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

Effect of inoculating Pichia spp. starters on flavor formation of fermented chili pepper: Metabolomics and genomics approaches

Sat, 07/10/2023 - 12:00
Food Res Int. 2023 Nov;173(Pt 2):113397. doi: 10.1016/j.foodres.2023.113397. Epub 2023 Aug 23.ABSTRACTThe influence of Pichia spp. on flavor formation and metabolic pathways during chili pepper fermentation was investigated in this study. Multiple omics approaches were employed, including metabolomics analysis to identify volatile and non-volatile flavor compounds, and genomic analysis to gain insights into the underlying molecular mechanism driving flavor formation of chili peppers inoculated with Pichia spp. The results showed that inoculation with Pichia spp. accelerated fermentation process of chili peppers compared to spontaneous fermentation. Metabolomics analysis showed P. fermentans promoted characteristic terpenes [e.g., (Z)-β-ocimene and linalool], L-glutamate, gamma-aminobutyric acid, and succinate production, while P. manshurica produced more alcohols (e.g., isoamyl alcohol and phenylethyl alcohol) and phenols (e.g., 4-ethylguaiacol and 2-methoxy-4-methylphenol). Genomics analysis revealed that a substantial portion of the genes in Pichia spp. were associated with amino acid and carbohydrate metabolism. Specifically, the pathways involved in amino acid metabolism and the release of glycoside-bound aromatic compounds were identified as the primary drivers behind the unique flavor of fermented chili peppers, facilitated by Pichia spp.PMID:37803735 | DOI:10.1016/j.foodres.2023.113397

Must protection, sulfites versus bioprotection: A metabolomic study

Sat, 07/10/2023 - 12:00
Food Res Int. 2023 Nov;173(Pt 2):113383. doi: 10.1016/j.foodres.2023.113383. Epub 2023 Aug 18.ABSTRACTThe reduction of chemical inputs in wine has become one of the main challenges of the wine industry. One of the alternatives to sulfites developed is bioprotection, which consists in using non-Saccharomyces strains to prevent microbial deviation. However, the impact of substituting sulfites by bioprotection on the final wine remains poorly studied. For the first time, we characterized this impact on Chardonnay wine through an integrative approach. Interestingly, physico-chemical analysis did not reveal any difference between both treatments regarding classical oenological parameters. Nevertheless, bioprotection did not seem to provide as much protection against oxidation as sulfites, as observed through phenolic compound analysis. At a deeper level, untargeted metabolomic analyses revealed substantial changes in wine composition according to must treatment. In particular, the specific footprint of each treatment revealed an impact on nitrogen-containing compounds. This observation could be related to modifications in S. cerevisiae metabolism, in particular amino acid biosynthesis and tryptophan metabolism pathways. Thus, the type of must treatment seemed to impact metabolic fluxes of yeast differently, leading to the production of different compounds. For example, we observed glutathione and melatonin, compounds with antioxidant properties, which were enhanced with sulfites, but not with bioprotection. However, despite substantial modifications in wines regarding their chemical composition, the change in must treatment did not seem to impact the sensory profile of wine. This integrative approach has provided relevant new insights on the impact of sulfite substitution by bioprotection on Chardonnay wines.PMID:37803722 | DOI:10.1016/j.foodres.2023.113383

Dynamic analysis of metabolomics reveals the potential associations between colonic peptides and serum appetite-related hormones

Sat, 07/10/2023 - 12:00
Food Res Int. 2023 Nov;173(Pt 2):113376. doi: 10.1016/j.foodres.2023.113376. Epub 2023 Aug 18.ABSTRACTGut signals, including hormones and metabolites are crucial zeitgebers that regulate the circadian rhythm of host metabolism, but the potential links have been explored more in rodents. Herein, we performed an hour-scale metabolomics analysis of serum and colonic digesta to characterize the circadian rhythmic metabolic patterns using a pig model under ad libitum feeding conditions. Importantly, our findings identified potential associations between colonic and body metabolism, revealing the potential relationships between colonic peptides and host appetite regulation. Concretely, amino acids accounted for the highest proportion in rhythmic serum metabolites, whereas lipids accounted for the highest proportion in rhythmic colonic metabolites. The diurnal difference analysis revealed that the levels of most amino acids and peptides were higher in the light phase, while the levels of most lipids were higher in the dark phase. And more correlations were be checked between serum amino acids, lipids, peptides and colonic metabolites in the light and more correlations were be checked between serum carbohydrates, cofactors and vitamins, energy, nucleotides, xenobiotics and colonic metabolites in the dark. Interestingly, peptides oscillated to a similar extent in serum and colonic digesta. Of note, colonic peptides composed of valine, proline and leucine were checked in positive associations to glucagon-like peptide-1 (GLP-1) in serum. And these peptides were positive with the genera Butyricicoccus, Streptococcus, Clostridioides, Bariatricus and Coriobacteriia_norank, and negative with Prevotella, and showed the potential relationships with colonic microbial biosynthesis of amino acids. Collectively, we mapped the rhythmic profiling on pig serum and colonic metabolites and revealed the relationships between host and gut metabolism. However, the underlying regulatory mechanisms remains to be further investigated.PMID:37803714 | DOI:10.1016/j.foodres.2023.113376

Corrigendum to "Comparative metabolomics of flavonoids in twenty vegetables reveal their nutritional diversity and potential health benefits" [Food Res. Int. 164 (2023) 112384]

Sat, 07/10/2023 - 12:00
Food Res Int. 2023 Nov;173(Pt 1):113439. doi: 10.1016/j.foodres.2023.113439. Epub 2023 Sep 22.NO ABSTRACTPMID:37803663 | DOI:10.1016/j.foodres.2023.113439

Integration of multi-omics analyses highlights the secondary metabolism response of tomato fruit to low temperature storage

Sat, 07/10/2023 - 12:00
Food Res Int. 2023 Nov;173(Pt 1):113316. doi: 10.1016/j.foodres.2023.113316. Epub 2023 Jul 24.ABSTRACTInappropriate low temperature storage usually leads to quality deterioration of harvested tomato fruits. In this study, we performed comparative metabolome, transcriptome, and proteome analyses to comprehensively understand the effects of low temperature on metabolic changes in tomato fruit (fresh fruit, C0d; 4 °C 8 days, C8d; 4 °C 7 days and then 25 °C 1 day, C7dS1). Large amounts of secondary metabolites (including flavonoids and phenolic acids) increased after low temperature treatment. The overlap differentially accumulated metabolites in three comparative groups (C0d vs. C8d, C0d vs. C7dS1, C8d vs. C7dS1) were mainly flavonoid metabolites. A total of 1438 differentially expressed genes identified in these three comparative groups were primarily enriched in metabolic pathways and secondary metabolites biosynthesis pathways. Similarly, proteomic analysis showed that the differentially expressed proteins were enriched in the secondary metabolites biosynthesis and phenylpropanoid biosynthesis pathways. There was a strong correlation between changes in flavonoid metabolites and the expression of chalcone synthase (SlCHS), chalcone isomerase-like (SlCHIL), and coumarate 3-hydroxylase (SlC3H), which are involved in the phenylpropanoid and flavonoid biosynthesis. Additionally, seven differentially expressed MYB transcription factors were identified; SlMYB91, SlMYB106, and SlMYB70 strongly correlated with flavonoid biosynthesis structural genes after low temperature treatment. Other genes involved in fruit ripening and quality were also affected by low temperature. The data generated in this study may unravel the transcriptional regulatory network of secondary metabolism associated with low-temperature storage and provide a solid foundation for future studies.PMID:37803628 | DOI:10.1016/j.foodres.2023.113316

2'-Fucosyllactose (2'-FL) changes infants gut microbiota composition and their metabolism in a host-free human colonic model

Sat, 07/10/2023 - 12:00
Food Res Int. 2023 Nov;173(Pt 1):113293. doi: 10.1016/j.foodres.2023.113293. Epub 2023 Jul 22.ABSTRACTBACKGROUND: Breast milk is critical for neonates, providing the necessary energy, nutrients, and bioactive compounds for growth and development. Research indicated that human milk oligosaccharides (HMOs) have been shown to shape a beneficial gut microbiota, as well as their metabolism (e.g. short-chain fatty acids). 2'-Fucosyllactose (2'-FL) is one major HMO that composed of 30% of total HMOs.OBJECTIVES: This study aimed to understand the impact of 2'-FL on the composition and metabolism of infant gut microbiota.METHODS: Our study utilized an in-vitro human colonic model (HCM) to investigate the host-free interactions between 2'-FL and infant gut microbiota. To simulate the infant gut microbiota, we inoculated the HCM system with eight representative bacterial species from infant gut microbiota. The effects of 2'-FL on the gut microbial composition and their metabolism were determined through real-time quantitative PCR and liquid-chromatography mass spectrometry (LC/MS). The obtained data were analyzed using Compound Discoverer 3.1 and MetaboAnalyst 4.0.RESULTS: Our study findings suggest that the intervention of 2'-FL in HCM resulted in a significant change in the abundance of representative bacterial species. PCR analysis showed a consistent increase in the abundance of Parabacteroides. distasonis in all three colon sections. Furthermore, analysis of free fatty acids revealed a significant increase in their levels in the ascending, transverse, and descending colons, except for caproic acid, which was significantly reduced to a non-detectable level. The identification of significant extracellular polar metabolites, such as glutathione and serotonin, enabled us to distinguish between the metabolomes before and after 2'-FL intervention. Moreover, correlation analysis revealed a significant association between the altered microbes and microbial metabolites.CONCLUSIONS: In summary, our study demonstrated the impact of 2'-FL intervention on the defined composition of infant gut microbiota and their metabolic pathways in an in vitro setting. Our findings provide valuable insights for future follow-up investigations into the role of 2'-FL in regulating the growth and development of infant gut microbiota in vivo.PMID:37803605 | DOI:10.1016/j.foodres.2023.113293

Camel milk peptides alleviate hyperglycemia by regulating gut microbiota and metabolites in type 2 diabetic mice

Sat, 07/10/2023 - 12:00
Food Res Int. 2023 Nov;173(Pt 1):113278. doi: 10.1016/j.foodres.2023.113278. Epub 2023 Jul 13.ABSTRACTThis study aimed to investigate the hypoglycemic effect of Camel milk peptides (CMPs) on Type 2 diabetes mellitus (T2DM) mice and reveal its related mechanism from the aspect of gut microbiota and metabolites. The administering CMPs significantly alleviated the weight loss, polydipsia and polyphagia, reduced fasting blood glucose (FBG), improved insulin resistance and sensitivity, and restored the level of serum hormones, lipopolysaccharide (LPS), lipid metabolic and tissue damage. Furthermore, CMPs intervention remarkably reversed gut microbiota dysbiosis in T2DM mice by reducing the relative abundance of Proteobacteria, Allobaculum, Clostridium, Shigella and the Firmicutes/Bacteroidetes ratio, while increasing the relative abundance of Bacteroidetes and Blautia. Metabolomic analysis identified 84 different metabolites between T2DM and CMPs-treated groups, participating in three pathways of Pantothenate and CoA biosynthesis, Phenylalanine metabolism and Linoleic acid metabolism. Ureidopropionic acid, pantothenic acid, hippuric acid, hydrocinnamic acid and linoleic acid were identified as key acidic metabolites closely related to hypoglycemic effect. Correlation analysis indicated that CMPs might have a hypoglycemic effect through their impact on gut microbiota, leading to variations in short-chain fatty acids (SCFAs), acidic metabolites and metabolic pathways. These findings suggest that CMPs could be a beneficial nutritional supplement for intervention T2DM.PMID:37803591 | DOI:10.1016/j.foodres.2023.113278

Determination of the effects of pre-harvest bagging treatment on kiwifruit appearance and quality via transcriptome and metabolome analyses

Sat, 07/10/2023 - 12:00
Food Res Int. 2023 Nov;173(Pt 1):113276. doi: 10.1016/j.foodres.2023.113276. Epub 2023 Jul 13.ABSTRACTBagging is an effective cultivation strategy to produce attractive and pollution-free kiwifruit. However, the effect and metabolic regulatory mechanism of bagging treatment on kiwifruit quality remain unclear. In this study, transcriptome and metabolome analyses were conducted to determine the regulatory network of the differential metabolites and genes after bagging. Using outer and inner yellow single-layer fruit bags, we found that bagging treatment improved the appearance of kiwifruit, increased the soluble solid content (SSC) and carotenoid and anthocyanin levels, and decreased the chlorophyll levels. We also identified 41 differentially expressed metabolites and 897 differentially expressed genes (DEGs) between the bagged and control 'Hongyang' fruit. Transcriptome and metabolome analyses revealed that the increase in SSC after bagging treatment was mainly due to the increase in D-glucosamine metabolite levels and eight DEGs involved in amino sugar and nucleotide sugar metabolic pathways. A decrease in glutamyl-tRNA reductase may be the main reason for the decrease in chlorophyll. Downregulation of lycopene epsilon cyclase and 9-cis-epoxycarotenoid dioxygenase increased carotenoid levels. Additionally, an increase in the levels of the taxifolin-3'-O-glucoside metabolite, flavonoid 3'-monooxygenase, and some transcription factors led to the increase in anthocyanin levels. This study provides novel insights into the effects of bagging on the appearance and internal quality of kiwifruit and enriches our theoretical knowledge on the regulation of color pigment synthesis in kiwifruit.PMID:37803588 | DOI:10.1016/j.foodres.2023.113276

GC/QQQ coupling with metabolomics for selection of predicator of tea fermentation

Sat, 07/10/2023 - 12:00
Food Res Int. 2023 Nov;173(Pt 1):113273. doi: 10.1016/j.foodres.2023.113273. Epub 2023 Jul 13.ABSTRACTFermentation is the most crucial process for manufacture of black tea. Signature components were desired for the establishment of accurate prediction of fermentation degree. In this study, finished black teas were prepared using leaves that had been fermented for various times, and sensory quality evaluation was performed. Tracking analysis of volatiles during fermentation was conducted to discriminate the iconic compounds. On the basis of both the sensory evaluation results and the enzymatic oxidation traits of fermentation, the ratio of β-cyclocitral to γ-pylpyrone was proposed as an indicator. A positive correlation was observed between this ratio and the sensory score of finished black tea with varied duration of fermentation, and the correlation coefficient was 0.78. Furthermore, widely plant-targeted metabolomics was applied to cognize the fermentation. Comparative analysis of metabolites was conducted by category, and special attention was paid to flavonoids and terpenes. Significant metabolic differences emerged discriminatively. The results would be useful for intelligent modulation of the manufacture of black tea.PMID:37803585 | DOI:10.1016/j.foodres.2023.113273

Transcriptomics and metabolomics reveal improved performance of Hu sheep on hybridization with Southdown sheep

Sat, 07/10/2023 - 12:00
Food Res Int. 2023 Nov;173(Pt 1):113240. doi: 10.1016/j.foodres.2023.113240. Epub 2023 Jul 11.ABSTRACTConsumers are increasingly demanding high-quality mutton. Cross breeding can improve meat quality and is widely used in sheep breeding. However, little is known about the molecular mechanism of cross breeding sheep meat quality. In this study, male Southdown and female Hu sheep were hybridized. The slaughter performance and longissimus dorsi quality of the 6-month-old hybrid offspring were measured, and the longissimus dorsi of the hybrid offspring was analyzed by transcriptomics and metabolomics to explore the effect of cross breeding on meat quality. The results showed that the production performance of Southdown × Hu F1 sheep was significantly improved, the carcass fat content was significantly decreased, and the eating quality of Southdown × Hu F1 sheep were better. Compared with the HS group (Hu × Hu), the NH group (Southdown × Hu) had 538 differentially expressed genes and 166 differentially expressed metabolites (P < 0.05), which were significantly enriched in amino acid metabolism and other related pathways. Up-regulated genes METTL21C, PPARGC1A and down-regulated gene WFIKKN2 are related to muscle growth and development. Among them, the METTL21C gene, which is related to muscle development, was highly correlated with carnosine, a metabolite related to meat quality (correlation > 0.6 and P < 0.05). Our results provide further understanding of the molecular mechanism of cross breeding for sheep muscle growth and meat quality optimization.PMID:37803553 | DOI:10.1016/j.foodres.2023.113240

Revealing the chemical differences and their application in the storage year prediction of Qingzhuan tea by SWATH-MS based metabolomics analysis

Sat, 07/10/2023 - 12:00
Food Res Int. 2023 Nov;173(Pt 1):113238. doi: 10.1016/j.foodres.2023.113238. Epub 2023 Jul 7.ABSTRACTIt's generally believed that the longer the storage, the better the quality of dark tea, but the chemical differences of Qingzhuan tea (QZT) with different storage years is still unclear. Herein, in this work, an untargeted metabolomic approach based on SWATH-MS was established to investigate the differential compounds of QZT with 0-9 years' storage time. These QZT samples were roughly divided into two categories by principal component analysis (PCA). After orthogonal projections to latent structures discriminant analysis (OPLS-DA), 18 differential compounds were putatively identified as chemical markers for the storage year variation of QZT. Heatmap visualization showed that the contents of catechins, fatty acids, and some phenolic acids significantly reduced, flavonoid glycosides, triterpenoids, and 8-C N-ethyl-2-pyrrolidinone-substituted flavan-3-ols (EPSFs) increased with the increase of storage time. Furthermore, these chemical markers were verified by the peak areas corresponding to MS2 ions from SWATH-MS. Based on the extraction chromatographic peak areas of MS and MS2 ions, a duration time prediction model was built for QZT with correlation coefficient R2 of 0.9080 and 0.9701, and RMSEP value of 0.85 and 1.24, respectively. This study reveals the chemical differences of QZT with different storage years and provides a theoretical basis for the quality evaluation of stored dark tea.PMID:37803551 | DOI:10.1016/j.foodres.2023.113238

Uncovering the phenolic diversity of Guabiju fruit: LC-MS/MS-based targeted metabolomics approach

Sat, 07/10/2023 - 12:00
Food Res Int. 2023 Nov;173(Pt 1):113236. doi: 10.1016/j.foodres.2023.113236. Epub 2023 Jul 14.ABSTRACTThe comprehensive composition of phenolic compounds (PC) from seven genotypes of guabiju were analyzed by high-performance liquid chromatography coupled to a diode array detector and mass spectrometry (HPLC-ESI-qTOF-MS/MS), and a targeted metabolomic approach was utilized to explore the PC-related similarities among the genotypes. Sixty-seven phenolic compounds were annotated and twenty-four were quantified in all genotypes of guabiju. The phenolic acids and anthocyanins were the major PC, representing more than 63% (w/w) of the total PC. Di-O-galloylquinic and tri-O-galloylquinic acids and ellagitannins were reported for the first time in guabiju. The results of hierarchical clustering and principal components analysis (PCA) suggested seven groups as suitable clusters to be formed according to phenolic composition. Eleven PC were selected as relevant for sample clustering, and six of them were highlighted as the most informative (in decreasing order of importance): epicatechin, catechin, (epi)gallocatechin gallate II, di-O-galloylquinic acid I, tri-O-galloylquinic acid and delphinidin 3-O-glucoside. To the best of our knowledge, this study contributes to the literature with the most complete phenolic profile of guabiju genotypes up to date. Moreover, guabiju susceptibility to fungal infestation related to PC composition was briefly discussed based on a parallel study using the same genotypes.PMID:37803550 | DOI:10.1016/j.foodres.2023.113236

Correction: <em>Sympathetic nervous activation, mitochondrial dysfunction and outcome in acutely decompensated cirrhosis: the metabolomic prognostic models (CLIF-C MET)</em>

Fri, 06/10/2023 - 12:00
Gut. 2023 Nov;72(11):e4. doi: 10.1136/gutjnl-2022-328708corr1.NO ABSTRACTPMID:37802539 | DOI:10.1136/gutjnl-2022-328708corr1

A PrP EGFR signalling axis controls neural stem cell senescence through modulating cellular energy pathways

Fri, 06/10/2023 - 12:00
J Biol Chem. 2023 Oct 4:105319. doi: 10.1016/j.jbc.2023.105319. Online ahead of print.ABSTRACTMis-folding of the prion protein (PrP) is known to cause neurodegenerative disease, however the native function of this protein remains poorly defined. PrP has been linked with many cellular functions, including cellular proliferation and senescence. It is also known to influence epidermal growth factor receptor (EGFR) signalling, a pathway that is itself linked with both cell growth and senescence. Adult neural stem cells (NSCs) persist at low levels in the brain throughout life and retain the ability to proliferate and differentiate into new neural lineage cells. Knock-out (KO) of PrP has previously been shown to reduce NSC proliferative capacity. We used PrP KO and wild type (WT) NSCs from adult mouse brain to examine the influence of PrP on cellular senescence, EGFR signalling, and the downstream cellular processes. PrP KO NSCs showed decreased cell proliferation and increased senescence in in vitro cultures. Expression of EGFR was decreased in PrP KO NSCs compared with WT NSCs and additional supplementation of EGF was sufficient to reduce senescence. RNAseq analysis confirmed that significant changes were occurring at the mRNA level within the EGFR signalling pathway and these were associated with reduced expression of mitochondrial components and correspondingly reduced mitochondrial function. Metabolomic analysis of cellular energy pathways showed that blockages were occurring at critical sites for production of energy and biomass, including catabolism of pyruvate. We conclude that, in the absence of PrP, NSC growth pathways are downregulated as a consequence of insufficient energy and growth intermediates.PMID:37802314 | DOI:10.1016/j.jbc.2023.105319

Human milk bioactive components and child growth and body composition in the first 2 years: a systematic review

Fri, 06/10/2023 - 12:00
Adv Nutr. 2023 Oct 4:S2161-8313(23)01388-1. doi: 10.1016/j.advnut.2023.09.015. Online ahead of print.ABSTRACTHuman milk (HM) contains macronutrients, micronutrients and a multitude of other bioactive factors, which can have a long-term impact on infant growth and development. We systematically searched Medline, EMBASE, Cochrane Library, Scopus, and Web of Science to synthesize evidence published between 1980-2022 on HM components and anthropometry through 2 years of age among term-born infants. From 9,992 abstracts screened, 141 articles were included and categorized based on their reporting of HM micronutrients, macronutrients, or bioactive components. Bioactives including hormones, HM oligosaccharides (HMOs), and immunomodulatory components are reported here, based on 75 articles from 69 unique studies reporting observations from 9,980 dyads. Research designs, milk collection strategies, sampling times, geographic and socioeconomic settings, reporting practices, and outcomes varied considerably. Meta-analyses were not possible because data collection times and reporting were inconsistent amongst the studies included. Few measured infant HM intake, adjusted for confounders, precisely captured breastfeeding exclusivity, or adequately described HM collection protocols. Only five studies (6%) had high overall quality scores. Hormones were the most extensively examined bioactive with 46 articles (n=6773 dyads), compared to 13 (n=2,640 dyads) for HMOs, and 12 (n=1422 dyads) for immunomodulatory components. Two studies conducted untargeted metabolomics. Leptin and adiponectin demonstrated inverse associations with infant growth, although several studies found no associations. No consistent associations were found between individual HMOs and infant growth outcomes. Among immunomodulatory components in HM, interleukin-6 (IL-6) demonstrated inverse relationships with infant growth. Current research on HM bioactives is largely inconclusive and is insufficient to address the complex composition of HM. Future research should ideally capture human milk intake, use biologically relevant anthropometrics, and integrate components across categories, embracing a systems biology approach to better understand how HM components work independently and synergistically to influence infant growth.PMID:37802214 | DOI:10.1016/j.advnut.2023.09.015

Postpartum defects in inflammatory response after gestational diabetes precede progression to type 2 diabetes: a nested case-control study within the SWIFT study

Fri, 06/10/2023 - 12:00
Metabolism. 2023 Oct 4:155695. doi: 10.1016/j.metabol.2023.155695. Online ahead of print.ABSTRACTBACKGROUND: Gestational diabetes (GDM) is a distinctive form of diabetes that first presents in pregnancy. While most women return to normoglycemia after delivery, they are nearly ten times more likely to develop type 2 diabetes than women with uncomplicated pregnancies. Current prevention strategies remain limited due to our incomplete understanding of the early underpinnings of progression.AIM: To comprehensively characterize the postpartum profiles of women shortly after a GDM pregnancy and identify key mechanisms responsible for the progression to overt type 2 diabetes using multi-dimensional approaches.METHODS: We conducted a nested case-control study of 200 women from the Study of Women, Infant Feeding and Type 2 Diabetes After GDM Pregnancy (SWIFT) to examine biochemical, proteomic, metabolomic, and lipidomic profiles at 6-9 weeks postpartum (baseline) after a GDM pregnancy. At baseline and annually up to two years, SWIFT administered research 2-h 75-g oral glucose tolerance tests. Women who developed incident type 2 diabetes within four years of delivery (incident case group, n = 100) were pair-matched by age, race, and pre-pregnancy body mass index to those who remained free of diabetes for at least 8 years (control group, n = 100). Correlation analyses were used to assess and integrate relationships across profiling platforms.RESULTS: At baseline, all 200 women were free of diabetes. The case group was more likely to present with dysglycemia (e.g., impaired fasting glucose levels, glucose tolerance, or both). We also detected differences between groups across all omic platforms. Notably, protein profiles revealed an underlying inflammatory response with perturbations in protease inhibitors, coagulation components, extracellular matrix components, and lipoproteins, whereas metabolite and lipid profiles implicated disturbances in amino acids and triglycerides at individual and class levels with future progression. We identified significant correlations between profile features and fasting plasma insulin levels, but not with fasting glucose levels. Additionally, specific cross-omic relationships, particularly among proteins and lipids, were accentuated or activated in the case group but not the control group.CONCLUSIONS: Overall, we applied orthogonal, complementary profiling techniques to uncover an inflammatory response linked to elevated triglyceride levels shortly after a GDM pregnancy, which is more pronounced in women who progress to overt diabetes.PMID:37802200 | DOI:10.1016/j.metabol.2023.155695

How far are we from reliable metabolomics-based biomarkers? The often-overlooked importance of addressing inter-individual variability factors

Fri, 06/10/2023 - 12:00
Biochim Biophys Acta Mol Basis Dis. 2023 Oct 4:166910. doi: 10.1016/j.bbadis.2023.166910. Online ahead of print.ABSTRACTMetabolomics has proven great potential to unravel the molecular basis of diseases. However, most attempts aimed at identifying reliable metabolomics-based biomarkers for diagnosis, prediction, and prognosis of diseases have repeatedly failed because of inconsistent results and unsatisfactory replication in independent cohorts. This review article explores the possible causes behind this reproducibility crisis, with special focus on the role that inter-individual variability factors play in modulating the susceptibility to disease development. Furthermore, we provide future perspectives on the applicability of metabolomics in biomedical research and its translatability into clinical practice.PMID:37802155 | DOI:10.1016/j.bbadis.2023.166910

Comprehensive quantification of metabolic flux during acute cold stress in mice

Fri, 06/10/2023 - 12:00
Cell Metab. 2023 Sep 27:S1550-4131(23)00337-6. doi: 10.1016/j.cmet.2023.09.002. Online ahead of print.ABSTRACTCold-induced thermogenesis (CIT) is widely studied as a potential avenue to treat obesity, but a thorough understanding of the metabolic changes driving CIT is lacking. Here, we present a comprehensive and quantitative analysis of the metabolic response to acute cold exposure, leveraging metabolomic profiling and minimally perturbative isotope tracing studies in unanesthetized mice. During cold exposure, brown adipose tissue (BAT) primarily fueled the tricarboxylic acid (TCA) cycle with fat in fasted mice and glucose in fed mice, underscoring BAT's metabolic flexibility. BAT minimally used branched-chain amino acids or ketones, which were instead avidly consumed by muscle during cold exposure. Surprisingly, isotopic labeling analyses revealed that BAT uses glucose largely for TCA anaplerosis via pyruvate carboxylation. Finally, we find that cold-induced hepatic gluconeogenesis is critical for CIT during fasting, demonstrating a key functional role for glucose metabolism. Together, these findings provide a detailed map of the metabolic rewiring driving acute CIT.PMID:37802078 | DOI:10.1016/j.cmet.2023.09.002

Coptidis Rhizoma processed with Evodia Rutaecarpa improves the effect on ulcerative colitis by increasing intestinal energy metabolites alpha-ketoglutarate and Lactobacillus reuteri

Fri, 06/10/2023 - 12:00
Phytomedicine. 2023 Sep 27;121:155115. doi: 10.1016/j.phymed.2023.155115. Online ahead of print.ABSTRACTBACKGROUND: Evodia Rutaecarpa-processed Coptidis Rhizoma (ECR) is a traditional Chinese medicine for the treatment of ulcerative colitis (UC) in China. However, the mechanisms underlying the ECR processing are not elucidated.PURPOSE: Coptidis Rhizoma (CR) regulates the gut microbiota in the treatment of gastrointestinal diseases. This study explored the mechanism of action of ECR before and after processing in UC in view of the regulation of gut microecology.STUDY DESIGN: A preclinical experimental investigation was performed using a mouse model of UC to examine the regulatory effect of ECR and its mechanisms through gut microbiota analysis and metabolomic assays.METHODS: Mice received 4% dextran sulfate sodium to establish a UC model and treated with ECR and CR. Colonic histopathology and inflammatory changes were observed. Gut microbiota was analyzed using 16 s rRNA sequencing. Transplants of Lactobacillus reuteri were used to explore the correlation between ECR processing and the gut microbiota. The expression of mucin-2, Lgr5, and PCNA in colonic epithelial cells was measured using immunofluorescence. Wnt3a and β-catenin levels were detected by western blotting. The metabolites in the colon tissue were analyzed using a targeted energy metabolomic assay. The effect of energy metabolite α-ketoglutarate (α-KG) on L. reuteri growth and UC were verified in mice.RESULTS: ECR improved the effects on UC in mice compared to CR, including alleviating colonic injury and inflammation, and modulating gut microbiota by increasing L. reuteri level. L. reuteri dose-dependently alleviated colonic injury, increased mucin-2 level, and promoted colonic epithelial regeneration by increasing Lgr5 and PCNA expression. This was consistent with the results before and after ECR processing. L. reuteri promoted epithelial regeneration by upregulating Wnt/β-catenin pathway. Moreover, ECR increased metabolites levels (especially α-KG) to promote energy metabolism in the colon tissue compared to CR. α-KG treatment increased L. reuteri level and alleviated mucosal damage in UC mice. It promoted L. reuteri growth by increasing the energy metabolic status by enhancing α-KG dehydrogenase activity.CONCLUSION: ECR processing improves the therapeutic effects of UC via the α-KG-L. reuteri-epithelial regeneration axis.PMID:37801896 | DOI:10.1016/j.phymed.2023.155115

GC × GC-ToF-MS combined with multivariate statistical methods to explore the effects of L. paracasei fermentation on bread flavor characteristics

Fri, 06/10/2023 - 12:00
Food Chem. 2023 Sep 30;435:137643. doi: 10.1016/j.foodchem.2023.137643. Online ahead of print.ABSTRACTGC × GC-ToF-MS is increasingly used to analyze complex food flavors due to its high resolution and sensitivity, but few studies have used the method to identify aroma components of bread. For the first time, this study combines GC × GC-ToF-MS and multivariate statistical methods to explore the effects of L. paracasei fermentation on bread flavor characteristics. A total of 1534 volatile organic compounds were identified, of which 447 were obtained by metabolome normalization. Based on the variable importance for the projection and p values, 82 different compounds were screened in L. paracasei bread compared with yeast bread, and the total relative content was 1.52 times higher than that of yeast bread. 2-Furancarboxaldehyde, 5-methyl-, pentanoic acid, 2-hydroxy-4-methyl-, ethyl ester, pyrazine, 2,5-dimethyl- and γ-terpinene are aroma-presenting substances specific to L. paracasei bread that could be potential identification compounds. This study provides a new techno-theoretical approach for the characterization and discrimination of LAB bread flavors.PMID:37801769 | DOI:10.1016/j.foodchem.2023.137643

Pages