PubMed

Cell Death Dis. 2023 Mar 6;14(3):183. doi: 10.1038/s41419-023-05701-7.ABSTRACTCancer or endothelial cells preferably catabolize glucose through aerobic glycolysis rather than oxidative phosphorylation. Intracellular ionic signaling has been shown to regulate glucose metabolism, but the underlying ion channel has yet to be identified. RNA-seq, metabolomics and genetic assay revealed that the TRPM7 channel regulated cellular glycolysis. Deletion of TRPM7 suppressed cancer cell glycolysis and reduced the xenograft tumor burden. Deficiency of endothelial TRPM7 inhibited postnatal retinal angiogenesis in mice. Mechanistically, TRPM7 transcriptionally regulated the solute carrier family 2 member 3 (SLC2A3, also known as GLUT3) via Ca2+ influx-induced calcineurin activation. Furthermore, CREB-regulated transcription coactivator 2 (CRTC2) and CREB act downstream of calcineurin to relay Ca2+ signal to SLC2A3 transcription. Expression of the constitutively active CRTC2 or CREB in TRPM7 knockout cell normalized glycolytic metabolism and cell growth. The TRPM7 channel represents a novel regulator of glycolytic reprogramming. Inhibition of the TRPM7-dependent glycolysis could be harnessed for cancer therapy.PMID:36878949 | DOI:10.1038/s41419-023-05701-7

Pediatr Obes. 2023 Mar 6:e13019. doi: 10.1111/ijpo.13019. Online ahead of print.ABSTRACTOBJECTIVE: The objective of this study was to identify the intestinal microbiota and faecal metabolic biomarkers associated with excess weight in Chinese children and adolescents.METHODS: This cross-sectional study included 163 children aged 6-14 years (including 72 with normal-weight and 91 with overweight/obesity from three Chinese boarding schools). We used 16S rRNA high-throughput sequencing to analyse the diversity and composition of intestinal microbiota. Of these participants, we selected 10 children with normal-weight and 10 with obesity (matched 1:1 for school, sex and age) and measured faecal metabolites using ultra-performance liquid chromatography coupled with tandem mass spectrometry.RESULTS: Alpha diversity was significantly elevated in children with normal-weight compared to overweight/obese. Principle coordinate analysis and permutational multivariate analysis of variance revealed a significant difference in intestinal microbial community structure between the normal-weight and overweight/obese groups. The two groups differed significantly in the relative abundances of Megamonas, Bifidobacterium and Alistipes. In faecal metabolomics analysis, we identified 14 differential metabolites and 2 main differential metabolic pathways associated with obesity.CONCLUSION: This study identified intestinal microbiota and metabolic markers associated with excess weight in Chinese children.PMID:36878714 | DOI:10.1111/ijpo.13019

Chemosphere. 2023 Mar 4:138228. doi: 10.1016/j.chemosphere.2023.138228. Online ahead of print.ABSTRACTEXPOSURE TO PER: and polyfluoroalkyl substances (PFAS) through the environment can lead to harmful health outcomes and the development of disease. However, little is known about how PFAS impact underlying biology that contributes to these adverse health effects. The metabolome represents the end product of cellular processes and has been used previously to understand physiological changes that lead to disease. In this study, we investigated whether exposure to PFAS was associated with the global, untargeted metabolome. In a cohort of 459 pregnant mothers and 401 children, we quantified plasma concentrations of six individual PFAS- PFOA, PFOS, PFHXS, PFDEA, and PFNA- and performed plasma metabolomic profiling by UPLC-MS. In adjusted linear regression analysis, we found associations between plasma PFAS and perturbations in lipid and amino acid metabolites in both mothers and children. In mothers, metabolites of 19 lipid pathways and 8 amino acid pathways were significantly associated with PFAS exposure at an FDR<0.05 threshold; in children, metabolites of 28 lipid pathways and 10 amino acid pathways exhibited significant associations at FDR<0.05 with PFAS exposure. Our investigation found that metabolites of the Sphingomyelin, Lysophospholipid, Long Chain Polyunsaturated Fatty Acid (n3 and n6), Fatty Acid- Dicarboxylate, and Urea Cycle showed the most significant associations with PFAS, suggesting these may be particular pathways of interest in the physiological response to PFAS. To our knowledge, this is the first study to characterize associations between the global metabolome and PFAS across multiple periods in the life course to understand impacts on underlying biology, and the findings presented here are relevant in understanding how PFAS disrupt normal biological function and may ultimately give rise to harmful health effects.PMID:36878362 | DOI:10.1016/j.chemosphere.2023.138228

Microb Pathog. 2023 Mar 4:106057. doi: 10.1016/j.micpath.2023.106057. Online ahead of print.ABSTRACTPseudomonas aeruginosa (P. aeruginosa) uses quorum sensing signaling (QS) molecules to control the expression of virulence factors and biofilm formation. In this study, the effects of the probiotic's (Lactobacillus plantarum (L. plantarum)) lysate and cell-free supernatant and the prebiotic (Fructooligosaccharides (FOS)) on the levels of P. aeruginosa QS molecules, virulence factors, biofilm density and metabolites were observed. These effects were investigated using exofactor assays, crystal violet and liquid chromatography-mass spectrometry (LC-MS)-based metabolomics approach. Results showed that in comparison to untreated P. aeruginosa, the L. plantarum cell-free supernatant (5%) and FOS (2%) significantly reduced the levels of the virulence factor pyoverdine (PVD) and several metabolites in the QS pathway including Pseudomonas autoinducer-2 (PAI-2). Metabolomics study revealed that the level of different secondary metabolites involved in the biosynthesis of vitamins, amino acids and the tricarboxylic acid (TCA) cycle were also affected. L. Plantarum was found to have a higher impact on the metabolomics profile of P. aeruginosa and its QS molecules compared to FOS. Lastly, a decrease in the formation of the P. aeruginosa biofilm was observed in a time-dependent pattern upon treatment with either cell-free supernatant of L. plantarum (5%), FOS (2%) or a combination of both treatments (5% + 2%). The latter showed the highest effect with 83% reduction in biofilm density at 72 h incubation. This work highlighted the important role probiotics and prebiotics play as potential QS inhibitors for P. aeruginosa. Moreover, it demonstrated the significant role of LC-MS metabolomics for investigating the altered biochemical and QS pathways in P. aeruginosa.PMID:36878335 | DOI:10.1016/j.micpath.2023.106057

Sci Total Environ. 2023 Mar 4:162615. doi: 10.1016/j.scitotenv.2023.162615. Online ahead of print.ABSTRACTPhthalate esters (PAEs) are one of the significant classes of emerging contaminants that are increasingly detected in environmental and human samples. Nevertheless, the current toxicity studies rarely report how PAEs affect the cardiovascular system, especially in obese individuals. In this study, diet-induced obese mice and corresponding normal mice were exposed to di(2-ethylhexyl) phthalate (DEHP) by oral gavage at environmentally relevant concentrations and key characteristics of cardiovascular risk were examined. The 16S rRNA and high-resolution mass spectrometry were used to investigate the alterations in the gut microbial profile and metabolic homeostasis. The results indicated that the cardiovascular system of fat individuals was more susceptible to DEHP exposure than mice in the lean group. 16S rRNA-based profiling and correlation analysis collectively suggested DEHP-induced gut microbial remodeling in fed a high-fat diet mice, represented by the abundance of the genus Faecalibaculum. Using metagenomic approaches, Faecalibaculum rodentium was identified as the top-ranked candidate bacterium. Additionally, metabolomics data revealed that DEHP exposure altered the gut metabolic homeostasis of arachidonic acid (AA), which is associated with adverse cardiovascular events. Finally, cultures of Faecalibaculum rodentium were treated with AA in vitro to verify the role of Faecalibaculum rodentium in altering AA metabolism. Our findings provide novel insights into DEHP exposure induced cardiovascular damage in obese individuals and suggest that AA could be used as a potential modulator of gut microbiota to prevent related diseases.PMID:36878288 | DOI:10.1016/j.scitotenv.2023.162615

Dtsch Med Wochenschr. 2023 Mar;148(6):331-334. doi: 10.1055/a-1924-3921. Epub 2023 Mar 6.ABSTRACTSince September 2022, there is a new, German-language glossary for the nomenclature of renal function and renal disease, aligned with international technical terms and KDIGO guidelines for a more precise and uniform description of the facts. Terms such as "renal disease," "renal insufficiency," or "acute renal failure" should be avoided and replaced with "disease" or "functional impairment."The KDIGO guideline recommends in patients with CKD stage G3a, in addition to the determination of serum creatinine, the additional determination of cystatin to confirm the CKD stage. A combination of serum creatinine and cystatin C to estimate GFR without taking into account the so-called race coefficient seems to be more accurate in African Americans than the previous eGFR formulas. However, there is no recommendation on this in international guidelines yet. For Caucasians, the formula does not change.Renal function impairment lasting more than 7 days but less than 3 months is called acute kidney disease (AKD). The AKD stage is the critical time window for therapeutic interventions to reduce the risk of progression in kidney disease.A future, expanded AKI definition incorporating biomarkers will allow patients to be divided into subclasses according to functional and structural limitations, thus mapping the two-dimensionality of AKI. By using artificial intelligence, large amounts of data from clinical parameters, blood and urine samples, histopathological and molecular markers (including proteomics and metabolomics data) can be used integratively for the graduation of CKD and thus contribute significantly to individualized therapy.PMID:36878233 | DOI:10.1055/a-1924-3921

PLoS One. 2023 Mar 6;18(3):e0281074. doi: 10.1371/journal.pone.0281074. eCollection 2023.ABSTRACTBACKGROUND: Accurate estimates of gestational age (GA) at birth are important for preterm birth surveillance but can be challenging to obtain in low income countries. Our objective was to develop machine learning models to accurately estimate GA shortly after birth using clinical and metabolomic data.METHODS: We derived three GA estimation models using ELASTIC NET multivariable linear regression using metabolomic markers from heel-prick blood samples and clinical data from a retrospective cohort of newborns from Ontario, Canada. We conducted internal model validation in an independent cohort of Ontario newborns, and external validation in heel prick and cord blood sample data collected from newborns from prospective birth cohorts in Lusaka, Zambia and Matlab, Bangladesh. Model performance was measured by comparing model-derived estimates of GA to reference estimates from early pregnancy ultrasound.RESULTS: Samples were collected from 311 newborns from Zambia and 1176 from Bangladesh. The best-performing model accurately estimated GA within about 6 days of ultrasound estimates in both cohorts when applied to heel prick data (MAE 0.79 weeks (95% CI 0.69, 0.90) for Zambia; 0.81 weeks (0.75, 0.86) for Bangladesh), and within about 7 days when applied to cord blood data (1.02 weeks (0.90, 1.15) for Zambia; 0.95 weeks (0.90, 0.99) for Bangladesh).CONCLUSIONS: Algorithms developed in Canada provided accurate estimates of GA when applied to external cohorts from Zambia and Bangladesh. Model performance was superior in heel prick data as compared to cord blood data.PMID:36877673 | DOI:10.1371/journal.pone.0281074

Calcif Tissue Int. 2023 Mar 6. doi: 10.1007/s00223-023-01069-0. Online ahead of print.ABSTRACTMounting evidence has supported osteoporosis (OP) as a metabolic disorder. Recent metabolomics studies have discovered numerous metabolites related to bone mineral density (BMD). However, the causal effects of metabolites on BMD at distinct sites remained underexplored. Leveraging genome-wide association datasets, we conducted two-sample Mendelian randomization (MR) analyses to investigate the causal relationship between 486 blood metabolites and bone mineral density at five skeletal sites including heel (H), total body (TB), lumbar spine (LS), femoral neck (FN), and ultra-distal forearm (FA). Sensitivity analyses were performed to test the presence of the heterogeneity and the pleiotropy. To exclude the influences of reverse causation, genetic correlation, and linkage disequilibrium (LD), we further performed reverse MR, linkage disequilibrium regression score (LDSC), and colocalization analyses. In the primary MR analyses, 22, 10, 3, 7, and 2 metabolite associations were established respectively for H-BMD, TB-BMD, LS-BMD, FN-BMD, and FA-BMD at the nominal significance level (IVW, P < 0.05) and passing sensitivity analyses. Among these, one metabolite, androsterone sulfate showed a strong effect on four out of five BMD phenotypes (Odds ratio [OR] for H-BMD = 1.045 [1.020, 1.071]; Odds ratio [OR] for TB-BMD = 1.061 [1.017, 1.107]; Odds ratio [OR] for LS-BMD = 1.088 [1.023, 1.159]; Odds ratio [OR] for FN-BMD = 1.114 [1.054, 1.177]). Reverse MR analysis provided no evidence for the causal effects of BMD measurements on these metabolites. Colocalization analysis have found that several metabolite associations might be driven by shared genetic variants such as mannose for TB-BMD. This study identified some metabolites causally related to BMD at distinct sites and several key metabolic pathways, which shed light on predictive biomarkers and drug targets for OP.PMID:36877247 | DOI:10.1007/s00223-023-01069-0

Microbiol Spectr. 2023 Mar 6:e0234422. doi: 10.1128/spectrum.02344-22. Online ahead of print.ABSTRACTDiabetic mellitus nephropathy (DMN) is a serious complication of diabetes and a major health concern. Although the pathophysiology of diabetes mellitus (DM) leading to DMN is uncertain, recent evidence suggests the involvement of the gut microbiome. This study aimed to determine the relationships among gut microbial species, genes, and metabolites in DMN through an integrated clinical, taxonomic, genomic, and metabolomic analysis. Whole-metagenome shotgun sequencing and nuclear magnetic resonance metabolomic analyses were performed on stool samples from 15 patients with DMN and 22 healthy controls. Six bacterial species were identified to be significantly elevated in the DMN patients after adjusting for age, sex, body mass index, and estimated glomerular filtration rate (eGFR). Multivariate analysis found 216 microbial genes and 6 metabolites (higher valine, isoleucine, methionine, valerate, and phenylacetate levels in the DMN group and higher acetate levels in the control group) that were differentially present between the DMN and control groups. Integrated analysis of all of these parameters and clinical data using the random-forest model showed that methionine and branched-chain amino acids (BCAAs) were among the most significant features, next to the eGFR and proteinuria, in differentiating the DMN group from the control group. Metabolic pathway gene analysis of BCAAs and methionine also revealed that many genes involved in the biosynthesis of these metabolites were elevated in the six species that were more abundant in the DMN group. The suggested correlation among taxonomic, genetic, and metabolic features of the gut microbiome would expand our understanding of gut microbial involvement in the pathogenesis of DMN and may provide potential therapeutic targets for DMN. IMPORTANCE Whole metagenomic sequencing uncovered specific members of the gut microbiota associated with DMN. The gene families derived from the discovered species are involved in the metabolic pathways of methionine and branched-chain amino acids. Metabolomic analysis using stool samples showed increased methionine and branched-chain amino acids in DMN. These integrative omics results provide evidence of the gut microbiota-associated pathophysiology of DMN, which can be further studied for disease-modulating effects via prebiotics or probiotics.PMID:36877076 | DOI:10.1128/spectrum.02344-22

Carbohydr Polym. 2023 Jan 1;299:120156. doi: 10.1016/j.carbpol.2022.120156. Epub 2022 Oct 7.ABSTRACTChitooligosaccharides (COS) have many bioactive functions and favorable prospects in the fields of biomedicine and functional foods. In this study, COS was found to significantly improve the survival rate of neonatal necrotizing enterocolitis (NEC) model rats, alter the composition of the intestinal microbiota, inhibit the expression of inflammatory cytokines, and alleviate intestinal pathological injury. In addition, COS also increased the abundance of Akkermansia, Bacteroides, and Clostridium sensu stricto 1 in the intestines of normal rats (the normal rat model is more universal). The in vitro fermentation results found that COS was degraded by the human gut microbiota to promote the abundance of Clostridium sensu stricto 1 and produced numerous short-chain fatty acids (SCFAs). In vitro metabolomic analysis revealed that COS catabolism was associated with significant increases in 3-hydroxybutyrate acid and γ-aminobutyric acid. This study provides evidence for the potential of COS as a prebiotic in food products and to ameliorate NEC development in neonatal rats.PMID:36876780 | DOI:10.1016/j.carbpol.2022.120156

Eur Rev Med Pharmacol Sci. 2023 Feb;27(4):1443-1449. doi: 10.26355/eurrev_202302_31384.ABSTRACTOBJECTIVE: Short-chain fatty acids (SCFAs) are microbial derived metabolites, which have multiple beneficial properties. The amount of SCFAs depends on several factors, such as age, diet (mainly intake of dietary fiber), and overall health condition. The normal proportion between SCFAs is 3:1:1 for acetate, proprionate and butyrate, respectively. In colorectal cancer (CRC) patients, microbiota alterations have been shown. Consequently, metabolome within the gut might change to a large extent. Therefore, the aim of this study was to analyse the content of SCFAs and the proportion between SCFAs in the stool obtained from CRC patients in preoperative period.PATIENTS AND METHODS: This study included 15 patients with CRC in preoperative period. The stool samples were taken and stored at -80°C in the Fahrenheit Biobank BBMRI.pl, Medical University of Gdansk, Poland. The analysis of SCFAs from stool samples was conducted by means of gas chromatography.RESULTS: This study included mainly males (66.67%, n=10). In all patients, there was abnormal proportion between SCFAs. The extremely higher concentration of butyrate was noted in 2 samples (13.33%) compared to the rest of patients. However, based on normal proportion between SCFAs, the results <1 for butyrate were noted in 93.33% of patients.CONCLUSIONS: SCFAs pool is altered in CRC patients, among others characterized by low level of butyrate. It should be considered to administer butyrate supplementation to CRC patients especially prior to surgery to support an appropriate preparation to this treatment.PMID:36876684 | DOI:10.26355/eurrev_202302_31384

Front Microbiol. 2023 Feb 16;14:1128394. doi: 10.3389/fmicb.2023.1128394. eCollection 2023.ABSTRACTIndustrial production of Gouda cheeses mostly relies on a rotated use of different mixed-strain lactic acid bacteria starter cultures to avoid phage infections. However, it is unknown how the application of these different starter culture mixtures affect the organoleptic properties of the final cheeses. Therefore, the present study assessed the impact of three different starter culture mixtures on the batch-to-batch variations among Gouda cheeses from 23 different batch productions in the same dairy company. Both the cores and rinds of all these cheeses were investigated after 36, 45, 75, and 100 weeks of ripening by metagenetics based on high-throughput full-length 16S rRNA gene sequencing accompanied with an amplicon sequence variant (ASV) approach as well as metabolite target analysis of non-volatile and volatile organic compounds. Up to 75 weeks of ripening, the acidifying Lactococcus cremoris and Lactococcus lactis were the most abundant bacterial species in the cheese cores. The relative abundance of Leuconostoc pseudomesenteroides was significantly different for each starter culture mixture. This impacted the concentrations of some key metabolites, such as acetoin produced from citrate, and the relative abundance of non-starter lactic acid bacteria (NSLAB). Cheeses with the least Leuc. pseudomesenteroides contained more NSLAB, such as Lacticaseibacillus paracasei that was taken over by Tetragenococcus halophilus and Loigolactobacillus rennini upon ripening time. Taken together, the results indicated a minor role of leuconostocs in aroma formation but a major impact on the growth of NSLAB. The relative abundance of T. halophilus (high) and Loil. rennini (low) increased with ripening time from rind to core. Two main ASV clusters of T. halophilus could be distinguished, which were differently correlated with some metabolites, both beneficial (regarding aroma formation) and undesirable ones (biogenic amines). A well-chosen T. halophilus strain could be a candidate adjunct culture for Gouda cheese production.PMID:36876114 | PMC:PMC9978159 | DOI:10.3389/fmicb.2023.1128394

Front Microbiol. 2023 Feb 15;14:1117355. doi: 10.3389/fmicb.2023.1117355. eCollection 2023.ABSTRACTOrganic and microbial fertilizers have potential advantages over inorganic fertilizers in improving soil fertility and crop yield without harmful side-effects. However, the effects of these bio-organic fertilizers on the soil microbiome and metabolome remain largely unknown, especially in the context of bamboo cultivation. In this study, we cultivated Dendrocalamus farinosus (D. farinosus) plants under five different fertilization conditions: organic fertilizer (OF), Bacillus amyloliquefaciens bio-fertilizer (Ba), Bacillus mucilaginosus Krassilnikov bio-fertilizer (BmK), organic fertilizer plus Bacillus amyloliquefaciens bio-fertilizer (OFBa), and organic fertilizer plus Bacillus mucilaginosus Krassilnikov bio-fertilizer (OFBmK). We conducted 16S rRNA sequencing and liquid chromatography/mass spectrometry (LC-MS) to evaluate the soil bacterial composition and soil metabolic activity in the different treatment groups. The results demonstrate that all the fertilization conditions altered the soil bacterial community composition. Moreover, the combination of organic and microbial fertilizers (i.e., in the OFBa and OFBmK groups) significantly affected the relative abundance of soil bacterial species; the largest number of dominant microbial communities were found in the OFBa group, which were strongly correlated with each other. Additionally, non-targeted metabolomics revealed that the levels of soil lipids and lipid-like molecules, and organic acids and their derivatives, were greatly altered under all treatment conditions. The levels of galactitol, guanine, and deoxycytidine were also markedly decreased in the OFBa and OFBmK groups. Moreover, we constructed a regulatory network to delineated the relationships between bamboo phenotype, soil enzymatic activity, soil differential metabolites, and dominant microbial. The network revealed that bio-organic fertilizers promoted bamboo growth by modifying the soil microbiome and metabolome. Accordingly, we concluded that the use of organic fertilizers, microbial fertilizers, or their combination regulated bacterial composition and soil metabolic processes. These findings provide new insights into how D. farinosus-bacterial interactions are affected by different fertilization regiments, which are directly applicable to the agricultural cultivation of bamboo.PMID:36876063 | PMC:PMC9975161 | DOI:10.3389/fmicb.2023.1117355

Front Mol Biosci. 2023 Feb 15;10:1111482. doi: 10.3389/fmolb.2023.1111482. eCollection 2023.ABSTRACTCOVID-19 currently represents one of the major health challenges worldwide. Albeit its infectious character, with onset affectation mainly at the respiratory track, it is clear that the pathophysiology of COVID-19 has a systemic character, ultimately affecting many organs. This feature enables the possibility of investigating SARS-CoV-2 infection using multi-omic techniques, including metabolomic studies by chromatography coupled to mass spectrometry or by nuclear magnetic resonance (NMR) spectroscopy. Here we review the extensive literature on metabolomics in COVID-19, that unraveled many aspects of the disease including: a characteristic metabotipic signature associated to COVID-19, discrimination of patients according to severity, effect of drugs and vaccination treatments and the characterization of the natural history of the metabolic evolution associated to the disease, from the infection onset to full recovery or long-term and long sequelae of COVID.PMID:36876049 | PMC:PMC9975567 | DOI:10.3389/fmolb.2023.1111482

Front Mol Biosci. 2023 Feb 15;10:1119588. doi: 10.3389/fmolb.2023.1119588. eCollection 2023.NO ABSTRACTPMID:36876048 | PMC:PMC9975730 | DOI:10.3389/fmolb.2023.1119588

Front Mol Biosci. 2023 Feb 17;10:1128542. doi: 10.3389/fmolb.2023.1128542. eCollection 2023.ABSTRACTTrichinella infections have been documented globally and have been detected in wild and/or domestic animals except Antarctica. There is paucity of information in the metabolic responses of hosts during Trichinella infections and biomarkers for infection that can be used in the diagnosis of the disease. The current study aimed to apply a non-targeted metabolomic approach to identify Trichinella zimbabwensis biomarkers including metabolic response from sera of infected Sprague-Dawley rats. Fifty-four male Sprague-Dawley rats were randomly assigned into T. zimbabwensis infected group (n = 36) and the non-infected control (n = 18). Results from the study showed that the metabolic signature of T. zimbabwensis infection consists of enriched methyl histidine metabolism, disturbance of the liver urea cycle, impeded TCA cycle, and upregulation of gluconeogenesis metabolism. The observed disturbance in the metabolic pathways was attributed to the effects caused by the parasite during its migration to the muscles resulting in downregulation of amino acids intermediates in the Trichinella-infected animals, and therefore affecting energy production and degradation of biomolecules. It was concluded that T. zimbabwensis infection caused an upregulation of amino acids; pipecolic acid, histidine, and urea, and upregulation of glucose and meso-Erythritol. Moreover, T. zimbabwensis infection caused upregulation of the fatty acids, retinoic acid, and acetic acid. These findings highlight the potential of metabolomics as a novel approach for fundamental investigations of host-pathogen interactions as well as for disease progression and prognosis.PMID:36876045 | PMC:PMC9983363 | DOI:10.3389/fmolb.2023.1128542

Curr Res Food Sci. 2023 Feb 18;6:100464. doi: 10.1016/j.crfs.2023.100464. eCollection 2023.ABSTRACTThe prevalence of obesity is rapidly increasing and poses serious health risks accompanied by a decrease in life expectancy and quality of life. Therefore, the therapeutic potential of natural-derived nutraceuticals against obesity and its comorbidities needs to be explored. Molecular inhibition of lipase enzymes and fat mass and obesity-associated (FTO) protein has attracted some recent interest in efforts to find antiobesity agents. This study aims to innovate a fermented drink from Clitoria ternatea kombucha (CTK), find out their metabolites profile, and determine the antiobesity potential through a molecular docking study. The CTK formulation refers to previous research while the metabolites profile was determined using HPLC-ESI-HRMS/MS. Major compounds were selected based on best match value > 99.0% of the M/Z cloud database. A total of 79 compounds were identified in CTK, and 13 ideal compounds were selected to be simulated in the molecular docking study against human pancreatic lipase, α-amylase, α-glucosidase, porcine pancreatic lipase, and FTO proteins. The study found that Kaempferol, Quercetin-3β-D-glucoside, Quercetin, Dibenzylamine, and α-Pyrrolidinopropiophenone showed the best potential as functional antiobesity compounds since their affinity value ranked high in each respective receptor. In conclusion, the major compounds of CTK metabolites have the potential to be promising functional foods against obesity. However, further in vitro and in vivo studies should validate these health benefits.PMID:36875892 | PMC:PMC9976213 | DOI:10.1016/j.crfs.2023.100464

Front Nutr. 2023 Feb 16;10:1110536. doi: 10.3389/fnut.2023.1110536. eCollection 2023.ABSTRACTNon-alcoholic fatty liver disease (NAFLD) is frequently associated with metabolic disorders, being highly prevalent in obese and diabetic patients. Many concomitant factors that promote systemic and liver inflammation are involved in NAFLD pathogenesis, with a growing body of evidence highlighting the key role of the gut microbiota. Indeed, the gut-liver axis has a strong impact in the promotion of NAFLD and in the progression of the wide spectrum of its manifestations, claiming efforts to find effective strategies for gut microbiota modulation. Diet is among the most powerful tools; Western diet negatively affects intestinal permeability and the gut microbiota composition and function, selecting pathobionts, whereas Mediterranean diet fosters health-promoting bacteria, with a favorable impact on lipid and glucose metabolism and liver inflammation. Antibiotics and probiotics have been used to improve NAFLD features, with mixed results. More interestingly, medications used to treat NAFLD-associated comorbidities may also modulate the gut microbiota. Drugs for the treatment of type 2 diabetes mellitus (T2DM), such as metformin, glucagon-like peptide-1 (GLP-1) agonists, and sodium-glucose cotransporter (SGLT) inhibitors, are not only effective in the regulation of glucose homeostasis, but also in the reduction of liver fat content and inflammation, and they are associated with a shift in the gut microbiota composition towards a healthy phenotype. Even bariatric surgery significantly changes the gut microbiota, mostly due to the modification of the gastrointestinal anatomy, with a parallel improvement in histological features of NAFLD. Other options with promising effects in reprogramming the gut-liver axis, such as fecal microbial transplantation (FMT) and next-generation probiotics deserve further investigation for future inclusion in the therapeutic armamentarium of NAFLD.PMID:36875849 | PMC:PMC9978194 | DOI:10.3389/fnut.2023.1110536

Front Nutr. 2023 Feb 16;10:1104446. doi: 10.3389/fnut.2023.1104446. eCollection 2023.ABSTRACTCordycepin, an important active substance in Cordyceps militaris, possesses antiviral and other beneficial activities. In addition, it has been reported to effectively promote the comprehensive treatment of COVID-19 and thus has become a research hotspot. The addition of naphthalene acetic acid (NAA) is known to significantly improve the yield of cordycepin; however, its related molecular mechanism remains unclear. We conducted a preliminary study on C. militaris with different concentrations of NAA. We found that treatment with different concentrations of NAA inhibited the growth of C. militaris, and an increase in its concentration significantly improved the cordycepin content. In addition, we conducted a transcriptome and metabolomics association analysis on C. militaris treated with NAA to understand the relevant metabolic pathway of cordycepin synthesis under NAA treatment and elucidate the relevant regulatory network of cordycepin synthesis. Weighted gene co-expression network analysis (WGCNA), transcriptome, and metabolome association analysis revealed that genes and metabolites encoding cordycepin synthesis in the purine metabolic pathway varied significantly with the concentration of NAA. Finally, we proposed a metabolic pathway by analyzing the relationship between gene-gene and gene-metabolite regulatory networks, including the interaction of cordycepin synthesis key genes; key metabolites; purine metabolism; TCA cycle; pentose phosphate pathway; alanine, aspartate, and glutamate metabolism; and histidine metabolism. In addition, we found the ABC transporter pathway to be significantly enriched. The ABC transporters are known to transport numerous amino acids, such as L-glutamate, and participate in the amino acid metabolism that affects the synthesis of cordycepin. Altogether, multiple channels work together to double the cordycepin yield, thereby providing an important reference for the molecular network relationship between the transcription and metabolism of cordycepin synthesis.PMID:36875834 | PMC:PMC9977999 | DOI:10.3389/fnut.2023.1104446

Front Aging Neurosci. 2023 Feb 17;15:1108205. doi: 10.3389/fnagi.2023.1108205. eCollection 2023.ABSTRACTOBJECTIVE: To investigate the role of gut microbiota and metabolites in POCD in elderly orthopedic patients, and screen the preoperative diagnostic indicators of gut microbiota in elderly POCD.METHOD: 40 elderly patients undergoing orthopedic surgery were enrolled and divided into Control group and POCD group following neuropsychological assessments. Gut microbiota was determined by 16S rRNA MiSeq sequencing, and metabolomics of GC-MS and LC-MS was used to screen the differential metabolites. We then analyzed the pathways enriched by metabolites.RESULT: There was no difference in alpha or beta diversity between Control group and POCD group. There were significant differences in 39 ASV and 20 genera bacterium in the relative abundance. Significant diagnostic efficiency analyzed by the ROC curves were found in 6 genera bacterium. Differential metabolites in the two groups including acetic acid, arachidic acid, pyrophosphate etc. were screened out and enriched to certain metabolic pathways which impacted the cognition function profoundly.CONCLUSION: Gut microbiota disorders exist preoperatively in the elderly POCD patients, by which there could be a chance to predict the susceptible population.CLINICAL TRIAL REGISTRATION: [http://www.chictr.org.cn/edit.aspx?pid=133843&htm=4], identifier [ChiCTR2100051162].PMID:36875700 | PMC:PMC9981628 | DOI:10.3389/fnagi.2023.1108205