PubMed

J Pineal Res. 2024 Aug;76(5):e12987. doi: 10.1111/jpi.12987.ABSTRACTSleep deprivation (SD) has been associated with a plethora of severe pathophysiological syndromes, including gut damage, which recently has been elucidated as an outcome of the accumulation of reactive oxygen species (ROS). However, the spatiotemporal analysis conducted in this study has intriguingly shown that specific events cause harmful damage to the gut, particularly to goblet cells, before the accumulation of lethal ROS. Transcriptomic and metabolomic analyses have identified significant enrichment of metabolites related to ferroptosis in mice suffering from SD. Further analysis revealed that melatonin could rescue the ferroptotic damage in mice by suppressing lipid peroxidation associated with ALOX15 signaling. ALOX15 knockout protected the mice from the serious damage caused by SD-associated ferroptosis. These findings suggest that melatonin and ferroptosis could be targets to prevent devastating gut damage in animals exposed to SD. To sum up, this study is the first report that proposes a noncanonical modulation in SD-induced gut damage via ferroptosis with a clearly elucidated mechanism and highlights the active role of melatonin as a potential target to maximally sustain the state during SD.PMID:38975671 | DOI:10.1111/jpi.12987

J Anim Sci Technol. 2024 May;66(3):587-602. doi: 10.5187/jast.2023.e62. Epub 2024 May 31.ABSTRACTThis research was conducted to study the effects of organic selenium (Se) supplements at different levels on pork loin quality during storage. Fifteen pork loins were procured randomly from three groups, Con (fed basal diet), Se15 (fed 0.15 ppm organic Se along with 0.10 ppm inorganic Se), and Se45 (fed 0.45 ppm organic Se along with 0.10 ppm inorganic Se). Each sample was analyzed for Se contents, antioxidant properties (glutathione peroxidase [GPx] activity, 2,2'-azinobis-[3-ethylbenzothiazoline-6-sulfonic acid] [ABTS] and 2,2-diphenyl-1-picrylhydrazyl [DPPH] radical scavenging activities, 2-thiobarbituric acid reactive substances), physicochemical properties (water holding capacity, pH, color), and metabolomic analysis during 14-day storage period. Se45-supplemented group showed significantly higher Se contents and GPx activity than the other groups throughout the storage period. However, other antioxidant properties were not significantly affected by Se supplementation. Selenium supplementation did not have an adverse impact on physicochemical properties. Nuclear Magnetic Resonance-based metabolomic analysis indicated that the selenium supply conditions were insufficient to induce metabolic change. These results suggest that organic Se (0.15 and 0.45 ppm) can accumulate high Se content in pork loins without compromising quality.PMID:38975577 | PMC:PMC11222120 | DOI:10.5187/jast.2023.e62

J Mol Cell Cardiol Plus. 2024 Jun;8:100076. doi: 10.1016/j.jmccpl.2024.100076. Epub 2024 Apr 24.ABSTRACTBarth syndrome (BTHS) is a mitochondrial lipid disorder caused by mutations in TAFAZZIN (TAZ), required for cardiolipin (CL) remodeling. Cardiomyopathy is a major clinical feature, with no curative therapy. Linoleic acid (LA) supplementation is proposed to ameliorate BTHS cardiomyopathy by enhancing linoleoyl group incorporation into CL. While the beneficial effect of dietary LA supplementation in delaying the development of BTHS cardiomyopathy has been recently tested, its potential to reverse established BTHS cardiomyopathy remains unclear. Our study revealed that LA supplementation cannot rescue established BTHS cardiomyopathy in mice, highlighting the importance of early initiation of LA supplementation for maximum benefits.PMID:38974772 | PMC:PMC11225933 | DOI:10.1016/j.jmccpl.2024.100076

J Oral Microbiol. 2024 Jul 3;16(1):2373040. doi: 10.1080/20002297.2024.2373040. eCollection 2024.ABSTRACTBACKGROUND: Curcumin is a multi-functional polyphenol with anti-bacterial and anti-inflammatory effects and may have potential for treatment of periodontal diseases. The present study was conducted to examine the molecular basis of the anti-bacterial effect of curcumin against Porphyromonas gingivalis using metabolome analysis.MATERIALS AND METHODS: P. gingivalis were incubated with 10 µg/mL curcumin, and then metabolites were analyzed with CE-TOF/MS. Expression levels of sigma factors were also evaluated using RT-PCR assays. The activities of dipeptidyl peptidases (DPPs) were assessed by examining the degradation reactions of MCA-labeled peptides.RESULTS: The relative amounts of various glycogenic amino acids were significantly decreased when P. gingivalis was incubated with curcumin. Furthermore, the metabolites on the amino acid degradation pathway, including high-energy compounds such as ATP, various intermediate metabolites of RNA/DNA synthesis, nucleoside sugars and amino sugars were also decreased. Additionally, the expression levels of sigma-54 and sigma-70 were significantly decreased, and the same results as noted following nutrient starvation. Curcumin also significantly suppressed the activities of some DPPs, while the human DPP-4 inhibitors markedly inhibited the growth of P. gingivalis and activities of the DPPs.CONCLUSIONS: Curcumin suppresses the growth of P. gingivalis by inhibiting DPPs and also interferes with nucleic acid synthesis and central metabolic pathways, beginning with amino acid metabolism.PMID:38974504 | PMC:PMC11225630 | DOI:10.1080/20002297.2024.2373040

iScience. 2024 May 25;27(6):110110. doi: 10.1016/j.isci.2024.110110. eCollection 2024 Jun 21.ABSTRACTIncreased cases of sepsis during COVID-19 in the absence of known bacterial pathogens highlighted role of viruses as causative agents of sepsis. In this study, we investigated clinical, laboratory, proteomic, and metabolomic characteristics of viral sepsis patients (n = 45) and compared them to non-sepsis patients with COVID-19 (n = 186) to identify molecular mechanisms underlying the pathology of viral sepsis in COVID-19. We identified unique metabolomic and proteomic signatures that suggest a substantial perturbation in the coagulation, complement, and platelet activation pathways in viral sepsis. Our proteomic data indicated elevated coagulation pathway protein (fibrinogen), whereas a decrease in many of the complement proteins was observed. These alterations were associated with the functional consequences such as susceptibility to secondary bacterial infections and potentially contributing to both local and systemic disease phenotypes. Our data provide novel aspect of COVID-19 pathology that is centered around presence of sepsis phenotype in COVID-19.PMID:38974472 | PMC:PMC11225851 | DOI:10.1016/j.isci.2024.110110

Front Mol Biosci. 2024 Jun 21;11:1430789. doi: 10.3389/fmolb.2024.1430789. eCollection 2024.NO ABSTRACTPMID:38974319 | PMC:PMC11224660 | DOI:10.3389/fmolb.2024.1430789

Food Chem X. 2024 Jun 12;23:101551. doi: 10.1016/j.fochx.2024.101551. eCollection 2024 Oct 30.ABSTRACTSweet potatoes are rich in flavonoids and phenolic acids, showing incomparable nutritional and health value. In this investigation, we comprehensively analyzed the secondary metabolite profiles in the flesh of different-colored sweet potato flesh. We determined the metabolomic profiles of white sweet potato flesh (BS), orange sweet potato flesh (CS), and purple sweet potato flesh (ZS) using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The CS vs. BS, ZS vs. BS, and ZS vs. CS comparisons identified a total of 4447 secondary metabolites, including 1540, 1949, and 1931 differentially accumulated metabolites. Among them, there were significant differences in flavonoids and phenolic acids. There were 20 flavonoids and 13 phenolic acids that were common differential metabolites among the three comparison groups. The accumulation of paeoniflorin-like and delphinidin-like compounds may be responsible for the purple coloration of sweet potato flesh. These findings provide new rationale and insights for the development of functional foods for sweet potatoes.LIST OF COMPOUNDS: Kaempferol (PubChem CID: 5280863); Peonidin 3-(6"-p-coumarylglucoside) (PubChem CID: 44256849); Swerchirin (PubChem CID: 5281660); Trilobatin (PubChem CID: 6451798); 3-Geranyl-4-hydroxybenzoate (PubChem CID: 54730540); Eupatorin (PubChem CID: 97214); Icaritin (PubChem CID: 5318980); Isorhamnetin (PubChem CID: 5281654); Glucoliquiritin apioside (PubChem CID: 74819335); Brazilin (PubChem CID: 73384).PMID:38974199 | PMC:PMC11225656 | DOI:10.1016/j.fochx.2024.101551

Food Chem X. 2024 Jun 11;23:101541. doi: 10.1016/j.fochx.2024.101541. eCollection 2024 Oct 30.ABSTRACTThe utilization of byproducts from foxtail millet polishing can reduce food loss and waste. Thus, it is necessary to know the chemical compounds from the millet and the segregation of the layers. The nutrients including minerals were compared among the husk, bran, and millet, and a LC-MS metabolomics analysis was also performed among them. The results showed that the protein, crude fat and 4 fatty acids, seven minerals, the nitrogen-containing compounds and phenolic acids were at much higher levels in the bran part than the husk and millet, whereas the husk only contained higher levels of dietary fibre, and some minerals. The millet section, as the edible part, contained the lowest level of chemical constituents. It illustrated that the bran part contained more functional and nutritional components than the millet and husk part. Therefore, the bran of the foxtail millet should be a food resources instead of wasting.PMID:38974197 | PMC:PMC11225707 | DOI:10.1016/j.fochx.2024.101541

J Inflamm Res. 2024 Jul 1;17:4199-4217. doi: 10.2147/JIR.S458928. eCollection 2024.ABSTRACTINTRODUCTION: Endometriosis (EM) is a chronic estrogen-dependent condition characterized by the growth of endometrial-like tissue outside the uterus, posing a significant burden on reproductive-aged women. Previous research has shown a correlation between gut microbiota dysbiosis and interleukin-17A (IL-17A) in EM patients. IL-17A, a promising immunomodulatory molecule, exerts dual roles in human physiology, driving inflammatory diseases. However, the functions and origins of IL-17A in EM remain poorly characterized.METHODS: Single-cell data analysis was employed to characterize IL-17A activity in EM lesions. Fecal microbiota transplantation was conducted to explore the impact of gut microbiota on EM. Gut microbiota and bile acid metabolism were assessed via 16S rRNA sequencing and targeted metabolomics. Th17 cell proportions were measured using flow cytometry.RESULTS: High expression of IL-17 receptor A (IL-17RA) was observed in myeloid cell subpopulations within EM lesions and may be involved in the migration and recruitment of inflammatory cells in lesions. Elevated IL-17A levels were further validated in peritoneal and follicular fluids of EM patients. Dysregulated bile acid levels, particularly elevated chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA), were found in the gut and peritoneal fluid of EM mouse models. Additional CDCA administration reduced EM lesions and modulated Th17 cell proportions, while UDCA showed no significant effects.DISCUSSION: Our findings shed light on the origins and functions of IL-17A in EM, implicating its involvement in lesion migration and recruitment. Dysregulated bile acid metabolism may contribute to EM pathogenesis, with CDCA exhibiting therapeutic potential.PMID:38974001 | PMC:PMC11225878 | DOI:10.2147/JIR.S458928

Food Chem (Oxf). 2024 Jun 3;9:100209. doi: 10.1016/j.fochms.2024.100209. eCollection 2024 Dec 30.ABSTRACTThis study conducted a combined transcriptomics and metabolomics analysis in premature and mature developmental stages of Gardenia jasminoides Ellis fruits to identify the molecular mechanisms of pigment synthesis. The transcriptomics data produced high-quality clean data amounting to 46.98 gigabytes, exhibiting a mapping ratio of 86.36% to 91.43%. Transcriptomics analysis successfully identified about 3,914 differentially expressed genes which are associated with pivotal biological processes, including photosynthesis, chlorophyll, biosynthetic processes, and protein-chromophore linkage pathways. Functional diversity was clarified by the Clusters of Orthologous Groups (COG) classification, which focused mainly on pigment synthesis functions. Pathways analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) revealed critical pathways affecting pigment development. Metabolomics studies were carried out utilizing Ultra Performance Liquid Chromatography and mass spectrometry (UPLC-MS). About 480 metabolites were detected via metabolomics investigation, the majority of that were significantly involved in pigment synthesis. Cluster and pathway analyses revealed the importance of pathways such as plant secondary metabolite biosynthesis, biosynthesis of phenylpropanoids and plant hormone signal transduction in pigment synthesis. Current research advances our comprehension of the underlying mechanisms at the molecular level governing pigment synthesis in gardenia fruits, furnishing valuable insights for subsequent investigations.PMID:38973987 | PMC:PMC11225661 | DOI:10.1016/j.fochms.2024.100209

Biomed Chromatogr. 2024 Jul 8:e5945. doi: 10.1002/bmc.5945. Online ahead of print.ABSTRACTTo investigate predictive biomarkers that could be used to identify patients' response to treatment, plasma metabolomics and proteomics analyses were performed in Kashin-Beck disease (KBD) patients treated with Fufang Duzhong Jiangu Granules (FDJG). Plasma was collected from 12 KBD patients before treatment and 1 month after FDJG treatment. LC-MS and olink proteomics were employed for obtaining plasma metabolomics profiling and inflammatory protein profiles. Patients were classified into responders and non-responders based on drug efficacy. Enrichment analyses of differential metabolites and proteins of the responders at baseline and after treatment were conducted to study the mechanism of drug action. Differential metabolites and proteins between the two groups were screened as biomarkers to predict the drug efficacy. The receiver operating characteristic curve was used to evaluate the prediction accuracy of biomarkers. The changes in metabolites and inflammatory proteins in responders after treatment reflected the mechanism of FDJG treatment for KBD, which may act on glycerophospholipid metabolism, d-glutamine and d-glutamate metabolism, nitrogen metabolism and NF-kappa B signaling pathway. Three metabolites were identified as potential predictors: N-undecanoylglycine, β-aminopropionitrile and PC [18:3(6Z,9Z,12Z)/20:4(8Z,11Z,14Z,17Z)]. For inflammatory protein, interleukin-8 was identified as a predictive biomarker to detect responders. Combined use of these four biomarkers had high predictive ability (area under the curve = 0.972).PMID:38973475 | DOI:10.1002/bmc.5945

Expert Rev Mol Diagn. 2024 Jul 8:1-3. doi: 10.1080/14737159.2024.2375235. Online ahead of print.NO ABSTRACTPMID:38973412 | DOI:10.1080/14737159.2024.2375235

Phytother Res. 2024 Jul 8. doi: 10.1002/ptr.8277. Online ahead of print.ABSTRACTAmerican ginseng (AG) has been reported to have anti-inflammatory effects in many diseases, but the key molecules and mechanisms are unclear. This study aims to evaluate the anti-inflammatory mechanism of AG and identify the key molecules by in vivo and in vitro models. Zebrafish was employed to assess the anti-inflammatory properties of AG and the compounds. Metabolomics was utilized to identify potential anti-inflammatory molecules in AG, while molecular dynamics simulations were conducted to forecast the interaction capabilities of these compounds with inflammatory targets. Additionally, macrophage cell was employed to investigate the anti-inflammatory mechanisms of the key molecules in AG by enzyme-linked immunosorbent assay and western blotting. Seven potential anti-inflammatory molecules were discovered in AG, with ginsenoside Rg1, ginsenoside Rs3 (G-Rs3), and oleanolic acid exhibiting the strongest affinity for signal transducer and activator of transcription 3. These compounds demonstrated inhibitory effects on macrophage migration in zebrafish models and the ability to regulate ROS levels in both zebrafish and macrophages. The cell experiments found that ginsenoside Rg1, ginsenoside Rs3, and oleanolic acid could promote macrophage M2/M1 polarization ratio and inhibit phosphorylation overexpression of signal transducer and activator of transcription 3. This study revealed the key anti-inflammatory molecules and mechanisms of AG, and provided new evidence of anti-inflammatory for the scientific use of AG.PMID:38973353 | DOI:10.1002/ptr.8277

J Med Chem. 2024 Jul 8. doi: 10.1021/acs.jmedchem.4c00481. Online ahead of print.ABSTRACTDespite significant advances over recent years, the treatment of T cell acute lymphoblastic leukemia (T-ALL) remains challenging. We have recently shown that a subset of T-ALL cases exhibited constitutive activation of the lymphocyte-specific protein tyrosine kinase (LCK) and were consequently responsive to treatments with LCK inhibitors and degraders such as dasatinib and dasatinib-based PROTACs. Here we report the design, synthesis and in vitro/vivo evaluation of SJ45566, a potent and orally bioavailable LCK PROTAC.PMID:38973320 | DOI:10.1021/acs.jmedchem.4c00481

J Chem Inf Model. 2024 Jul 8;64(13):4939-4940. doi: 10.1021/acs.jcim.4c01021.NO ABSTRACTPMID:38973305 | DOI:10.1021/acs.jcim.4c01021

CNS Neurosci Ther. 2024 Jul;30(7):e14847. doi: 10.1111/cns.14847.ABSTRACTAIMS: Growing evidence suggests that an imbalanced gut microbiota composition plays a crucial role in the development of neuromyelitis optica spectrum disorders (NMOSD), an inflammatory demyelinating disease primarily affecting the optic nerves and central nervous system (CNS). In light of this, we explored the potential therapeutic benefits of GV-971 in NMOSD. GV-971 is a drug used for treating mild-to-moderate Alzheimer's disease, which targets the gut-brain axis and reduces neuroinflammation.METHODS: To evaluate GV-971's effects, we employed the experimental autoimmune encephalomyelitis (EAE) mouse model to establish NMOSD animal models. This was achieved by injecting NMO-IgG into aged mice (11 months old) or using NMO-IgG along with complement injection and microbubble-enhanced low-frequency ultrasound (MELFUS) techniques in young mice (7 weeks old). We assessed the impact of GV-971 on incidence rate, clinical scores, body weight, and survival, with methylprednisolone serving as a positive control. In NMOSD models of young mice, we analyzed spinal cord samples through H&E staining, immunohistochemistry, and Luxol Fast Blue staining. Fecal samples collected at different time points underwent 16S rRNA gene sequencing, while plasma samples were analyzed using cytokine array and untargeted metabolomics analysis.RESULTS: Our findings indicated that GV-971 significantly reduced the incidence of NMOSD, alleviated symptoms, and prolonged survival in NMOSD mouse models. The NMOSD model exhibited substantial neuroinflammation and injury, accompanied by imbalances in gut microbiota, peripheral inflammation, and metabolic disorders, suggesting a potentially vicious cycle that accelerates disease pathogenesis. Notably, GV-971 effectively reduces neuroinflammation and injury, and restores gut microbiota composition, as well as ameliorates peripheral inflammation and metabolic disorders.CONCLUSIONS: GV-971 attenuates the progression of NMOSD in murine models and reduces neuroinflammation and injury, likely through its effects on remodeling gut microbiota and peripheral inflammation and metabolic disorders.PMID:38973196 | DOI:10.1111/cns.14847

CNS Neurosci Ther. 2024 Jul;30(7):e14826. doi: 10.1111/cns.14826.ABSTRACTAIM: We aimed to confirm the inhibitory effect of nicotinamide on fibrotic scar formation following spinal cord injury in mice using functional metabolomics.METHODS: We proposed a novel functional metabolomics strategy to establish correlations between gene expression changes and metabolic phenotypes using integrated multi-omics analysis. Through the integration of quantitative metabolites analysis and assessments of differential gene expression, we identified nicotinamide as a functional metabolite capable of inhibiting fibrotic scar formation and confirmed the effect in vivo using a mouse model of spinal cord injury. Furthermore, to mimic fibrosis models in vitro, primary mouse embryonic fibroblasts and spinal cord fibroblasts were stimulated by TGFβ, and the influence of nicotinamide on TGFβ-induced fibrosis-associated genes and its underlying mechanism were examined.RESULTS: Administration of nicotinamide led to a reduction in fibrotic lesion area and promoted functional rehabilitation following spinal cord injury. Nicotinamide effectively downregulated the expression of fibrosis genes, including Col1α1, Vimentin, Col4α1, Col1α2, Fn1, and Acta2, by repressing the TGFβ/SMADs pathway.CONCLUSION: Our functional metabolomics strategy identified nicotinamide as a metabolite with the potential to inhibit fibrotic scar formation following SCI by suppressing the TGFβ/SMADs signaling. This finding provides new therapeutic strategies and new ideas for clinical treatment.PMID:38973179 | DOI:10.1111/cns.14826

J Epidemiol. 2024 Jul 6. doi: 10.2188/jea.JE20240099. Online ahead of print.ABSTRACTBackgroundDementia is the leading cause of disability and imposes a significant burden on society. Previous studies have suggested an association between metabolites and cognitive decline. Although the metabolite composition differs between Western and Asian populations, studies targeting Asian populations remain scarce.MethodsThis cross-sectional study used data from a cohort survey of community-dwelling older adults aged ≥ 60 years living in Miyagi, Japan, conducted by Tohoku Medical Megabank Organization between 2013 and 2016. Forty-three metabolite variables quantified using nuclear magnetic resonance spectroscopy were used as explanatory variables. Dependent variable was the presence of cognitive decline (≤ 23 points), assessed by the Mini-Mental State Examination. Principal component (PC) analysis was performed to reduce the dimensionality of metabolite variables, followed by logistic regression analysis to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for cognitive decline.ResultsA total of 2,940 participants were included (men: 49.0%, mean age: 67.6 years). Among them, 1.9% showed cognitive decline. The first 12 PC components (PC1-PC12) accounted for 71.7% of the total variance. Multivariate analysis showed that PC1, which mainly represented essential amino acids, was associated with lower odds of cognitive decline (OR = 0.89; 95% CI, 0.80-0.98). PC2, which mainly included ketone bodies, was associated with cognitive decline (OR = 1.29; 95% CI, 1.11-1.51). PC3, which included amino acids, was associated with lower odds of cognitive decline (OR = 0.81; 95% CI, 0.66-0.99).ConclusionAmino acids are protectively associated with cognitive decline, whereas ketone metabolites are associated with higher odds of cognitive decline.PMID:38972731 | DOI:10.2188/jea.JE20240099

Clin Immunol. 2024 Jul 5:110305. doi: 10.1016/j.clim.2024.110305. Online ahead of print.ABSTRACTAuto-inflammatory skin diseases place considerable symptomatic and emotional burden on the affected and put pressure on healthcare expenditures. Although most apparent symptoms manifest on the skin, the systemic inflammation merits a deeper analysis beyond the surface. We set out to identify systemic commonalities, as well as differences in the metabolome and lipidome when comparing between diseases and healthy controls. Lipidomic and metabolomic LC-MS profiling was applied, using plasma samples collected from patients suffering from atopic dermatitis, plaque-type psoriasis or hidradenitis suppurativa or healthy controls. Plasma profiles revealed a notable shift in the non-enzymatic anti-oxidant defense in all three inflammatory disorders, placing cysteine metabolism at the center of potential dysregulation. Lipid network enrichment additionally indicated the disease-specific provision of lipid mediators associated with key roles in inflammation signaling. These findings will help to disentangle the systemic components of autoimmune dermatological diseases, paving the way to individualized therapy and improved prognosis.PMID:38972618 | DOI:10.1016/j.clim.2024.110305

J Ethnopharmacol. 2024 Jul 5:118526. doi: 10.1016/j.jep.2024.118526. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Lean nonalcoholic steatohepatitis (NASH) poses a serious threat to public health worldwide. Herbs of the genus Gentiana have been used for centuries to treat hepatic disease or have been consumed for hepatic protection efficiency. Gentiopicroside (GPS), the main bioactive component of Gentiana herbs, has been shown to be beneficial for protecting the liver, improving intestinal disorders, modulating bile acid profiles, ameliorating alcoholic hepatosteatosis, and so on. It is plausible to speculate that GPS may hold potential as a therapeutic strategy for lean NASH. However, no related studies have been conducted thus far.AIM OF THE STUDY: The present work aimed to investigate the benefit of GPS on NASH in a lean mouse model.MATERIALS AND METHODS: NASH in a lean mouse model was successfully established via a published method. GPS of 50 and 100 mg/kg were orally administered to verify the effect. Untargeted metabolomics, 16S rDNA sequencing and bile acid (BA) profiling, as well as qPCR analysis were employed to investigate the mechanism underlying the alleviating effect.RESULTS: GPS significantly reduced the increase in serum biochemicals and liver index, and attenuated the accumulation of fat in the livers of lean mice with NASH. Forty-two potential biomarkers were identified by metabolomics analysis, leading to abnormal metabolic pathways of primary bile acid biosynthesis and fatty acid biosynthesis, which were subsequently rebalanced by GPS. A decreased Firmicutes/Bacteroidetes (F/B) ratio and disturbed BA related GM profiles were revealed in lean mice with NASH but were partially recovered by GPS. Furthermore, serum profiling of 23 BAs confirmed that serum BA levels were elevated in the lean model but downregulated by GPS treatment. Pearson correlation analysis validated associations between BA profiles, serum biochemical indices and related GM. qPCR and Western blotting analysis further elucidated the regulation of genes associated with liver lipid synthesis and bile acid metabolism.CONCLUSIONS: GPS may ameliorate steatosis in lean mice with NASH, regulating the metabolomic profile, BA metabolism, fatty acid biosynthesis, and BA-related GM. All these factors may contribute to its beneficial effect.PMID:38972531 | DOI:10.1016/j.jep.2024.118526