Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Alterations of gut microbiota and metabolome are associated with primary nephrotic syndrome in children

Thu, 05/12/2024 - 12:00
BMC Microbiol. 2024 Dec 5;24(1):519. doi: 10.1186/s12866-024-03667-w.ABSTRACTBACKGROUND: Primary nephrotic syndrome (PNS) is a common glomerular disease in children. Dysbiosis of gut microbiota acts as a cause of Treg abnormalities. However, the intestinal metabolic impact of PNS with children remains poorly understood. This study aims to investigate the dynamic changes of gut microbiota and it's metabolism in children with PNS.METHODS: Fecal and peripheral blood samples were separately collected from patients with initial diagnosis of PNS (PNS_In group), recurrence of PNS (PNS_Re group), and healthy controls (HCs group). The fecal samples were subjected to the microbiome and metabolome by the multi-omics analysis. Additionally, the peripheral blood samples were collected and associated inflammatory indicators were determined.RESULTS: We found that in PNS_In group, lipopolysaccharide (LPS), pro-inflammatory interleukin (IL)-6, IL-17A, IL-23p19, and IL-1β were significantly increased compared with those in HCs group. However, these abnormalities were dramatically reversed in PNS_Re group treated with prednisone acetate. Moreover, the crucial Treg/Th17 axis in PNS inflammation was also proved to be discriminated between PNS and HCs. Gut microbial dysbiosis was identified in PNS_In and PNS_Re patients. At the genus level, compared to HCs group, the abundance of Faecalibacterium notably changed in PNS_In and PNS_Re groups, showing negatively correlated with inflammatory factors. Moreover, the fecal metabolome of PNS_In and PNS_Re remarkably altered with the major impacts in the metabolism of phenylalanine, ABC transporters, arginine and proline.CONCLUSION: The dynamic changes of gut microbiota and associated metabolites are closely correlated with initial period and recurrence of PNS in children via probably regulating inflammatory Th17/Treg axis, which may potentially provide novel targets for the control of the disease.CLINICAL TRIAL NUMBER: Not applicable.PMID:39633292 | DOI:10.1186/s12866-024-03667-w

Author Correction: APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes

Thu, 05/12/2024 - 12:00
Nature. 2024 Dec 4. doi: 10.1038/s41586-024-08434-5. Online ahead of print.NO ABSTRACTPMID:39633058 | DOI:10.1038/s41586-024-08434-5

Combined transcriptome and metabolome analysis revealed the antimicrobial mechanism of Griseorhodin C against Methicillin-resistant Staphylococcus aureus

Thu, 05/12/2024 - 12:00
Sci Rep. 2024 Dec 4;14(1):30242. doi: 10.1038/s41598-024-76212-4.ABSTRACTThe global rise of multidrug-resistant pathogens, particularly Methicillin-resistant Staphylococcus aureus (MRSA), has become a critical public health concern, necessitating the urgent discovery of new antimicrobial agents. Griseorhodin C, a hydroxyquinone compound isolated from Streptomyces, has demonstrated significant inhibitory effects against MRSA. In this study, we employed a comprehensive approach combining transcriptome and metabolome analyses to investigate the underlying antimicrobial mechanism of Griseorhodin C. Our findings reveal that Griseorhodin C interferes with multiple bacterial metabolic pathways, including those essential for the biosynthesis and metabolism of amino acids, purine metabolism and energy metabolism, ultimately leading to bacterial growth inhibition and cell death. Notably, Griseorhodin C showed superior inhibitory effects compared to the clinical standard, vancomycin, both in vivo and vitro. These results highlight the potential of Griseorhodin C as a promising candidate for the development of new therapeutic strategies aimed at combating MRSA infections. The study underscores the importance of exploring natural products as sources of novel antibiotics in the ongoing fight against antimicrobial resistance.PMID:39632874 | DOI:10.1038/s41598-024-76212-4

Bifidobacterium animalis Probio-M8 improves sarcopenia physical performance by mitigating creatine restrictions imposed by microbial metabolites

Thu, 05/12/2024 - 12:00
NPJ Biofilms Microbiomes. 2024 Dec 5;10(1):144. doi: 10.1038/s41522-024-00618-1.ABSTRACTSarcopenia is a major health challenge due to an aging population. Probiotics may improve muscle function through gut-muscle axis, but their efficacy and mechanisms in treating sarcopenia remain unclear. This study investigated the impact of Bifidobacterium animalis subsp. lactis Probio-M8 (Probio-M8) on old mice and sarcopenia patients. We analyzed 43 subjects, including gut microbiome, fecal metabolome, and serum metabolome, using a multi-omics approach to assess whether Probio-M8 can improve sarcopenia by modulating gut microbial metabolites. Probio-M8 significantly improved muscle function in aged mice and enhanced physical performance in sarcopenia patients. It reduced pathogenic gut species and increased beneficial metabolites such as indole-3-lactic acid, acetoacetic acid, and creatine. Mediating effect analyses revealed that Probio-M8 effectively reduced n-dodecanoyl-L-homoserine lactone level in gut concurrent with increased creatine circulation, to significantly enhance host physical properties. These findings provide new insights into probiotics as a potential treatment for sarcopenia by modulating gut microbiota metabolism.PMID:39632843 | DOI:10.1038/s41522-024-00618-1

Dietary <em>Antrodia cinnamomea</em> Polysaccharide Intervention Modulates Clinical Symptoms by Regulating Ovarian Metabolites and Restructuring the Intestinal Microbiota in Rats with Letrozole-Induced PCOS

Thu, 05/12/2024 - 12:00
J Agric Food Chem. 2024 Dec 5. doi: 10.1021/acs.jafc.4c06855. Online ahead of print.ABSTRACTPolycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder. This study investigated the mitigating effects of the Antrodia cinnamomea polysaccharide (ACP) on a letrozole-induced PCOS rat model. Results demonstrated that ACP reduced obesity and ameliorated dyslipidemia in PCOS rats. Moreover, ACP restored estrous cycle regularity, suppressed polycystic ovarian changes, and regulated serum levels of sex hormones, SOD, and MDA. Furthermore, ACP increased the α-diversity and modulated the abundance of phyla (Bacteroidetes, Firmicutes, and Verrucomicrobia) and genera (Lactobacillus, Helicobacter, Akkermansia, Oscillospira, Coprococcus, Roseburia, Blautia, and Allobaculum) in the gut microbiota. ACP also restored compromised intestinal barriers by upregulating the expression of ZO1, Occludin, Claudin1, and Claudin7 in the colon. ACP mitigated ovarian fibrosis by preventing activation of the NLRP3 inflammasome, decreasing the expression of fibrotic markers (TGF-β1, collagen-I, α-SMA, and CTGF), and regulating four ovarian fibrosis-associated metabolomics pathways. Generally, dietary ACP effectively ameliorated clinical symptoms and inhibited ovarian fibrosis in PCOS rats.PMID:39632724 | DOI:10.1021/acs.jafc.4c06855

Systematic Review and Meta-Analysis: Taurine and Its Association With Colorectal Carcinoma

Thu, 05/12/2024 - 12:00
Cancer Med. 2024 Dec;13(23):e70424. doi: 10.1002/cam4.70424.ABSTRACTBACKGROUND: Colorectal cancer (CRC) is one of the most common cancers. Various options are available for treatment, but prognosis is still poor in the more advanced stages. Current screening methods are not as accurate for distinguishing between benign and malignant growths, resulting in unnecessary invasive procedures. Recently a focus has been placed on identifying metabolites. Of these, taurine has frequently been detected, and this particular compound has a multifactorial role in human physiology.METHODS: We conducted a systematic review of studies up till November 2023. Searches were done in three databases- MEDLINE, CINAHL-Ebsco, and PubMed. Three independent reviewers filter titles, abstracts, and full-texts according to selection criteria. Ten studies (samples = 1714) were identified showing a differential level of taurine in CRC patient samples. Quality assessment accounted for the risk of bias of each study using the 'robvis' tool. Where meaningful comparisons could be made, meta-analyses were carried out using the 'R' program for precalculated effect sizes with 'metagen' in R. The 'meta' package was utilised for creation of forest plots.FINDINGS: Taurine was shown to significantly increase odds of CRC. It was also significantly associated with being a discriminator for CRC as a diagnostic metabolite. This was maintained at various stages of CRC. Taurine had increased expression in CRC patients, especially when the matrix utilised was blood. Nevertheless, there was significant heterogeneity for some outcomes.INTERPRETATION: In conclusion, these findings highlight the potential of using taurine as well as other bile acid metabolites (lithocholic and ursodeoxycholic acid) to diagnose CRC and illustrate the link with microbiome interactions. Overall increased taurine concentration are associated with significantly increased odds for CRC. There was mostly an increase in relative expression of taurine in CRC samples, excluding results from Wang et al.PMID:39632512 | DOI:10.1002/cam4.70424

Phosphatidylcholine ameliorates lipid accumulation and liver injury in high-fat diet mice by modulating bile acid metabolism and gut microbiota

Thu, 05/12/2024 - 12:00
Int J Food Sci Nutr. 2024 Dec 4:1-14. doi: 10.1080/09637486.2024.2437469. Online ahead of print.ABSTRACTPhosphatidylcholine (PC) has garnered considerable attention due to its involvement in a wide array of crucial biological functions. However, there is still much to active explore regarding the precise mechanisms that underlie PC's actions in the context of high-fat diet. In this study, we found that both PC intervention and treatment significantly mitigated lipid accumulation, liver damage, and body weight gaining triggered by the high-fat diet. Untargeted and targeted metabolomic analyses uncovered substantial effects of PC on bile acid metabolism, especially led to a substantial reduction in elevated levels of free bile acids. 16S rRNA gene sequencing revealed that PC modulated the gut microbiota structures and compositions in high-fat diet mice, particularly exhibiting a positive association with Pseudoflavonifractor abundance, and a negative correlation with Olsenella, Parasutterella, and Allobaculum abundance. Our study suggested that PC held promise as a potential candidate for alleviating lipid metabolism injury, liver disease or obesity.PMID:39632393 | DOI:10.1080/09637486.2024.2437469

Omic characterizing and targeting gut dysbiosis in children with autism spectrum disorder: symptom alleviation through combined probiotic and medium-carbohydrate diet intervention - a pilot study

Thu, 05/12/2024 - 12:00
Gut Microbes. 2024 Jan-Dec;16(1):2434675. doi: 10.1080/19490976.2024.2434675. Epub 2024 Dec 4.ABSTRACTAutism spectrum disorder (ASD) currently lacks effective diagnostic and therapeutic approaches. Disruptions in the gut ecosystem have been observed in individuals with ASD, suggesting that targeting gut microbiota through probiotic and dietary supplementation may serve as a potential treatment strategy. This two-phase study aimed to characterize the fecal metagenome of children with ASD and investigate the beneficial effects of a combined probiotic and medium-carbohydrate intervention in ASD. Fecal metagenomes of children with ASD were compared to those of typically developing children, revealing intestinal dysbiosis in ASD, characterized by reduced levels of Prevotella sp. Dialister invisus, and Bacteroides sp. along with increased predicted abundances of inosine, glutamate, xanthine, and methylxanthine. The gut bacteriome and phageome exhibited high cooperativity. In a 3-month pilot study, Bifidobacterium animalis subsp. lactis Probio-M8 (Probio-M8) was administered alongside a medium-carbohydrate diet to Chinese children with ASD. The primary endpoint was the Childhood Autism Rating Scale (CARS), while the secondary endpoint was the Gastrointestinal Symptom Rating Scale (GSRS). A total of 72 autistic children were initially recruited for the intervention study, but only 53 completed the intervention. Probio-M8, in combination with dietary intervention, significantly improved CARS and GSRS scores, increased fecal levels of Bifidobacterium animalis, Akkermansia muciniphila, Fusicatenibacter saccharivorans, and Sutterella sp. while also reducing Blautia obeum (Benjamini-Hochberg corrected p ≤ 0.05 for all cases). The intervention also modulated fecal metabolites associated with the metabolism of amino acids (lysine), neurotransmitters (glutamate, γ-aminobutyric acid), polyunsaturated fatty acids (arachidonate, myristic acid), and vitamin B3. In conclusion, Probio-M8 combined with medium-carbohydrate diet effectively improved ASD symptoms, with associated changes in the gut microbiome and metabolome, supporting its potential as an adjunctive therapy for ASD.PMID:39632378 | DOI:10.1080/19490976.2024.2434675

Exploring the effects of perfluorooctanoic acid (PFOA) and tetrabromobisphenol A (TBBP-A) on silkworm from the insights of metabolome

Wed, 04/12/2024 - 12:00
Ecotoxicol Environ Saf. 2024 Dec 3;289:117444. doi: 10.1016/j.ecoenv.2024.117444. Online ahead of print.ABSTRACTPerfluorooctanoic acid (PFOA) and tetrabromobisphenol A (TBBP-A) are emerging environmental contaminants with recognized potential health and ecological risks. This study investigated the effects of PFOA and TBBP-A exposure on the global of metabolites of silkworm gut with GC-MS metabolomics. Our results revealed distinct metabolic alterations in silkworms exposed to PFOA and TBBP-A, highlighting their differential impacts on silkworm health and productivity. Exposure to these chemicals significantly altered metabolic profiles, leading to disruptions in pathways related to lipid, carbohydrate, and amino acid metabolism. These findings suggest that PFOA and TBBP-A disrupt crucial metabolic processes in silkworms, indicating potential toxicity and prompting further investigation into their effects on human health and the environment. Ongoing research is crucial to develop safer alternatives and mitigate the risks associated with these persistent contaminants.PMID:39632329 | DOI:10.1016/j.ecoenv.2024.117444

The promising role of proteomes and metabolomes in defining the single-cell landscapes of plants

Wed, 04/12/2024 - 12:00
New Phytol. 2024 Dec 4. doi: 10.1111/nph.20303. Online ahead of print.ABSTRACTThe plant community has a strong track record of RNA sequencing technology deployment, which combined with the recent advent of spatial platforms (e.g. 10× genomics) has resulted in an explosion of single-cell and nuclei datasets that can be positioned in an in situ context within tissues (e.g. a cell atlas). In the genomics era, application of proteomics technologies in the plant sciences has always trailed behind that of RNA sequencing technologies, largely due in part to upfront cost, ease-of-use, and access to expertise. Conversely, the use of early analytical tools for characterizing small molecules (metabolites) from plant systems predates nucleic acid sequencing and proteomics analysis, as the search for plant-based natural products has played a significant role in improving human health throughout history. As the plant sciences field now aims to fully define cell states, cell-specific regulatory networks, metabolic asymmetry and phenotypes, the measurement of proteins and metabolites at the single-cell level will be paramount. As a result of these efforts, the plant community will unlock exciting opportunities to accelerate discovery and drive toward meaningful translational outcomes.PMID:39632263 | DOI:10.1111/nph.20303

Metabolomic changes in Citrus reticulata peel after conventional and ultrasound-assisted solid-state fermentation with Aspergillus niger: A focus on flavonoid metabolism

Wed, 04/12/2024 - 12:00
Food Chem. 2024 Nov 24:142224. doi: 10.1016/j.foodchem.2024.142224. Online ahead of print.ABSTRACTThis study explored the changes in nutrients, metabolites, and enzyme activity in Citrus reticulata peel powders (CRPP) under conventional or ultrasound-assisted solid-state fermentation (SSF) using Aspergillus niger CGMCC 3.6189. Compared to nonfermented CRPP (NF-CRPP), ultrasound-assisted fermented CRPP (UIS-CRPP) significantly increased total protein and carotenoid levels by 85.26 % and 179.68 %, respectively, surpassing conventionally-fermented CRPP (FO-CRPP). Among the 521 identified differential metabolites, organic acids, lipids, and flavonoids were predominant. Flavonoid accumulation was primarily driven by the flavone and flavonol biosynthesis pathway, with 90.47 % and 90.00 % of differential flavonoids upregulated in FO-CRPP and UIS-CRPP, respectively. SSF significantly increased phenylalanine, tyrosine, and methionine levels, and tyrosine ammonia-lyase and β-D-glucosidase activities, with higher levels in UIS-CRPP. These findings suggest that conventional and ultrasound-assisted fermentation enhances flavonoid levels in CRPP by modulating key enzyme activities in flavonoid biosynthesis and biotransformation. Our study offers a feasible approach for producing value-added products from citrus peel waste.PMID:39632168 | DOI:10.1016/j.foodchem.2024.142224

Comparative Analysis of Metabolomic Responses in On-Pump and Off-Pump Coronary Artery Bypass Grafting

Wed, 04/12/2024 - 12:00
Ann Thorac Cardiovasc Surg. 2024;30(1). doi: 10.5761/atcs.oa.24-00126.ABSTRACTPURPOSE: Although the clinical outcomes of on-pump (ONCAB) and off-pump CABG (OPCAB) are well established, their metabolomic impacts remain underexplored. This study aims to compare the metabolic profiles of ONCAB and OPCAB to identify differential metabolites associated with clinical outcomes.METHODS: In a prospective cohort study conducted between January 2023 and September 2023, 100 plasma samples from 20 patients undergoing isolated elective CABG (10 per group) were analyzed. Samples were collected preoperatively and at multiple postoperative time points (Days 0-3) and processed using proton nuclear magnetic resonance (1H-NMR). Advanced statistical modeling was applied to identify differential metabolites.RESULTS: No significant differences were found in clinical outcomes, although ONCAB showed higher postoperative CKMB levels. Both procedures induced metabolomic alterations, with ONCAB demonstrating a more substantial impact, particularly on Day 0. Key metabolites, including leucine, succinate, creatine, glucose, and adenine, affected starch and sucrose metabolism.CONCLUSION: ONCAB induces more pronounced metabolic shifts immediately postsurgery, involving protein and energy turnover, oxidative stress, and disrupted glucose metabolism, indicative of cellular stress responses. A comprehensive understanding of these metabolic changes is critical for informing targeted interventions and supports the use of OPCAB as a preferred strategy for patients with elevated metabolic risks.PMID:39631940 | DOI:10.5761/atcs.oa.24-00126

Non-targeted Metabolomics-based Exploration ofRadiation-induced Metabolic Alterations in Mouse Lung Epithelial Cells

Wed, 04/12/2024 - 12:00
Zhongguo Fei Ai Za Zhi. 2024 Oct 20;27(10):725-734. doi: 10.3779/j.issn.1009-3419.2024.106.28.ABSTRACTBACKGROUND: Metabolic change is one of the important characteristics of radiation pneumonitis. Radiotherapy, as a conventional method for the treatment of thoracic tumors, can not only effectively kill tumor cells, but also cause adverse reactions such as local inflammation and fibrosis, which leads to limited therapeutic effect and profound impact on the quality of life of patients. Therefore, it is of great significance to explore the metabolic changes caused by radiotherapy. The aim of this study was to investigate the effects of X-ray irradiation on the metabolism of a mouse lung epithelial cell line (murine lung epithelial-12, MLE12).METHODS: MLE12 cells were' cultured in vitro and randomly divided into radiation group (IR) and control group (NC). Cells in the IR group were irradiated at a dose of 10 Gy using a Hitachi X-ray irradiator. Cell supernatant samples were collected at 48 h after irradiation. Metabolomic analysis of the samples was performed by liquid chromatograph mass spectrometer (LC/MS).RESULTS: LC/MS metabolomics analysis revealed the metabolic changes of MLE12 cells at 48 h after irradiation. A total of 38 secretory metabolites were altered in the IR group compared with the NC group. According to the annotation of Kyoto Encyclopedia of Genes and Genomes (KEGG) database, the differential metabolites are mainly involved in nucleotide metabolism, amino acid metabolism and lipid metabolism, among which the difference in nucleotide metabolism is the most significant.CONCLUSIONS: The metabolism of MLE12 cells was significantly affected by X-ray irradiation, mainly affecting the nucleotide metabolic pathways, including purine and pyrimidine metabolites and related metabolic pathways.PMID:39631829 | DOI:10.3779/j.issn.1009-3419.2024.106.28

Dynamic Changes in Microbiome and Metabolome during Sun-Drying of Oysters (Crassostrea gigas), a Traditional Procedure in South China

Wed, 04/12/2024 - 12:00
J Microbiol Biotechnol. 2024 Jul 17;34(12):2558-2567. doi: 10.4014/jmb.2312.12033. Online ahead of print.ABSTRACTSun-drying constitutes a traditional method employed in the preparation of dried oysters within the coastal regions of South China. However, its ramifications on nutritional attributes and the genesis of flavor-contributory compounds in the resultant dried oysters remain significantly unexplored. This research endeavors to scrutinize the repercussions of the production process on the microbiota and metabolites within dried oysters. Utilizing 16s rRNA amplicon sequencing, the identification of 409 operational taxonomic units (OTUs) ensued, wherein Proteobacteria, Bacteroidetes, Firmicutes, Tenericutes, and Actinobacteria surfaced as the primary pathogenic bacteria present in oyster samples. Analysis of the dried oyster sample metabolomes via LC-MS unveiled a discernible augmentation in compounds associated with steroid hormone biosynthesis, arachidonic acid metabolism, biosynthesis of unsaturated fatty acids, and linoleic acid metabolism throughout the entirety of the drying process. Subsequent exploration into the association between metabolites and bacterial communities highlighted the prevailing coexistence of Mycoplasma, Psychrilyobacter, and Vibrio demonstrating negative correlations with a substantial number of metabolites across categories including organic acid and its derivatives, nucleotide and its metabolites, free fatty acids, and amino acids. Conversely, Shewanella and Arcobacter exhibited positive correlations with these metabolite categories. This exhaustive investigation offers invaluable insights into the dynamic alterations within the microbiota and metabolites of dried oysters across diverse drying periods. These findings are anticipated to significantly contribute to the advancement of production techniques and the formulation of enhanced safety measures for the processing of dried oysters.PMID:39631783 | DOI:10.4014/jmb.2312.12033

Broad range lipidomics and metabolomics coupled with 16S rRNA sequencing to reveal the mechanisms of Huangkui Capsule against cisplatin-induced nephrotoxicity

Wed, 04/12/2024 - 12:00
J Ethnopharmacol. 2024 Dec 2:119197. doi: 10.1016/j.jep.2024.119197. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Huangkui Capsule (HKC) is a traditional Chinese medicinal preparation. Numerous clinical studies have reported that HKC has a good nephroprotection effect. The clinical application of cisplatin is greatly limited by its nephrotoxicity, and HKC shows promise in preventing cisplatin-induced nephrotoxicity (CIN).AIM OF THE STUDY: To evaluate the effectiveness of HKC in alleviating CIN and explore its underlying action mechanisms.MATERIALS AND METHODS: A rat model of CIN was established via single-dose injection of cisplatin. The effectiveness of HKC was evaluated by biochemical indices and pathological sections. Then, serum, kidney, and cecal endogenous metabolic profiles as well as the gut microbiota were characterized using lipidomics, metabolomics, and 16S rRNA high-throughput sequencing technique. Spearman's correlation analysis was carried out between gut microbiota, biomarkers, and biochemical indices. Finally, antibiotic treatment was performed to establish pseudo-sterile rat model and validate the nephroprotection of HKC in a gut microbiota-dependent manner.RESULTS: HKC could significantly attenuate the abnormal elevation of serum creatinine and urea nitrogen, kidney index, and kidney injury score in CIN rats, remarkably alleviate the disturbance of metabolic profiles of serum, kidney, and cecal contents, corresponding to the endogenous metabolites such as fatty acids, phosphatidylcholines, amino acids, acylcarnitines, and short-chain fatty acids, and enrich the diversity of gut microbiota. Spearman's correlation analysis revealed that Clostridium_sensu_stricto_1 was positively correlated with the altered short-chain fatty acids in serum and negatively correlated with the altered acylcarnitine in the kidney. In the pseudo-sterile rat model, the attenuation effect of HKC on the abnormal elevation of serum creatinine and urea nitrogen, along with the alleviation of metabolic profile disorders, was greatly diminished or even abolished, demonstrating the nephroprotective effect of HKC in a gut microbiota-dependent manner.CONCLUSIONS: HKC exerted the nephroprotective effect on CIN in a gut microbiota-dependent manner, mainly by regulating Clostridium_sensu_stricto_1 mediated metabolisms of phosphatidylcholines, acylcarnitines, fatty acids, tryptophan and short-chain fatty acids, thereby reducing the inflammatory response. The present study could provide reliable scientific evidence for gut microbiota-dependent mechanisms of HKC in the treatment of kidney injury and may widen the clinical application of HKC in cisplatin-containing cancer therapy.PMID:39631718 | DOI:10.1016/j.jep.2024.119197

Probiotic Bacillus cereus regulates metabolic disorders and activates the cholic acid-FXR axis to alleviate DSS-induced colitis

Wed, 04/12/2024 - 12:00
J Proteomics. 2024 Dec 2:105360. doi: 10.1016/j.jprot.2024.105360. Online ahead of print.ABSTRACTInflammatory bowel disease is characterized by severe imbalance of intestinal flora and metabolic disorders. Recent studies have demonstrated that probiotics can effectively alleviate inflammatory bowel disease by restoring the intestinal flora structure and modulating the immune response. However, the role of probiotics in regulating intestinal metabolism disorders is still unclear. This study explores the role of probiotic B. cereus in alleviating DSS-induced colitis. The findings indicated probiotic B. cereus treatment mitigated tissue damage and apoptosis during inflammation. Metabolome and transcriptome analysis revealed B. cereus activated the cholic acid-FXR axis by increasing cholic acid levels, which promoted the gene expression level of NF-κB inhibitor α, reduced the IL-1β, IL-6, IL-18 and TNF-α concentrations. Furthermore, it effectively mitigated the DSS-induced disruption of bile acid metabolism, arginine metabolism, and linoleic acid metabolism. This study explores the effect and mechanisms of probiotic B. cereus on alleviating DSS-induced colitis. It aims to provide a theoretical basis for microbial therapy in inflammatory bowel disease. SIGNIFICANCE: This study used metabolome and transcriptome to reveal the roles and mechanisms, which probiotic Bacillus cereus modulates metabolic disorders and alleviate DSS-induced colitis. We identified the cholic acid-FXR axis as an important target for alleviating DSS-induced colitis. These findings provide new insights into microbial treatment strategies for IBD.PMID:39631667 | DOI:10.1016/j.jprot.2024.105360

Species differences in glycerol-3-phosphate metabolism reveals trade-offs between metabolic adaptations and cell proliferation

Wed, 04/12/2024 - 12:00
Biochim Biophys Acta Bioenerg. 2024 Dec 2:149530. doi: 10.1016/j.bbabio.2024.149530. Online ahead of print.ABSTRACTThe temperate climate-adapted brown hare (Lepus europaeus) and the cold-adapted mountain hare (Lepus timidus) are closely related and interfertile species. However, their skin fibroblasts display distinct gene expression profiles related to fundamental cellular processes. This indicates important metabolic divergence between the two species. Through targeted metabolomics and metabolite tracing, we identified species-specific variations in glycerol 3-phosphate (G3P) metabolism. G3P is a key metabolite of the G3P shuttle, which transfers reducing equivalents from cytosolic NADH to the mitochondrial electron transport chain (ETC), consequently regulating glycolysis, lipid metabolism, and mitochondrial bioenergetics. Alterations in G3P metabolism have been implicated in multiple human pathologies including cancer and diabetes. We observed that mountain hare mitochondria exhibit elevated G3P shuttle activity, alongside increased membrane potential and decreased mitochondrial temperature. Silencing mitochondrial G3P dehydrogenase (GPD2), which couples the conversion of G3P to the ETC, uncovered its species-specific role in controlling mitochondrial membrane potential and highlighted its involvement in skin fibroblast thermogenesis. Unexpectedly, GPD2 silencing enhanced wound healing and cell proliferation rates in a species-specific manner. Our study underscores the pivotal role of the G3P shuttle in mediating physiological, bioenergetic, and metabolic divergence between these hare species.PMID:39631556 | DOI:10.1016/j.bbabio.2024.149530

Transcriptome and metabolome revealed the effects of hypoxic environment on ovarian development of Tibetan sheep

Wed, 04/12/2024 - 12:00
Genomics. 2024 Dec 2:110973. doi: 10.1016/j.ygeno.2024.110973. Online ahead of print.ABSTRACTMany studies on the adaptability of Tibetan sheep to hypoxia have been reported, but little attention has been paid to the reproduction of Tibetan sheep living at an altitude of more than 4000 m. In this study, the ovaries of Alpine Merino sheep (AM) living in middle-high altitude areas (2500 m) and the ovaries of Gangba Tibetan sheep (GB) and Huoba Tibetan sheep (HB) living in ultra-high altitude areas (4400 m or more) were collected. Through morphological, transcriptomics and metabolomics, the effects of ultra-high altitude areas on Tibetan sheep ovarian development and the molecular mechanism of sheep's adaptability to ultra-high altitude environment were explored. The results showed that the number of granulosa cells in AM was significantly higher than that in GB and HB. The transcriptome revealed several genes related to follicular development, such as DAPL1, IGFBP1, C5, GPR12, STRA6, BMPER, etc., which were mainly enriched in related pathways such as cell growth and development. Through metabolomics analysis, it was found that the differential metabolites between the three groups of sheep were mainly lipids and lipid-like small molecules, such as Glycerol 3-Phosphate, PC (16: 0 / 18: 3 (9Z, 12Z, 15Z)), mainly enriched in lipid metabolism and other related pathways. The results of combined analysis showed that Tryptophan metabolism and Steroid hormone biosynthesis may have a significant effect on Tibetan sheep follicular development. Some genes (including HSD17B7, CYP11A1, CYP19, HSD3B1, CYP17, etc.) and some metabolites (including Cortisone, 2-Methoxyestrone, etc.) are enriched in these pathways, regulating ovarian and follicular development by affecting estrogen, progesterone, etc.. The results further revealed the molecular mechanism of Tibetan sheep to adapt to the ultra-high altitude environment and maintain normal ovarian and follicular development through the regulation of genes and metabolites.PMID:39631551 | DOI:10.1016/j.ygeno.2024.110973

Industrial hemp (Cannabis sativa L.) adapts to cadmium stress by reshaping rhizosphere fungal community

Wed, 04/12/2024 - 12:00
Sci Total Environ. 2024 Dec 3;957:177851. doi: 10.1016/j.scitotenv.2024.177851. Online ahead of print.ABSTRACTIncreasing evidence indicates that plants under environmental stress can actively seek the help of microbes ('cry-for-help' hypothesis). However, empirical evidence underlying this strategy is limited under metal-stress conditions. Here, we employed integrated microbial community profiling in cadmium (Cd) polluted soil and culture-based methods to investigate the three-way interactions between the industrial hemp (Cannabis Sativa L.), rhizospheric microbes, and Cd stress. Results from the pot and three cycles of the successful hemp planting experiments showed that Cd stress significantly affected the composition of rhizosphere fungi in industrial hemp and induced enrichment of the fungal operational taxonomic unit (OTU)3 (Cladosporium). A representative of OTU3 (strain DM-2) was successfully isolated. In a hydroponic experiment, inoculation of DM-2 significantly increased the shoot length (by 25.84 %) and fresh weight (by 92.66 %) of hemp seedlings when compared to the absence of DM-2 under the Cd stress. The findings indicate that DM-2 inoculation could effectively alleviate the Cd stress in hemp seedlings. Metabolomic analysis of spent media with or without DM-2 revealed the association of DM-2 with the transformation of root exudates to melatonin, which may be a key chemical in plant-microbe interactions against abiotic stresses. The findings will inform efforts to manipulate the root microbiome to enhance plant growth in polluted environments.PMID:39631339 | DOI:10.1016/j.scitotenv.2024.177851

Correction: Investigation into potential mechanisms of metabolic syndrome by integrative analysis of metabolomics and proteomics

Wed, 04/12/2024 - 12:00
PLoS One. 2024 Dec 4;19(12):e0315213. doi: 10.1371/journal.pone.0315213. eCollection 2024.ABSTRACT[This corrects the article DOI: 10.1371/journal.pone.0270593.].PMID:39630706 | DOI:10.1371/journal.pone.0315213

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