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

PubMed

Mid-Level Data Fusion Techniques of LC-MS and HS-GC-MS for Distinguishing Green and Ripe Forsythiae Fructus

Sat, 26/04/2025 - 12:00
Molecules. 2025 Mar 21;30(7):1404. doi: 10.3390/molecules30071404.ABSTRACTForsythia suspensa is a crucial plant resource due to its considerable edible and medicinal value. Its fruit, named Forsythiae Fructus (FF), has been widely used in Traditional Chinese Medicine (TCM). According to the fruit maturity stage, FF is categorized into GFF (green Forsythiae Fructus) and RFF (ripe Forsythiae Fructus). In this study, metabolomics based on UPLC-Q/Orbitrap MS and HS-GC-MS, combined with chemometric methods, was employed to differentiate GFF from RFF and identify potential differential metabolites. Additionally, the mid-level data fusion method was employed to integrate data from both techniques, and the performance of the OPLS-DA model (R2Y = 0.986, Q2 = 0.974) surpassed that of the single HS-GC-MS technique (R2Y = 0.968, Q2 = 0.930). Moreover, using the criteria of VIP > 1 and p-value < 0.05, 30 differential compounds were selected via mid-level data fusion, compared to the initial 61 differential compounds identified by single techniques, effectively reducing data noise and eliminating irrelevant variables. This study provides a comprehensive analysis of volatile and non-volatile compounds in FF, offering valuable insights into quality control and clinical differentiation between GFF and RFF. The findings highlight the potential use of multi-technology metabolomics in the quality control of TCM and offer new perspectives for future research on medicinal plants.PMID:40286068 | DOI:10.3390/molecules30071404

Radioprotective Effects and Mechanisms of One-Year and Seven-Year White Tea Extracts Against <sup>137</sup>Cs Radiation-Induced Cell Damage

Sat, 26/04/2025 - 12:00
Molecules. 2025 Mar 25;30(7):1448. doi: 10.3390/molecules30071448.ABSTRACTIonizing radiation (IR) is widely present in the environment, with 137Cesium (Cs) radiation having particularly severe impacts during nuclear accidents. The objective of our study was to assess the radiation protection or repair effect of one year (WT-1Y) or seven years (WT-7Y) of storage on white teas, as well as to investigate the mechanism of radioprotection. HGC-27 cells exposed to 137Cs γ-rays (30 Gy) exhibited significant changes in cell structure, apoptosis, ROS, LDH, and their expression of p53 and Caspase-3. The results showed that WT-1Y and WT-7Y acted as antioxidants, showed reduced ROS and LDH levels, and had increased CAT and SOD activities as well as cell survival rate. The WT treatments significantly inhibited apoptosis in both the pre- and post-radiation groups, with WT-1 showing stronger effects in pretreatment by reducing LDH, p53, and Caspase-3 levels and enhancing ROS scavenging and enzyme activities. Post-treatment analysis revealed WT-7 had greater effects on cell viability and SOD activity. Overall, both WT-1 and WT-7 mitigated radiation damage, likely by inhibiting the p53/Caspase-3 apoptosis pathway. A Spearman analysis of the differential metabolites in WT-1Y and WT-7Y with cellular radioprotective indicators revealed that metabolites, such as EGC, procyanidin B4, and phenolic acids (abundant in WT-1Y), quercetin-3-glucosylrutinoside, and caffeine (enriched in WT-7Y) contributed to their distinct effects in the pre- and post-treatment of 137Cs γ-rays.PMID:40286032 | DOI:10.3390/molecules30071448

A Targeted Mass Spectrometric Approach to Evaluate the Anti-Inflammatory Activity of the Major Metabolites of <em>Foeniculum vulgare</em> Mill. Waste in Human Bronchial Epithelium

Sat, 26/04/2025 - 12:00
Molecules. 2025 Mar 21;30(7):1407. doi: 10.3390/molecules30071407.ABSTRACTFennel waste is rich in compounds that may have beneficial effects on human health. For this reason, the most abundant metabolites in fennel were isolated as the following: quercetin-3-O-glucoside, quinic acid, 1,5-dicaffeoylquinic acid, kaempferol-3-O-glucuronide, and quercetin-3-O-glucuronide. After inducing inflammation in human bronchial epithelial cells by stimulating them with IL-1β, the cells were treated with the specialized Foeniculum vulgare metabolites at different concentrations to assess their anti-inflammatory effect. Eicosanoids, fatty acids, and sphingolipids were extracted from the cell medium and quantified by UPLC-ESI-QTRAP-MS/MS analysis. The anti-inflammatory activity of the metabolites isolated from fennel waste was demonstrated. They were able to alleviate the inflammatory state in human bronchial epithelium by modulating the metabolic expression of both pro- and anti-inflammatory eicosanoids, fatty acids, and sphingolipids. These findings suggest the potential use of fennel waste in the production of dietary supplements to alleviate the symptoms of chronic inflammatory diseases like asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF), where the continuous use of antiphlogistics may have significant side effects.PMID:40286023 | DOI:10.3390/molecules30071407

Metabolic effects of high-dose glucocorticoid following out-of-hospital cardiac arrest

Sat, 26/04/2025 - 12:00
Intensive Care Med Exp. 2025 Apr 26;13(1):46. doi: 10.1186/s40635-025-00754-8.ABSTRACTBACKGROUND AND AIM: Patients resuscitated after out-of-hospital cardiac arrest (OHCA) face high morbidity and mortality rates, primarily due to ischemia-reperfusion injury, a complex metabolic disorder that triggers a significant systemic inflammatory response. Glucocorticoids mitigate inflammation but also impact the cells beyond the immune response. This study aims to identify glucocorticoid effects on plasma metabolites.METHODS: This explorative sub-study is part of a two-center, blinded, randomized controlled trial (NCT04624776) examining the effects of high-dose glucocorticoid on comatose patients resuscitated from OHCA of presumed cardiac origin. Following resuscitation, patients received 250 mg of methylprednisolone or a placebo in the prehospital setting. Blood samples were collected upon hospital admission and 48 h later. Sixty metabolites were quantified in the plasma using mass spectrometry and compared between groups.RESULTS: In the modified intention-to-treat population, 68 patients received methylprednisolone, and 69 received placebo [median age was 66 years (IQR: 56-74) and 83% were men]. Blood samples were available for 130 patients, 121 (88%) at admission and 117 patients (94% of patients alive) after 48 h. Although a nominal difference was observed at admission, no significant metabolic effects were found after correcting for multiple testing. After 48 h, the placebo group had 83.4% (95% CI 16.9-187.6%) higher prostaglandin E2 and higher levels of linolenic acid and arachidonic acid. The methylprednisolone group had higher levels of tryptophan (47.6%; 95% CI 27.9-70.2%), arginine, and propionylcarnitine (C3).CONCLUSIONS: In this exploratory study, early administration of 250 mg of methylprednisolone after resuscitation appeared to drive sustained metabolic effects over 48 h. Specifically, methylprednisolone led to reductions in ω-6 fatty acids and increases in several amino acids, with a notable rise in tryptophan.PMID:40285920 | DOI:10.1186/s40635-025-00754-8

Unveiling Salt Tolerance Mechanisms in Plants: Integrating the KANMB Machine Learning Model With Metabolomic and Transcriptomic Analysis

Sat, 26/04/2025 - 12:00
Adv Sci (Weinh). 2025 Apr 26:e2417560. doi: 10.1002/advs.202417560. Online ahead of print.ABSTRACTSalt stress presents a substantial threat to cereal crop productivity, especially in coastal agricultural regions where salinity levels are high. Addressing this challenge requires innovative approaches to uncover genetic resources that support molecular breeding of salt-tolerant crops. In this study, a novel machine learning model, KANMB is introduced, designed to analyze integrated multi-omics data from the natural halophyte Spartina alterniflora under various NaCl concentrations. Using KANMB, 226 metabolic biomarkers significantly linked to salt stress responses, grounded in metabolomic and transcriptomic profiles are identified. These biomarkers correlate with metabolic pathways associated with salt tolerance, providing insight into the underlying biochemical mechanisms. A co-expression analysis further highlights the MYB gene SaMYB35 as a pivotal regulator in the flavonoid biosynthesis pathway under salt stress. When overexpressed SaMYB35 in rice (ZH11) grown under high salinity, it triggers the upregulation of key flavonoid biosynthetic genes, elevates flavonoid content, and enhances salt tolerance compared to wild-type plants. The findings from this study offer a valuable genetic toolkit for breeding salt-tolerant cereal varieties and demonstrate the power of machine learning in accelerating biomarker discovery for stress resilience in non-model plant species.PMID:40285579 | DOI:10.1002/advs.202417560

Multiomics Reveal the Effects and Regulatory Mechanism of Naringin on Metabolic Dysfunction-Associated Fatty Liver Disease of Laying Hens

Sat, 26/04/2025 - 12:00
Mol Nutr Food Res. 2025 Apr 26:e70082. doi: 10.1002/mnfr.70082. Online ahead of print.ABSTRACTThis study aimed to utilize aged laying hens as a model to investigate the effects of naringin on the occurrence and progression of metabolic dysfunction-associated fatty liver disease (MAFLD), along with its underlying regulatory mechanisms. A total of 288 aged laying hens, 50-week-old, were divided into four groups: a normal diet (ND) group, and three naringin groups receiving 200 mg/kg (N1), 400 mg/kg (N2), and 600 mg/kg (N3). The experiment lasted for 10 weeks, after which serum, liver, and cecal contents were collected from the hens. Results indicated that dietary naringin supplementation reduced hepatic lipid deposition, lowered blood lipid levels, improved antioxidant capacity, and promoted estradiol secretion. Additionally, 16S rDNA analysis revealed that naringin enhanced microbial diversity in the cecum and regulated the abundance of gut microbes associated with fatty liver. Untargeted metabolomics of blood demonstrated that naringin decreased the concentration of glycerophospholipid and sterol lipid metabolites while increasing levels of pantothenic acids and amino acid metabolites. Furthermore, liver transcriptome analysis indicated that naringin interfered with fatty acid synthesis and transport processes while enhancing fatty acid oxidation. Dietary naringin supplementation can mitigate the occurrence of MAFLD by regulating the gut-liver axis and estrogen signaling, particularly in postmenopausal women.PMID:40285552 | DOI:10.1002/mnfr.70082

Warming Disrupts Plant-Fungal Endophyte Symbiosis More Severely in Leaves Than Roots

Sat, 26/04/2025 - 12:00
Glob Chang Biol. 2025 Apr;31(4):e70207. doi: 10.1111/gcb.70207.ABSTRACTDisruptions to functionally important symbionts with global change will negatively impact plant fitness, with broader consequences for species' abundances, distribution, and community composition. Fungal endophytes that live inside plant leaves and roots could potentially mitigate plant heat stress from global warming. Conversely, disruptions of these symbioses could exacerbate the negative impacts of warming. To better understand the consistency and strength of warming-induced changes to fungal endophytes, we examined fungal leaf and root endophytes in three grassland warming experiments in the US ranging from 2 to 25 years and spanning 2000 km, 12°C of mean annual temperature, and 600 mm of precipitation. We found that experimental warming disrupted symbiosis between plants and fungal endophytes. Colonization of plant tissues by septate fungi decreased in response to warming by 90% in plant leaves and 35% in roots. Warming also reduced fungal diversity and changed community composition in plant leaves, but not roots. The strength, but not direction, of warming effects on fungal endophytes varied by up to 75% among warming experiments. Finally, warming decoupled fungal endophytes from host metabolism by decreasing the correlation between endophyte community and host metabolome dissimilarity. These effects were strongest in the shorter-term experiment, suggesting endophyte-host metabolome function may acclimate to warming over decades. Overall, warming-driven disruption of fungal endophyte community structure and function suggests that this symbiosis may not be a reliable mechanism to promote plant resilience and ameliorate stress responses under global change.PMID:40285541 | DOI:10.1111/gcb.70207

Risk Factors for Chronic Kidney Disease in Patients With Crohn's Disease

Sat, 26/04/2025 - 12:00
Inflamm Bowel Dis. 2025 Apr 25:izaf039. doi: 10.1093/ibd/izaf039. Online ahead of print.ABSTRACTBACKGROUND: Patients with inflammatory bowel diseases (IBD), including Crohn's disease (CD), are at risk of complications, including kidney disease. It is important to identify IBD patients at higher risk of chronic kidney disease (CKD) to improve prevention and treatment. Here, we investigated the clinical and metabolomic characteristics of CD patients who develop CKD.METHODS: We identified adult CD patients with (CD + CKD, n = 87) and selected CD patients without CKD (CD controls) matched by age, race, and gender. We collected data on demographic characteristics (age, smoking status, ethnicity, gender), IBD characteristics (diagnosis, Montreal classification, medication use, IBD-related surgeries, perianal disease), and kidney-related factors (primary sclerosing cholangitis, end-stage renal disease, hypertension, diabetes, organ transplantation, and nephrolithiasis). Univariate and multivariate analyses were conducted and odds ratios were calculated to identify risk factors for CKD. Serum samples were collected for untargeted metabolomic analysis.RESULTS: Chronic kidney disease was far more common in CD patients than UC patients. Crohn's disease patients with kidney stones had a 10-fold higher risk of developing CKD than those without kidney stones. Crohn's disease patients with more than 2 IBD-related surgeries had a 7.3-fold higher risk of developing CKD than those who had not undergone surgery. There was no relationship between the number of biologics used or mesalamine use and the risk of CKD. The serum of CD + CKD patients had elevated levels of pro-inflammatory metabolites and those linked to kidney injury.CONCLUSIONS: We recommend regular kidney function monitoring and ensuring proper hydration to prevent or manage potential kidney-related complications in CD patients. Patients with resections and kidney stones are particularly vulnerable.PMID:40285478 | DOI:10.1093/ibd/izaf039

Insights Into the Role of Leuconostoc Mesenteroides SB1075 Fermentation in Enhancing the Shelf-Life of Soy Yogurt

Sat, 26/04/2025 - 12:00
J Food Sci. 2025 Apr;90(4):e70220. doi: 10.1111/1750-3841.70220.ABSTRACTFermented foods with extended shelf life, free from synthetic preservatives, offer significant commercial and health advantages. With increasing consumer demand for plant-based alternatives, soy yogurt has gained substantial market interest. However, improving its shelf-life at ambient temperature without compromising quality remains challenging. This study investigates the application of Leuconostoc mesenteroides SB1075, a promising probiotic strain isolated from yellow-cultivar soybean seeds of Manipur (India), as a biopreservative starter culture for soy yogurt fermentation. Unlike conventional dairy-origin lactic acid bacteria, L. mesenteroides SB1075 demonstrated superior adaptability to soy fermentation. The resulting soy yogurt exhibited an impressive shelf-life of 40 days at room temperature (25°C), significantly outperforming the control (spontaneous fermentation without starter, <5 days) while maintaining its organoleptic and nutritional qualities. Sensory evaluation with a hedonic scale of 10 indicated that flavor, aroma, and taste consistently received a score >6, while color, firmness, consistency, syneresis, and overall acceptance were rated >7. Microscopic analysis, including atomic force and scanning electron microscopy, revealed that the flocculation behavior of L. mesenteroides SB1075 effectively inhibited spoilage microbes, thereby extending product stability. Genomic analysis highlighted its heterofermentative and biopreservative potential, while time-course metabolomics identified bioactive compounds, such as monobactam, organic acids, and neomycin, from the 5th day of storage. This study provides key insights into biopreservation strategies for plant-based fermented foods, offering a valuable alternative to chemical preservatives. The findings support the commercial development of naturally preserved soy yogurt, enhancing the sustainability and market expansion of plant-based dairy alternatives. PRACTICAL APPLICATION: Our research addresses a critical need in the food industry: prolonging the shelf life of soy yogurt without relying on preservatives, which is achieved using a plant-derived probiotic bacterium L. mesenteroides SB1075. The findings outlined in this manuscript propose an innovative and sustainable approach to improving the quality and shelf life of soy yogurt, meeting the increasing demand for vegan, healthier, and preservative-free food choices.PMID:40285465 | DOI:10.1111/1750-3841.70220

Effects of Chicken Protein Hydrolysate as a Protein Source to Partially Replace Chicken Meal on Gut Health, Gut Microbial Structure, and Metabolite Composition in Cats

Sat, 26/04/2025 - 12:00
Vet Sci. 2025 Apr 21;12(4):388. doi: 10.3390/vetsci12040388.ABSTRACTProtein hydrolysates positively affect intestinal function in both humans and animals, but their impact on gut health and the gut microbial profile in cats has not been thoroughly investigated. In this study, a total of 30 adult cats were randomly assigned to one of three dietary treatments for a 60-day feeding trial. The three dietary treatments were as follows: (1) basal diet (CON), (2) diet containing 15% powdered chicken protein hydrolysate (HP15%), and (3) diet containing 15% liquid chicken protein hydrolysate (HL15%). Compared to the CON group, the HP15% group had a decreased calprotectin levels and fecal gases emissions (p < 0.05). A higher abundance of Bacteroidota, Veillonellaceae, and Bacteroidaceae, while a lower abundance of Firmicutes was showed in the HL15% group than that in the CON group (p < 0.05). At the genus level, compared with the CON group, an increased abundance of Bacteroides spp. and Bifidobacterium spp. was showed, whereas a reduced abundance of Alloprevotella spp. was presented in the HP15% and HL15% groups (p < 0.05). The metabolomic analysis revealed 1405 distinct metabolites between the HP15% and CON groups (p < 0.05, VIP-pred-OPLS-DA > 1), and the level of cholic acid decreased while the level of isodeoxycholic acid increased in the HP15% group (p < 0.05). The metabolomic analysis revealed 1910 distinct metabolites between the HL15% and CON groups (p < 0.05, VIP-pred-OPLS-DA > 1), and the levels of 4-coumaryl alcohol and enterolactone increased in the HL15% group (p < 0.05). In summary, this study suggested that partially replacing chicken meat with chicken protein hydrolysate in the diet of cats helps regulate the gut microbial community and metabolite profile and improves intestinal health.PMID:40284890 | DOI:10.3390/vetsci12040388

Analysis of Fecal Microbiome and Metabolome Changes in Goats When Consuming a Lower-Protein Diet with Varying Energy Levels

Sat, 26/04/2025 - 12:00
Microorganisms. 2025 Apr 18;13(4):941. doi: 10.3390/microorganisms13040941.ABSTRACTThe objective of this study was to evaluate the effect of fecal bacterial community and metabolomics in goats when consuming a lower-protein diet with different energy levels. Eight healthy Leizhou goats, with 11 ± 0.78 kg of body weight, were selected and housed individually in cages. The animals were randomly allocated to a lower-protein diet that varied with four metabolites energy levels (7.01, 8.33, 9.66, and 10.98 MJ/kg DM) in a replicated 4 × 4 Latin square design. Notably, energy-dependent microbial restructuring was observed at both phylum and genus levels. At the phylum level, the relative abundances of Firmicutes and Spirochaetote increased linearly, whereas the Bacteroidota and Patescibacteria decreased linearly with increasing dietary energy levels (p < 0.05). The relative abundances of Verrucomicrobiota increased quadratically, whereas others decreased quadratically with increasing dietary energy levels (p < 0.05). At the genus level, a total of 316 bacteria were identified in the 32 fecal samples. The relative abundances of Christensenellaceae_R-7_group, unclassified_f__Lachnospiraceae, Ruminococcus, norank_o__Clostridia_UCG-014, Treponema, [Eubacterium]_siraeum_group, and [Eubacterium]_ruminantium_group increased linearly, whereas the Oscillospiraceae_UCG-005, norank_f__[Eubacterium]_coprostanoligenes_group, Prevotellaceae_UCG-004, unclassified_c__Clostridia, norank_f__Ruminococcaceae, unclassified_f__ Oscillospiraceae, and others decreased linearly with an increasing dietary energy levels (p < 0.05). In addition, the metabolomic analysis of feces showed that there are many differential metabolites in goats when consuming a lower-protein diet with different energy levels; for example, lipid metabolism and amino acid metabolic pathways were increased in MLE, MHE, and HE groups compared to the LE group. In conclusion, this study provides further information regarding the effects on fecal bacterial community composition and metabolites in goats when consuming a lower-protein diet with different energy levels.PMID:40284777 | DOI:10.3390/microorganisms13040941

Microbiomic and Metabolomic Insights into the Roles of Hydrolysable Versus Condensed Tannins on the Growth Performance, Nutrient Digestion, and Rumen Fermentation in Liaoning Cashmere Goats

Sat, 26/04/2025 - 12:00
Microorganisms. 2025 Apr 17;13(4):933. doi: 10.3390/microorganisms13040933.ABSTRACTThis study was conducted to compare the effects of hydrolysable versus condensed tannins on growth performance, nutrient digestion, and rumen fermentation in goats. A total of 27 Liaoning cashmere goats with similar initial body weights were randomly distributed into three groups: a basal diet, a basal diet +0.5% tannic acid (hydrolysable tannin, HT), or a basal diet +0.5% quebracho tannin (condensed tannin, CT), respectively. Compared to the control group, HT showed a decreased (p < 0.05) feed intake, while CT showed an increased (p < 0.05) feed intake and body weight gain. Digestibility of dry matter, crude protein, neutral detergent fiber, and acid detergent fiber did not differ (p > 0.05) among groups. The HT group showed lower pH and acetic acid concentration in the rumen (p < 0.05), while the CT group showed a decrease (p < 0.05) in the abundances of Verrucomicrobia and Methanobrevibacter. Supplementation of CT decreased (p < 0.05) the levels of dihydrouracil, xanthosine, alpha-D-mannose, and L-tryptophan, while HT increased (p < 0.05) these metabolites. In conclusion, this study suggested that responses of ruminal microbiota and metabolite profiles to the type of tannins varied, and CT displayed a more positive effect on the growth performance of goats than HT when supplemented at the same level in the diets.PMID:40284769 | DOI:10.3390/microorganisms13040933

Effects of Seawater from Different Sea Areas on Abalone Gastrointestinal Microorganisms and Metabolites

Sat, 26/04/2025 - 12:00
Microorganisms. 2025 Apr 16;13(4):915. doi: 10.3390/microorganisms13040915.ABSTRACTSignificant regional variations in seawater characteristics (temperature, salinity, pH, nutrients) exist across marine environments, yet their impacts on abalone gastrointestinal microbiota and metabolites remain underexplored. This study investigated seawater nutrient and pH interactions on abalone gut ecosystems through comparative analysis of three marine regions (Pingtan (PT), Xiapu (XP), Lianjiang (LJ)). Seawater characteristics revealed distinct patterns: LJ exhibited the lowest total phosphorus (TP: 0.12 mg/L), total nitrogen (TN: 2.8 mg/L), NH3-N (0.05 mg/L) but the highest salinity (32.1‱) and lowest pH (7.82), while PT/XP showed elevated nutrients (TP: 0.24-0.28 mg/L; TN: 4.2-4.5 mg/L). Microbial diversity peaked in LJ samples (Shannon index: 5.8) with dominant genera Psychrilyobacter (12.4%) and Bradyrhizobium (9.1%), contrasting with PT's Mycoplasma-enriched communities (18.7%) and XP's Vibrio-dominant profiles (14.3%). Metabolomic analysis identified 127 differential metabolites (VIP > 1.5, p < 0.05), predominantly lipids (38%) and organic acids (27%), with pathway enrichment in sulfur relay (q = 4.2 × 10-5) and tryptophan metabolism (q = 1.8 × 10-4). Stomach-specific metabolites correlated with fatty acid degradation (e.g., inosine diphosphate, r = -0.82 with vibrionimonas) and glutathione metabolism (methionine vs. mycoplasma, r = -0.79). Critically, pH showed negative correlations with beneficial Psychrilyobacter (oleamide: r = -0.68) and positive associations with pathogenic Vibrio (trigonelline: r = 0.72). Elevated NH3-N (>0.15 mg/L) and TP (>0.25 mg/L) promoted Mycoplasma proliferation (R2 = 0.89) alongside cytotoxic metabolite accumulation. These findings demonstrate that higher pH (>8.0) and nutrient overload disrupt microbial symbiosis, favoring pathogens over beneficial taxa.PMID:40284752 | DOI:10.3390/microorganisms13040915

Proposing Bromo-Epi-Androsterone (BEA) for Stiff Person Syndrome (SPS)

Sat, 26/04/2025 - 12:00
Microorganisms. 2025 Apr 5;13(4):824. doi: 10.3390/microorganisms13040824.ABSTRACTSPS is characterized by progressive spasmodic muscular rigidity. SPS is thought to be an autoimmune disease with a prominent feature of antibodies against glutamic acid decarboxylase (GAD). GAD is responsible for the enzymatic conversion of glutamic acid (glutamate) into the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Reduced GABA activity leads to increased excitability in the central nervous system, resulting in muscle rigidity and spasms characteristic of SPS. While SPS is rare, anti-GAD antibodies seen in SPS are also seen in the much more common autoimmune disease, type 1 diabetes (T1D). There is evolving research showing that the anti-GAD antibodies of T1D are produced in response to the presence of mycobacterial heat shock protein 65 (mHSP65), and the mHSP65 is produced in response to an occult infection by a bacterium, Mycobacterium avium subspecies Paratuberculosis (MAP). Humans are broadly exposed to MAP in food, water, and air. There are linear and conformational similarities between the epitopes of GAD and mHSP65. This article proposes that MAP is also an infectious trigger for SPS. Dehydroepiandrosterone (DHEA) is a principal component of the steroid metabolome; it plateaus in young adults and then steadily declines. Bromo-epi-androsterone (BEA) is a potent synthetic analog of DHEA; unlike DHEA, it is non-androgenic, non-anabolic, and an effective modulator of immune dysregulation. BEA is also an anti-infective agent and has been shown to benefit mycobacterial infections, including tuberculosis and leprosy. With the immune stabilizing capacity of BEA as well as its anti-mycobacterial properties, there is reason to believe that a randomized clinical trial with BEA may be beneficial for SPS.PMID:40284660 | DOI:10.3390/microorganisms13040824

Differences in Microbial Community Structure Determine the Functional Specialization of Gut Segments of <em>Ligia exotica</em>

Sat, 26/04/2025 - 12:00
Microorganisms. 2025 Apr 2;13(4):808. doi: 10.3390/microorganisms13040808.ABSTRACTLigia feed on seashore algae and remove organic debris from the coastal zone, thereby playing an important role in the intertidal ecosystem. Nevertheless, the specific roles of distinct gut segments in the gut transit remain unclear. We collected and identified Ligia exotica specimens in the coast of Aoshanwei, Qingdao, Shandong Province, and analyzed their foreguts and hindguts for 16S rRNA, metagenomics, metabolomics, and proteomics. The concentrations of common metabolites, NO3--N and NH4+-N, and the contents of C and N were measured. The gut transit decreased the abundances of the dominant phyla Cyanobacteria but increased Proteobacteria, Firmicutes, and Actinobacteria, and Planctomycetes and Bacteroidetes remained relatively constant. The foregut gut microbiota is involved in the carbohydrates and amino acids metabolism, as well as the decomposition of polysaccharides. The hindgut gut microbiota performs a variety of functions, including carbohydrate and amino acid metabolism, fermentation, cell motility, intracellular transport, secretion, and vesicular translocation, and the decomposition of polysaccharides, disaccharides, and oligosaccharides. The results of omics analyses and molecular experiments demonstrated that the metabolic processes involving amino acids and carbohydrates are more active in the foregut, whereas the fermentation, absorption, and assimilation processes are more active in the hindgut. Taken together, the differences in microbial community structure determine the functional specialization of different gut segments, i.e., the foregut appears to be the primary site for digesting food, while the hindgut further processes and absorbs nutrients and then excretes them.PMID:40284644 | DOI:10.3390/microorganisms13040808

The Role of Membrane-Bound Extracellular Vesicles During Co-Stimulation and Conjugation in the Ciliate <em>Tetrahymena thermophila</em>

Sat, 26/04/2025 - 12:00
Microorganisms. 2025 Apr 1;13(4):803. doi: 10.3390/microorganisms13040803.ABSTRACTDuring sexual reproduction, the freshwater ciliate Tetrahymena thermophila sheds membrane-bound vesicles into the extracellular environment (cEMVs: ciliary extracellular micro-vesicles). We provide evidence that 100 nm vesicles shed from the cilia of starved cells promote mating between cells of complementary mating types. A proteomic analysis revealed that these EMVs are decorated with mating-type proteins expressed from the MAT locus, proteins that define a cell's sex (one of seven). Once the mating junction is established between cells, smaller 60 nm vesicles (junction vesicles) appear within the extracellular gap that separates mating partners. Junction vesicles (jEMVs) may play a role in remodeling the mating junction through which gametic pronuclei are exchanged. Evidence is presented demonstrating that cells must be able to internalize extracellular signals via some form of endocytosis in order to trigger conjugation. Finally, an evolutionarily conserved fusogen (Hap2) implicated in pore formation also appears necessary for jEMV processing. This system offers an excellent opportunity for studies on ectosome shedding, intercellular signaling and shed vesicle uptake by macro-pinocytosis, as they relate to sexual reproduction in the ciliate Tetrahymena thermophila.PMID:40284639 | DOI:10.3390/microorganisms13040803

Gastrointestinal Microorganisms and Blood Metabolites in Holstein Calves with Different Heat Stress Responses in the Same Hot Environment

Sat, 26/04/2025 - 12:00
Microorganisms. 2025 Mar 31;13(4):801. doi: 10.3390/microorganisms13040801.ABSTRACTThis study investigated differences in gastrointestinal microbiota and blood metabolomes in calves with different heat stress (HS) responses in the same hot environment. Ten high (H) and ten low (L) HS response preweaning Holstein calves were selected based on their heat stress level (respiratory rate and rectal temperature), jugular vein blood samples and ruminal and fecal samples were collected. Notable variations were observed in the serum levels of heat shock protein 70 (HSP-70) and IL-2 between the two calf groups (p < 0.05). In group H, rumen and fecal microbiota synergism was disrupted. In the H group, the host metabolome exhibited enrichment in pyruvate metabolism and the tricarboxylic acid cycle (p < 0.05). Key factors bridging the relationship between gastrointestinal microbiota and serum metabolites included the rumen bacterial genus g__Ruminococcus, serum HSP-70, malic acid, and fumaric acid. These hubs served as potential indicators for distinguishing the response to heat stress in calves (p < 0.05). In conclusion, this study identified the relationship between gastrointestinal microbiota characteristics and different HS responses of the host, thus providing evidence and new directions for future studies aimed at understanding HS in individual calves (gut microbiota-host interactions).PMID:40284637 | DOI:10.3390/microorganisms13040801

Eco-Friendly Algicidal Potential of <em>Zanthoxylum bungeanum</em> Leaf Extracts: Extraction Optimization and Impact on Algal Growth

Sat, 26/04/2025 - 12:00
Microorganisms. 2025 Mar 27;13(4):760. doi: 10.3390/microorganisms13040760.ABSTRACTZanthoxylum bungeanum leaves were regarded as a waste byproduct for a long period of time, yet their functional components presented potential as novel antimicrobial agents. However, their effectiveness in controlling algal blooms remains unexplored. In this study, the inhibition effect of Z. bungeanum leaf extracts on algal blooms was firstly demonstrated, and the flavonoid profiles of the leaf extract were identified using non-targeted metabolomics analysis. Then, response surface methodology was performed for extraction to further evaluate the feasibility of industrial application. Specifically, the effects of extracts on the cell density, photosynthetic efficiency, and antioxidant activity of Tetrodesmus obliquus was investigated. The results showed that the extraction yield of flavonoids from Z. bungeanum leaves reached 6.85% under the optimized conditions of an ultrasonic power of 600 W, an LSR of 20:1 mL/g, an ethanol concentration of 77.5%, an ultrasonic duration of 18 min, and an ultrasonic temperature of 80 °C, which significantly decreased the Fv/Fm and PIabs values by 54.60% and 98.22%, respectively, after exposure of T. obliquus to 40.0 mg/L Z. bungeanum leaf extract for 66 h. Meanwhile, treatment with Z. bungeanum leaf extract at a dose of 40.0 mg/L generated T-AOC values that were 4.0 times higher than the control without the addition of Z. bungeanum leaf extracts. These results suggest that Z. bungeanum leaf extracts could be used in the development of potentially effective biological algicides. Our study provides data to support the development of algicides and realizes the resource application of Z. bungeanum leaf waste, achieving a synergistic outcome of both economic and ecological benefits.PMID:40284597 | DOI:10.3390/microorganisms13040760

Role of Gut Microbiota and Metabolomics in Predicting Response to Vedolizumab in Inflammatory Bowel Disease: A Systematic Review

Sat, 26/04/2025 - 12:00
Pharmaceutics. 2025 Apr 6;17(4):476. doi: 10.3390/pharmaceutics17040476.ABSTRACTBackground: This review explores the impact of gut microbiota profiles in predicting the response to anti-integrin biologic therapy, particularly vedolizumab, in inflammatory bowel disease (IBD) patients. IBD, encompassing Crohn's disease and ulcerative colitis, is a chronic inflammatory condition with a growing prevalence linked to industrialization and lifestyle changes. Disruption in the gut microbiota balance, characterized by reduced diversity and altered short-chain fatty acid (SCFA) production, is associated with IBD and its symptoms. Current pharmacological treatments target healing and remission, with vedolizumab offering a gut-selective treatment approach. Methods: A search of the literature was performed on the relationship between anti-integrin treatment and the microbiome profile in IBD. Articles were examined from the PubMed, Medline, Cochrane, and Web of Science databases. Results: This review identified five human studies investigating the relationship between gut microbiome composition, SCFAs, and response to vedolizumab, revealing an increased abundance of beneficial bacteria and levels of SCFAs like butyrate in remission cases. Despite promising findings, the small sample sizes and limited scope of the existing studies highlight the need for larger, comprehensive research. Conclusions: This review underscores the potential of gut microbiome and metabolite profiling as non-invasive biomarkers for IBD severity and treatment outcomes, advocating for personalized therapeutic strategies to enhance efficacy. The insights gained could lead to novel diagnostic and treatment modalities, although further validation is necessary to fully understand the intricate connections between gut microbiota and IBD prognosis.PMID:40284471 | DOI:10.3390/pharmaceutics17040476

Selective Influence of Hemp Fiber Ingestion on Post-Exercise Gut Permeability: A Metabolomics-Based Analysis

Sat, 26/04/2025 - 12:00
Nutrients. 2025 Apr 19;17(8):1384. doi: 10.3390/nu17081384.ABSTRACTObjectives: This study investigated the effects of 2-week ingestion of hemp fiber (high and low doses) versus placebo bars on gut permeability and plasma metabolite shifts during recovery from 2.25 h intensive cycling. Hemp hull powder is a rich source of two bioactive compounds, N-trans-caffeoyl tyramine (NCT) and N-trans-feruloyl tyramine (NFT), with potential gut health benefits. Methods: The study participants included 23 male and female cyclists. A three-arm randomized, placebo-controlled, double-blind, crossover design was used with two 2-week supplementation periods and 2-week washout periods. Supplement bars provided 20, 5, or 0 g/d of hemp hull powder. Participants engaged in an intensive 2.25 h cycling bout at the end of each of the three supplementation periods. Five blood samples were collected before and after supplementation (overnight fasted state), and at 0 h-, 1.5 h-, and 3 h-post-exercise. Five-hour urine samples were collected pre-supplementation and post-2.25 h cycling after ingesting a sugar solution containing 5 g of lactulose, 100 mg of 13C mannitol, and 1.9 g of mannitol in 450 mL of water. An increase in the post-exercise lactulose/13C mannitol ratio (L:13CM) was used as the primary indicator of altered gut permeability. Other outcome measures included muscle damage biomarkers (serum creatine kinase, myoglobin), serum cortisol, complete blood cell counts, and shifts in plasma metabolites using untargeted metabolomics. Results: No trial differences were found for L:13CM, cortisol, blood cell counts, and muscle damage biomarkers. Orthogonal partial least-squares discriminant analysis (OPLSDA) showed distinct trial differences when comparing high- and low-dose hemp fiber compared to placebo supplementation (R2Y = 0.987 and 0.995, respectively). Variable Importance in Projection (VIP) scores identified several relevant metabolites, including 3-hydroxy-4-methoxybenzoic acid (VIP = 1.9), serotonin (VIP = 1.5), 5-hydroxytryptophan (VIP = 1.4), and 4-methoxycinnamic acid (VIP = 1.4). Mummichog analysis showed significant effects of hemp fiber intake on multiple metabolic pathways, including alpha-linolenic acid, porphyrin, sphingolipid, arginine and proline, tryptophan, and primary bile acid metabolism. Conclusions: Hemp fiber intake during a 2-week supplementation period did not have a significant effect on post-exercise gut permeability in cyclists (2.25 h cycling bout) using urine sugar data. On the contrary, untargeted metabolomics showed that the combination of consuming nutrient-rich hemp fiber bars and exercising for 135 min increased levels of beneficial metabolites, including those derived from the gut in healthy cyclists.PMID:40284247 | DOI:10.3390/nu17081384

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