PubMed

Sci Rep. 2024 Apr 4;14(1):7933. doi: 10.1038/s41598-024-55925-6.ABSTRACTThis study investigates the effects of a 12-week brisk walking exercise regimen on motor function improvements in elderly women. Twenty-six elderly women, aged 84.2 ± 3.2 years, participated in a 12-week brisk walking exercise program. Fitness assessments and blood biomarker analyses (including CHO, HDLC, LDLC, TC) were conducted pre- and post-intervention. Additionally, targeted metabolomics was employed to measure short-chain fatty acids, amino acids, and vitamin metabolites. The intervention led to significant enhancements in participants' flexibility (p < 0.05), lower limb muscle strength (p < 0.01), and cardiorespiratory endurance (p < 0.01), while muscle mass showed no significant changes. Fifteen significant differential metabolites were identified (VIP > 1.0, FC > 1.2 or < 0.8, and p < 0.05), with arginine, ornithine, aspartic acid, glutamine, phenylalanine, tyrosine, and pantothenic acid playing key roles across seven metabolic pathways. A 12-week brisk walking exercise program significantly enhanced flexibility, lower limb muscle strength, and cardiorespiratory endurance among elderly women. These improvements did not extend to muscle mass or upper limb muscle strength. The observed enhancement in exercise capacity may be attributed to improved regulation of neurotransmitters.PMID:38575643 | DOI:10.1038/s41598-024-55925-6

J Nat Prod. 2024 Apr 4. doi: 10.1021/acs.jnatprod.3c01233. Online ahead of print.ABSTRACTWe report on the use of nitric oxide-mediated transcriptional activation (NOMETA) as an innovative means to detect and access new classes of microbial natural products encoded within silent biosynthetic gene clusters. A small library of termite nest- and mangrove-derived fungi and actinomyces was subjected to cultivation profiling using a miniaturized 24-well format approach (MATRIX) in the presence and absence of nitric oxide, with the resulting metabolomes subjected to comparative chemical analysis using UPLC-DAD and GNPS molecular networking. This strategy prompted study of Talaromyces sp. CMB-TN6F and Coccidiodes sp. CMB-TN39F, leading to discovery of the triterpene glycoside pullenvalenes A-D (1-4), featuring an unprecedented triterpene carbon skeleton and rare 6-O-methyl-N-acetyl-d-glucosaminyl glycoside residues. Structure elucidation of 1-4 was achieved by a combination of detailed spectroscopic analysis, chemical degradation, derivatization and synthesis, and biosynthetic considerations.PMID:38575516 | DOI:10.1021/acs.jnatprod.3c01233

Vector Borne Zoonotic Dis. 2024 Apr 4. doi: 10.1089/vbz.2023.0059. Online ahead of print.ABSTRACTBackground: Clonorchiasis remains a serious public health problem. However, the molecular mechanism underlying clonorchiasis remains largely unknown. Amino acid (AA) metabolism plays key roles in protein synthesis and energy sources, and improves immunity in pathological conditions. Therefore, this study aimed to explore the AA profiles of spleen in clonorchiasis and speculate the interaction between the host and parasite. Methods: Here targeted ultrahigh performance liquid chromatography multiple reaction monitoring mass spectrometry was applied to discover the AA profiles in spleen of rats infected with Clonorchis sinensis. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis (KEGG) was performed to characterize the dysregulated metabolic pathways. Results: Pathway analysis revealed that phenylalanine, tyrosine, and tryptophan biosynthesis and β-alanine metabolism were significantly altered in clonorchiasis. There were no significant correlations between 14 significant differential AAs and interleukin (IL)-1β. Although arginine, asparagine, histidine, lysine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine were positively correlated with IL-6, IL-10, tumor necrosis factor (TNF)-α as well as aspartate aminotransferase and alanine aminotransferase; β-alanine and 4-hydroxyproline were negatively correlated with IL-6, IL-10, and TNF-α. Conclusion: This study reveals the dysregulation of AA metabolism in clonorchiasis and provides a useful insight of metabolic mechanisms at the molecular level.PMID:38574253 | DOI:10.1089/vbz.2023.0059

J Nat Prod. 2024 Apr 4. doi: 10.1021/acs.jnatprod.3c00843. Online ahead of print.ABSTRACTNine bacteria were isolated from the episphere of Suaeda maritima (L.) Dumort. Among them, the bacterial strain YSL2 displayed the highest antimicrobial activity on agar plates and exhibited significant novelty compared with other bacteria based on 16S rRNA analysis. Consequently, Nocardiopsis maritima YSL2T was subjected to phenotypic characterization and whole-genome sequencing. Phylogenetic analysis revealed its close association with Nocardiopsis aegyptia SNG49T. Furthermore, genomic analysis of strain YSL2T revealed the presence of various gene clusters, indicating its potential for producing antimicrobial secondary metabolites. Upon cultivation on a large scale, maritiamides A and B (1 and 2) were isolated and characterized as cyclic hexapeptides based on nuclear magnetic resonance, ultraviolet, infrared, and mass spectrometric data. The absolute configurations of the amino acid residues in the maritiamides were determined through chiral derivatization, utilizing FDAA and GITC. Maritiamides 1 and 2 exhibited promising antibacterial activities against Staphylococcus epidermidis and weakly inhibited the growth of Escherichia coli and Pseudomonas fluorescens.PMID:38573876 | DOI:10.1021/acs.jnatprod.3c00843

Elife. 2024 Apr 4;12:RP87674. doi: 10.7554/eLife.87674.ABSTRACTMetabolic pathways are plastic and rapidly change in response to stress or perturbation. Current metabolic profiling techniques require lysis of many cells, complicating the tracking of metabolic changes over time after stress in rare cells such as hematopoietic stem cells (HSCs). Here, we aimed to identify the key metabolic enzymes that define differences in glycolytic metabolism between steady-state and stress conditions in murine HSCs and elucidate their regulatory mechanisms. Through quantitative 13C metabolic flux analysis of glucose metabolism using high-sensitivity glucose tracing and mathematical modeling, we found that HSCs activate the glycolytic rate-limiting enzyme phosphofructokinase (PFK) during proliferation and oxidative phosphorylation (OXPHOS) inhibition. Real-time measurement of ATP levels in single HSCs demonstrated that proliferative stress or OXPHOS inhibition led to accelerated glycolysis via increased activity of PFKFB3, the enzyme regulating an allosteric PFK activator, within seconds to meet ATP requirements. Furthermore, varying stresses differentially activated PFKFB3 via PRMT1-dependent methylation during proliferative stress and via AMPK-dependent phosphorylation during OXPHOS inhibition. Overexpression of Pfkfb3 induced HSC proliferation and promoted differentiated cell production, whereas inhibition or loss of Pfkfb3 suppressed them. This study reveals the flexible and multilayered regulation of HSC glycolytic metabolism to sustain hematopoiesis under stress and provides techniques to better understand the physiological metabolism of rare hematopoietic cells.PMID:38573813 | DOI:10.7554/eLife.87674

Alzheimers Dement. 2024 Apr 4. doi: 10.1002/alz.13794. Online ahead of print.ABSTRACTINTRODUCTION: Emerging evidence links changes in the gut microbiome to late-onset Alzheimer's disease (LOAD), necessitating examination of AD mouse models with consideration of the microbiome.METHODS: We used shotgun metagenomics and untargeted metabolomics to study the human amyloid beta knock-in (hAβ-KI) murine model for LOAD compared to both wild-type (WT) mice and a model for early-onset AD (3xTg-AD).RESULTS: Eighteen-month female (but not male) hAβ-KI microbiomes were distinct from WT microbiomes, with AD genotype accounting for 18% of the variance by permutational multivariate analysis of variance (PERMANOVA). Metabolomic diversity differences were observed in females, however no individual metabolites were differentially abundant. hAβ-KI mice microbiomes were distinguishable from 3xTg-AD animals (81% accuracy by random forest modeling), with separation primarily driven by Romboutsia ilealis and Turicibacter species. Microbiomes were highly cage specific, with cage assignment accounting for more than 40% of the PERMANOVA variance between the groups.DISCUSSION: These findings highlight a sex-dependent variation in the microbiomes of hAβ-KI mice and underscore the importance of considering the microbiome when designing studies that use murine models for AD.HIGHLIGHTS: Microbial diversity and the abundance of several species differed in human amyloid beta knock-in (hAβ-KI) females but not males. Correlations to Alzheimer's disease (AD) genotype were stronger for the microbiome than the metabolome. Microbiomes from hAβ-KI mice were distinct from 3xTg-AD mice. Cage effects accounted for most of the variance in the microbiome and metabolome.PMID:38572865 | DOI:10.1002/alz.13794

J Proteome Res. 2024 Apr 4. doi: 10.1021/acs.jproteome.3c00781. Online ahead of print.ABSTRACTThe plant surveillance system confers specificity to disease and immune states by activating distinct molecular pathways linked to cellular functionality. The extracellular matrix (ECM), a preformed passive barrier, is dynamically remodeled at sites of interaction with pathogenic microbes. Stem rot, caused by Macrophomina phaseolina, adversely affects fiber production in jute. However, how wall related susceptibility affects the ECM proteome and metabolome remains undetermined in bast fiber crops. Here, stem rot responsive quantitative temporal ECM proteome and metabolome were developed in jute upon M. phaseolina infection. Morpho-histological examination revealed that leaf shredding was accompanied by reactive oxygen species production in patho-stressed jute. Electron microscopy showed disease progression and ECM architecture remodeling due to necrosis in the later phase of fungal attack. Using isobaric tags for relative and absolute quantitative proteomics and liquid chromatography-tandem mass spectrometry, we identified 415 disease-responsive proteins involved in wall integrity, acidification, proteostasis, hydration, and redox homeostasis. The disease-related correlation network identified functional hubs centered on α-galactosidase, pectinesterase, and thaumatin. Gas chromatography-mass spectrometry analysis pointed toward enrichment of disease-responsive metabolites associated with the glutathione pathway, TCA cycle, and cutin, suberin, and wax metabolism. Data demonstrated that wall-degrading enzymes, structural carbohydrates, and calcium signaling govern rot responsive wall-susceptibility. Proteomics data were deposited in Pride (PXD046937; PXD046939).PMID:38572503 | DOI:10.1021/acs.jproteome.3c00781

RSC Adv. 2024 Apr 3;14(15):10799-10813. doi: 10.1039/d4ra00100a. eCollection 2024 Mar 26.ABSTRACTPiper nigrum L. (black and white peppercorn) is one of the most common culinary spices used worldwide. The current study aims to dissect pepper metabolome using 1H-NMR targeting of its major primary and secondary metabolites. Eighteen metabolites were identified with piperine detected in black and white pepper at 20.2 and 23.9 μg mg-1, respectively. Aroma profiling using HS-SPME coupled to GC-MS analysis and in the context of autoclave treatment led to the detection of a total of 52 volatiles with an abundance of β-caryophyllene at 82% and 59% in black and white pepper, respectively. Autoclaving of black and white pepper revealed improvement of pepper aroma as manifested by an increase in oxygenated compounds' level. In vitro remote antimicrobial activity against food-borne Gram-positive and Gram-negative bacteria revealed the highest activity against P. aeruginosa (VP-MIC 16.4 and 12.9 mg mL-1) and a direct effect against Enterobacter cloacae at ca. 11.6 mg mL-1 for both white and black pepper.PMID:38572341 | PMC:PMC10989240 | DOI:10.1039/d4ra00100a

Mol Genet Metab Rep. 2024 Mar 29;39:101078. doi: 10.1016/j.ymgmr.2024.101078. eCollection 2024 Jun.ABSTRACTLeigh syndrome is a severe progressive mitochondrial disorder mainly affecting children under the age of 5 years. It is caused by pathogenic variants in any one of more than 75 known genes in the nuclear or mitochondrial genomes. A 19-week-old male infant presented with lactic acidosis and encephalopathy following a 2-week history of irritability, neuroregression and poor weight gain. He was hypotonic with pathological reflexes, impaired vision, and nystagmus. Brain MRI showed extensive bilateral symmetrical T2 hyperintense lesions in basal ganglia, thalami, and brainstem. Metabolic workup showed elevated serum alanine, and heavy lactic aciduria with increased ketones, fumarate, malate, and alpha-ketoglutarate as well as reduced succinate on urine organic acid analysis. Lactic acidemia persisted, with only a marginally elevated lactate:pyruvate ratio (16.46, ref. 0-10). He demised at age 7 months due to respiratory failure. Exome sequencing followed by virtual gene panel analysis for pyruvate metabolism and mitochondrial defects could not identify any nuclear cause for Leigh syndrome. Mitochondrial DNA (mtDNA) genome sequencing revealed 88% heteroplasmy for a novel variant, NC_012920.1(MT-ND6):m.14430A>C p.(Trp82Gly), in blood DNA. This variant was absent from the unaffected mother's blood, fibroblast, and urine DNA, and detected at a level of 5% in her muscle DNA. Mitochondrial respiratory chain analysis revealed markedly reduced mitochondrial complex I activity in patient fibroblasts (34% of parent and control cells), and reduced NADH-linked respirometry (less than half of parental and control cells), while complex II driven respirometry remained intact. The combined clinical, genetic, and biochemical findings suggest that the novel MT-ND6 variant is the likely cause of Leigh syndrome in this patient. The mitochondrial ND6 protein is a subunit of complex I. An interesting finding was the absence of a significantly elevated lactate:pyruvate ratio in the presence of severe lactatemia, which directed initial diagnostic efforts towards excluding a pyruvate metabolism defect. This case highlights the value of a multidisciplinary approach and complete genetic workup to diagnosing mitochondrial disorders in South African patients.PMID:38571879 | PMC:PMC10987324 | DOI:10.1016/j.ymgmr.2024.101078

Saudi Pharm J. 2024 May;32(5):102045. doi: 10.1016/j.jsps.2024.102045. Epub 2024 Mar 23.ABSTRACTThe ergosterol from mushrooms has gained significant ethnopharmacological importance in various cultures, including China, Japan, and Europe. This compound has been found to possess immune-boosting and anti-inflammatory properties, making it useful in the treatment of immune disorders. In this study, we focused on investigating the potential anticancer properties of ergosterol isolated from the edible mushroom Leucocalocybe mongolica in breast cancer cell lines. The ergosterol was purified and identified using advanced analytical techniques such as ESI-MS and NMR. We conducted cell proliferation assays on 4 T1 breast cancer cells to assess the cytotoxic effects of ergosterol. Furthermore, we analyzed the transcription levels of BAX, caspase-7, BCL-2, STAT-3, and PARP proteins using real-time PCR and Western blot analysis. Additionally, we employed non-targeted ultra-high-performance liquid chromatography and high-resolution mass spectrometry (UPLC-MS/MS) to study the potential mechanisms underlying the anticancer effects of ergosterol at the metabolomics level. The results demonstrated a significant reduction in cell viability and the induction of apoptosis upon treatment with ergosterol, especially at higher concentrations (P < 0.05). Moreover, ergosterol affected the expression of cancer-related genes, upregulating pro-apoptotic proteins such as BAX, caspase-7, and PARP, while downregulating the anti-apoptotic proteins BCL-2 and STAT-3 (P < 0.05). Western blot analysis confirmed these findings and provided further evidence of ergosterol's role in inducing apoptosis. Metabolomics analysis revealed substantial changes in pathways related to amino acid, antioxidant, and carbohydrate metabolism. In conclusion, our study demonstrates that ergosterol exhibits anticancer effects by inducing apoptosis and modulating metabolic pathways in breast cancer cells.PMID:38571766 | PMC:PMC10988126 | DOI:10.1016/j.jsps.2024.102045

Front Plant Sci. 2024 Mar 20;15:1349401. doi: 10.3389/fpls.2024.1349401. eCollection 2024.ABSTRACTClimate change poses a major threat to global food security, significantly reducing crop yields as cause of abiotic stresses, and for boosting the spread of new and old pathogens and pests. Sustainable crop management as a route to mitigation poses the challenge of recruiting an array of solutions and tools for the new aims. Among these, the deployment of positive interactions between the micro-biotic components of agroecosystems and plants can play a highly significant role, as part of the agro-ecological revolution. Endophytic microorganisms have emerged as a promising solution to tackle this challenge. Among these, Arbuscular Mycorrhizal Fungi (AMF) and endophytic bacteria and fungi have demonstrated their potential to alleviate abiotic stresses such as drought and heat stress, as well as the impacts of biotic stresses. They can enhance crop yields in a sustainable way also by other mechanisms, such as improving the nutrient uptake, or by direct effects on plant physiology. In this review we summarize and update on the main types of endophytes, we highlight several studies that demonstrate their efficacy in improving sustainable yields and explore possible avenues for implementing crop-microbiota interactions. The mechanisms underlying these interactions are highly complex and require a comprehensive understanding. For this reason, omic technologies such as genomics, transcriptomics, proteomics, and metabolomics have been employed to unravel, by a higher level of information, the complex network of interactions between plants and microorganisms. Therefore, we also discuss the various omic approaches and techniques that have been used so far to study plant-endophyte interactions.PMID:38571718 | PMC:PMC10988515 | DOI:10.3389/fpls.2024.1349401

Heliyon. 2024 Mar 20;10(7):e28464. doi: 10.1016/j.heliyon.2024.e28464. eCollection 2024 Apr 15.ABSTRACTMetschnikowia persimmonesis, a novel endophytic yeast strain isolated from Diospyros kaki calyx, possesses strong antimicrobial activity. We investigated its potential use as an environmentally safe food biocontrol agent through genomics, transcriptomics, and metabolomics. Secondary metabolites were isolated from M. persimmonesis, followed by chemical structure elucidation, PUL gene cluster identification, and RNA sequencing. Pulcherrimin was isolated using 2 M NaOH, its structure was confirmed, and the yield was quantified. Biocontrol efficacy of M. persimmonesis on persimmon fruits and calyx was evaluated by assessing lesion diameter and disease incidence. Following compounds were isolated from M. persimmonesis co-culture with Botrytis cinerea and Fusarium oxysporum: fusaric acid, benzoic acid, benzeneacetic acid, 4-hydroxybenzeneacetic acid, 4-(-2-hydoxyethyl)-benzoic acid, cyclo (Leu-Leu), benzenemethanol, 4-hydroxy-benzaldehide, 2-hydroxy-4-methoxy-benzoic acid, 4-hydroxy-benzoic acid, lumichrome, heptadecanoic acid, and nonadecanoic acid. Exposing M. persimmonesis to different growth media conditions (with or without sugar) resulted in the isolation of five compounds: Tyrosol, Cyclo (Pro-Val), cyclo(L-Pro-L-Tyr), cyclo(Leu-Leu), and cyclo(l-tyrosilylicine). Differentially expressed gene analysis revealed 3264 genes that were significantly expressed (fold change ≥2 and p-value ≤0.05) during M. persimmonesis growth in different media, of which only 270 (8.27%) showed altered expression in all sample combinations with Luria-Bertani Agar as control. Minimal media with ferric ions and tween-80 triggered the most gene expression changes, with the highest levels of PUL gene expression and pulcherrimin yield (262.166 mg/L) among all media treatments. M. persimmonesis also produced a higher amount of pulcherrimin (209.733 mg/L) than Metschnikowia pulcherrima (152.8 mg/L). M. persimmonesis inhibited the growth of Fusarium oxysporum in persimmon fruit and calyx. Toxicity evaluation of M. persimmonesis extracts showed no harmful effects on the liver and mitochondria of zebrafish, and no potential risk of cardiotoxicity in hERG-HEK293 cell lines. Thus, M. persimmonesis can be commercialized as a potent and safe biocontrol agent for preserving food products.PMID:38571591 | PMC:PMC10988027 | DOI:10.1016/j.heliyon.2024.e28464

Heliyon. 2024 Mar 22;10(7):e27940. doi: 10.1016/j.heliyon.2024.e27940. eCollection 2024 Apr 15.ABSTRACTOBJECTIVES: This study aimed to conduct a non-targeted metabolomic analysis of plasma from patients with spinal tuberculosis (STB) to systematically elucidate the metabolomic alterations associated with STB, and explore potential diagnostic biomarkers for STB.METHODS: From January 2020 to January 2022, 30 patients with spinal tuberculosis (STBs) clinically diagnosed at the General Hospital of Ningxia Medical University and 30 age- and sex-matched healthy controls (HCs) were selected for this study. Using ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) based metabolomics, we analyzed the metabolic profiles of 60 plasma samples. Statistical analyses, pathway enrichment, and receiver operating characteristic (ROC) analyses were performed to screen and evaluate potential diagnostic biomarkers.RESULTS: Metabolomic profiling revealed distinct alterations between the STBs and HCs cohorts. A total of 1635 differential metabolites were screened, functionally clustered, and annotated. The results showed that the differential metabolites were enriched in sphingolipid metabolism, tuberculosis, cutin, suberine and wax biosynthesis, beta-alanine metabolism, methane metabolism, and other pathways. Through the random forest algorithm, LysoPE (18:1(11Z)/0:0), 8-Demethyl-8-formylriboflavin 5'-phosphate, Glutaminyl-Gamma-glutamate, (2R)-O-Phospho-3-sulfolactate, and LysoPE (P-16:0/0:0) were determined to have high independent diagnostic value.CONCLUSIONS: STBs exhibited significantly altered metabolite profiles compared with HCs. Here, we provide a global metabolomic profile and identify potential diagnostic biomarkers of STB. Five potential independent diagnostic biomarkers with high diagnostic value were screened. This study provides novel insights into the pathogenesis, diagnosis, and treatment strategies of STB.PMID:38571585 | PMC:PMC10987919 | DOI:10.1016/j.heliyon.2024.e27940

Cancer Discov. 2024 Apr 4;14(4):658-662. doi: 10.1158/2159-8290.CD-23-1484.ABSTRACTPathogenic shifts in the gut microbiota are part of the "ecological" alterations that accompany tumor progression and compromise immunosurveillance. The future management of health and disease including cancer will rely on the diagnosis of such shifts and their therapeutic correction by general or personalized strategies, hence restoring metaorganismal homeostasis.PMID:38571436 | DOI:10.1158/2159-8290.CD-23-1484

Proteomics Clin Appl. 2024 Apr 3:e2300136. doi: 10.1002/prca.202300136. Online ahead of print.ABSTRACTBACKGROUND: Breast cancer (BC) is the second leading cause of cancer-related deaths among women, primarily due to metastases to other organs rather than the primary tumor.METHODS: In this study, a comprehensive analysis of plasma proteomics and metabolomics was conducted on a cohort of 51 BC patients. Potential biomarkers were screened by the Least Absolute Shrinkage and Selection Operator (LASSO) regression and Random Forest algorithm. Additionally, enzyme-linked immunosorbent assay (ELISA) kits and untargeted metabolomics were utilized to validate the prognostic biomarkers in an independent cohort.RESULTS: In the study, extracellular matrix (ECM)-related functional enrichments were observed to be enriched in BC cases with bone metastases. Proteins dysregulated in retinol metabolism in liver metastases and leukocyte transendothelial migration in lung metastases were also identified. Machine learning models identified specific biomarker panels for each metastasis type, achieving high diagnostic accuracy with area under the curve (AUC) of 0.955 for bone, 0.941 for liver, and 0.989 for lung metastases.CONCLUSIONS: For bone metastasis, biomarkers such as leucyl-tryptophan, LysoPC(P-16:0/0:0), FN1, and HSPG2 have been validated. dUDP, LPE(18:1/0:0), and aspartylphenylalanine have been confirmed for liver metastasis. For lung metastasis, dUDP, testosterone sulfate, and PE(14:0/20:5) have been established.PMID:38571380 | DOI:10.1002/prca.202300136

Am J Clin Nutr. 2024 Apr;119(4):885-895. doi: 10.1016/j.ajcnut.2023.12.027. Epub 2024 Feb 19.ABSTRACTBACKGROUND: Predicting response to exclusive enteral nutrition (EEN) in active Crohn's disease (CD) could lead to therapy personalization and pretreatment optimization.OBJECTIVES: This study aimed to explore the ability of pretreatment parameters to predict fecal calprotectin (FCal) levels at EEN completion in a prospective study in children with CD.METHODS: In children with active CD, clinical parameters, dietary intake, cytokines, inflammation-related blood proteomics, and diet-related metabolites, metabolomics and microbiota in feces, were measured before initiation of 8 wk of EEN. Prediction of FCal levels at EEN completion was performed using machine learning. Data are presented with medians (IQR).RESULTS: Of 37 patients recruited, 15 responded (FCal < 250 μg/g) to EEN (responders) and 22 did not (nonresponders). Clinical and immunological parameters were not associated with response to EEN. Responders had lesser (μmol/g) butyrate [responders: 13.2 (8.63-18.4) compared with nonresponders: 22.3 (12.0-32.0); P = 0.03], acetate [responders: 49.9 (46.4-68.4) compared with nonresponders: 70.4 (57.0-95.5); P = 0.027], phenylacetate [responders: 0.175 (0.013-0.611) compared with nonresponders: 0.943 (0.438-1.35); P = 0.021], and a higher microbiota richness [315 (269-347) compared with nonresponders: 243 (205-297); P = 0.015] in feces than nonresponders. Responders consumed (portions/1000 kcal/d) more confectionery products [responders: 0.55 (0.38-0.72) compared with nonresponders: 0.19 (0.01-0.38); P = 0.045]. A multicomponent model using fecal parameters, dietary data, and clinical and immunological parameters predicted response to EEN with 78% accuracy (sensitivity: 80%; specificity: 77%; positive predictive value: 71%; negative predictive value: 85%). Higher taxon abundance from Ruminococcaceae, Lachnospiraceae, and Bacteroides and phenylacetate, butyrate, and acetate were the most influential variables in predicting lack of response to EEN.CONCLUSIONS: We identify microbial signals and diet-related metabolites in feces, which could comprise targets for pretreatment optimization and personalized nutritional therapy in pediatric CD.PMID:38569785 | DOI:10.1016/j.ajcnut.2023.12.027

Arch Bronconeumol. 2024 Apr;60(4):215-225. doi: 10.1016/j.arbres.2024.02.009. Epub 2024 Feb 19.ABSTRACTSevere bronchiolitis (i.e., bronchiolitis requiring hospitalization) during infancy is a heterogeneous condition associated with a high risk of developing childhood asthma. Yet, the exact mechanisms underlying the bronchiolitis-asthma link remain uncertain. Birth cohort studies have reported this association at the population level, including only small groups of patients with a history of bronchiolitis, and have attempted to identify the underlying biological mechanisms. Although this evidence has provided valuable insights, there are still unanswered questions regarding severe bronchiolitis-asthma pathogenesis. Recently, a few bronchiolitis cohort studies have attempted to answer these questions by applying unbiased analytical approaches to biological data. These cohort studies have identified novel bronchiolitis subtypes (i.e., endotypes) at high risk for asthma development, representing essential and enlightening evidence. For example, one distinct severe respiratory syncytial virus (RSV) bronchiolitis endotype is characterized by the presence of Moraxella catarrhalis and Streptococcus pneumoniae, higher levels of type I/II IFN expression, and changes in carbohydrate metabolism in nasal airway samples, and is associated with a high risk for childhood asthma development. Although these findings hold significance for the design of future studies that focus on childhood asthma prevention, they require validation. However, this scoping review puts the above findings into clinical context and emphasizes the significance of future research in this area aiming to offer new bronchiolitis treatments and contribute to asthma prevention.PMID:38569771 | DOI:10.1016/j.arbres.2024.02.009

Cell Host Microbe. 2024 Mar 12:S1931-3128(24)00058-1. doi: 10.1016/j.chom.2024.02.015. Online ahead of print.ABSTRACTMicrobiota assembly in the infant gut is influenced by diet. Breastfeeding and human breastmilk oligosaccharides promote the colonization of beneficial bifidobacteria. Infant formulas are supplemented with bifidobacteria or complex oligosaccharides, notably galacto-oligosaccharides (GOS), to mimic breast milk. To compare microbiota development across feeding modes, this randomized controlled intervention study (German Clinical Trial DRKS00012313) longitudinally sampled infant stool during the first year of life, revealing similar fecal bacterial communities between formula- and breast-fed infants (N = 210) but differences across age. Infant formula containing GOS sustained high levels of bifidobacteria compared with formula containing B. longum and B. breve or placebo. Metabolite and bacterial profiling revealed 24-h oscillations and circadian networks. Rhythmicity in bacterial diversity, specific taxa, and functional pathways increased with age and was strongest following breastfeeding and GOS supplementation. Circadian rhythms in dominant taxa were further maintained ex vivo in a chemostat model. Hence, microbiota rhythmicity develops early in life and is impacted by diet.PMID:38569545 | DOI:10.1016/j.chom.2024.02.015

Cell. 2024 Mar 21:S0092-8674(24)00305-2. doi: 10.1016/j.cell.2024.03.014. Online ahead of print.ABSTRACTAccumulating evidence suggests that cardiovascular disease (CVD) is associated with an altered gut microbiome. Our understanding of the underlying mechanisms has been hindered by lack of matched multi-omic data with diagnostic biomarkers. To comprehensively profile gut microbiome contributions to CVD, we generated stool metagenomics and metabolomics from 1,429 Framingham Heart Study participants. We identified blood lipids and cardiovascular health measurements associated with microbiome and metabolome composition. Integrated analysis revealed microbial pathways implicated in CVD, including flavonoid, γ-butyrobetaine, and cholesterol metabolism. Species from the Oscillibacter genus were associated with decreased fecal and plasma cholesterol levels. Using functional prediction and in vitro characterization of multiple representative human gut Oscillibacter isolates, we uncovered conserved cholesterol-metabolizing capabilities, including glycosylation and dehydrogenation. These findings suggest that cholesterol metabolism is a broad property of phylogenetically diverse Oscillibacter spp., with potential benefits for lipid homeostasis and cardiovascular health.PMID:38569543 | DOI:10.1016/j.cell.2024.03.014

Cell Metab. 2024 Apr 2;36(4):684-701. doi: 10.1016/j.cmet.2024.03.007.ABSTRACTOne of the key modes of microbial metabolism occurring in the gut microbiome is fermentation. This energy-yielding process transforms common macromolecules like polysaccharides and amino acids into a wide variety of chemicals, many of which are relevant to microbe-microbe and microbe-host interactions. Analogous transformations occur during the production of fermented foods, resulting in an abundance of bioactive metabolites. In foods, the products of fermentation can influence food safety and preservation, nutrient availability, and palatability and, once consumed, may impact immune and metabolic status, disease expression, and severity. Human signaling pathways perceive and respond to many of the currently known fermented food metabolites, though expansive chemical novelty remains to be defined. Here we discuss several aspects of fermented food-associated microbes and metabolites, including a condensed history, current understanding of their interactions with hosts and host-resident microbes, connections with commercial probiotics, and opportunities for future research on human health and disease and food sustainability.PMID:38569469 | DOI:10.1016/j.cmet.2024.03.007