Search Results (710)

Background: Chronic kidney disease (CKD) represents a state of persistent, sterile low-grade inflammation in which sustained innate immune activation accelerates renal decline and cardiovascular complications. Diet-induced gut dysbiosis and intestinal barrier dysfunction lower mucosal immune tolerance, promote metabolic endotoxemia, and position the gut as an upstream modulator of systemic inflammatory signaling along the gut–kidney axis. Scope: Most studies address microbiota-derived metabolites, food-derived bioactive peptides, or omega-3 fatty acids separately. This review integrates evidence across these domains and examines their convergent actions on epithelial barrier integrity, immune polarization, oxidative-inflammatory stress, and inflammasome-dependent pathways relevant to CKD progression. Key mechanisms: CKD-associated dysbiosis is characterized by reduced short-chain fatty acid (SCFA) production and increased generation and accumulation of uremic toxins and co-metabolites, including indoxyl sulfate, p-cresyl sulfate, trimethylamine N-oxide, and altered bile acids. Reduced SCFA availability weakens tight junction-dependent barrier function and regulatory immune programs, favoring Th17-skewed inflammation and endotoxin translocation. Bioactive peptides modulate inflammatory mediator networks and barrier-related pathways through effects on NF-κB/MAPK signaling and redox balance, while omega-3 fatty acids and specialized pro-resolving mediators support resolution-phase immune responses. Across these modalities, shared control points include barrier integrity, metabolic endotoxemia, oxidative stress, and NLRP3 inflammasome activation. Conclusions: Although evidence remains heterogeneous and largely preclinical, combined nutritional modulation targeting these convergent pathways may offer greater immunomodulatory benefit than isolated interventions. Future multi-omics-guided, factorial trials are required to define responder phenotypes and translate precision immunonutrition strategies into clinical CKD care. Full article

Background: Atherosclerosis and its associated chronic inflammation of the arterial wall disrupt fatty acid metabolism, leading to changes in plasma fatty acid composition. These alterations can be used to improve disease diagnosis and risk stratification by the development and application of specific lipidomic indices. Objectives: The objectives of this study are to evaluate the performance of conventional fatty acid indices and enhance diagnostic efficiency in atherosclerosis by introducing novel index based on plasma PUFA n-6 and n-3 content (Omega-6/3 Balance Index, O6/3-BI), as well as the perspective SFA/MUFA ratio (stearic/oleic acid ratio, C18:0/C18:1n-9) and a logit function combining PUFA and SFA/MUFA biomarkers. Methods: Plasma fatty acids were quantified by LC-MS/MS in healthy controls (n = 50) and patients with carotid atherosclerosis (n = 52), stratified by atorvastatin, rosuvastatin, or no statin therapy. The conventional indices (the Omega-3 Status (EPA + DHA), AA/EPA, and the omega-6/omega-3 ratio), and pathway ratios (C18:0/C18:1n-9; and C20:4n-6/C22:4n-6), as well as the newly introduced PUFA index and combined PUFA-SFA/MUFA logit function, were calculated. Their diagnostic performance for distinguishing atherosclerosis was assessed by a receiver operating characteristic (ROC) analysis with the cross-validation and calculation of Cliff’s Δ effect size. Results: The conventional parameters demonstrated a poor to low discrimination ability of the atherosclerosis patients’ groups from healthy controls (area under the ROC curve, AUC 0.548–0.711). In statin-treated patients, these conventional markers lost significance. The newly introduced PUFA index and SFA/MUFA ratio demonstrated improved patients’ discrimination with AUC 0.734–0.780 for the former and strong predictive power with AUC 0.831–0.858 for the latter marker and maintained their diagnostic value under statin therapy. The most significant positive effect size was observed for the SFA/MUFA ratio with Cliff’s Δ = 0.67–0.71. The combined PUFA-SFA/MUFA logit function also demonstrated a strong predictive power with AUC = 0.880 (Cliff’s Δ = −0.76), outperforming any single index. Conclusions: The newly introduced lipidomic index based on the PUFA content, SFA/MUFA ratio, and a logit function combining PUFA-SFA/MUFA biomarkers demonstrated a substantially better discrimination of atherosclerosis-related fatty acid metabolic disturbances than conventional fatty acid biomarkers. Full article

Background: China is currently developing standards for Food for Special Medical Purposes (FSMP) targeting for oncology patients. However, substantial challenges remain in defining optimal fortification levels of omega-3 polyunsaturated fatty acids (ω-3 PUFAs). Accumulating evidence suggests that ω-3 PUFA intake improves postoperative prognosis by modulating oncological parameters in colorectal cancer (CRC) patients. This meta-analysis aimed to evaluate the therapeutic efficacy of ω-3 PUFA supplementation in enhancing postoperative safety and recovery stability following CRC surgery, to address critical gaps in nutritional interventions for optimizing clinical outcomes. These findings are expected to FSMP standard development, clinical nutrition protocols and product innovation. Methods: A systematic literature search was conducted, in accordance with PRISMA guidelines, across major databases until June 16, 2025. Data were analyzed using RevMan v5.4 (Cochrane Collaboration). Results: Thirty-four randomized controlled trials (RCTs) (n = 2889) were included. Compared to controls, the ω-3 PUFAs group showed significantly increased levels of nutritional markers: total protein (p < 0.00001), albumin (p = 0.001); immunological parameters: CD3⁺/CD4⁺/CD8⁺ T-cells, CD4⁺/CD8⁺ ratio (all p < 0.0001); Karnofsky Performance Status (KPS) scores (p = 0.04); and serum ω-3 PUFA concentrations (p = 0.0004). Significant reductions were observed in inflammatory markers, such as procalcitonin, C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) (p = 0.004 to < 0.00001); and clinical outcomes, such as hospitalization duration (p < 0.00001), infectious complications (p < 0.00001), anastomotic leakage (p = 0.0005), surgical site infections (p = 0.03). No significant intergroup differences were detected for white blood cells, transcription factor activity, mortality, or crypt cell proliferation indices (p = 0.06–0.55). Conclusions: Overall, ω-3 PUFA supplementation significantly attenuates postoperative inflammation, enhances immune function, shortens hospitalization, and improves the quality of life in CRC patients, though without mortality benefit. Notably, post hoc dose–response analysis identified a supplementation range of 0.16–0.30 g/kg/day as a potentially optimal supplementation range for Chinese CRC populations, providing foundational evidence for clinical practice and FSMP standardization. Full article

Background/Objectives: Human serum albumin (HSA) is a major endogenous inhibitor of angiotensin-converting enzyme (ACE) and helps fine-tune the activity of the renin–angiotensin–aldosterone system (RAAS), thereby potentially influencing the development of cardiovascular (CV) diseases. As the principal transport protein for free fatty acids (FFAs), HSA may have its ACE-inhibitory capacity modified by its FFA cargo and, through this mechanism, may also affect CV disease risk. We therefore tested the hypothesis that the composition of HSA-bound FFAs determines the magnitude of endogenous ACE inhibition. Methods: We quantified endogenous ACE inhibition and examined the effect of FFA concentration on this inhibition in clinical patients (n = 161 and n = 101, respectively). We measured the effects of HSA treated with saturated, monounsaturated, and polyunsaturated FFAs, as well as FFA-free HSA, on recombinant ACE and on tissue ACE. Results: Endogenous ACE inhibition was stronger in patients with higher serum HSA concentrations (Spearman’s rho = 0.422, 95% CI 0.281–0.544, p < 0.001), whereas total FFA concentration was not associated with endogenous ACE inhibition (Spearman’s rho = 0.088, p = 0.38, n = 101). However, removal of free fatty acids substantially worsened the ACE-inhibitory effect of HSA on recombinant ACE (charcoal-treated HSA: IC₅₀ = 23.24 [19.40–29.78] g/L vs. control HSA: 7.84 [6.58–9.75] g/L, p < 0.001) and on tissue ACE isolated from lung, heart, and lymph node. FFA chain length, degree and position of unsaturation, and cis/trans configuration all differentially modulated endogenous ACE inhibition. Among saturated fatty acids, stearic acid (IC₅₀ = 7.98 [7.04–9.23] g/L), and among omega-3 and omega-6 fatty acids, α-linolenic (IC₅₀ = 5.60 [4.28–6.15] g/L) and γ-linolenic acids (IC₅₀ = 5.09 [4.28–6.15] g/L) produced the greatest enhancement of the ACE-inhibitory capacity of HSA. Conclusions: The present results indicate that HSA concentration relates to endogenous ACE inhibition in serum, and in vitro experiments demonstrate that HSA-bound FFAs can modulate HSA-mediated ACE inhibition, a mechanism that may be relevant to cardiovascular physiology and disease. Full article

Pulsoximeters are widely used in the medical care of preclinical patients to evaluate the cardiorespiratory status and monitor basic vital signs, such as pulse rate (PR) and oxygen saturation (SpO₂). In many preclinical situations, air transport of the patient by helicopter is necessary. Conventional pulse oximeters, mostly used on the patient’s finger, are prone to motion artifacts during transportation. Therefore, this study aims to determine whether simulated helicopter vibration has an impact on the photoplethysmogram (PPG) derived from an in-ear sensor at the external ear canal and whether the vibration influences the calculation of vital signs PR and SpO₂. The in-ear PPG signals of 17 participants were measured at rest and under exposure to vibration generated by a helicopter simulator. Several signal quality indicators (SQI), including perfusion index, skewness, entropy, kurtosis, omega, quality index, and valid pulse detection, were extracted from the in-ear PPG recordings during rest and vibration. An intra-subject comparison was performed to evaluate signal quality changes under exposure to vibration. The analysis revealed no significant difference in any SQI between vibration and rest (all p > 0.05). Furthermore, the vital signs PR and SpO₂ calculated using the in-ear PPG signal were compared to reference measurements by a clinical monitoring system (ECG and SpO₂ finger sensor). The results for the PR showed substantial agreement (${\mathrm{CCC}}_{rest}$ = 0.96; ${\mathrm{CCC}}_{vibration}$ = 0.96) and poor agreement for SpO₂ (${\mathrm{CCC}}_{rest}$ = 0.41; ${\mathrm{CCC}}_{vibration}$ = 0.19). The results of our study indicate that simulated helicopter vibration had no significant impact on the calculation of the SQIs, and the calculation of vital signs PR and SpO₂ did not differ between rest and vibration conditions. Full article

Endometriosis is a chronic, oestrogen-dependent inflammatory condition affecting approximately 10% of women of reproductive age, frequently associated with chronic pelvic pain, dysmenorrhoea and infertility, substantially impairing quality of life. While pharmacological and surgical therapies represent the standard of care, growing evidence indicates that lifestyle and dietary factors play an important complementary role in symptom management and may influence disease progression. Regular physical activity appears to attenuate systemic inflammation, improve hormonal regulation and support psychological well-being. Dietary patterns rich in anti-inflammatory components, particularly Mediterranean-diets and low-inflammatory diets, have been associated with reduced pain and improved gastrointestinal symptoms, whereas high consumption of red and processed meats may increase disease risk. Micronutrients and selected supplements, including vitamins C, E and D, magnesium, zinc, folate, omega-3 fatty acids, N-acetylcysteine, curcumin, probiotics and green tea polyphenols, show promising but variable evidence for symptom relief. Additional lifestyle factors, such as avoiding endocrine-disrupting chemicals, moderating alcohol intake, ensuring adequate sleep and managing psychological stress, may further modulate inflammatory and hormonal pathways relevant to the disorder. Overall, current evidence indicates that integrating lifestyle interventions alongside conventional treatments offers clinically relevant benefits, although larger, well-designed clinical studies are needed to clarify the magnitude of these effects and to explore further promising lifestyle-based therapeutic approaches. Full article

Background: Chronic inflammation contributes to functional decline in older adults, yet interventions targeting inflammatory pathways have shown inconsistent results. Metabolomics offers a promising approach to identify biological heterogeneity and uncover molecular signatures underlying differential functional trajectories. Objective: Our objective was to examine whether untargeted serum metabolomics can identify metabolic signatures associated with baseline physical function, functional trajectories, and treatment response in older adults with chronic inflammation participating in the ENRGISE trial. Methods: We performed untargeted metabolomic profiling on serum samples (n = 731) collected at baseline, 6, and 12 months from participants (mean age ≥ 70) enrolled in the ENRGISE pilot randomized trial. Participants were randomized to losartan, omega-3 supplementation, both, or placebo. Functional measures included grip strength and 400 m gait speed. Group-based trajectory modeling classified participants into functional trajectories over 12 months. Partial least squares-discriminant analysis (PLS-DA) and pathway enrichment (mummichog algorithm) were used to identify differentially abundant metabolites and perturbed pathways. Results: Baseline metabolomic profiles differed by physical function status. Participants with low grip strength showed enrichment in vitamin A metabolism pathways, while slower gait speed was associated with higher levels of prostaglandin and eicosanoid metabolites. Baseline metabolic profiles distinguished individuals who later declined versus improved in functional performance. Omega-3 supplementation, but not losartan, induced distinct changes in lipid-related pathways, including fatty acid activation, omega-3 metabolism, and prostaglandin biosynthesis, indicating that individuals responded to these interventions metabolically despite null clinical outcomes. Conclusions: Serum metabolomic signatures were associated with baseline physical function, predicted functional trajectories, and revealed pharmacologic activity of omega-3 supplementation. These findings support the use of metabolomics to uncover biological heterogeneity and inform precision geroscience strategies in aging populations. Full article

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are essential omega-3 polyunsaturated fatty acids (n-3 PUFAs) with well-established health benefits. They occur primarily in marine resources, while their quantitative distribution within the glycerolipidome is rarely analyzed. Therefore, we investigated major commercial sources, including 12 microalgal species, the protist Schizochytrium sp., four fish species, and nine commercial n-3 supplements (fish, krill and Schizochytrium-derived “algal” oils) by high-performance thin-layer chromatography–gas chromatography–mass spectrometry (HPTLC–GC–MS). The class-resolved mapping of EPA and DHA revealed signature lipid profiles across all sources. In microalgae, 60–80% of EPA was localized in glycolipids, whereas in Schizochytrium and fish, >90% of DHA occurred in triacylglycerols. Krill oils exhibited phospholipid-rich profiles with ~70% of phosphatidylcholine-bound DHA. Nutritional indices also highlighted major differences: fish and fish oils showed favorable PUFA-to-saturated FA ratios (>0.45) and hypocholesterolemic-to-hypercholesterolemic ratios (>1), while Schizochytrium-based “algal” oils even surpassed these values. The microalgae Nannochloropsis granulata contained the highest EPA content in biomass form, combined with favorable nutritional indices. Beyond total n-3 content in relation to recommended daily intake values, the lipid-class distribution and nutritional indices should be considered decisive metrics for evaluating the health relevance of n-3 resources in the human diet. Full article

Background/Objectives: Increasing evidence supports the hypothesis that dietary intervention can improve pain among individuals with headaches, including migraine, a highly prevalent condition that can be disabling. Non-pharmacologic treatments for migraine are particularly attractive. In this secondary analysis of 182 participants enrolled in a randomized controlled trial of a dietary intervention designed to increase omega-3 (n-3) compared with a control diet, we examined the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), both thought to decrease inflammatory processes. Methods: Path models with two time points (baseline and 16 weeks after randomization), were used to test the relationships between exposures of n-3 blood levels and self-reported dietary intake on outcomes of pain interference using the PROMIS pain interference scale and the Headache Impact Test (HIT-6). Model building was based on our published conceptual model. Results: Good fit was demonstrated for both models (EPA model: CFI = 0.984, RMSEA = 0.039, and SRMR = 0.045; DHA model: CFI = 0.981, RMSEA = 0.040, and SRMR = 0.040). Both EPA and DHA in the blood at 16 weeks were associated with lower levels of pain interference, but the effect for EPA was stronger (B = −0.56, p < 0.001 for EPA, and B = −0.43, p = 0.057 for DHA). Conclusions: Our findings are consistent with an indirect pathway linking diet to pain interference through blood levels of EPA and DHA in migraine. Full article

Background/Objectives: The delayed effects of organophosphate poisoning may manifest years after exposure, often masked by age-related diseases. The aim of this retrospective cohort study was to identify the biochemical “trace” that could remain in patients decades after poisoning. We determined a wide range of biochemical parameters, along with the spectrum of esterified and non-esterified fatty acids (EFAs and NEFAs, respectively), in the blood plasma of a cohort of elderly patients diagnosed with occupational pathology (OP) due to (sub)chronic exposure to organophosphates in the 1980s. Methods: Elderly patients with and without a history of exposure to organophosphates were retrospectively divided into two groups: controls (n = 59, aged 73 ± 4, men 29% and women 71%) and those with OP (n = 84, aged 74 ± 4, men 29% and women 71%). The period of neurological examination and blood sampling for subsequent analysis was from mid-2022 to the end of 2023. Determination of the content of biomarkers of metabolic syndrome, NEFAs, and EFAs in blood plasma was performed by HPLC-MS/MS and GC-MS. Results: The medical histories of the examined elderly individuals with OP and the aged control group included common age-related diseases. However, patients with OP more often had hepatitis, gastrointestinal diseases, polyneuropathy, and an increased BMI. Analysis of metabolic biomarkers revealed, in the OP group, a decrease in the concentrations of 3-hydroxybutyrate (p < 0.05), 2-hydroxybutyrate (p < 0.0001), and acetyl-L-carnitine (p < 0.001) and the activity of butyrylcholinesterase (BChE) (p < 0.05), but an increase in the esterase activity of albumin (p < 0.05). Correlation analysis revealed significant relationships between albumin esterase activity and arachidonic acid concentrations in the OP group (0.64, p < 0.0001). A study of a wide range of fatty acids in patients with OP revealed reciprocal relationships between EFAs and NEFAs. A statistically significant decrease in concentration was shown for esters of margaric, stearic, eicosadienoic, eicosatrienoic, arachidonic, eicosapentaenoic, and docosahexaenoic fatty acids. A statistically significant increase in concentration was shown for non-esterified heptadecenoic, eicosapentaenoic, eicosatrienoic, docosahexaenoic, γ-linolenic, myristic, eicosenoic, arachidonic, eicosadienoic, oleic, linoleic, palmitic, linoelaidic, stearic, palmitoleic, pentadecanoic, and margaric acids. Decreases in the ratios of omega-3 to other unsaturated fatty acids were observed only for the esterified forms. Conclusions: The data obtained allow us to consider an increased level of NEFAs as one of the main cytotoxic factors for the vascular endothelium. Modification of albumin properties and decreased bioavailability of docosahexaenoic acid could be molecular links that cause specific manifestations of organophosphate-induced pathology at late stages after exposure. Full article

The present study investigated the effects of copper oxide nanoparticles (CuO NPs) at concentrations of 0, 5, 10, 20, and 40 mg/L on micropropagation and the accumulation of lipophilic metabolites in Ajuga multiflora, a medicinally valuable ornamental species. The highest number of adventitious shoots (29.4 shoots per explant) was obtained on the shoot induction medium with 5 mg/L CuO NPs. Shoot production gradually decreased at higher CuO NPs concentrations, falling to just 1.1 shoots per explant at 40 mg/L CuO NPs. A similar pattern was seen in axillary shoot multiplication (22.4 shoots per explant at 5 mg/L CuO NPs). However, the maximum shoot fresh weight (0.269 g) was reached on the shoot multiplication medium containing 10 mg/L CuO NPs. Root induction was most effective at 5–10 mg/L CuO NPs, while higher concentrations (20 or 40 mg/L CuO NPs) suppressed or inhibited root formation and altered plantlet morphology. Notably, this study is among the first to assess CuO NPs’ effects across multiple regeneration stages rather than focusing on just one morphogenic event. This emphasizes the importance of optimizing the dose not only for initial shoot induction but also for later multiplication and rooting, ensuring effective micropropagation. Metabolite analysis showed that both the type of organ (microshoots vs. leaves) and CuO NPs concentration significantly affected the levels of α-tocopherol, carotenoids, sterols, and fatty acids. Leaves had higher amounts of α-tocopherol and total carotenoids compared to microshoots. The phytosterol levels also varied, with leaves containing more 22-dehydroclerosterol and total phytosterols, while microshoots had more clerosterol. Treatment with 5 mg/L CuO NPs increased phytosterol accumulation in both organs. CuO NPs significantly influenced the fatty acid profiles. In microshoots, total polyunsaturated fatty acids (PUFAs) increased and total saturated fatty acids (SFAs) decreased with higher CuO NPs levels. Conversely, in leaves, higher CuO NPs concentrations led to increased SFAs and decreased PUFAs, along with a significant rise in the omega-6 (n-6)/n-3 PUFAs ratio. These findings suggest that controlled application of CuO NPs can serve as an elicitor to boost phytochemical production during micropropagation. Full article

Chronic low-grade inflammation is a central contributor to the development of cardiovascular disease, metabolic dysfunction, autoimmune disorders, and cognitive decline. Blood-based biomarkers, such as C-reactive protein (CRP), ferritin, homocysteine, white blood cell (WBC) count, and anti-thyroid peroxidase (anti-TPO) antibodies enable quantification and monitoring of systemic inflammation over time. We aimed to evaluate the impact of a 12-week personalized, biomarker-guided supplementation program including micronutrients, hormone support, and peptides on inflammatory and immune-related biomarkers across age- and sex-stratified adult cohorts. Participants (n = 48; 8 per group) were stratified by sex and age (40–49, 50–59, 60–69 years) and underwent blood testing at baseline and 12 weeks. Personalized protocols were developed based on individual biomarker profiles and included targeted interventions with vitamin D, omega-3 fatty acids, B vitamins, zinc, selenium, hormone optimization, and other supportive agents. Primary outcomes were percent changes in CRP, ferritin, homocysteine, WBC count, and anti-TPO antibody levels. CRP levels decreased by 33–46% across all groups, with similarly consistent declines in homocysteine (29–37%) and WBC count (22–28%). Ferritin reductions were most notable in men, particularly in older age groups (up to 48%), while anti-TPO antibody levels declined more prominently in women (up to 22%). These changes are consistent with reduced systemic inflammation, improved methylation status, and potential modulation of autoimmune activity. This biomarker-guided, personalized supplementation protocol was associated with clinically meaningful reductions in key markers of inflammation and immune dysregulation. These findings are suggestive of potential efficacy for precision-based health optimization programs and highlight the need for larger randomized controlled trials (RCTs) to confirm causal effects. Full article

Oxylipins are specialized lipid mediators that can have dual functions, either promoting inflammation or supporting resolution. Exposure to air pollution is associated with systemic inflammation that may be modified by oxylipins derived from polyunsaturated fatty acids (FA). In this study, we examined whether short-term air pollution exposure is associated with changes in circulating oxylipins in healthy adults, who were on high- or low-dietary omega-3 fatty acid (n-3 FA) intakes. We measured 56 oxylipin species from participants’ plasma samples and employed mixed-effects models to assess the associations, stratified by n-3 FA groups. Plasma concentrations of oxylipins derived from n-3 FA [e.g., 14-hydroxydocosahexaenoic acid (14-HDHA) & 11-hydroxydocosahexaenoic acid (11-HDoHE), and 12-hydroxyeicosapentaenoic acid (12-HEPE)] were significantly higher in the high n-3 FA group compared to the low group. Conversely, selected oxylipins derived from n-6 FA [e.g., 15-hydroxyeicosatetraenoic acid (15-HETE) and 14,15-Dihydroxyeicosatrienoic acid (14,15-DiHETrE)] were significantly lower in the high n-3 group. Exposure to PM_2.5, O₃, and NO₂ was associated with reductions in pro-inflammatory oxylipins produced by lipoxygenase in the high n-3 FA group, but not in the low group; for example, 12-HETE. Furthermore, participants in the high n-3 group exposed to PM_2.5, O₃, and NO₂ had elevated levels of n-3 FA-derived pro-resolving oxylipins compared to those in the low n-3 group; for instance, 12-HEPE and 14-HDHA & 11-HDoHE. In conclusion, short-term air pollution exposure was associated with lower pro-inflammatory and higher pro-resolving oxylipin levels in the high n-3 FA group. These findings suggest n-3-derived lipid metabolites may promote inflammation resolution induced by air pollution. Full article

Background/Objectives: Diet–microbiota interactions shape ageing; however, their sex-specific dimensions remain poorly defined. Human studies rarely stratify analyses by sex, while most evidence of sex-dependent microbial and metabolic responses comes from preclinical models. This review synthesizes current findings on the sex-specific pathways linking diet, microbiota, and healthy ageing. Methods: A narrative review was conducted by integrating human observational studies, randomized controlled trials, and mechanistic animal research. Evidence was organized into four domains: (1) age-related changes in gut microbial composition; (2) microbiota-derived metabolites; (3) dietary patterns and functional nutrients; and (4) sex-specific endocrine and immunometabolism interactions influenced by the gut microbiota. Results: Ageing is characterized by dysbiosis, loss of short-chain fatty acid (SCFA)-producing taxa, expansion of Proteobacteria, and reduced production of key metabolites including butyrate, indoles, and polyamines. Dietary fiber, polyphenols, omega-3 fatty acids, and plant-based proteins help restore these pathways and mitigate inflammaging. Sex differences persist into later life: women show reduced estrobolome activity and SCFA decline after menopause, whereas men display higher levels of pro-atherogenic metabolites such as trimethylamine N-oxide (TMAO). Nutritional interventions, probiotics, and microbial metabolites exhibit sex-dependent responses in both human and animal studies. Conclusions: Diet–microbiota interactions shape ageing outcomes through sex-specific metabolic, hormonal, and immunological pathways. Incorporating sex as a biological variable is essential for developing personalized, nutrition-based strategies to support healthy ageing. Full article

Background: Type 2 diabetes (T2DM) and prediabetes are growing public health problems worldwide. Oxidative stress plays a key role in the pathogenesis and progression of carbohydrate metabolism disorders. Metformin is an antidiabetic drug that significantly affects the oxidative-antioxidant balance. This study aimed to compare serum total antioxidant capacity (TAC) in individuals with T2DM, prediabetes, and healthy controls, and to assess the impact of dietary factors and metformin treatment on antioxidant parameters. Methods: The study involved 49 adults (aged 40–70 years) assigned to three groups: those with T2DM (n = 19), those with prediabetes (n = 12), and healthy controls (n = 18). Serum TAC was assessed using three spectrophotometric assays: DPPH, ABTS, and FRAP. A nutritional assessment was performed based on a three-day dietary recall, analysed using DietetykPro software. Statistical analyses included Kruskal–Wallis tests with post hoc corrections and Spearman correlation. Results: The prediabetes group demonstrated the lowest TAC values across all tests, while individuals with T2DM demonstrated higher levels using the ABTS and FRAP tests, which may reflect group-specific factors such as treatment or metabolic regulation. The differences between groups showed moderate to large effect sizes, including η² = 0.24 for ABTS, η² = 0.14 for DPPH and η² = 0.13 for FRAP, indicating biologically meaningful alterations in antioxidant capacity. Negative correlations were observed between antioxidant activity, as measured by the DPPH test, and body weight (p = 0.0095) and BMI (p = 0.0381), indicating that increased body weight may impair serum antioxidant capacity. After applying the FDR correction, significant correlations were observed between ABTS values and vitamin B5 (p = 0.0004, q = 0.0135), omega-6 (p = 0.0042, q = 0.0220), phosphorus (p = 0.0009, q = 0.0328), calcium (p = 0.0024, q = 0.0176) and zinc (p = 0.0012, q = 0.0138) intake. Other associations with anthropometric and dietary variables were observed as non-significant trends. Conclusions: The prediabetes group exhibited lower TAC, indicating a redox profile that differs from both healthy individuals and those with T2DM. Dietary quality, including adequate intake of selenium, could support antioxidant defence mechanisms, whereas excess body weight and high intake of omega-6 may impair them. The results also suggest that metformin may modulate TAC, supporting adaptive responses to oxidative stress in T2DM. These findings highlight the potential importance of dietary and pharmacological interventions in maintaining oxidative-antioxidant balance in metabolic disorders. Full article