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

Development of a multi-epitope vaccine candidate to combat SARS-CoV-2 and dengue virus co-infection through an immunoinformatic approach

Thu, 13/03/2025 - 11:00
Front Immunol. 2025 Feb 26;16:1442101. doi: 10.3389/fimmu.2025.1442101. eCollection 2025.ABSTRACTBACKGROUND: Although the SARS-CoV-2 and dengue viruses seriously endanger human health, there is presently no vaccine that can stop a person from contracting both viruses at the same time. In this study, four antigens from SARS-CoV-2 and dengue virus were tested for immunogenicity, antigenicity, allergenicity, and toxicity and chosen to predict dominant T- and B-cell epitopes.METHODS: For designing a multi-epitope vaccine, the sequences were retrieved, and using bioinformatics and immunoinformatics, the physicochemical and immunological properties, as well as secondary structures, of the vaccine were predicted and studied. Additionally, the three-dimensional structure was estimated, improved upon, and confirmed using bioinformatics methods before being docked with TLR-2 and TLR-4. Eight helper T-cell lymphocyte (HTL) epitopes, ten cytotoxic T-cell lymphocyte (CTL) epitopes, nine B-cell epitopes, and TLR agonists were used to create a new multi-epitope vaccine. Furthermore, according to the immunological stimulation hypothesis, the vaccine could stimulate T and B cells to create large quantities of Th1 cytokines and antibodies.RESULTS: The study indicates that the developed vaccine is a favorable vaccine candidate with antigenicity, immunogenicity, non-toxicity, and non-allergenicity properties. The vaccine construct was made up of 460 amino acids, had an MW of 49391.51 Da, a theoretical pI of 9.86, and the formula C2203H3433N643O618S18, a lipid index of 39.84, a GRAVY of -0.473, an aliphatic index of 63.80, and an instability index of 39.84, which classifies the protein to be stable.CONCLUSION: The acquired data showed that both vaccine designs had a considerable chance of preventing the co-infection of SARS-CoV-2 and dengue virus and that they demonstrate good results following in-silico testing. Furthermore, the vaccine may be an effective strategy in preventing SARS-CoV-2 and dengue since it can cause noticeably high levels of Th1 cytokines and antibodies.PMID:40079004 | PMC:PMC11897530 | DOI:10.3389/fimmu.2025.1442101

Diagnosis of Primary Trimethylaminuria in an Affected Patient With a Rare Genotype in Sub-Saharan Africa

Thu, 13/03/2025 - 11:00
JIMD Rep. 2025 Mar 12;66(2):e70005. doi: 10.1002/jmd2.70005. eCollection 2025 Mar.ABSTRACTPrimary trimethylaminuria (TMAU) is characterized by systemic accumulation of trimethylamine (TMA) due to the deficient activity of flavin-containing monooxygenase 3 (FMO3). The disorder does not have detrimental pathophysiological consequences, but patients develop psychological symptoms due to the emotionally debilitating bodily odor defined as decaying fish that affects their quality of life. Here, we illustrate the utility of a diagnostic workup on an adolescent with primary TMAU, including biochemical and genetic investigations that confirm the diagnosis. A direct substrate (TMA) loading protocol was used, followed by the collection of urine samples at predetermined intervals. The conversion of TMA to trimethylamine oxide (TMAO), monitored by 1H-NMR spectrometry, showed a compromised FMO3 metabolic capacity at baseline, becoming more pronounced after loading commenced. The eight coding exons of the FMO3 gene were Sanger sequenced, revealing a homozygous missense variant, c.23T>C (p.Ile8Thr), as well as two known homozygous variants, c.472G>A (p.Glu158Lys) and c.923A>G (pGlu308Gly), associated with no to mild presentation of TMAU. The advantage of direct substrate-to-product monitoring is the elimination of alternative contributors to the odor that would result in the diagnosis of secondary TMAU. The combined functional and genetic approach provided adequate evidence to describe the first primary TMAU patient reported in sub-Saharan Africa with a genotype not yet described in a homozygous state. Our findings motivate a comprehensive biochemical and genetic approach to discriminate between primary and secondary TMAU. Subsequently, this targeted approach can provide advice on therapeutic management for optimal emotional well-being.PMID:40078825 | PMC:PMC11897904 | DOI:10.1002/jmd2.70005

A premature termination codon mutation in the onion <em>AcCER2</em> gene is associated with both glossy leaves and thrip resistance

Thu, 13/03/2025 - 11:00
Hortic Res. 2025 Jan 14;12(4):uhaf006. doi: 10.1093/hr/uhaf006. eCollection 2025 Apr.ABSTRACTPlant epicuticular waxes (EW) play a critical role in defending against biotic and abiotic stresses. Notably, onions (Allium cepa L.) present a distinctive case where the mutant with defect in leaf and stalk EW showed resistance to thrips compared with the wild type with integral EW. We identified a premature stop codon mutation in the AcCER2 gene, an ortholog of CER2 gene in Arabidopsis thaliana that has been proved essential for the biosynthesis of very long-chain fatty acids (VLCFAs), in the onions with glossy leaf and stalks in our experiments. The data hinted at the possibility that this mutation might impede the elongation process of VLCFAs from C28 to C32, thereby hindering the production of 16-hentriacontanone, a primary constituent of onion EW. Transcriptomic analysis revealed substantial alterations in expression of genes in the pathways related not only to lipid synthesis and transport but also to signal transduction and cell wall modification in glossy mutants. Meanwhile, metabolomic profiling indicates a remarkable increase in flavonoid accumulation and a significant reduction in soluble sugar content in glossy mutants. These findings suggested that the enhanced resistance of glossy mutants to thrips might be a consequence of multiple physiological changes, and our integrated multiomics analysis highlighting the regulatory role of AcCER2 in these processes. Our study has yielded valuable insights into the biosynthesis of onion EW and has provided an initial hypothesis for the mechanisms underlying thrip resistance. These findings hold significant promise for the breeding programs of thrip-resistant onion.PMID:40078716 | PMC:PMC11896967 | DOI:10.1093/hr/uhaf006

Mapping the landscape of vitamin D in cancer studies: a systematic global investigation

Thu, 13/03/2025 - 11:00
J Diabetes Metab Disord. 2025 Mar 10;24(1):78. doi: 10.1007/s40200-025-01594-9. eCollection 2025 Jun.ABSTRACTPURPOSE: This comprehensive study examines the multifaceted relationship between vitamin D and cancer, synthesizing key scientific advancements and global research trends to guide future investigations and address critical gaps in the field.METHODS: Publications on vitamin D and cancer were retrieved from Scopus up to November 2024. English-language original and review articles were analyzed using Excel, VOSviewer, and Scimago Graphica, focusing on publication trends, citation impacts, and research themes.RESULTS: A total of 11,442 publications (80.01% original articles, 19.98% reviews; 51.24% open access) were analyzed. The United States of America led in publications (38.3%) and citations (56.2%), followed by China (7.7%) and the United Kingdom (7.2%) in output, and the United Kingdom (10.6%) and Germany (6.4%) in citations. Countries with the highest citations per document were Belgium (103.4), Slovenia (87.9), and Puerto Rico (76.6). The most frequently studied cancers in relation to vitamin D were breast, colorectal, prostate, skin, lung, ovarian, pancreatic, gastric, hepatocellular, thyroid, leukemia, multiple myeloma, bladder, lymphoma, osteosarcoma, cervical, endometrial, and glioblastoma, respectively. Cluster analysis revealed key patterns related to vitamin D: Calcitriol's chemopreventive role in breast, prostate, and colorectal cancers, dietary vitamin D for its involvement in ovarian cancer, vitamin D for regulation of cancer-related hypercalcemia, vitamin D deficiency links to inflammation-obesity-cancer risk, VDR polymorphisms affecting outcomes in lung and colorectal cancers, and vitamin D's photoprotective effects on skin malignancies, and vitamin D in ulcerative colitis-related cancer. The most cited articles emphasized optimal vitamin D levels and cancer prevention.CONCLUSION: This study highlights the extensive research on vitamin D and its complex links to cancer, emphasizing future prospects with a focus on precision medicine approaches, including targeted supplementation and genomic analyses, to better address individual variability in cancer prevention and treatment.PMID:40078705 | PMC:PMC11893971 | DOI:10.1007/s40200-025-01594-9

Integrated transcriptome and metabolome analyses reveals the mechanisms of function loss of Lr29 leaf rust resistance gene at high temperatures in wheat

Thu, 13/03/2025 - 11:00
Front Plant Sci. 2025 Feb 26;16:1537921. doi: 10.3389/fpls.2025.1537921. eCollection 2025.ABSTRACTLeaf rust (LR) is one of the most common diseases of wheat. The resistance gene Lr29 provides wide resistance to LR, but loses its function under high temperatures. Despite the importance of this gene, the mechanism of resistance is unclear. In this study we investigated the resistance mechanism of the Lr29 gene to LR at the seedling stage, as well as the reasons behind the loss of gene function at high temperatures by using integrated transcriptome and metabolome analyses. Results suggests that the pathways of reactive oxygen species (ROS), which could be due to expression of genes including LOX (lipoxygenase), APX (ascorbate peroxidase) and GST (glutathione S-transferase), play a key role in the resistance of Lr29 to LR, furthermore flavonoids, such as epicatechin, cosmosiin, apiin, vitexin and rutin, were identified as the key metabolites linked to Lr29 resistance. We also found that, at high temperatures, Lr29 downregulated the genes and metabolites associated with glycolysis and the tricarboxylic acid (TCA) cycle, while genes and metabolites related to the shikimic acid pathway were upregulated. This study might provide a valuable theoretical foundation for the cloning of the Lr29 gene, the analysis of its disease resistance mechanism, and the understanding of how temperature affects gene function.PMID:40078637 | PMC:PMC11897511 | DOI:10.3389/fpls.2025.1537921

Clinicopathological and molecular features of HR <sup>+</sup> /HER2 <sup>-</sup> breast cancer patients with distinct endocrine resistance patterns

Thu, 13/03/2025 - 11:00
Chin J Cancer Res. 2025 Jan 30;37(1):48-65. doi: 10.21147/j.issn.1000-9604.2025.01.04.ABSTRACTOBJECTIVE: Recurrence continues to be a pivotal challenge among hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancers. In the international consensus guidelines, HR+/HER2- breast cancer relapse patterns are divided into three distinct types: primary resistant, secondary resistant, and endocrine sensitive. However, owing to the lack of cohorts with treatment and follow-up data, the heterogeneity among different recurrence patterns remains uncharted. Current treatments still lack precision.METHODS: This analysis included data from a large-scale multiomics study of a HR+/HER2- breast cancer cohort (n=314). Through the analysis of transcriptomics (n=312), proteomics (n=124), whole-exome sequencing (n=290), metabolomics (n=217), and digital pathology (n=228) data, we explored distinctive molecular features and identified putative therapeutic targets for patients experiencing recurrence.RESULTS: We explored distinct clinicopathological characteristics, biological heterogeneity, and potential therapeutic strategies for recurrence. Based on a shared relapse signature, we stratified patients into high- and low-recurrence-risk groups. Patients with different relapse patterns presented unique molecular features in primary tumors. Specifically, receptor tyrosine kinase (RTK) pathway activation in the primary resistant group suggested the utility of RTK inhibitors, whereas mammalian target of rapamycin (mTOR) and cell cycle pathway activation in the secondary resistant group highlighted the potential of mTOR and CDK4/6 inhibitors. Interestingly, the endocrine-sensitive group displayed a quiescent state and high genomic instability, suggesting that targeting quiescent cells and using poly-ADP-ribose polymerase (PARP) inhibitors could be effective strategies.CONCLUSIONS: These findings illuminate the clinicopathological and molecular landscape of HR+/HER2- breast cancer patients with distinct recurrence patterns, highlighting potential targeted therapies.PMID:40078562 | PMC:PMC11893345 | DOI:10.21147/j.issn.1000-9604.2025.01.04

Non-invasive treatment of Clostridioides difficile infection with a human-origin probiotic cocktail through gut microbiome-gut metabolome modulations

Thu, 13/03/2025 - 11:00
Front Microbiol. 2025 Feb 26;16:1555220. doi: 10.3389/fmicb.2025.1555220. eCollection 2025.ABSTRACTClostridioides difficile (C. difficile) is a leading cause of hospital-associated diarrhea, primarily due to gut dysbiosis following antibiotic use. Probiotics have been found to provide several benefits to hosts via modulation of the gut microbiota and their metabolites. However, till now, no conventional probiotics have been clearly proven to be an effective prophylactic option for CDI prevention. Therefore, more studies on developing specific probiotic candidates targeting CDI and improving diversity of probiotics administrated are needed. In this study, a human-origin highly diverse and highly targeted probiotic cocktail (Pro11) containing 11 various probiotic species was developed against C. difficile. Pro11 protected mice against CDI with lower clinical scores and higher survival rates, and inhibited C. difficile in vivo with less C. difficile burden and toxins production determined in colon. Histological analysis demonstrated that Pro11 strengthened gut barrier, reducing gut permeability (less secreted sCD14 in serum) and gut inflammation. In addition, gut microbiome analysis demonstrated that Pro11 increased gut microbiome diversity and beneficial species. Along with gut microbiome modulation, gut metabolites including butyrate, were significantly increased in the probiotics-fed group. Results from this study highlighted probiotics as a promising CDI therapy as gut microbiota modulators, which will lay the foundation for translating probiotics in mitigating CDI and other intestinal pathogens for clinical use.PMID:40078549 | PMC:PMC11897039 | DOI:10.3389/fmicb.2025.1555220

Biliary-intestinal anastomosis leads to alterations in intestinal flora and its flora metabolites and increases the risk of long-term postoperative complications: a case-control study

Thu, 13/03/2025 - 11:00
Front Microbiol. 2025 Feb 26;16:1531955. doi: 10.3389/fmicb.2025.1531955. eCollection 2025.ABSTRACTOBJECTIVE: Pancreaticoduodenectomy (PD) is a major surgical intervention that encompasses the resection of multiple organs and the reconstruction of the digestive tract, with reconstructive procedures including pancreatico-enteric, bilioenteric, and gastroenteric anastomoses. Prior research has documented a high incidence of long-term complications following PD, which significantly impact patient prognosis and survival, however, the underlying mechanisms remain elusive. Evidence from previous studies suggests that biliary-intestinal anastomosis modifies biliary tract anatomy, altering bile flow into the gut and potentially affecting the gut microbiota and its metabolites. Given the close association between biliary tract infections and alterations in gut microbiota, we hypothesize that changes in intestinal flora and its metabolites post-PD may be a critical factor in the development of long-term complications. The objective of this study is to investigate whether biliary-intestinal anastomosis during PD induces changes in the intestinal microbiota and its metabolites, which in turn may increase the risk of long-term postoperative complications.METHODS: This study included 17 patients who underwent the procedure (group T) and 20 sex- and age-matched controls who did not (group N), patients in group T were stratified into those with (complication group) and without (non-complication group) long-term postoperative complications. Faecal samples were collected from all subjects and DNA was extracted from the samples using 16S rRNA gene sequencing to analyse the composition of the faecal flora and detect flora metabolites.RESULTS: 1. Alpha diversity analysis of the two sample groups indicated a trend towards lower microbial abundance in Group T relative to Group N, however, no significant differences were observed in the Shannon and Simpson diversity indices. 2. At the genus level, Group T patients exhibited markedly higher levels of Escherichia-Shigella, Veillonella, and Enterobacter, while showing significantly lower abundance of Blautia and Bifidobacterium compared to Group N subjects. Analysis of Spearman's correlation and degree of correlation between genera showed a significant negative correlation between Escherichia shigella and Blautia. Veillonella showed a significant positive correlation with both Escherichia shigella and Enterobacter. In addition, Blautia and Bifidobacterium showed a significant positive correlation with each other. 3. Subsequent comparative analysis of the bacterial flora between the complication and non-complication groups revealed a significantly elevated abundance of Escherichia-Shigella in the complication group as compared to the non-complication group. 4. Faecal metabolomic analysis revealed that L-palmitoylcarnitine, arachidic acid and PG 13:0_15:0 were significantly increased in the T group compared to the N group, whereas 3-isopropylmalic acid was significantly decreased in the T group. 5. KEGG pathway analysis identified nine crucial metabolic pathways associated with these microbial shifts: alterations in starch and sucrose metabolism, steroid hormone biosynthesis, caffeine metabolism, the citric acid cycle, riboflavin metabolism, sulfur metabolism, and the biosynthesis of valine, leucine, and isoleucine, as well as pyruvate metabolism and ABC transporter protein pathways.CONCLUSION: 1. The biliary-intestinal anastomosis, which is performed as part of a pancreaticoduodenectomy, induces significant shifts in the intestinal flora. 2. Increased abundance of Escherichia-Shigella may promote long-term complications after biliary-intestinal anastomosis. 3. Biliary-intestinal anastomosis leads to alterations in the metabolites of the patient's intestinal flora. 4. Intestinal flora and their metabolites in patients after biliary-intestinal anastomosis may contribute to the development of long-term complications through nine metabolic pathways.PMID:40078541 | PMC:PMC11900546 | DOI:10.3389/fmicb.2025.1531955

Impact of <em>Ligilactobacillus salivarius</em> Li01 on benzo[<em>a</em>]pyrene-induced colitis, based on host-microbiome interactions in Mongolian gerbils

Thu, 13/03/2025 - 11:00
Front Nutr. 2025 Feb 26;12:1494525. doi: 10.3389/fnut.2025.1494525. eCollection 2025.ABSTRACTBACKGROUND: Probiotics supplementations have been regarded as an effective strategy for colitis treatment. However, the effect of Ligilactobacillus salivarius Li01 on benzo[a]pyrene (BaP)-induced colitis in Mongolian gerbils remains unclear. In this study, we leverage a BaP-induced model of colitis that exhibits significant remission following Ligilactobacillus salivarius Li01 intervention, to conduct an animal experiment that integrates histopathological assessment, inflammatory cytokines, 16S rRNA sequencing, targeted metabolomic profiling to investigate the relationship between Ligilactobacillus salivarius Li01, gut microbiota, and colitis.RESULTS: We demonstrated that the improvements in colon histopathological assessment and inflammatory cytokines by Ligilactobacillus salivarius Li01 supplementation are accompanied by alterations in gut microbiota structure marked by increased abundance of strains with probiotic potential belonging to Bifidobacterium and Eubacterium_coprostanoligenes. Targeted metabolomic profiling analysis showed that Ligilactobacillus salivarius Li01 supplementation increases the concentration of acetic, propionic, butyric, and valeric acid. Correlation analysis showed that the alteration in the indicators associated with colitis is closely correlated to the changed microbial taxa and short-chain fatty acids (SCFAs).CONCLUSION: These data highlighted that Ligilactobacillus salivarius Li01 supplementation ameliorated the BaP-induced colitis, probably via modulating the structure of gut microbiota and promoting the production of SCFAs. Our findings provide preliminary evidence for a possible therapeutic strategy for the treatment of colitis based on host-microbiome interactions.PMID:40078411 | PMC:PMC11896860 | DOI:10.3389/fnut.2025.1494525

Microbiota and metabolomic profiling coupled with machine learning to identify biomarkers and drug targets in nasopharyngeal carcinoma

Thu, 13/03/2025 - 11:00
Front Pharmacol. 2025 Feb 26;16:1551411. doi: 10.3389/fphar.2025.1551411. eCollection 2025.ABSTRACTBACKGROUND: Nasopharyngeal carcinoma (NPC) is a prevalent malignancy in certain regions, with radiotherapy as the standard treatment. However, resistance to radiotherapy remains a critical challenge, necessitating the identification of novel biomarkers and therapeutic targets. The tumor-associated microbiota and metabolites have emerged as potential modulators of radiotherapy outcomes.METHODS: This study included 22 NPC patients stratified into radiotherapy-responsive (R, n = 12) and radiotherapy-non-responsive (NR, n = 10) groups. Tumor tissue and fecal samples were subjected to 16S rRNA sequencing to profile microbiota composition and targeted metabolomics to quantify short-chain fatty acids (SCFAs). The XGBoost algorithm was applied to identify microbial taxa associated with radiotherapy response, and quantitative PCR (qPCR) was used to validate key findings. Statistical analyses were conducted to assess differences in microbial diversity, relative abundance, and metabolite levels between the groups.RESULTS: Significant differences in alpha diversity at the species level were observed between the R and NR groups. Bacteroides acidifaciens was enriched in the NR group, while Propionibacterium acnes and Clostridium magna were more abundant in the R group. Machine learning identified Acidosoma, Propionibacterium acnes, and Clostridium magna as key predictors of radiotherapy response. Metabolomic profiling revealed elevated acetate levels in the NR group, implicating its role in tumor growth and immune evasion. Validation via qPCR confirmed the differential abundance of these microbial taxa in both tumor tissue and fecal samples.DISCUSSION: Our findings highlight the interplay between microbiota and metabolite profiles in influencing radiotherapy outcomes in NPC. These results suggest that targeting the microbiota-metabolite axis may enhance radiotherapy efficacy in NPC.PMID:40078290 | PMC:PMC11897916 | DOI:10.3389/fphar.2025.1551411

Integrated microbiome and metabolomics analysis reveals the alleviating effect of Pediococcus acidilactici on colitis

Thu, 13/03/2025 - 11:00
Front Vet Sci. 2025 Feb 26;12:1520678. doi: 10.3389/fvets.2025.1520678. eCollection 2025.ABSTRACTColitis is a complicated disease caused by multiple factors, seriously threatening the host health and the development of animal husbandry. Probiotics have been demonstrate to participate in the active regulation of multiple gastrointestinal disease, gut microbiota and metabolism, but research on the efficacy of Pediococcus acidilactici isolated from dogs in alleviating colitis remains scarce. Here, we aimed to investigate the ameliorative effects of Pediococcus acidilactici isolated from dogs on colitis induced by LPS and its underlying molecular mechanisms. For this purpose, we collected colon contents from 15 mice for amplicon sequencing and metabolic analysis. Results showed that Pediococcus acidilactici could relieve the colon damage and cytokine disorder caused by colitis. Microbiome analysis showed that colitis could cause a significant decrease in the gut microbial diversity and abundance, but Pediococcus acidilactici administration could restore the microbial index to the control level. Metabolomics analysis showed that 8 metabolic pathways and 5 (spermine, L-Arginine, 15-Deoxy-Delta12,14-PGJ2, prostaglandin J2, and 15(S)-HETE) metabolites may be involved in the alleviation of colitis by Pediococcus acidilactici. In summary, these findings demonstrated that the positive regulation effect of Pediococcus acidilactici on gut microbiota and metabolism may be one of its underlying mechanisms to alleviate colitis. Additionally, this study also conveyed a vital message that Pediococcus acidilactici isolated from dogs may serve as a promising candidate to ameliorate Pediococcus acidilactici.PMID:40078208 | PMC:PMC11897304 | DOI:10.3389/fvets.2025.1520678

Thymol Alleviates Colitis by Modulating Intestinal Barrier Damage, Gut Microbiota, and Amino Acid Metabolic Pathways

Thu, 13/03/2025 - 11:00
J Agric Food Chem. 2025 Mar 12. doi: 10.1021/acs.jafc.4c10406. Online ahead of print.ABSTRACTThymol (THY) is a phenolic monoterpene compound that has garnered attention due to its various biological properties, including antioxidant, anti-inflammatory, and immune-regulatory effects. The purpose of this study was to determine the therapeutic and protective effects of THY in colitic mice, with a particular focus on the mechanisms involving gut microbiota. The results showed that early intervention with THY (40 and 80 mg/kg) not only alleviated the clinical symptoms and colonic damage in mice with dextran sodium sulfate (DSS)-induced colitis but also suppressed the colonic production of inflammatory cytokines (IL-1β, IL-6, and IL-18) and enhanced the expression of mucins (MUC1 and MUC2) and trefoil factor family 3 (TFF3), thereby improving the integrity of the intestinal epithelial barrier. In addition, THY altered the composition of the gut microbiota in colitis mice by increasing the abundance of Bacteroides and reducing the abundance of Proteobacteria. Fecal microbial transplantation (FMT) results demonstrated that FM from THY donor mice significantly improved symptoms of inflammatory bowel disease (IBD), confirming the crucial role of the gut microbiota. Metagenomic and untargeted metabolomic studies found that the characteristic microbiota of THY is Prevotellaceae, and THY significantly upregulated the amino acid metabolic pathways related to arginine and proline metabolism, arginine biosynthesis, and glycerophospholipid metabolism. In summary, THY holds significant potential as a functional additive to enhance host intestinal activity.PMID:40077957 | DOI:10.1021/acs.jafc.4c10406

Untargeted Metabolomics and Chemometrics Elucidate Dynamic Plasma Profile Changes Induced by Cocoa Shell in Female Rats

Thu, 13/03/2025 - 11:00
Nutrients. 2025 Feb 28;17(5):885. doi: 10.3390/nu17050885.ABSTRACTOBJECTIVE: This study aimed to explore the effects of cocoa shell extract (CSE) supplementation on the plasma metabolome of female rats.METHODS: Female rats were supplemented with CSE (250 mg/kg/day) over seven days, and plasma samples were collected at baseline, day 4, and day 7 for untargeted metabolomic profiling using LC-ESI-QTOF.RESULTS: A total of 244 plasma metabolites were identified, while 180 were detected in the CSE. Among these, only 21 compounds were consistently detected in both the CSE and the plasma at baseline and day 7. Notably, just three compounds, caffeine, theobromine, and N-isovaleroylglycine, were bioavailable, detected only in plasma after supplementation on day 7, confirming their absorption and systemic distribution. Pathways related to caffeine metabolism, glycerophospholipid biosynthesis, nicotinate, and nicotinamide metabolism were significantly upregulated, indicating enhanced lipid metabolism and energy homeostasis. Conversely, reductions were observed in pathways involving tryptophan, glutathione, arginine, and proline, pointing to shifts in amino acid metabolism and antioxidant defense mechanisms. Network analysis revealed significant changes in the cholinergic synapse, retrograde endocannabinoid signaling, and glutamatergic synapse pathways, which are crucial for cellular communication and neurotransmission.CONCLUSIONS: The observed metabolic reconfiguration demonstrates CSE's rapid modulation of the metabolome, highlighting the bioavailability of its key components. These findings suggest potential mechanisms for CSE as a functional food ingredient with health-promoting effects, potentially supporting cognitive function and metabolic health through energy metabolism, neurotransmission, and lipid signaling pathways.PMID:40077756 | DOI:10.3390/nu17050885

Relevance of Milk Composition to Human Longitudinal Growth from Infancy Through Puberty: Facts and Controversies

Thu, 13/03/2025 - 11:00
Nutrients. 2025 Feb 27;17(5):827. doi: 10.3390/nu17050827.ABSTRACTMilk is the principal nutrient of newborn humans and a diagnostic feature of the order Mammalia. Its release is elicited as a reflex by infant sucking under the control of the hormone oxytocin. While it is recognized that breast milk optimally promotes infant longitudinal growth and development, this review explores facts and controversies regarding the extent to which the milks of several dairy animals and infant formula milk (IF) approximate special properties and bioactivities of breast milk. It also provides evidence that early exposure to undernutrition during the very rapid fetal and early infancy growth predominantly and permanently stunts longitudinal growth trajectory in both animals and humans and is often followed in later life by obesity and metabolic dysfunction, and sometimes also by precocious timing of sexual maturation. There is a knowledge gap as to whether there may be additional critical periods of nutritional vulnerability in human development, which is characterized by a relatively prolonged period of slow childhood growth bracketed by the rapid fetal-neonatal and pubertal growth spurts. It is also unclear whether any quantitative differences in caloric intake and supply during neonatal period may influence developmental fatness programming. A further knowledge gap exists regarding the role of infant microbiome composition and development in the possible epigenetic programming of longitudinal growth or fatness in later life. Extending the research of early developmental programming to the entire period of human growth from conception to the end of puberty, examining infant caloric intake and supply as possible factors modulating the epigenetic programming in favor of obesity, and examining the role of infant gut microbiome in developing infant's capacity to process nutrients may provide a better understanding of the interaction between critical nutritional influences in the control of human longitudinal growth and later-life obesity.PMID:40077697 | DOI:10.3390/nu17050827

Complex Probiotics Ameliorate Fecal Microbiota Transplantation-Induced IBS in Mice via Gut Microbiota and Metabolite Modulation

Thu, 13/03/2025 - 11:00
Nutrients. 2025 Feb 26;17(5):801. doi: 10.3390/nu17050801.ABSTRACTBackground/Objectives: Irritable bowel syndrome (IBS) is a highly prevalent functional gastrointestinal disorder. Emerging evidence implicates gut microbiota dysbiosis in IBS pathogenesis, and probiotic interventions targeting microbial modulation hold therapeutic promise. Methods: this study used fecal microbiota transplantation to establish a mouse model of IBS before evaluating the effects of the complex probiotic by using metagenomics and targeted metabolomics to explore the potential mechanism. Results: After 14 days, the probiotic relieved constipation, reduced inflammation and intestinal permeability, lowered 5-HT levels and increased serotonin transporter (SERT) expression in tissues. Metagenomic analysis showed a reduced inflammation-related species abundance. It also decreased fecal butyric acid, acetic acid and tryptophan levels in IBS mice. Conclusions: The probiotic complex effectively alleviated IBS symptoms in mice by modulating gut microbiota and fecal metabolites, providing insights for future IBS research and treatment.PMID:40077671 | DOI:10.3390/nu17050801

Associations Between Dietary Patterns and the Occurrence of Hospitalization and Gastrointestinal Disorders-A Retrospective Study of COVID-19 Patients

Thu, 13/03/2025 - 11:00
Nutrients. 2025 Feb 26;17(5):800. doi: 10.3390/nu17050800.ABSTRACTDuring the COVID-19 pandemic, dietary habits in the population changed and sometimes deviated from healthy eating patterns, such as the Mediterranean diet. Based on reports on the quality of the diet of respondents to studies conducted at the beginning of the pandemic, it could be concluded that these new dietary habits are unfavorable for a good prognosis and the course of any disease and its severity of symptoms. This study decided to confront these assumptions with the results of people who had COVID-19. Background/Objectives: This study aimed to assess the associations between dietary patterns and the occurrence of hospitalization and gastrointestinal disorders among patients diagnosed with COVID-19. Methods: This study included 550 respondents who completed a survey up to 8 months after being diagnosed with COVID-19. The survey included 62 items from the FFQ-6®, GSRS, PAC-SYM and FACT-G7 standardized questionnaires. Results: Two dietary patterns (DPs) were identified: 'Processed high fat/sugar/salt/meat/dairy/potatoes' and 'Semi-vegetarian'. Higher adherence to the 'Processed' DP was associated with higher odds of hospitalization due to COVID-19, a more severe course of the disease, and the highest intensity of gastrointestinal symptoms. Higher adherence to the 'Semi-vegetarian' DP was associated with lower odds of hospitalization due to COVID-19, a less severe course of the disease, and the lowest intensity of gastrointestinal symptoms. Conclusions: This study showed a strong harmful effect of high adherence to a processed dietary pattern on an increased incidence of hospitalization and gastrointestinal disorders among northwestern Polish adults during the COVID-19 pandemic, emphasizing the importance of a healthy diet.PMID:40077670 | DOI:10.3390/nu17050800

L-Arabinose Alleviates Functional Constipation in Mice by Regulating Gut Microbiota and Metabolites

Thu, 13/03/2025 - 11:00
Foods. 2025 Mar 6;14(5):900. doi: 10.3390/foods14050900.ABSTRACTFunctional constipation ranks among the most common disorders impacting human health, which is manifested by difficulty in defecation and a complex etiology. L-Arabinose, a pentose found naturally in fruit rinds and cereal husks, has been reported to regulate glycolipid metabolism, improve glucose homeostasis, and exhibit anti-inflammatory effects. However, the effect and precise mechanism of L-Arabinose on functional constipation remain unclear. In this study, the effect of L-Arabinose in alleviating functional constipation induced by diphenoxylate was evaluated. The model group consisted of functional constipation mice that did not receive any intervention. The positive drug group was treated with 2.0 g/kg lactulose, while the intervention group was given 0.5 g/kg, 0.75 g/kg, 1.0 g/kg, and 2.0 g/kg L-Arabinose, respectively. The data suggested that 20 days of L-Arabinose intervention could shorten the first black stool defecation time, increase fecal water content, and enhance the rate of small intestinal propulsion in mice with functional constipation induced by diphenoxylate. Additionally, L-Arabinose reversed the protein expression of functional constipation-related intestinal factors in the colon, characterized by a decrease in the expression of water channel proteins AQP3 and AQP4, as well as an increase in the expression of tight-junction proteins ZO-1, Claudin-1 and Occludin. Furthermore, L-Arabinose modulated the levels of hormones (MTL, Gas) and neurotransmitters (5-HT, VIP) related to the digestive systems of mice with constipation, resulting in elevated levels of 5-HT, MTL, and Gas and decreasing levels of VIP. Histopathological analysis also revealed that L-Arabinose intervention improved the intestinal inflammatory response. Furthermore, 16S rRNA sequencing and metabolomics of the intestinal microbiota demonstrated that L-Arabinose treatment improved both the intestinal microbiota composition and the metabolite levels. This study suggests that L-Arabinose can serve as a potential functional ingredient to promote intestinal health, enhance gastrointestinal motility and barrier function, regulate osmotic pressure, restore neurotransmitter levels, and effectively relieve functional constipation.PMID:40077603 | DOI:10.3390/foods14050900

Dynamics Changes in Physicochemical Properties, Antioxidant Activity, and Non-Volatile Metabolites During Bulang Pickled Tea Fermentation

Thu, 13/03/2025 - 11:00
Foods. 2025 Mar 4;14(5):878. doi: 10.3390/foods14050878.ABSTRACTThe present study investigated the dynamics changes in physicochemical properties and non-volatile metabolites during Bulang pickled tea fermentation. A combination of artificial sensory evaluation, chemical-physical analysis, ultra performance liquid chromatography coupled with quadrupole/time-of-flight mass spectrometry (UPLC-QTOF-MS), and multivariate statistical analysis were employed to examine the differences among four fermentation stages of Bulang pickled tea. The bitterness, astringency, sweetness after taste, sourness and fermentation taste tended to increase with fermentation. The highest lactic acid bacteria, aerobic bacteria, total titratable acidity, total soluble sugar, total polyphenols, and total flavonoids were recorded at the second month of fermentation, while fungi, total free amino acids, total antioxidant capacity and hydroxyl free radical scavenging capacity increased with fermentation. Mantel test demonstrated significant associations between lactic acid bacteria /fungal communities and taste characteristics. UPLC-QTOF-MS analysis led to the identification of 35 differential non-volatile metabolites, predominantly comprising heterocyclic compounds, organic acids with their derivatives, and flavonoids. Nine non-volatile metabolites are related to antioxidant activity, and morin, malvidin and 7-methylxanthine exhibit relatively strong antioxidant activity. This study provides comprehensive insights into the non-volatile metabolites and antioxidant function of Bulang pickled tea.PMID:40077581 | DOI:10.3390/foods14050878

Immunomodulation of Glycyrrhiza Polysaccharides In Vivo Based on Microbiome and Metabolomics Approaches

Thu, 13/03/2025 - 11:00
Foods. 2025 Mar 4;14(5):874. doi: 10.3390/foods14050874.ABSTRACTGlycyrrhiza uralensis Fisch. is a medicinal herb that can be added to food to provide therapeutic effects and reduce the burden of medications. Herein, the immunomodulatory effects of Glycyrrhiza polysaccharides (GPs) were verified and illustrated by intervening immunocompromised rats treated with different doses of GPs, which were reflected for adjusting the composition and structure of the intestinal microbiota and altering the metabolic profile. The immunomodulatory effects of GPs were exerted by regulating the intestinal microenvironment. In particular, GPs could promote the growth of probiotic bacteria Allobaculum, norank__o_Clostridia_UCG-014, Dubosiella, and g__norank_o___RF39 and curb the growth of harmful bacteria Enterococcus. The results showed that GPs had a prebiotic effect, which contributed to improving the intestinal environment and maintaining intestinal health. In addition, the content of beneficial differential metabolites was up-regulated, especially short-chain fatty acids, with alanine, aspartate, and glutamate metabolism; arginine biosynthesis; glyoxylate and dicarboxylate metabolism being the most enriched pathways. These metabolic pathways imply the metabolic process of GPs, and the metabolic pathways and differential effector metabolites of it are focused. Overall, the purpose of this article lies in providing support for the application of GPs for regulating immune function.PMID:40077577 | DOI:10.3390/foods14050874

Supplementation with Lentil (<em>Lens culinaris</em>) Hull Soluble Dietary Fiber Ameliorates Sodium Dextran Sulfate-Induced Colitis and Behavioral Deficits via the Gut-Brain Axis

Thu, 13/03/2025 - 11:00
Foods. 2025 Mar 3;14(5):870. doi: 10.3390/foods14050870.ABSTRACTIn this study, the impact of lentil hull soluble dietary fibers (SDFs) on colitis and behavioral deficits in mice was assessed. Structural characterizations of SDFs confirmed that cellulase-modified soluble dietary fiber exhibited better physicochemical properties: more porous microstructure; similar polysaccharide structure; more stable particle size distribution; higher crystallinity; better adsorption capacity; and lower viscosity. Additionally, we explored its potential cognitive benefits via the gut-brain axis by behavioral tests, histopathology, 16S rRNA sequencing, gas chromatography and metabolomics analysis. The results showed that SDFs significantly improved inflammatory symptoms in colon and brain and cognitive behaviors. LSDF had better efficacy than HSDF. LSDF intervention decreased the harmful bacteria abundance (Bacteroides, Flexispira and Escherichia, etc.) and increased beneficial bacteria abundance (Aggregatibacter and Helicobacter, etc.). LSDF also affected brain metabolites through the sphingolipid metabolism. Spearman correlation analysis showed that there was a positive correlation between harmful bacteria with inflammatory factors (LPS, IL-1β, IL-6, and TNF-α, etc.) and sphingolipid metabolites, while beneficial bacteria were positively correlated with brain-derived neurotrophic factor (BDNF), IL-10, and cognitive behavior. This study highlights the value of SDFs in future diet-based therapeutic strategies targeting gut-brain interactions.PMID:40077572 | DOI:10.3390/foods14050870

Pages