Postmenopausal women are approximately twice as likely to develop cardiometabolic diseases (CMDs) as premenopausal women. Plant-based diets rich in fruits and vegetables, due to their high content of bioactive compounds such as (poly)phenols, represent a promising strategy to reduce the risk of CMDs in this population. However, the cardioprotective effects of (poly)phenols depend largely on inter-individual variability, which is strongly influenced by the gut microbiota composition. Menopause is often associated with gut dysbiosis, characterized by a reduced microbial diversity and a lower abundance of beneficial bacteria. This imbalance in the gut microbiota profile of postmenopausal women could influence (poly)phenol metabolism and, consequently, the health benefits attributed to (poly)phenol-rich food (PP-rich food) consumption. Therefore, this study aimed to assess the impact of a daily consumption of PP-rich foods (dark chocolate, green tea and fruit juice) for 2 months on the urinary phenolic profile in postmenopausal women at high cardiometabolic risk. To this end, 116 urinary phenolic metabolites were determined using UHPLC-ESI-QqQ-MS/MS. Dietary intervention with PP-rich foods led to a significant increase in the urinary excretion of phenolic metabolites derived from gut microbiota activity and phase II metabolism. Notably, there was a significant increase in the excretion of glucuronidated and/or sulfated conjugates of phenyl-γ-valerolactones, phenylvaleric acids, phenylacetic acids, benzoic acids, and urolithins. It is expected that these phenolic metabolites could be the bioactive compounds responsible for the potential beneficial effects derived from the daily intake of dark chocolate, green tea, and fruit juice on the reduction of the risk of CMDs in postmenopausal women.

Obesity and its associated metabolic disorders pose a major global health challenge. Theaflavins (TFs), bioactive polyphenols derived from black tea, have demonstrated potential in alleviating metabolic diseases. This study aimed to investigate the ameliorative effects and underlying mechanisms of TFs on high-fat diet (HFD)-induced obesity from the perspectives of oxidative stress, the branched-chain amino acid (BCAA) degradation pathway, and the gut microbiota. In vitro, TFs exhibited potent free-radical scavenging capacity. In vivo, TFs dose-dependently attenuated HFD-induced weight gain, dyslipidemia and glucose intolerance. Concurrently, TF administration alleviated hepatic steatosis and ultrastructural damage and improved liver function. Importantly, TFs suppressed hepatic oxidative stress and downregulated the HFD-induced overexpression of the valine, leucine, and isoleucine degradation pathway at both mRNA and protein levels (HADH, HMGCL, ACSF3, ACADS, ALDH3A2, and ACAA2). Furthermore, gut microbiota analysis revealed that TFs improved HFD-induced gut dysbiosis, characterized by the enrichment of butyrate-producing genera (e.g., Akkermansia and Gastranaerophilales_norank) and a reduction in the relative abundance of harmful taxa (e.g., Enterococcus and Streptococcus). Correlation analysis integrated these findings, revealing significant associations between the TF-induced microbial shifts, the ameliorated metabolic phenotypes, and the suppressed hepatic BCAA catabolism. Our study demonstrated that the alleviation of obesity by TFs was associated with multifaceted improvements, including enhanced antioxidant capacity, amelioration of dysregulated hepatic BCAA catabolism, and modulation of gut microbial homeostasis, highlighting their potential as a dietary intervention for metabolic diseases.

Intrahepatic fat accumulation is a characteristic feature of non-alcoholic fatty liver disease (NAFLD), a chronic metabolic liver disorder. Hawthorn fruit is a common fruit in East Asia with fat-reducing properties, although its active components and mechanisms of action are still unclear. The purpose of this study was to utilize 70% ethanol for the extraction of hawthorn fruit and to investigate the mechanism and therapeutic impact of hawthorn fruit extracts (HFE) in the treatment of NAFLD. A 12-week high-fat diet was used to establish an NAFLD mouse model, and oleate/palmitate-induced HepG2 cells were used to create an NAFLD cell model. Mass spectrometry was employed to characterize HFE constituents and metabolic profiling of the liver. Network pharmacology and molecular docking were used to identify potential targets of HFE for the treatment of NAFLD and to analyze the possible interactions between HFE compounds and targets. A total of 17 primary compounds were identified in HFE. HFE significantly inhibited lipid accumulation in hepatic cells both in vivo and in vitro, and mitigated liver damage. Hepatic metabolomics indicated that HFE notably improved metabolic disorders in NAFLD mice, particularly in the purine metabolism pathway. Integrative analysis combining network pharmacology, molecular docking, and western blotting demonstrated that HFE primarily targets ERK and effectively suppresses its hyperactivation. Quercetin and rutin, present in HFE, emerged as potential key components, exerting effects through direct binding with ERK1/2. In conclusion, this study found that HFE alleviated NAFLD by inhibiting ERK and regulating hepatic purine metabolism.

Reduced levels of circulating gonadal hormones in post-menopausal women can negatively affect various physiological functions, including brain and gut deficits. There is an urgent need to find novel strategies to mitigate estrogen-gut-microbiome-brain axis (EGMBA) dysfunction. This study aimed to investigate the effect of fructooligosaccharide (FOS), a non-digestible prebiotic fiber, on estrogen deficiency-induced alterations in the EGMBA using an ovariectomized (OVX) rat model. Adult female SD rats were bilaterally OVX to induce estrogen deficiency and associated EGMBA dysfunction. Rats were administered FOS (50 mg kg-1 p.o.-1) for 28 consecutive days. To assess EGMBA dysfunction, after 28 days, we performed behavioral tests, biochemical estimations (oxidative stress), molecular estimations (inflammatory markers via ELISA), gene expression analysis (HPA axis, monoamine neurotransmission, apoptosis, gut microbiota alterations, & gut barrier integrity via RT-PCR/qPCR), and histopathological analysis. Administration of FOS significantly improved behavioral outcomes (reducing anxiety and depression, and improving memory). FOS also attenuates oxidative stress and inflammatory markers. FOS regulates apoptosis (upregulation of BCL-2 and downregulation of Bax), HPA axis functioning (corticosterone, GR, MR, & CRH), and monoamine neurotransmission (MAO-A & COMT) in the hippocampus of OVX rats. FOS also promoted healthy cell growth and prevented apoptosis. Additionally, FOS restored gut microbial eubiosis, improved mucus secretion (MUC-2), preserved tight junction protein expression (Lipocalin-2, Claudin, & TLR-4), and maintained the colon microstructure. FOS exerts multifaceted protective effects on the EGMBA by modulating gut and brain functions. These findings support its potential as a non-hormonal therapeutic approach for managing postmenopausal complications.

Resistant starch (RS) stabilizes postprandial blood glucose levels through multiple mechanisms and offers distinct advantages in preventing and managing metabolic diseases such as diabetes. This study introduces a novel plant exosome-starch composite system, combining Tartary buckwheat starch (TBS) and ginger exosomes (GELNs), referred to as the TBS-GELNs composite resistant starch (GTBS). Multi-scale physicochemical analysis revealed the molecular interaction mechanisms: composite formation significantly altered the microstructure of gelatinized starch. GELNs interacted with TBS through hydrogen bonds, enhancing starch crystallinity and short-range ordering, thus reducing its digestibility. The metabolic effects of GTBS on type 2 diabetes mellitus (T2DM) mice were further examined. The results indicated that GTBS markedly decreased fasting blood glucose and lipid levels, alleviated some organ damage, and improved gut microbiota composition by enhancing the structure and abundance of beneficial bacterial populations. This study provides novel insights and a theoretical basis for the regulation of postprandial blood glucose via composite starch-based biomolecules, offering promising strategies for developing staple food products that integrate nutritional value with biological activity.

Correction for 'Inhibition of pro-atherogenic trimethylamine production from choline by human gut bacteria is not determined by varying chlorogenic acid content in highbush blueberries' by Ashley M. McAmis et al., Food Funct., 2025, 16, 8004-8020, https://doi.org/10/1039/D5FO02676H.

Existing evidence indicates that pre-existing metabolic dysfunction-associated steatotic liver disease (MASLD) confers susceptibility to acute liver injury (ALI). Nevertheless, the underlying mechanism prompting ALI risk in such a condition is not fully uncovered yet. Gut dysbiosis has been well-documented in MASLD patients which prompts us to hypothesize that gut dysbiosis may serve as a contributing factor and a regulatory target to ALI susceptibility. A case-control study was performed and the increased risk of ALI in MASLD patients was verified. Mice pretreated with MASLD mouse/patient-derived fecal microbiota transplantation (FMT) demonstrated worsened ALI after D-GalN/LPS injection. We identified significant gut dysbiosis with decreased microbial α-diversity, beneficial genus Lactobacillus, and increased potentially harmful bacteria Campylobacter and Helicobacter. Probiotic Akkermansia muciniphila (A. muciniphila) was reported to improve gut dysbiosis. Thus, we tested the effect of A. muciniphila on ALI mice pretreated with MASLD mouse-derived FMT. A. muciniphila significantly ameliorated the worsened ALI and improved gut dysbiosis. Transcriptomic analysis revealed that A. muciniphila restored the impaired liver PPAR-α signaling, alleviating the aggravated NF-κB signaling and downstream inflammation response in the liver. Specifically, A. muciniphila restored the decreased abundance of the PPAR-α agonist daidzein in the colon, thereby restoring PPAR-α activation and inhibiting NF-κB signaling in the liver. Daidzein is also capable of ameliorating ALI aggravated by MASLD-associated dysbiosis, accompanied by PPAR-α activation and NF-κB inhibition. Our findings revealed that gut dysbiosis in MASLD increased the risk of ALI. A. muciniphila exhibited preventive potential for MASLD patients to reduce ALI risk. Daidzein/PPAR-α/NF-κB signaling is important to maintain host resistance to hepatoxic challenge.

Burdock is consumed as a vegetable in the Asian region and is also used in medicinal dishes or health soups. Our previous studies demonstrated that arctigenin, a natural agonist of estrogen receptor β (ERβ) occurring in burdock, can promote colonic mucosal healing in the context of ulcerative colitis (UC). Whether and how arctigenin intervenes in focal adhesion disassembly, a critical step for migration and wound healing of colon epithelial cells, were examined within this research. The results showed that arctigenin substantially accelerated focal adhesion disassembly and therefore facilitated migration and wound healing of colonic epithelial cells. Mechanistically, arctigenin reduced excitatory amino acid transport to specifically enhance autophagic degradation of paxillin, thereby accelerating focal adhesion disassembly through an ERβ-dependent pathway. In colitis-induced mice, ERβ knockout significantly attenuated promotion of colonic mucosal healing by arctigenin. These findings indicate that arctigenin is a promising mucosal healing promoter, which functions by accelerating focal adhesion disassembly in an ERβ-dependent manner.

This study investigated the potential role of Lacticaseibacillus rhamnosus DACN152 (DACN152) in ameliorating polycystic ovary syndrome (PCOS). Using a letrozole-induced PCOS murine model, we demonstrated that DACN152 attenuated ovarian histopathological damage, restored estrous cyclicity, and normalized sex hormone levels. Furthermore, DACN152 enhanced ovarian steroidogenesis by regulating key steroidogenic genes (StAR, CYP17A1, and CYP19A1) and sex hormone receptors (Lhr and Pgr), while concurrently suppressing ovarian apoptosis through modulation of apoptotic regulators (Bax and Bcl-2). These changes were corroborated at the protein level. Additionally, DACN152 significantly restructured the gut microbiota composition in PCOS mice, marked by reduced abundances of Bacteroidota, Verrucomicrobiota, Dubosiella, and Akkermansia, alongside increased abundances of Firmicutes, Campylobacterota, Allobaculum, Ruminococcus, and Blautia. Serum metabolomic analysis revealed elevated levels of bile acids, including chenodeoxycholic acid (CDCA), taurocholic acid (TCA), taurochenodeoxycholic acid (TCDCA), and cholic acid (CA). Collectively, these findings provide a theoretical basis for the development of probiotic-functional foods for PCOS.

Vulvovaginal candidiasis (VVC) is a common vaginal disease characterized by inflammatory cell infiltration and vaginal microbiota dysbiosis. In this study, Limosilactobacillus fermentum 50 not only exhibited the strongest growth-inhibitory activity against Candida albicans using a spot assay, but also significantly suppressed hyphal formation and decreased the expression of virulence-associated genes, including HWP1, ALS3, and ECE1. Furthermore, the effects of L. fermentum 50 on C. albicans-induced VVC were investigated in a mouse model. Oral administration of L. fermentum 50 increased body weight, reduced vaginal epithelial cell exfoliation, and decreased fungal burden. Real-time quantitative PCR analysis revealed that L. fermentum 50 significantly downregulated expression of S100A8, S100A9 and TNF-α, and upregulated IL-10 expression at the transcription level in vaginal tissue. ELISA analysis further confirmed that L. fermentum 50 increased the level of IL-10 and decreased the level of TNF-α in both vaginal tissue and serum. Histopathological analysis showed that L. fermentum 50 significantly reduced epithelial cell exfoliation and alleviated vaginal structural damage by increasing the expression of occludin. In addition, L. fermentum 50 modulated the composition of the vaginal microbiota, characterized by an increased abundance of Lactobacillus and a decreased abundance of Escherichia-Shigella. It is noteworthy that L. fermentum 50 also reshaped composition of the gut microbiota, also enriching the abundance of Lactobacillus. Correlation analyses further revealed that Lactobacillus abundance in feces was positively associated with vaginal Lactobacillus and negatively correlated with vaginal Escherichia-Shigella abundance. Collectively, these findings suggested that L. fermentum 50 may serve as a potential strategy to ameliorate VVC by modulating the gut microbiota to alleviate vaginal inflammation, enhancing mucosal barrier function, and restoring vaginal microbiota composition.