Metabolites

5 pages, 200 KiB

Open AccessCorrection

Correction: Florêncio et al. Synergistic Effects of Probiotics and Lifestyle Interventions on Intestinal Microbiota Composition and Clinical Outcomes in Obese Adults. Metabolites 2025, 15, 70

by Glauber Pimentel Florêncio, Analicy Rodrigues Xavier, Ana Catarina de Castro Natal, Lorena Prado Sadoyama, Geórgia das Graças Pena, Ralciane de Paula Menezes, Geraldo Sadoyama Leal, Lislei Jorge Patrizzi and Denise Von Dolinger de Brito Röder

Metabolites 2025, 15(5), 293; https://doi.org/10.3390/metabo15050293 (registering DOI) - 27 Apr 2025

Abstract

Because the corresponding authors found the odds ratio (OR) in the table to be imprecise and unnecessary [...] Full article

17 pages, 3089 KiB

Open AccessArticle

Utilizing Untargeted Lipidomics Technology to Elucidate Differences in Lipid Compositions Among Sensitive Dry, Sensitive Oily and Healthy Skin Types

by Agui Xie, Xingjiang Zhang, Qing Huang and Jianxin Wu

Metabolites 2025, 15(5), 292; https://doi.org/10.3390/metabo15050292 (registering DOI) - 26 Apr 2025

Abstract

Background: Sensitive skin exhibits impaired skin barrier function. The lipid composition of the skin, a pivotal element within the stratum corneum’s “brick-and-mortar” structure, plays a dual role: it is integral to cell differentiation processes and serves as a vital nutrient reservoir for cutaneous [...] Read more.

Background: Sensitive skin exhibits impaired skin barrier function. The lipid composition of the skin, a pivotal element within the stratum corneum’s “brick-and-mortar” structure, plays a dual role: it is integral to cell differentiation processes and serves as a vital nutrient reservoir for cutaneous microbiota, thereby influencing the skin’s microecological balance. There is a notable research gap concerning the comparative analysis of physiological parameters and lipid profiles among individuals with sensitive dry skin (SDS), sensitive oily skin (SOS), and healthy skin (HS). Methods: A total of 95 females (18–25 years) were grouped: SDS (n = 32), SOS (n = 31), and HS (n = 32). Stratum corneum water content, oil content, and TEWL were measured. Lipids from sebaceous glands and stratum corneum (tape-stripping) underwent UPLC-QTOF-MS analysis. Differential lipids were identified via OPLS-DA, volcano plots, and LMSD. Results: In terms of physiological indicators, notable disparities emerged in oil content and stratum corneum water content between the SOS and both the HS and the SDS. Sensitive skin, whether dry or oily, displayed a higher transepidermal water loss (TEWL) value than healthy skin, reflecting a declined state of skin barrier function. Regarding the sebum samples, the relative percentages of sphingolipids (SP) and glycerophospholipids (GP) were significantly higher in SDS. Regarding the stratum corneum samples, the percentages of SP in SDS were significantly higher. Conclusions: This study, for the first time, conducted a comprehensive analysis of the skin’s physiological properties, lipidomics of sebum, and stratum corneum lipids among groups with SDS, SOS, and HS. These observations indicate a profound association between skin barrier dysfunction in SDS individuals and, in particular, sphingolipids (SP). Full article

(This article belongs to the Section Advances in Metabolomics)

21 pages, 4124 KiB

Open AccessArticle

Xanthoceras sorbifolium Oil Attenuates Hyperlipidemia Through Dual Modulation of Gut Microbiota and Lipid Metabolites: Mechanistic Insights from Lipidomics and 16S rRNA Sequencing

by Yameng Tao, Miaomiao Yao, Qi He, Xiaoyang Kang, Fangkai Shi, Xuan Hu, Zhiyun Meng, Hui Gan, Ruolan Gu, Yunbo Sun, Guifang Dou and Shuchen Liu

Metabolites 2025, 15(5), 291; https://doi.org/10.3390/metabo15050291 - 25 Apr 2025

Abstract

Background/Objectives: Xanthoceras sorbifolium oil (XSO), containing nervonic acid and unsaturated fatty acids (93%), exhibits lipid-lowering potential; yet, its mechanisms involving gut–liver crosstalk remain unclear. This study investigated XSO’s anti-hyperlipidemic effects and gut microbiota interactions. Methods: Forty-eight Sprague Dawley male rats were [...] Read more.

Background/Objectives: Xanthoceras sorbifolium oil (XSO), containing nervonic acid and unsaturated fatty acids (93%), exhibits lipid-lowering potential; yet, its mechanisms involving gut–liver crosstalk remain unclear. This study investigated XSO’s anti-hyperlipidemic effects and gut microbiota interactions. Methods: Forty-eight Sprague Dawley male rats were divided into: normal control (NC), high-fat diet (HFD), XSO prevention (XOP, 1.4 mL/kg pre-HFD), and XSO treatment (XOT, post-HFD). Serum lipids, fecal short-chain fatty acids (SCFAs), gut microbiota (16S rRNA), and lipidomics (UPLC-MS/MS) were analyzed after 12 weeks. Results: XOP significantly reduced serum total cholesterol (TC, 26.8%), triglycerides (TG, 35.9%), and low-density lipoprotein cholesterol (LDL-C, 45.9%) versus HFD (p < 0.05), while increasing high-density lipoprotein cholesterol (HDL-C, 7.98%). XOP showed enhanced hepatoprotection (AST↓ 32.6%, p < 0.01). Although XSO elevated fecal acetate (1.5-fold) and butyrate (1.3-fold), these changes lacked significance (p > 0.05). The analysis of gut microbiota showed that the pro-inflammatory Coriobacteriaceae and Erysipelibacteriaceae were reduced at the family level in the XOP group (p < 0.05). Lipidomics identified 69 differential metabolites: XSO downregulated atherogenic cholesteryl esters and triglycerides, upregulated six phosphatidylethanolamines, and modulated aberrant lysophosphatidylcholines. Conclusions: XSO alleviates hyperlipidemia through direct modulation of lipid metabolism pathways and suppression of pro-inflammatory gut microbiota. While its prebiotic potential warrants further validation, these findings highlight XSO as a functional dietary adjunct for improving lipid homeostasis and mitigating cardiovascular risks. XSO alleviates hyperlipidemia through direct modulation of lipid metabolism pathways and suppression of pro-inflammatory gut microbiota, while its prebiotic potential warrants further validation. These findings support XSO as a dietary adjunct for lipid homeostasis improvement, offering a nutritional strategy for early-stage cardiovascular risk management. Full article

(This article belongs to the Section Lipid Metabolism)

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25 pages, 8600 KiB

Open AccessArticle

Integrated Metabolomics and Lipidomics Analysis Reveals the Mechanism Behind the Action of Chiglitazar on the Protection Against Sepsis-Induced Acute Lung Injury

by Liu-Liu Lu, Yu-Li Cao, Zhen-Chen Lu, Han Wu, Shan-Song Hu, Bing-Qing Ye, Jin-Zhi He, Lei Di, Xu-Lin Chen and Zhi-Cheng Liu

Metabolites 2025, 15(5), 290; https://doi.org/10.3390/metabo15050290 - 25 Apr 2025

Abstract

Background: Sepsis-induced acute lung injury (SALI) is a critical clinical challenge with high mortality. Metabolic dysregulation drives SALI pathogenesis, disrupting lung function and energy metabolism. Despite proven benefits, metabolic restoration is underused in sepsis. This study explores chiglitazar’s role in balancing metabolism to [...] Read more.

Background: Sepsis-induced acute lung injury (SALI) is a critical clinical challenge with high mortality. Metabolic dysregulation drives SALI pathogenesis, disrupting lung function and energy metabolism. Despite proven benefits, metabolic restoration is underused in sepsis. This study explores chiglitazar’s role in balancing metabolism to protect against SALI. Methods: The protective effects of chiglitazar in CLP rats were demonstrated by the survival curve, histological analysis, and immunohistochemical analysis in the lung tissue. Metabolomic and lipidomic analyses of lung tissue samples using gas chromatography–mass spectrometry (GC-MS) and liquid chromatography–mass spectrometry (LC-MS) were performed to evaluate metabolic shifts induced by CLP surgery and chiglitazar pretreatment. The mRNA and protein levels of the underlying targets directing nicotinamide adenine dinucleotide (NAD+) and triglyceride synthesis were analyzed by qPCR and Western blotting. To validate the mechanism by which chiglitazar protected against SALI, the SIRT1 inhibitor EX-527 was applied to human normal lung epithelial (BEAS-2B) cells and another batch of rats to observe its reverse effect against chiglitazar’s action. Results: Chiglitazar pretreatment significantly restored NAD+ and improved dysregulated lipid metabolism by enhancing the synthesis of triglycerides (TGs) and suppressing accumulated fatty acids (FAs). The metabolic modulation mediated by chiglitazar was associated with the upregulations of the SIRT1/PGC-1α/PPARα/GPAT3 axis. Co-treatment with EX-527 in LPS-stimulated BEAS-2B cells and CLP rats inhibited the effects of chiglitazar on the aforementioned signaling pathways and worsened the protective effects of chiglitazar on lung injury, respectively. Conclusions: Chiglitazar alleviates SALI by restoring NAD+ and TG synthesis, highlighting the balancing of metabolism as a promising therapeutic strategy in the management of SALI. Full article

(This article belongs to the Special Issue New Analytical Techniques and Applications of Metabolomics and Lipidomics)

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18 pages, 954 KiB

Open AccessArticle

Alcohol Exposure May Increase Prenatal Choline Needs Through Redirection of Choline into Lipid Synthesis Rather than Methyl Donation

by Hannah G. Petry, Nipun Saini, Susan M. Smith and Sandra M. Mooney

Metabolites 2025, 15(5), 289; https://doi.org/10.3390/metabo15050289 - 24 Apr 2025

Abstract

Background: Prenatal alcohol exposure (PAE) can reduce fetal growth and cause neurodevelopmental disability. Prenatal choline supplements attenuate PAE-induced behavioral and growth deficits; however, the underlying mechanisms are unknown. Alcohol alters nutrient metabolism and potentially increases nutrient needs. Here, we investigate how alcohol [...] Read more.

Background: Prenatal alcohol exposure (PAE) can reduce fetal growth and cause neurodevelopmental disability. Prenatal choline supplements attenuate PAE-induced behavioral and growth deficits; however, the underlying mechanisms are unknown. Alcohol alters nutrient metabolism and potentially increases nutrient needs. Here, we investigate how alcohol affects choline metabolism in the maternal–fetal dyad and the role of supplemental choline. Methods: Pregnant C57BL/6J mice were assigned to one of four groups: alcohol-exposed (3 g/kg alcohol/day) or control +/− 100 mg/kg choline daily from embryonic day (E)8.5–17.5. We performed an exploratory hypothesis-generating analysis of targeted metabolomics on choline-related metabolites in the maternal liver, plasma, placenta, and fetal brain at E17.5 and Spearman correlation analyses to determine their association with gestational and fetal growth outcomes. Results: Although choline levels were largely unaffected by alcohol or choline, alcohol increased many lipid products in the CDP–choline pathway; this was not normalized by choline. Alcohol increased placental CDP–ethanolamine and reduced the maternal hepatic SAM/SAH ratio as well as dimethylglycine and the serine/glycine ratio across the dyad, suggesting a functional insufficiency in methyl donor pools. These outcomes were rescued by supplemental choline. Correlation analyses among choline metabolites and fetal growth outcomes suggest that maternal plasma methionine, serine, and the serine/glycine ratio may be predictive of maternal–fetal choline status. Conclusions: The increased hepatic lipid synthesis that characterizes chronic alcohol exposure may draw choline into phospholipid biosynthesis at the expense of its use as a methyl donor. We propose that PAE increases choline needs, and that its supplementation is necessary to fulfill these competing demands for lipid and methyl use. Full article

(This article belongs to the Special Issue One-Carbon Metabolism in Pregnant Women, Fetuses, and Infants)

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12 pages, 665 KiB

Open AccessArticle

Probiotic Supplementation Improves Glucose Homeostasis and Modulates Interleukin (IL)-21 and IL-22 Levels in Pediatric Patients with Type 1 Diabetes: A Randomized Placebo-Controlled Trial

by Amira Abdel Moneam Adly, Eman Abdel Rahman Ismail, Mahasen Mohamed Abd-Elgawad and Nouran Yousef Salah

Metabolites 2025, 15(5), 288; https://doi.org/10.3390/metabo15050288 - 24 Apr 2025

Abstract

Background: Probiotics alter gut microbiota and have beneficial effects on immune homeostasis. The role of probiotics in diabetes has been shown in some studies. Interleukin (IL)-21 and IL-22 have been implicated in the pathogenesis of type 1 diabetes mellitus (T1DM). Objectives: This study [...] Read more.

Background: Probiotics alter gut microbiota and have beneficial effects on immune homeostasis. The role of probiotics in diabetes has been shown in some studies. Interleukin (IL)-21 and IL-22 have been implicated in the pathogenesis of type 1 diabetes mellitus (T1DM). Objectives: This study aimed to assess the effect of oral supplementation with probiotics on glycemic control and IL-21 and IL-22 levels in pediatric patients with T1DM. Methods: This randomized controlled trial was registered in ClinicalTrials (NCT04579341) and included 70 children and adolescents with T1DM. They were randomly assigned into two groups to receive either an oral probiotic tablet containing 0.5 mg Lactobacillus acidophilus once daily or a matching placebo. Both groups were followed up for 6 months with assessment of fasting blood glucose (FBG), lipids, hemoglobin A1c (HbA1c), and IL-21 and IL-22 levels. Results: Baseline clinical characteristics and laboratory parameters were similar between both groups (p > 0.05). After six months, probiotic supplementation for the intervention group resulted in significant decreases in FBG, HbA1c, total cholesterol, and IL-21 levels, while IL-22 was increased compared with baseline levels (p < 0.001) and compared with the placebo group (p < 0.001). No adverse reactions were reported. Baseline IL-21 was positively correlated to FBG, HbA1c, and total cholesterol while there were negative correlations between these variables and IL-22 levels. Conclusions: Probiotic supplementation improved glucose homeostasis and glycemic control, possibly through their immunomodulatory effects on cytokines IL-21 and IL-22. Thus, probiotics could be a safe adjuvant therapy to intensive insulin in pediatric patients with T1DM. Full article

(This article belongs to the Special Issue Diet and Nutrition in Relation to Metabolic Health)

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34 pages, 1818 KiB

Open AccessReview

From Childhood Obesity to Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and Hyperlipidemia Through Oxidative Stress During Childhood

by Siham Accacha, Julia Barillas-Cerritos, Ankita Srivastava, Frances Ross, Wendy Drewes, Shelly Gulkarov, Joshua De Leon and Allison B. Reiss

Metabolites 2025, 15(5), 287; https://doi.org/10.3390/metabo15050287 - 24 Apr 2025

Abstract

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is rapidly becoming the most prevalent form of chronic liver disease in both pediatric and adult populations. It encompasses a wide spectrum of liver abnormalities, ranging from simple [...] Read more.

Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is rapidly becoming the most prevalent form of chronic liver disease in both pediatric and adult populations. It encompasses a wide spectrum of liver abnormalities, ranging from simple fat accumulation to severe conditions such as inflammation, fibrosis, cirrhosis, and liver cancer. Major risk factors for MASLD include obesity, insulin resistance, type 2 diabetes, and hypertriglyceridemia. Methods: This narrative review employed a comprehensive search of recent literature to identify the latest studies on the relationship between MAFLD and obesity, the health consequences and the latest treatment options to prevent long-term damage to the liver and other organs. Additionally, the article presents perspectives on diagnostic biomarkers. Results: Childhood obesity is linked to a multitude of comorbid conditions and remains a primary risk factor for adult obesity. This abnormal fat accumulation is known to have long-term detrimental effects into adulthood. Scientific evidence unequivocally demonstrates the role of obesity-related conditions, such as insulin resistance, dyslipidemia, and hyperglycemia, in the development and progression of MASLD. Oxidative stress, stemming from mitochondrial dysfunction, is a leading factor in MASLD. This review discusses the interconnections between oxidative stress, obesity, dyslipidemia, and MASLD. Conclusions: Atherogenic dyslipidemia, oxidative stress, inflammation, insulin resistance, endothelial dysfunction, and cytokines collectively contribute to the development of MASLD. Potential treatment targets for MASLD are focused on prevention and the use of drugs to address obesity and elevated blood lipid levels. Full article

(This article belongs to the Special Issue Metabolic Dysregulation in Fatty Liver Disease)

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30 pages, 1477 KiB

Open AccessReview

The Influence of the Sympathetic Nervous System on Cardiometabolic Health in Response to Weight Gain or Weight Loss

by Gavin W. Lambert, Mariya Patel and Elisabeth A. Lambert

Metabolites 2025, 15(5), 286; https://doi.org/10.3390/metabo15050286 - 23 Apr 2025

Abstract

Alterations in sympathetic nervous activity are evident in response to changes in body weight. Sympathetic nervous activity and sympathetic responses to weight change are regionalized, with alterations in end organ function dependent on the changes occurring in the brain regulatory pathways invoked and [...] Read more.

Alterations in sympathetic nervous activity are evident in response to changes in body weight. Sympathetic nervous activity and sympathetic responses to weight change are regionalized, with alterations in end organ function dependent on the changes occurring in the brain regulatory pathways invoked and in the effector organs engaged. The obesity-induced activation of the sympathetic nervous system likely contributes to the initiation and worsening of cardiometabolic risk factors, including elevated blood pressure, cardiac dysfunction, dyslipidaemia, increased fasting blood glucose, insulin resistance, and non-alcoholic steatohepatitis. Unintended weight loss, as occurs in cachexia, is driven, at least in part, by the activation of sympathetic nervous-stimulated thermogenesis. The complexity of sympathetic nervous regulation renders the use of global measures of sympathetic activity problematic and the development of targeted therapies difficult, but these are not without promise or precedent. Knowledge of the central and peripheral pathways involved in sympathetic nervous regulation has opened up opportunities for pharmacological, surgical, and device-based approaches to mitigating the burden of disease development and progression. In this narrative review, we elaborate on sympathetic activity in response to changes in body weight, the brain pathways involved, and the cardiovascular and metabolic risks associated with perturbations in regional sympathetic activity. Full article

(This article belongs to the Special Issue Adrenal Neuroendocrine System and Cardiometabolic Health)

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21 pages, 2740 KiB

Open AccessArticle

Metabolic Reprogramming in HIV+ CD4⁺ T-Cells: Implications for Immune Dysfunction and Therapeutic Targets in M. tuberculosis Co-Infection

by Suheena Ayrga and Gerrit Koorsen

Metabolites 2025, 15(5), 285; https://doi.org/10.3390/metabo15050285 - 22 Apr 2025

Abstract

Background/Objectives: HIV and Mycobacterium tuberculosis (M.tb) co-infection presents a major global health burden. The immune response to M.tb is largely orchestrated by cluster of differentiation 4-positive (CD4⁺) T cells, with CD8⁺ T cells playing an auxiliary role. This [...] Read more.

Background/Objectives: HIV and Mycobacterium tuberculosis (M.tb) co-infection presents a major global health burden. The immune response to M.tb is largely orchestrated by cluster of differentiation 4-positive (CD4⁺) T cells, with CD8⁺ T cells playing an auxiliary role. This study aims to investigate the immunometabolic response of CD4⁺ and CD8⁺ T cells to M.tb antigens, analysed using metabolomics, to elucidate metabolic shifts that may influence immune function in an HIV+ environment. Methods: Whole blood samples from newly diagnosed, treatment-naïve HIV+ individuals were stimulated with M.tb antigens early secreted antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10) using the QuantiFERON^® (QFT) Gold Plus assay. Following incubation, plasma samples were analysed through untargeted nuclear magnetic resonance (1^H-NMR) spectroscopy. Metabolomic data were processed using MetaboAnalyst, with differential metabolites identified through multivariate statistical analyses. Results: Metabolic profiling of PBMCs revealed distinct differences in response to M.tb antigens between CD4⁺ and CD4⁺/CD8⁺ T-cell activation. CD4⁺ T cells exhibited enhanced glycolysis, with elevated levels of metabolites that are linked largely to the Warburg effect. Additionally, vitamin D levels were found to correlate with certain metabolites, suggesting a role in modulating immune responses. Conclusions: These findings suggest a complex interplay between immune cell metabolism and activation in HIV+ individuals. The study demonstrates that HIV and M.tb co-infection significantly influences the broader metabolic profile of peripheral blood mononuclear cells (PBMCs), highlighting the altered metabolic pathways that are critical in immune responses and disease progression. These findings contribute to the understanding of immunometabolism in co-infection and emphasise the need for further research into targeted metabolic interventions. Full article

(This article belongs to the Section Cell Metabolism)

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16 pages, 2448 KiB

Open AccessArticle

Lactobacillus johnsonii N6.2 Phospholipids Induce T Cell Anergy upon Cognate Dendritic Cell Interactions

by Alexandra E. Cuaycal, Monica F. Torrez Lamberti, Graciela L. Lorca and Claudio F. Gonzalez

Metabolites 2025, 15(5), 284; https://doi.org/10.3390/metabo15050284 - 22 Apr 2025

Abstract

Background/Objectives: Lactobacillus johnsonii N6.2 is a gut symbiont with probiotic properties. L. johnsonii N6.2 delayed the progression of type 1 diabetes (T1D) in diabetic-prone rats. The probiotic intake demonstrated immune cell modulation in healthy volunteers, leading to improved wellness and fewer reported [...] Read more.

Background/Objectives: Lactobacillus johnsonii N6.2 is a gut symbiont with probiotic properties. L. johnsonii N6.2 delayed the progression of type 1 diabetes (T1D) in diabetic-prone rats. The probiotic intake demonstrated immune cell modulation in healthy volunteers, leading to improved wellness and fewer reported symptoms like headaches and abdominal pain. These systemic immune-modulating benefits are attributed to L. johnsonii N6.2’s bioactive fractions, including extracellular vesicles (EVs) and purified phospholipids (PLs). We have previously shown that L. johnsonii N6.2 PLs modulate dendritic cell (DC) function towards a regulatory-like phenotype. Here, we further characterize the immune regulatory effects of L. johnsonii N6.2 PLs on adaptive immunity, specifically upon DC and T cell interactions. We hypothesized that PL-stimulated DCs suppress T cell-mediated responses to maintain tolerance in intra- and extra-intestinal sites. Methods: Bone marrow-derived dendritic cells (BMDCs) were generated from Sprague-Dawley rats and stimulated with L. johnsonii N6.2 PLs. Isogenic T cells were isolated from PBMCs obtained via terminal exsanguination. In vitro cellular assays, co-culture experiments, gene expression analysis by qRT-PCR, and flow cytometry assays were conducted to assess the immune regulatory effects of L. johnsonii N6.2 PLs. Results: The PL-stimulated BMDCs upregulated DC regulatory markers and exhibited an immature-like phenotype with reduced surface expression of maturation markers but increased surface migratory molecules (ICAM-1). These BMDCs presented immunosuppressive functions upon cognate T cell interactions and in the presence of TCR stimulation. Specifically, PL-stimulated BMCDs suppressed Th1 effector function and induced the expression of T cell anergy-related genes after co-culturing for 72 h. Conclusions: This study highlights the immune regulatory capacity of L. johnsonii N6.2’s bioactive components on adaptive immunity, specifically that of purified PLs on DC:T cell-mediated responses leading to immunosuppression. Our findings suggest that L. johnsonii N6.2-purified PLs play a role in regulating adaptive immunity, offering potential benefits for managing immune-related diseases like T1D. Full article

(This article belongs to the Special Issue Targeting Microbiota and Metabolites for Prevention and Treatment of Human Diseases)

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Metabolites, Volume 15, Issue 5 (May 2025) – 10 articles

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