PubMed

Trends Genet. 2024 May 22:S0168-9525(24)00099-4. doi: 10.1016/j.tig.2024.04.012. Online ahead of print.ABSTRACTIntimate links between epigenome modifications and metabolites allude to a crucial role of cellular metabolism in transcriptional regulation. Retina, being a highly metabolic tissue, adapts by integrating inputs from genetic, epigenetic, and extracellular signals. Precise global epigenomic signatures guide development and homeostasis of the intricate retinal structure and function. Epigenomic and metabolic realignment are hallmarks of aging and highlight a link of the epigenome-metabolism nexus with aging-associated multifactorial traits affecting the retina, including age-related macular degeneration and glaucoma. Here, we focus on emerging principles of epigenomic and metabolic control of retinal gene regulation, with emphasis on their contribution to human disease. In addition, we discuss potential mitigation strategies involving lifestyle changes that target the epigenome-metabolome relationship for maintaining retinal function.PMID:38782642 | DOI:10.1016/j.tig.2024.04.012

JMIR Res Protoc. 2024 May 23;13:e53905. doi: 10.2196/53905.ABSTRACTBACKGROUND: Heart failure (HF) is a significant health problem that is often associated with major morbidity and mortality. Metabolic abnormalities occur in HF and may be used to identify individuals at risk of developing the condition. Furthermore, these metabolic changes may play a role in the pathogenesis and progression of HF. Despite this knowledge, the utility of metabolic changes in diagnosis, management, prognosis, and therapy for patients with chronic HF has not been systematically reviewed.OBJECTIVE: This scoping review aims to systematically appraise the literature on metabolic changes in patients with HF, describe the role of these changes in pathogenesis, progression, and care, and identify knowledge gaps to inform future research.METHODS: This review will be conducted using a strategy based on previous reports, the JBI Manual for Evidence Synthesis, and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews (PRISMA-ScR) guidelines. A comprehensive search of electronic databases (Medline, EBSCOhost, Scopus, and Web of Science) will be conducted using keywords related to HF, myocardial failure, metabolomes, metabonomics, and analytical chemistry techniques. The search will include original peer-reviewed research papers (clinical studies conducted on humans and systematic reviews with or without a meta-analysis) published between January 2010 and September 2023. Studies that include patients with HF younger than 18 years or those not published in English will be excluded. Two authors (UGA and MB) will screen the titles and abstracts independently and perform a full-text screen of the relevant and eligible papers. Relevant data will be extracted and synthesized, and a third author or group will be consulted to resolve discrepancies.RESULTS: This scoping review will span from January 2010 to September 2023, and the results will be published in a peer-reviewed, open-access journal as a scoping review in 2024. The presentation of the findings will use the PRISMA-ScR flow diagram and descriptive and narrative formats, including tables and graphical displays, to provide a comprehensive overview of the extracted data.CONCLUSIONS: This review aims to collect and analyze the available evidence on metabolic changes in patients with HF, aiming to enhance our current understanding of this topic. Additionally, this review will identify the most commonly used and suitable sample, analytical method, and specific metabolomes to facilitate standardization, reproducibility of results, and application in the diagnosis, treatment, and risk stratification of patients with HF. Finally, it is hoped that this review's outcomes will inspire further research into the metabolomes of patients with HF in low- and middle-income countries.TRIAL REGISTRATION: Open Science Framework; https://osf.io/sp6xj.INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53905.PMID:38781584 | DOI:10.2196/53905

J Nat Prod. 2024 May 23. doi: 10.1021/acs.jnatprod.3c01071. Online ahead of print.ABSTRACTCurrent small-molecule-based SARS-CoV-2 treatments have limited global accessibility and pose the risk of inducing viral resistance. Therefore, a marine algae and cyanobacteria extract library was screened for natural products that could inhibit two well-defined and validated COVID-19 drug targets, disruption of the spike protein/ACE-2 interaction and the main protease (Mpro) of SARS-CoV-2. Following initial screening of 86 extracts, we performed an untargeted metabolomic analysis of 16 cyanobacterial extracts. This approach led to the isolation of an unusual saturated fatty acid, jobosic acid (2,5-dimethyltetradecanoic acid, 1). We confirmed that 1 demonstrated selective inhibitory activity toward both viral targets while retaining some activity against the spike-RBD/ACE-2 interaction of the SARS-CoV-2 omicron variant. To initially explore its structure-activity relationship (SAR), the methyl and benzyl ester derivatives of 1 were semisynthetically accessed and demonstrated acute loss of bioactivity in both SARS-CoV-2 biochemical assays. Our efforts have provided copious amounts of a fatty acid natural product that warrants further investigation in terms of SAR, unambiguous determination of its absolute configuration, and understanding of its specific mechanisms of action and binding site toward new therapeutic avenues for SARS-CoV-2 drug development.PMID:38781491 | DOI:10.1021/acs.jnatprod.3c01071

J Infect Dis. 2024 May 23:jiae265. doi: 10.1093/infdis/jiae265. Online ahead of print.ABSTRACTOBJECTIVE: The fecal microbiota and metabolome are hypothesized to be altered before late-onset neonatal meningitis (LOM), in analogy to late-onset sepsis (LOS). The present study aimed to identify fecal microbiota composition and volatile metabolomics preceding LOM.METHODS: Cases and gestational age-matched controls were selected from a prospective, longitudinal preterm cohort study (born <30 weeks' gestation) at nine neonatal intensive care units. The microbial composition (16S rRNA sequencing) and volatile metabolome (gas chromatography-ion mobility spectrometry (GC-IMS) and GC-time-of-flight-mass spectrometry (GC-TOF-MS)), were analyzed in fecal samples 1-10 days pre-LOM.RESULTS: Of 1397 included infants, 21 were diagnosed with LOM (1.5%), and 19 with concomitant LOS (90%). Random Forest classification and MaAsLin2 analysis found similar microbiota features contribute to the discrimination of fecal pre-LOM samples versus controls. A Random Forest model based on six microbiota features accurately predicts LOM 1-3 days before diagnosis with an area under the curve (AUC) of 0.88 (n=147). Pattern recognition analysis by GC-IMS revealed an AUC of 0.70-0.76 (P<0.05) in the three days pre-LOM (n=92). No single discriminative metabolites were identified by GC-TOF-MS (n=66).CONCLUSION: Infants with LOM could be accurately discriminated from controls based on preclinical microbiota composition, while alterations in the volatile metabolome were moderately associated with preclinical LOM.PMID:38781449 | DOI:10.1093/infdis/jiae265

Eur J Endocrinol. 2024 May 23:lvae054. doi: 10.1093/ejendo/lvae054. Online ahead of print.ABSTRACTOBJECTIVE: The metabolic phenotype of totally pancreatectomised patients includes hyperaminoacidaemia and predisposition to hypoglycaemia and hepatic lipid accumulation. We aimed to investigate whether the loss of pancreatic glucagon may be responsible for these changes.METHODS: Nine middle-aged, normal-weight totally pancreatectomised patients, nine patients with type 1 diabetes (C-peptide negative), and nine matched controls underwent two separate experimental days, each involving a 150-minute intravenous infusion of glucagon (4 ng/kg/min) or placebo (saline) under fasting conditions while any basal insulin treatment was continued.RESULTS: Glucagon infusion increased plasma glucagon to similar high physiological levels in all groups. The infusion increased hepatic glucose production and decreased plasma concentration of most amino acids in all groups, with more pronounced effects in the totally pancreatectomised patients compared to the other groups. Glucagon infusion diminished fatty acid re-esterification and tended to decrease plasma concentrations of fatty acids in the totally pancreatectomised patients but not in the type 1 diabetes patients.CONCLUSION: Totally pancreatectomised patients were characterised by increased sensitivity to exogenous glucagon at the level of hepatic glucose, amino acid, and lipid metabolism; suggesting that the metabolic disturbances characterising these patients may be rooted in perturbed hepatic processes normally controlled by pancreatic glucagon.PMID:38781444 | DOI:10.1093/ejendo/lvae054

Science. 2024 May 24;384(6698):eadh7688. doi: 10.1126/science.adh7688. Epub 2024 May 24.ABSTRACTRNA splicing is highly prevalent in the brain and has strong links to neuropsychiatric disorders; yet, the role of cell type-specific splicing and transcript-isoform diversity during human brain development has not been systematically investigated. In this work, we leveraged single-molecule long-read sequencing to deeply profile the full-length transcriptome of the germinal zone and cortical plate regions of the developing human neocortex at tissue and single-cell resolution. We identified 214,516 distinct isoforms, of which 72.6% were novel (not previously annotated in Gencode version 33), and uncovered a substantial contribution of transcript-isoform diversity-regulated by RNA binding proteins-in defining cellular identity in the developing neocortex. We leveraged this comprehensive isoform-centric gene annotation to reprioritize thousands of rare de novo risk variants and elucidate genetic risk mechanisms for neuropsychiatric disorders.PMID:38781356 | DOI:10.1126/science.adh7688

PLoS One. 2024 May 23;19(5):e0303273. doi: 10.1371/journal.pone.0303273. eCollection 2024.ABSTRACTLithified layers of complex microbial mats known as microbialites are ubiquitous in the fossil record, and modern forms are increasingly identified globally. A key challenge to developing an understanding of microbialite formation and environmental role is how to investigate complex and diverse communities in situ. We selected living, layered microbialites (stromatolites) in a peritidal environment near Schoenmakerskop, Eastern Cape, South Africa to conduct a spatial survey mapping the composition and small molecule production of the microbial communities from environmental samples. Substrate core samples were collected from nine sampling stations ranging from the upper point of the freshwater inflow to the lower marine interface where tidal overtopping takes place. Substrate cores provided material for parallel analyses of microbial community diversity by 16S rRNA gene amplicon sequencing and metabolomics using LC-MS2. Species and metabolite diversities were correlated, and prominent specialized metabolites were targeted for preliminary characterization. A new series of cyclic hexadepsipeptides, named ibhayipeptolides, was most abundant in substrate cores of submerged microbialites. These results demonstrate the detection and identification of metabolites from mass-limited environmental samples and contribute knowledge about microbialite chemistry and biology, which facilitates future targeted studies of specialized metabolite function and biosynthesis.PMID:38781236 | DOI:10.1371/journal.pone.0303273

PLoS One. 2024 May 23;19(5):e0304258. doi: 10.1371/journal.pone.0304258. eCollection 2024.ABSTRACTCorydalis yanhusuo W.T. Wang is a traditional herb. Benzylisoquinoline alkaloids (BIAs) are the main pharmacological active ingredients that play an important role in sedation, relieving pain, promoting blood circulation, and inhibiting cancer cells. However, there are few studies on the biosynthetic pathway of benzylisoquinoline alkaloids in Corydalis yanhusuo, especially on some specific components, such as tetrahydropalmatine. We carried out widely targeted metabolome and transcriptomic analyses to construct the biosynthetic pathway of benzylisoquinoline alkaloids and identified candidate genes. In this study, 702 metabolites were detected, including 216 alkaloids. Protoberberine-type and aporphine-type alkaloids are the main chemical components in C. yanhusuo bulbs. Key genes for benzylisoquinoline alkaloids biosynthesis, including 6-OMT, CNMT, NMCH, BBE, SOMT1, CFS, SPS, STOX, MSH, TNMT and P6H, were successfully identified. There was no significant difference in the content of benzylisoquinoline alkaloids and the expression level of genes between the two suborgans (mother-bulb and son-bulb). The expression levels of BIA genes in the expansion stage (MB-A and SB-A) were significantly higher than those in the maturity stage (MB-C and SB-C), and the content of benzylisoquinoline alkaloids was consistent with the pattern of gene regulation. Five complete single genes were likely to encode the functional enzyme of CoOMT, which participated in tetrahydropalmatine biosynthesis in C. yanhusuo bulbs. These studies provide a strong theoretical basis for the subsequent development of metabolic engineering of benzylisoquinoline alkaloids (especially tetrahydropalmatine) of C. yanhusuo.PMID:38781178 | DOI:10.1371/journal.pone.0304258

Environ Sci Pollut Res Int. 2024 May 23. doi: 10.1007/s11356-024-33735-7. Online ahead of print.ABSTRACTExposure to heavy metals in various populations can lead to extensive damage to different organs, as these metals infiltrate and bioaccumulate in the human body, causing metabolic disruptions in various organs. To comprehensively understand the metal homeostasis, inter-organ "traffic," and extensive metabolic alterations resulting from heavy metal exposure, employing complementary analytical methods is crucial. Metabolomics is pivotal in unraveling the intricacies of disease vulnerability by furnishing thorough understandings of metabolic changes linked to different metabolic diseases. This field offers exciting prospects for enhancing the disease prevention, early detection, and tailoring treatment approaches to individual needs. This article consolidates the existing knowledge on disease-linked metabolic pathways affected by the exposure of diverse heavy metals providing concise overview of the underlying impact mechanisms. The main aim is to investigate the connection between the altered metabolic pathways and long-term complex health conditions induced by heavy metals such as diabetes mellitus, cardiovascular diseases, renal disorders, inflammation, neurodegenerative diseases, reproductive risks, and organ damage. Further exploration of common pathways may unveil the shared targets for treating associated pathological conditions. In this article, the role of metabolomics in disease susceptibility is emphasized that metabolomics is expected to be routinely utilized for the diagnosis and monitoring of diseases and practical value of biomarkers derived from metabolomics, as well as determining their appropriate integration into extensive clinical settings.PMID:38780845 | DOI:10.1007/s11356-024-33735-7

JCI Insight. 2024 May 21:e177997. doi: 10.1172/jci.insight.177997. Online ahead of print.ABSTRACTCaloric restriction improves metabolic health, but is often complicated by bone loss. We studied bone parameters in humans during a 10-day fast and identified candidate metabolic regulators of bone turnover. P1NP, a bone formation marker, decreased within 3 days of fasting. Whereas dual-energy X-ray absorptiometry measures of bone mineral density were unchanged after 10 days of fasting, high-resolution peripheral quantitative CT demonstrated remodeling of bone microarchitecture. Pathway analysis of longitudinal metabolomics data identified one-carbon metabolism as fasting-dependent. In cultured osteoblasts, we tested the functional significance of one-carbon metabolites modulated by fasting, finding that methionine - which surged after 3 days of fasting - impacted markers of osteoblast cell state in a concentration dependent manner, in some instances exhibiting a U-shaped response with both low and high concentrations driving putative anti-bone responses. Administration of methionine to mice for 5 days recapitulated some fasting effects on bone, including a reduction in serum P1NP. In conclusion, a 10-day fast in humans led to remodeling of bone microarchitecture, potentially mediated by a surge in circulating methionine. These data support an emerging model that points to a window of optimal methionine exposure for bone health.PMID:38780544 | DOI:10.1172/jci.insight.177997

Journal of physiological investigation. 2024 Mar 1;67(2):88-102. doi: 10.4103/ejpi.EJPI-D-23-00031. Epub 2024 Apr 30.ABSTRACTThe traditional Chinese herbal prescription Buyang Huanwu decoction (BHD), effectively treats atherosclerosis. However, the mechanism of BHD in atherosclerosis remains unclear. We aimed to determine whether BHD could alleviate atherosclerosis by altering the microbiome-associated metabolic changes in atherosclerotic mice. An atherosclerotic model was established in apolipoprotein E-deficient mice fed high-fat diet, and BHD was administered through gavage for 12 weeks at 8.4 g/kg/d and 16.8 g/kg/d. The atherosclerotic plaque size, composition, serum lipid profile, and inflammatory cytokines, were assessed. Mechanistically, metabolomic and microbiota profiles were analyzed by liquid chromatography-mass spectrometry and 16S rRNA gene sequencing, respectively. Furthermore, intestinal microbiota and atherosclerosis-related metabolic parameters were correlated using Spearman analysis. Atherosclerotic mice treated with BHD exhibited reduced plaque area, aortic lumen occlusion, and lipid accumulation in the aortic root. Nine perturbed serum metabolites were significantly restored along with the relative abundance of microbiota at the family and genus levels but not at the phylum level. Gut microbiome improvement was strongly negatively correlated with improved metabolite levels. BHD treatment effectively slows the progression of atherosclerosis by regulating altered intestinal microbiota and perturbed metabolites.PMID:38780293 | DOI:10.4103/ejpi.EJPI-D-23-00031

mSystems. 2024 May 23:e0021424. doi: 10.1128/msystems.00214-24. Online ahead of print.ABSTRACTThe gut microbiota contributes to skeletal muscle energy metabolism and is an indirect factor affecting meat quality. However, the role of specific gut microbes in energy metabolism and fiber size of skeletal muscle in chickens remains largely unknown. In this study, we first performed cecal microbiota transplantation from Chinese indigenous Jingyuan chickens (JY) to Arbor Acres chickens (AA), to determine the effects of microbiota on skeletal muscle fiber and energy metabolism. Then, we used metagenomics, gas chromatography, and metabolomics analysis to identify functional microbes. Finally, we validated the role of these functional microbes in regulating the fiber size via glucose metabolism in the skeletal muscle of chickens through feeding experiments. The results showed that the skeletal muscle characteristics of AA after microbiota transplantation tended to be consistent with that of JY, as the fiber diameter was significantly increased, and glucose metabolism level was significantly enhanced in the pectoralis muscle. L. plantarum, L. ingluviei, L. salivarius, and their mixture could increase the production of the microbial metabolites protoporphyrin IX and short-chain fatty acids, therefore increasing the expression levels of genes related to the oxidative fiber type (MyHC SM and MyHC FRM), mitochondrial function (Tfam and CoxVa), and glucose metabolism (PFK, PK, PDH, IDH, and SDH), thereby increasing the fiber diameter and density. These three Lactobacillus species could be promising probiotics to improve the meat quality of chicken.IMPORTANCEThis study revealed that the L. plantarum, L. ingluviei, and L. salivarius could enhance the production of protoporphyrin IX and short-chain fatty acids in the cecum of chickens, improving glucose metabolism, and finally cause the increase in fiber diameter and density of skeletal muscle. These three microbes could be potential probiotic candidates to regulate glucose metabolism in skeletal muscle to improve the meat quality of chicken in broiler production.PMID:38780275 | DOI:10.1128/msystems.00214-24

mSystems. 2024 May 23:e0025724. doi: 10.1128/msystems.00257-24. Online ahead of print.ABSTRACTAutism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition characterized by social communication deficiencies and stereotypic behaviors influenced by hereditary and/or environmental risk factors. There are currently no approved medications for treating the core symptoms of ASD. Human fecal microbiota transplantation (FMT) has emerged as a potential intervention to improve autistic symptoms, but the underlying mechanisms are not fully understood. In this study, we evaluated the effects of human-derived FMT on behavioral and multi-omics profiles of the BTBR mice, an established model for ASD. FMT effectively alleviated the social deficits in the BTBR mice and normalized their distinct plasma metabolic profile, notably reducing the elevated long-chain acylcarnitines. Integrative analysis linked these phenotypic changes to specific Bacteroides species and vitamin B6 metabolism. Indeed, vitamin B6 supplementation improved the social behaviors in BTBR mice. Collectively, these findings shed new light on the interplay between FMT and vitamin B6 metabolism and revealed a potential mechanism underlying the therapeutic role of FMT in ASD.IMPORTANCEAccumulating evidence supports the beneficial effects of human fecal microbiota transplantation (FMT) on symptoms associated with autism spectrum disorder (ASD). However, the precise mechanism by which FMT induces a shift in the microbiota and leads to symptom improvement remains incompletely understood. This study integrated data from colon-content metagenomics, colon-content metabolomics, and plasma metabolomics to investigate the effects of FMT treatment on the BTBR mouse model for ASD. The analysis linked the amelioration of social deficits following FMT treatment to the restoration of mitochondrial function and the modulation of vitamin B6 metabolism. Bacterial species and compounds with beneficial roles in vitamin B6 metabolism and mitochondrial function may further contribute to improving FMT products and designing novel therapies for ASD treatment.PMID:38780265 | DOI:10.1128/msystems.00257-24

J Agric Food Chem. 2024 May 23. doi: 10.1021/acs.jafc.4c02186. Online ahead of print.ABSTRACTThe monofloral honey from Schefflera octophylla (Lour.) Harms (MH-Sco) are of high economic value due to their rarity and potential medicinal benefits. However, the limited investigations on the relationship of phytogenic components between the plant S. octophylla (P-Sco) and MH-Sco have an impact on MH-Sco authentication. Herein, the tentative phytogenic markers of MH-Sco were screened by comparing the metabolites of MH-Sco obtained by ultrahigh-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF-MS/MS)-based untargeted metabolomics with the identified phytogenic chemicals from P-Sco. Combined with the mass and NMR spectral information, 3α-hydroxylup-20(29)-ene-23,28-dioic acid (HLEDA) was finally identified as the phytogenic marker of MH-Sco. A targeted ultrahigh-performance liquid chromatography-triple quadrupole mass spectrometry (UHPLC-QqQ-MS/MS)-based method was established and validated based on the purified monomer standard to measure HLEDA levels in honey samples. HLEDA determined in MH-Sco was with the content from 0.303 to 0.440 mg/kg, while HLEDA was absent in honey samples from other botanical origins, indicating the reliability of HLEDA as a chemical marker in MH-Sco authentication. This study provides the theoretical basis and industry guidance for honey quality control for commercial consumption.PMID:38779705 | DOI:10.1021/acs.jafc.4c02186

Food Front. 2024 Mar;5(2):259-266. doi: 10.1002/fft2.323. Epub 2024 Jan 29.ABSTRACTFamilial adenomatous polyposis (FAP) patients face an almost certain 100% risk of developing colorectal cancer, necessitating prophylactic colectomy to prevent disease progression. A crucial goal is to hinder this progression. In a recent clinical trial involving 14 FAP patients, half received 60 g of black raspberry (BRB) powder orally and BRB suppositories at bedtime, while the other half received only BRB suppositories at bedtime over 9 months. This intervention led to a notable reduction in rectal polyps for 11 patients, although 3 showed no response. In this study, we delved into the metabolic changes induced by BRBs in the same patient cohort. Employing mass spectrometry-based non-targeted metabolomics, we analyzed pre- and post-BRB urinary and plasma samples from the 11 responders. The results showed significant alterations in 23 urinary and 6 plasma metabolites, influencing various pathways including polyamine, glutathione metabolism, the tricarboxylic acid cycle, inositol metabolism, and benzoate production. BRBs notably elevated levels of several metabolites associated with these pathways, suggesting a potential mechanism through which BRBs facilitate rectal polyp regression in FAP patients by modulating multiple metabolic pathways. Notably, metabolites derived from BRB polyphenols were significantly increased post-BRB intervention, emphasizing the potential therapeutic value of BRBs in FAP management.PMID:38779578 | PMC:PMC11107796 | DOI:10.1002/fft2.323

Front Cell Infect Microbiol. 2024 May 8;14:1366192. doi: 10.3389/fcimb.2024.1366192. eCollection 2024.ABSTRACTBACKGROUND: Ulcerative colitis (UC) is a multifactorial chronic inflammatory bowel disease (IBD) that affects the large intestine with superficial mucosal inflammation. A dysbiotic gut microbial profile has been associated with UC. Our study aimed to characterize the UC gut bacterial, fungal, and metabolic fingerprints by omic approaches.METHODS: The 16S rRNA- and ITS2-based metataxonomics and gas chromatography-mass spectrometry/solid phase microextraction (GC-MS/SPME) metabolomic analysis were performed on stool samples of 53 UC patients and 37 healthy subjects (CTRL). Univariate and multivariate approaches were applied to separated and integrated omic data, to define microbiota, mycobiota, and metabolic signatures in UC. The interaction between gut bacteria and fungi was investigated by network analysis.RESULTS: In the UC cohort, we reported the increase of Streptococcus, Bifidobacterium, Enterobacteriaceae, TM7-3, Granulicatella, Peptostreptococcus, Lactobacillus, Veillonella, Enterococcus, Peptoniphilus, Gemellaceae, and phenylethyl alcohol; and we also reported the decrease of Akkermansia; Ruminococcaceae; Ruminococcus; Gemmiger; Methanobrevibacter; Oscillospira; Coprococus; Christensenellaceae; Clavispora; Vishniacozyma; Quambalaria; hexadecane; cyclopentadecane; 5-hepten-2-ol, 6 methyl; 3-carene; caryophyllene; p-Cresol; 2-butenal; indole, 3-methyl-; 6-methyl-3,5-heptadiene-2-one; 5-octadecene; and 5-hepten-2-one, 6 methyl. The integration of the multi-omic data confirmed the presence of a distinctive bacterial, fungal, and metabolic fingerprint in UC gut microbiota. Moreover, the network analysis highlighted bacterial and fungal synergistic and/or divergent interkingdom interactions.CONCLUSION: In this study, we identified intestinal bacterial, fungal, and metabolic UC-associated biomarkers. Furthermore, evidence on the relationships between bacterial and fungal ecosystems provides a comprehensive perspective on intestinal dysbiosis and ecological interactions between microorganisms in the framework of UC.PMID:38779566 | PMC:PMC11109417 | DOI:10.3389/fcimb.2024.1366192

Front Cell Infect Microbiol. 2024 May 8;14:1359576. doi: 10.3389/fcimb.2024.1359576. eCollection 2024.ABSTRACTWhile enteric pathogens have been widely studied for their roles in causing foodborne infection, their impacts on the gut microbial community have yet to be fully characterized. Previous work has identified notable changes in the gut microbiome related to pathogen invasion, both taxonomically and genetically. Characterization of the metabolic landscape during and after enteric infection, however, has not been explored. Consequently, we investigated the metabolome of paired stools recovered from 60 patients (cases) during and after recovery from enteric bacterial infections (follow-ups). Shotgun metagenomics was applied to predict functional microbial pathways combined with untargeted metametabolomics classified by Liquid Chromatography Mass Spectrometry. Notably, cases had a greater overall metabolic capacity with significantly higher pathway richness and evenness relative to the follow-ups (p<0.05). Metabolic pathways related to central carbon metabolism, amino acid metabolism, and lipid and fatty acid biosynthesis were more highly represented in cases and distinct signatures for menaquinone production were detected. By contrast, the follow-up samples had a more diverse metabolic landscape with enhanced richness of polar metabolites (p<0.0001) and significantly greater richness, evenness, and overall diversity of nonpolar metabolites (p<0.0001). Although many metabolites could not be annotated with existing databases, a marked increase in certain clusters of metabolites was observed in the follow-up samples when compared to the case samples and vice versa. These findings suggest the importance of key metabolites in gut health and recovery and enhance understanding of metabolic fluctuations during enteric infections.PMID:38779558 | PMC:PMC11109446 | DOI:10.3389/fcimb.2024.1359576

iScience. 2024 Apr 26;27(6):109816. doi: 10.1016/j.isci.2024.109816. eCollection 2024 Jun 21.ABSTRACTMuscle fiber type composition (% slow-twitch and % fast-twitch fibers) is associated with metabolism, with increased slow-twitch fibers alleviating metabolic disorders. Previously, we reported that dietary fish oil intake induced a muscle fiber-type transition in a slower direction in rats. The aim of this study was to determine the functionality of eicosapentaenoic acid (EPA), a unique fatty acid in fish oil, to skeletal muscle fiber type and metabolism in rats. Here, we showed that dietary EPA promotes whole-body oxidative metabolism and improves muscle function by increasing proportion of slow-twitch type 1 fibers in rats. Transcriptomic and metabolomic analyses revealed that EPA supplementation activated the peroxisome proliferator-activated receptor δ (PPARδ) and AMP-activated protein kinase (AMPK) pathways in L6 myotube cultures, which potentially increasing slow-twitch fiber share. This highlights the role of EPA as an exercise-mimetic dietary component that improves metabolism and muscle function, with potential benefits for health and athletic performance.PMID:38779480 | PMC:PMC11108975 | DOI:10.1016/j.isci.2024.109816

Biofilm. 2024 May 11;7:100201. doi: 10.1016/j.bioflm.2024.100201. eCollection 2024 Jun.ABSTRACTListeria monocytogenes is one of the leading causative agents of foodborne disease outbreaks worldwide. Herein, the antibiofilm effect and mechanism of Mannosylerythritol Lipid-A against L. monocytogenes EGD-e is reported for the first time. MEL-A effectively attenuated biofilm formation while reducing the viability and motility of bacteria within the biofilm in the early stage, and influenced bacterial adhesion by affecting the secretion of extracellular polysaccharides and eDNA. RT-qPCR revealed that MEL-A significantly suppressed the expression of genes involved in flagellar movement and virulence. Untargeted LC-MS metabolomics indicated that MEL-A affected the fluidity and permeability of cell membranes by significantly upregulating unsaturated fatty acids, lipids and glycoside metabolites, and affected protein biosynthesis, nucleotide metabolism and DNA synthesis and repair by significantly downregulating amino acid metabolism and nucleic acid metabolism. These pathways may constitute the key targets of biofilm formation inhibition by MEL-A. Furthermore, MEL-A showed good removal effects on mature biofilms under different temperatures, different materials and milk. Our data indicated that MEL-A could be used as a novel antibiofilm agent to improve food safety. Our study provides new insights into the possible inhibitory mechanism of MEL-A and the response of L. monocytogenes EGD-e to MEL-A.PMID:38779407 | PMC:PMC11108854 | DOI:10.1016/j.bioflm.2024.100201

Front Physiol. 2024 May 8;15:1421654. doi: 10.3389/fphys.2024.1421654. eCollection 2024.NO ABSTRACTPMID:38779320 | PMC:PMC11109390 | DOI:10.3389/fphys.2024.1421654