo03083a","url":null,"abstract":"<p><p>Rosmarinic acid (RA) significantly alleviates DSS-induced colitis by repairing the damaged colonic mucus barrier and reversing gut microbiota dysbiosis. However, it remains unclear whether the gut microbiota is required for this protective effect. To address this, pseudo-germ-free mouse models and fecal microbiota transplantation (FMT) were used to evaluate whether the gut microbiota is required for RA to restore mucus barrier integrity and alleviate colitis. The study showed that transplanting fecal microbiota from RA-pretreated donor mice into pseudo-germ-free recipients with colitis markedly alleviated colitic pathology. This was reflected by an 52% reduction in the disease activity index (DAI) score, improved histological scores, markedly lower serum pro-inflammatory cytokines (IL-6 and TNF-α), and upregulated mRNA expression of anti-inflammatory cytokines (<i>IL-10</i> and <i>IL-25</i>). Moreover, the mucus barrier was substantially restored in recipient mice: goblet cell numbers increased approximately 5-fold (RH-FMT (recipient mice were transplanted with microbiota derived from the high-dose RA treatment group) <i>vs</i>. DSS group), mucus coverage rose from 5.24% (DSS) to 35.4% (RHF), and mRNA levels of tight junction proteins and mucins (<i>e.g.</i>, <i>ZO-1</i>, <i>MUC1</i>) were elevated. Short-chain fatty acid (SCFA) levels recovered, with total SCFAs increasing by about 130.77%. Meanwhile, the gut microbiota of recipient mice was remodeled: beneficial bacteria such as <i>Akkermansia</i> and <i>Limosilactobacillus</i> increased, while harmful bacteria like <i>Proteobacteria</i> and <i>Klebsiella</i> decreased. However, direct oral administration of RA (at either high or low doses) to pseudo-germ-free mice did not produce these protective effects. Further correlation analysis revealed that the abundance of SCFA-producing beneficial genera-including <i>Akkermansia</i>, <i>Limosilactobacillus</i>, and <i>Blautia_A</i>-in recipient mice was significantly positively correlated with the expression of genes involved in the mucus barrier and tight junctions, as well as with SCFA levels. Thus, RA alleviates colitis through mucus barrier repair and modulation of SCFAs metabolism, a process that critically depends on the gut microbiota.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":"8368-8386"},"PeriodicalIF":6.3,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148885675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Adjunctive psychobiotic <i>Lactiplantibacillus plantarum</i> PS128 ameliorates gastrointestinal comorbidities and alters circulating miRNAs and gut microbiota in children with Tourette syndrome: a randomized controlled trial.","authors":"Yu-Tzu Chang, Syuan-Yu Hong, Sheng-Shing Lin, Chien-Heng Lin, Po-Yen Wu, I-Ching Chou","doi":"10.1039/d6fo03349k","DOIUrl":"10.1039/d6fo03349k","url":null,"abstract":"<p><p>Tourette syndrome (TS) is a neuropsychiatric disorder characterized by involuntary motor and vocal tics. Emerging evidence suggests that microRNA (miRNA) regulation and the gut-brain axis (GBA) may contribute to TS pathophysiology. <i>Lactiplantibacillus plantarum</i> PS128 (PS128) is a well-studied psychobiotic strain known to influence brain function through neurotransmitter modulation. This double-blind, randomized, placebo-controlled trial investigated the efficacy of a 12-week PS128 intervention on clinical symptoms-including tic severity, attention, and gastrointestinal discomfort-alongside circulating miRNA expression and gut microbiota composition in children aged 4-18 years with TS. Clinical outcomes were assessed using the Yale Global Tic Severity Scale (YGTSS), Clinical Global Impression (CGI), Visual Analogue Scale of Gastrointestinal Discomfort (VAS-GI), Continuous Performance Test (CPT), and neuropsychological assessments. Blood-based miRNA profiling and fecal microbiota analyses were conducted to explore potential mechanisms. Seventy-three participants completed the study. Improvements in YGTSS, CGI, and neuropsychological outcomes were comparable between groups. The primary endpoint, reduction in YGTSS score, did not differ significantly between groups. However, the PS128 group exhibited significantly greater reductions in gastrointestinal symptoms, particularly upper abdominal pain, and showed a trend toward improved attentional performance on the CPT. miRNA sequencing identified eight differentially expressed miRNAs following PS128 intervention, which were predicted to be involved in nervous system development and synaptic regulation. The qRT-PCR validation confirmed significant upregulation of miR-199a-3p and miR-143-3p in the PS128 group compared with placebo. Fecal microbiota analysis revealed increased <i>Lactiplantibacillus</i> abundance after PS128 intervention, which positively correlated with miR-199a-3p expression and negatively correlated with CGI scores. No intervention-related adverse events were reported. Despite no significant effect on core tic severity, PS128 improved gastrointestinal and attentional symptoms with accompanying GBA molecular changes, supporting further investigation as an adjunctive therapy for pediatric TS.</p>","PeriodicalId":77,"journal":{"name":"Food & Function","volume":" ","pages":"8101-8113"},"PeriodicalIF":6.3,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148785682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}