Food & Function最新文献

Menopause increases cardiometabolic risk, partly by reducing the protective effects of estrogens and inducing gut microbiota dysbiosis, which can promote the production of atherogenic metabolites such as trimethylamine N-oxide (TMAO). Polyphenols may reduce TMAO levels, though interindividual variability limits reproducibility. We compared urinary and serum TMAO levels, and urinary trimethylamine (TMA) and dimethylamine (DMA) levels between healthy women of reproductive age (Pre-M, n = 120) and non-medicated postmenopausal women (Post-M, n = 90) using UPLC-QqQ-MS/MS. In Post-M women, we conducted a randomised, placebo-controlled crossover study to evaluate the effects of a polyphenol-rich extract mixture containing pomegranate, Polygonum cuspidatum, and red clover (sources of ellagitannins, resveratrol, and isoflavones) on TMAO, TMA, and DMA in the whole group and after metabotyping. Because medication is common in Post-M women due to age and cardiometabolic risk, trials in non-medicated participants are challenging, yet avoiding drug-diet interactions allows clearer attribution of dietary effects. Urinary TMAO and DMA levels were higher in Post-M than in Pre-M. No changes were observed in serum TMAO. However, the intervention reduced urinary TMAO and DMA versus baseline and placebo. The effects varied by metabotype. TMAO reduction was significant in urolithin A metabotype (UMA), equol producers (EP), and lunularin non-producers (LNP). Reductions and effect sizes were most pronounced in the metabotype clusters MC3 (UMA + EP + LP) and MC7 (UMA + EP + LNP), which represented 39% of participants. DMA decreased selectively in UMA. No correlations were found between TMAO or DMA changes and BMI, age at menopause onset, or years since menopause. These findings show that polyphenol supplementation reduces urinary TMAO in a metabotype-dependent manner and support metabotyping as a precision-health strategy to mitigate cardiometabolic risk after menopause.

Childhood and adolescence are critical periods for rapid bone mass accumulation and the achievement of peak bone mass. However, low-calcium diets disrupt bone metabolism, and traditional inorganic calcium supplements, such as calcium carbonate, have certain limitations in bioavailability and in their effects on bone mass. Prebiotics can improve skeletal health, but the mechanism of action of konjac oligosaccharides (KOS) in calcium-deficient growing mice remains insufficiently explored. This study aimed to investigate the effects of KOS on bone health in mice subjected to a low-calcium diet during growth, as well as its potential mechanisms. A low-calcium juvenile mouse model was established, with interventions including calcium carbonate alone or in combination with KOS. After six weeks, supplementation with 8% KOS significantly enhanced calcium absorption, reduced serum PTH, ALP, TRAP-5b, and CTX-1 levels, increased serum OCN and P1NP levels, and improved bone mineral density, trabecular structure, and bone strength. Meanwhile, KOS markedly modulated the gut microbiota composition in hypocalcemic mice, increasing the abundance of beneficial bacteria such as Bifidobacterium, Lactobacillus, and Bacteroides, while decreasing the proportion of potentially harmful bacteria. It also significantly lowered cecal pH and increased cecal content weight. Compared with the reference compound, inulin, KOS exhibited similar but more pronounced effects on promoting bone formation and regulating the microbiota. This study confirms the bone health-promoting effects of KOS in calcium-deficient mice during growth, providing experimental evidence for the development of KOS-calcium composite dietary supplements.

Momordicine I (M-I), a key bioactive and bitter-tasting triterpenoid in Momordica charantia L., has attracted significant research interest due to its potential hepatoprotective effects. This study investigated the mechanism by which M-I ameliorates lipid accumulation and metaflammation in alcohol-associated liver disease (ALD). Mouse primary hepatocytes were stimulated with ethanol and silenced with Nurr1-siRNA, treated with a conditioned medium from mouse peritoneal macrophages (MPMs), and then treated with M-I. M-I was administered to ALD mice by gavage, and a Nurr1-deficient model was established to systematically evaluate the effect of M-I and the function of Nurr1. Results indicated that M-I could significantly upregulate Nurr1 expression, thereby inhibiting the key factors of lipid synthesis. Meanwhile, it improves mitochondrial respiratory function, inhibits NLRC4/NLRC5 inflammasome activation, and reduces pro-inflammatory factor release. It is notable that M-I or C-DIM12 inhibits the expression of NLRC4 inflammasome and pyroptosis-related proteins in cells, reducing IL-1β as well as IL-18 secretion. Furthermore, M-I can effectively block the pro-inflammatory effect of the conditioned culture of activated macrophages on hepatocytes. Silencing of Nurr1 eliminates M-I's beneficial effects. In vivo, M-I intervention effectively improved liver steatosis, serum transaminase levels and mitochondrial function, while Nurr1 knockdown mice exhibited more severe ALD. In summary, M-I exerts liver-protective effects by targeting Nurr1, synergistically regulating lipid metabolism and mitochondrial function in hepatocytes, and inhibiting inflammatory responses. This study clarifies the new mechanism of M-I based on Nurr1, providing an important basis for its development as a therapeutic drug for ALD.

Dietary fibre is vital for a healthy diet, yet many people avoid it because of symptoms induced by colonic gas. Slowing rapid fermentation decreases colonic distention and reduces symptoms, allowing for better tolerance of prebiotics. Co-administration of inulin, a fermentable fibre, with psyllium, a gel-forming fibre, reduces gas production in irritable bowel syndrome patients compared to administering inulin alone, but the underlying mechanism is unclear. We hypothesise that psyllium polysaccharides' physically cross-linked gel resists gastrointestinal shear forces and impairs microbial access to inulin, thereby delaying fermentation. Methylcellulose is another physically cross-linked fibre ingredient, widely used in food production for its tunability and affordability. Our aim was to develop a preparation of methylcellulose of comparable functionality to psyllium. A formulation of methylcellulose with comparable rheological and inulin release behaviour was developed in vitro. We subsequently performed a randomised, three-way, placebo-controlled non-inferiority study with healthy volunteers (n = 30), comparing the slowing of fermentation of inulin by co-administering with psyllium, methylcellulose or a control maltodextrin. Fermentation in vivo was assessed by breath hydrogen measurements for 24 hours after ingestion. While psyllium significantly reduced initial breath hydrogen production compared to the placebo, a non-inferior effect on reduction in initial breath hydrogen with methylcellulose was not demonstrated. Despite similar physicochemical properties, psyllium and methylcellulose hydrogels exhibited different transit behaviour based on the breath hydrogen time to rise >10 ppm and time to peak. We hypothesise that the fast reformation of psyllium's polysaccharide network or "self-healing" properties after deformation by intestinal pressure waves may underpin its effectiveness in slowing fermentation. The clinical trial registry number is NCT05911347 (https://clinicaltrials.gov).

Managing diabetes mellitus (DM) and its long-term complications remains a major global health challenge. Dihydromyricetin (DHM), a natural flavonoid abundant in Ampelopsis grossedentata and Hovenia dulcis, has attracted increasing attention for its multi-target anti-diabetic properties. Growing evidence indicates that DHM improves glucose metabolism, alleviates oxidative stress and inflammation, regulates autophagy and cell death, and exerts beneficial effects in DM and a range of related complications, including diabetic nephropathy, cardiomyopathy, cognitive impairment, and wound healing impairment, and other related complications. Overall, this review provides an overview of preclinical research on DHM in DM and its main complications, emphasizing its therapeutic benefits and underlying molecular mechanisms. Although DHM is promising, future research should improve its delivery, clarify its mechanisms, and carry out clinical trials to enable therapeutic use.

Epidemiological and animal studies have suggested that early-life overfeeding (ELOF) triggers lasting metabolic dysfunction. However, the role of gut microbiota in this process remains largely unelucidated. Here, we established a mouse model of ELOF through reducing litter size and revealed that ELOF accelerated growth during lactation, induced obesity at weaning, and left a lasting obesity imprinting and gut microbiota dysbiosis. Notably, a detailed analysis of gut microbiota revealed that a pivotal differential species, Lactobacillus johnsonii, demonstrated significant depletion exclusively in weaned ELOF mice, with no analogous reduction observed in adult ELOF mice. Furthermore, while post-weaning microbiota reconstitution proved insufficient to reverse diet-induced obesity in adult ELOF mice, early supplementation with Lactobacillus johnsonii during the lactation period substantially mitigated these programmed metabolic alterations. Our findings causally link ELOF, early-life gut microbial imbalance, and late-onset obesity in mice, and suggest that probiotic intervention during critical developmental periods may serve as an effective strategy to mitigate the obesity imprint in infants and young children.

Bone mineral density (BMD) reduction leads to osteoporosis. Polypeptides and polysaccharides are often used individually as supplements to improve BMD; however, the efficacy of their combined use relative to single components, as well as the underlying synergistic mechanisms, remains unclear. Therefore, this study screened bovine bone collagen peptide (BBCP) and Astragalus polysaccharide (APS) based on the theories of food-medicine homology and multi-target network regulation to investigate the synergistic ameliorative effects of a BBCP/APS combination (1 : 1, w/w) on BMD and the mechanisms underlying these effects. In vitro osteoblast models, in vivo ovariectomy (OVX) rat models, and network pharmacology analyses were employed to elucidate the underlying mechanisms. In vitro, compared with BBCP or APS alone, the BBCP/APS combination significantly enhanced osteoblast proliferation by 20.3 ± 5.80% and 22.9 ± 6.15%, respectively, and markedly upregulated osteogenic markers-alkaline phosphatase, osteocalcin, and type I collagen-relative to the model group (p < 0.01). In vivo, treatment with BBCP/APS (800 mg kg^-1) increased femoral BMD in OVX rats from 0.193 g cm^-3 (model group) to 0.411 g cm^-3 (p < 0.05) and significantly improved trabecular bone microarchitecture. Concurrently, network pharmacology analysis identified ADRA1A and ADRA2A as core targets and predicted the p38 MAPK pathway as the principal signaling pathway involved. Activation of the p38 MAPK pathway by BBCP/APS was further confirmed via RT-qPCR and western blot analyses. These findings demonstrate that the BBCP/APS combination synergistically enhances BMD, overcomes single-component limitations, and provides valuable insights for functional food development.

Gut microbiota-derived lipopolysaccharide (LPS) is a critical mediator in the pathogenesis of nonalcoholic fatty liver disease and metabolic syndrome. The liver plays a crucial role in mediating immune responses and detoxifying endotoxins through bile secretion. However, the precise role of bile acid metabolism in LPS-induced liver injury and the underlying regulatory mechanisms remain poorly understood. RNA sequencing of liver and ileum tissues, combined with targeted metabolomic profiling of liver and cecal chyme and full-length 16S rRNA sequencing of cecal microbiota, revealed that LPS disrupted the enterohepatic circulation of bile acids. This disruption was characterized by reduced hepatic bile acid secretion and uptake, impaired ileal bile acid reabsorption, and increased fecal excretion of bile acids. Moreover, LPS altered the gut microbiota composition involved in secondary bile acid metabolism, particularly reducing Ligilactobacillus. Supplementation with Lactobacillus rhamnosus GG (LGG) alleviated LPS-induced inflammation and liver injury while restoring hepatic conjugated secondary bile acids, particularly taurodeoxycholic acid (TDCA). The regulatory effect of LGG on hepatic conjugated secondary bile acids was associated with enhanced ileal bile acid reabsorption and a balanced gut microbiota composition. Notably, the hepatoprotective effects were abolished by heat-killed LGG or by co-treatment with caffeic acid phenethyl ester, which diminished LGG's activity in the intestine. TDCA treatment alleviated LPS-induced hepatic inflammation in part through modulation of the oxidative phosphorylation pathway. Collectively, these findings identify disrupted bile acid metabolism as a key event in LPS-induced liver injury and highlight the modulation of TDCA metabolism by probiotics as a promising therapeutic target for endotoxin-related disorders.

Inflammatory arthritis is a term used to describe a diverse group of rheumatic disorders involving the inflammation and hyperproliferation of synovial joints and systemic manifestations. Oleacein (OLA) is one of the most abundant secoiridoids in extra virgin olive oil, the principal source of fat in the Mediterranean diet, which has been shown to exhibit beneficial effects. The objective of the study was to explore the antioxidant and anti-inflammatory effects induced by OLA in a human cell line of synovial cells (SW982), as well as to evaluate its possible role as an epigenetic modulator through the regulation of DNA methylation. Sulforhodamine B assay was utilised to assess cell viability. The levels of inflammatory marker production (MMP-1, MMP-3, TNF-α, IL-1β, IL-6, and PGE2) were evaluated by ELISA, and IL-8 gene expression was analysed by RT-qPCR. The expression of pro-inflammatory enzymes, including COX-2 and mPGES-1, and signaling pathways (MAPK, NF-κB, Keap1/Nrf-2/HO-1 and inflammasome) were evaluated by western blotting. In addition, global DNA methylation was analysed by ELISA, and we studied the gene expression of DNMT1/3A enzymes by RT-qPCR. OLA exhibited anti-inflammatory and antioxidant effects through the regulation of key inflammatory signaling pathways such as inflammasome, MAPK, NF-κB, and the Keap1/Nrf-2/HO-1 axis. In addition, it reduced the production and expression of pro-inflammatory markers (COX-2, mPGES-1, MMP-1, MMP-3, IL-8, IL-6, TNF-α and PGE₂) and regulated IL-1β-induced changes in DNA methylation modulating DNMT1 and DNMT3 gene expression and global DNA methylation. These results show OLA as a promising epigenetic regulator of the inflammatory response in rheumatic diseases.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social interaction and comorbid symptoms including anxiety and cognitive problems. The main pathological mechanisms underlying ASD are synaptic abnormalities and neuroinflammation. Ginger, commonly used as a spice, has been reported to enhance neurogenesis and attenuate inflammation in neurological disease; however, its effects on ASD remain unknown. This study aimed to investigate the therapeutic effects and molecular mechanisms of ginger extract (GE) in ASD. Prenatally valproic acid (VPA)-exposed mice were orally administered GE for 4 weeks from 6 weeks of age. Behavioral tests were performed to assess social interaction, anxiety, and cognitive functions. Network pharmacology and molecular docking analyses were used to predict targets and mechanisms of GE in ASD, which were verified using western blotting. Histological changes, including neurogenesis, neuroinflammation, and synaptic formation, were analyzed using immunostaining, western blotting, and qRT-PCR. GE ameliorated VPA-induced social deficits, anxiety-like behavior, and memory impairments. Network pharmacology identified AKT as a core molecular target of GE, and its active compounds exhibited high binding affinity for AKT. Consistent with these predictions, GE increased AKT and GSK3β phosphorylation in the hippocampus of mice, thereby restoring neuronal development, as evidenced by the increased Ki67- and DCX-positive cells. GE also mitigated gliosis and reduced STAT3 phosphorylation and TNF-α upregulation, thereby suppressing neuroinflammation and synaptic loss. GE alleviates ASD-like behaviors by promoting neuronal and synaptic development while suppressing neuroinflammation through AKT/GSK3β signaling, highlighting its potential as a natural supplement for ASD prevention.