PubMed

Life Sci Alliance. 2023 Jul 24;6(10):e202201886. doi: 10.26508/lsa.202201886. Print 2023 Oct.ABSTRACTTubulointerstitial fibrosis is the common pathological substrate for many etiologies leading to chronic kidney disease. Although perturbations in the circadian rhythm have been associated with renal disease, the role of the molecular clock in the pathogenesis of fibrosis remains incompletely understood. We investigated the relationship between the molecular clock and renal damage in experimental models of injury and fibrosis (unilateral ureteral obstruction, folic acid, and adenine nephrotoxicity), using genetically modified mice with selective deficiencies of the clock components Bmal1, Clock, and Cry We found that the molecular clock pathway was enriched in damaged tubular epithelial cells with marked metabolic alterations. In human tubular epithelial cells, TGFβ significantly altered the expression of clock components. Although Clock played a role in the macrophage-mediated inflammatory response, the combined absence of Cry1 and Cry2 was critical for the recruitment of neutrophils, correlating with a worsening of fibrosis and with a major shift in the expression of metabolism-related genes. These results support that renal damage disrupts the kidney peripheral molecular clock, which in turn promotes metabolic derangement linked to inflammatory and fibrotic responses.PMID:37487638 | DOI:10.26508/lsa.202201886

PLoS Pathog. 2023 Jul 24;19(7):e1011536. doi: 10.1371/journal.ppat.1011536. Online ahead of print.ABSTRACTCentral metabolic pathways control virulence and antibiotic resistance, and constitute potential targets for antibacterial drugs. In Staphylococcus aureus the role of the pentose phosphate pathway (PPP) remains largely unexplored. Mutation of the 6-phosphogluconolactonase gene pgl, which encodes the only non-essential enzyme in the oxidative phase of the PPP, significantly increased MRSA resistance to β-lactam antibiotics, particularly in chemically defined media with physiologically-relevant concentrations of glucose, and reduced oxacillin (OX)-induced lysis. Expression of the methicillin-resistance penicillin binding protein 2a and peptidoglycan architecture were unaffected. Carbon tracing and metabolomics revealed extensive metabolic reprogramming in the pgl mutant including increased flux to glycolysis, the TCA cycle, and several cell envelope precursors, which was consistent with increased β-lactam resistance. Morphologically, pgl mutant cells were smaller than wild-type with a thicker cell wall and ruffled surface when grown in OX. The pgl mutation reduced resistance to Congo Red, sulfamethoxazole and oxidative stress, and increased resistance to targocil, fosfomycin and vancomycin. Levels of lipoteichoic acids (LTAs) were significantly reduced in pgl, which may limit cell lysis, while the surface charge of pgl cells was significantly more positive. A vraG mutation in pgl reversed the increased OX resistance phenotype, and partially restored wild-type surface charge, but not LTA levels. Mutations in vraF or graRS from the VraFG/GraRS complex that regulates DltABCD-mediated d-alanylation of teichoic acids (which in turn controls β-lactam resistance and surface charge), also restored wild-type OX susceptibility. Collectively these data show that reduced levels of LTAs and OX-induced lysis combined with a VraFG/GraRS-dependent increase in cell surface positive charge are accompanied by significantly increased OX resistance in an MRSA pgl mutant. (266 words).PMID:37486930 | DOI:10.1371/journal.ppat.1011536

PLoS Negl Trop Dis. 2023 Jul 24;17(7):e0011133. doi: 10.1371/journal.pntd.0011133. Online ahead of print.ABSTRACTAcute febrile illnesses are still a major cause of mortality and morbidity globally, particularly in low to middle income countries. The aim of this study was to determine any possible metabolic commonalities of patients infected with disparate pathogens that cause fever. Three liquid chromatography-mass spectrometry (LC-MS) datasets investigating the metabolic effects of malaria, leishmaniasis and Zika virus infection were used. The retention time (RT) drift between the datasets was determined using landmarks obtained from the internal standards generally used in the quality control of the LC-MS experiments. Fitted Gaussian Process models (GPs) were used to perform a high level correction of the RT drift between the experiments, which was followed by standard peakset alignment between the samples with corrected RTs of the three LC-MS datasets. Statistical analysis, annotation and pathway analysis of the integrated peaksets were subsequently performed. Metabolic dysregulation patterns common across the datasets were identified, with kynurenine pathway being the most affected pathway between all three fever-associated datasets.PMID:37486920 | DOI:10.1371/journal.pntd.0011133

Oral Dis. 2023 Jul 24. doi: 10.1111/odi.14696. Online ahead of print.ABSTRACTOBJECTIVE: Disease metabolomes have been studied for identifying diagnostic and predictive biomarkers of pathology. Oral tongue squamous cell carcinoma (OTSCC) is one of the most prevalent subtypes of head and neck squamous cell carcinoma, yet the profile and diagnostic value of its tissue metabolite are unclear.SUBJECTS AND METHODS: Tumor tissue samples and matched normal mucosal tissue samples were collected from 40 OTSCC patients. Untargeted metabolic analysis by liquid chromatography-mass spectrometry/mass spectrometry, in positive and negative ion modes, was used to identify dysregulated metabolites in OTSCC. Further, utilizing LASSO regression and receiver operating characteristic analyses, biomarker metabolites were selected and validated, and a diagnostic model was established.RESULTS: One hundred and ninety metabolites were detected. The OTSCC had a total of 89 dysregulated metabolites, of which 73 were elevated. A diagnostic panel of nine metabolites was subsequently created that could accurately identify OTSCC with 100% sensitivity of 100%, 100% specificity and an AUC of 1.00.CONCLUSIONS: This study identified distinct metabolic characteristics of OTSCC and established a diagnostic model. Our research also contributes to the investigation of the pathogenesis of OTSCC.PMID:37486619 | DOI:10.1111/odi.14696

Metabolomics. 2023 Jul 24;19(8):68. doi: 10.1007/s11306-023-02032-8.ABSTRACTINTRODUCTION: Lantana trifolia L. (Verbenaceae) is a shrubby plant. In folk medicine, its leaves are used in the form of infusions and syrups to treat angina, coughs, and colds; they are also applied as tranquilizer. Previous studies have reported the antimicrobial potential of the compounds present in L. trifolia leaves.OBJECTIVES: To report the anti-Candida activities of the fractions obtained from the fruits and leaves of two L. trifolia specimens.METHODS: The L. trifolia fractions were submitted to UFLC-DAD-(+)-ESI-MS/MS, and the data were analyzed by using multivariate statistical tools (PCA, PLS-DA) and spectral similarity analyses based on molecular networking, which aided dereplication of the bioactive compounds. Additionally, NMR analyses were performed to confirm the chemical structure of some of the major compounds in the fractions.RESULTS: The ethyl acetate fractions presented MIC values lower than 100 µg mL-1 against the three Candida strains evaluated herein (C. albicans, C. tropicalis, and C. glabrata). Fractions FrPo AcOEt, FrPe AcOEt, and FrPe nBut had MIC values of 1.46, 2.93, and 2.93 µg mL-1 against C. glabrata, respectively. These values resembled the MIC value of amphotericin B, the positive control (0.5-1.0 µg mL-1), against this same strain. Cytotoxicity was measured and used to calculate the selectivity index.CONCLUSION: On the basis of our data, the most active fractions in the antifungal assay were more selective against C. glabrata than against non-infected cells. The analytical approach adopted here allowed us to annotate 29 compounds, nine of which were bioactive (PLS-DA results) and belong to the class of phenolic compounds.PMID:37486581 | DOI:10.1007/s11306-023-02032-8

J Plant Res. 2023 Jul 24. doi: 10.1007/s10265-023-01483-3. Online ahead of print.ABSTRACTThe ecological niche centrality hypothesis states that population abundance is determined by the position in the ecological niche, expecting higher abundances towards the center of the niche and lower at the periphery. However, the variations in the conditions that favor the persistence of populations between the center and the periphery of the niche can be a surrogate of stress factors that are reflected in the production of metabolites in plants. In this study we tested if metabolomic similarity and diversity in populations of the tree species Eucryphia cordifolia Cav. vary according to their position with respect to the structure of the ecological niche. We hypothesize that populations growing near the centroid should exhibit lower metabolites diversity than plants growing at the periphery of the niche. The ecological niche of the species was modeled using correlative approaches and bioclimatic variables to define central and peripheral localities from which we chose four populations to obtain their metabolomic information using UHPLC-DAD-QTOF-MS. We observed that populations farther away from the centroid tend to have higher metabolome diversity, thus supporting our expectation of the niche centrality hypothesis. Nonetheless, the Shannon index showed a marked variation in metabolome diversity at the seasonal level, with summer and autumn being the periods with higher metabolite diversity compared to winter and spring. We conclude that both the environmental variation throughout the year in combination with the structure of the ecological niche are relevant to understand the variation in expression of metabolites in plants.PMID:37486392 | DOI:10.1007/s10265-023-01483-3

Phytopathology. 2023 Jul 24. doi: 10.1094/PHYTO-12-22-0459-R. Online ahead of print.ABSTRACTSweet sorghum [Sorghum bicolor (L.) Moench] lines M81-E and Colman were previously shown to differ in responses to Fusarium thapsinum and Macrophomina phaseolina, stalk rot pathogens that can reduce yields and quality of biomass and extracted sugars. Inoculated tissues were compared for transcriptomic, phenolic metabolite, and enzymatic activity during disease development 3 and 13 days after inoculation (DAI). At 13 DAI M81-E had shorter mean lesion lengths than Colman when inoculated with either pathogen. Transcripts encoding monolignol biosynthetic and modification enzymes were associated with transcriptional wound (control) responses of both lines at 3 DAI. Monolignol biosynthetic genes were differentially coexpressed with transcriptional activator SbMyb76 in all Colman inoculations, but only following M. phaseolina inoculation in M81-E, suggesting that SbMyb76 is associated with lignin biosynthesis during pathogen responses. In control inoculations, defense-related genes were expressed at higher levels in M81-E than Colman. Line, treatment, and timepoint differences observed in phenolic metabolite and enzyme activities did not account for observed differences in lesions. However, generalized additive models were able to relate metabolites, but not enzyme activities, to lesion length, for quantitatively modeling disease progression: in M81-E, but not Colman, sinapic acid levels positively predicted lesion length at 3 DAI when cell wall-bound syringic acid was low, soluble caffeic acid was high, and lactic acid was high, suggesting that sinapic acid may contribute to responses at 3 DAI. These results provide potential gene targets for development of sweet sorghum varieties with increased stalk rot resistance to ensure biomass and sugar quality.PMID:37486162 | DOI:10.1094/PHYTO-12-22-0459-R

ACS Nano. 2023 Jul 24. doi: 10.1021/acsnano.3c04449. Online ahead of print.ABSTRACTDietary pollution by polystyrene microplastics (MPs) can cause hepatic injuries and microbial dysbiosis. Epigallocatechin-3-gallate (EGCG), the major polyphenol in green tea, exerts beneficial effects on the liver by modulating the gut microbiota. However, the role of microbiota in MPs-induced hepatic injuries and the protective effect of EGCG have not been clarified. Here, 5 μm MPs were orally administered to mice to induce hepatic injuries. Subsequently, antibiotic cocktail (ABX) and fecal microbial transplant (FMT) experiments were performed to investigate the underlying microbial mechanisms. Additionally, EGCG was orally administered to mice to explore its protection against MPs-induced hepatic injuries. Our results showed that MPs activated systemic and hepatic inflammation, promoted fibrosis, and altered the liver metabolome; meanwhile, MPs damaged the gut homeostasis by disturbing the gut microbiome, promoting colonic inflammation, and impairing the intestinal barrier. Notably, MPs reduced the abundance of the probiotics Akkermansia, Mucispirillum, and Faecalibaculum while increasing the pathogenic Tuzzerella. Interestingly, the elimination of gut microbiota mitigated MPs-induced colonic inflammation and intestinal barrier impairment. Moreover, ABX ameliorated MPs-induced systemic and hepatic inflammation but not fibrosis. Correspondingly, microbiota from MPs-administered mice induced colonic, systemic, and hepatic inflammation, while their profibrosis effect on the liver was not observed. Finally, EGCG elevated the abundance of probiotics and effectively repressed MPs-induced colonic inflammation. MPs-induced systemic and hepatic inflammation, fibrosis, and remodeling of the liver metabolome were also attenuated by EGCG. These findings illustrated that gut microbiota contributed to MPs-induced colonic and hepatic injuries, while EGCG could serve as a potential prevention strategy for these adverse consequences.PMID:37486121 | DOI:10.1021/acsnano.3c04449

J Integr Bioinform. 2023 Jul 25. doi: 10.1515/jib-2023-0012. Online ahead of print.ABSTRACTCrop plant breeding involves selecting and developing new plant varieties with desirable traits such as increased yield, improved disease resistance, and enhanced nutritional value. With the development of high-throughput technologies, such as genomics, transcriptomics, and metabolomics, crop breeding has entered a new era. However, to effectively use these technologies, integration of multi-omics data from different databases is required. Integration of omics data provides a comprehensive understanding of the biological processes underlying plant traits and their interactions. This review highlights the importance of integrating omics databases in crop plant breeding, discusses available omics data and databases, describes integration challenges, and highlights recent developments and potential benefits. Taken together, the integration of omics databases is a critical step towards enhancing crop plant breeding and improving global food security.PMID:37486120 | DOI:10.1515/jib-2023-0012

Phytopathology. 2023 Jul 24. doi: 10.1094/PHYTO-04-23-0134-R. Online ahead of print.ABSTRACTCitrus greening disease or huanglonbing (HLB) has devastated citrus crops globally in recent years. The causal bacterium, Candidatus Liberibacter asiaticus, presents a sampling issue for qPCR diagnostics and results in a high false negative rate. In this work, we compared six metabolomics assays to identify HLB-infected citrus trees from extracted leaf tissue from 30 control and 30 HLB-infected trees. A liquid chromatography-mass spectrometry (LC-MS) based assay was most accurate. A final partial least squares-discriminant analysis (PLS-DA) model was trained and validated on 690 leaf samples with corresponding qPCR measures from three citrus varieties (Rio Red grapefruit, Hamlin sweet orange and Valencia sweet orange) from orchards in Florida and Texas. Trees were naturally infected with HLB transmitted by the insect vector Diaphorina citri. In a randomized validation set, the assay was 99.9% accurate to classify diseased from non-diseased samples. This model was applied to samples from trees receiving plant defense inducer compounds (PDIs) or biological treatments (BLXs) to prevent or cure HLB infection. From two trials, HLB-related metabolite abundances and PLS-DA scores were tracked longitudinally and compared to control trees. We demonstrate how our assay can assess tree health and efficacy of HLB treatments, concluding no trialed treatment was efficacious.PMID:37486097 | DOI:10.1094/PHYTO-04-23-0134-R

Phytopathology. 2023 Jul 24. doi: 10.1094/PHYTO-01-23-0002-V. Online ahead of print.ABSTRACTPlant viruses infect a wide range of commercially important crop plants and cause significant crop production losses worldwide. Numerous alterations in plant physiology related to the reprogramming of gene expression may result from viral infections. While conventional IPM-based strategies have been effective in reducing the impact of several viral diseases, continued emergence of new viruses and strains, expanding host ranges, and emergence of resistance breaking strains necessitate a sustained effort toward the development and application of new approaches for virus management that would complement existing tactics. RNA interference-based techniques, and more recently, Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based genome editing technologies have paved the way for precise targeting of viral transcripts and manipulation of viral genomes and host factors. In-depth knowledge of the molecular mechanisms underlying the development of disease would further expand the applicability of these recent methods. Advances in next generation/high throughput sequencing have made possible more intensive studies into host-virus interactions. Utilizing the omics data and its application has the potential to expedite in fast tracking traditional plant breeding methods, as well as applying modern molecular tools for trait enhancement, including virus resistance. Here, we summarize the recent developments in CRISPR/Cas system, transcriptomics, endogenous RNA interference and exogenous application of dsRNA in virus disease management.PMID:37486077 | DOI:10.1094/PHYTO-01-23-0002-V

Food Funct. 2023 Jul 24. doi: 10.1039/d3fo00809f. Online ahead of print.ABSTRACTThe anti-obesity potential of probiotics has been widely reported, however their utilization in high-risk patients and potential adverse reactions have led researchers to focus their attention on postbiotics. Herein, pseudo-targeted lipidomics linked with deep learning-based metabolomics was utilized to dynamically characterize the postbiotic potential of heat-inactivated Lactobacillus casei JCM1134 supplementation after a high-fat diet in treating obesity. MG (ranged from 423.0 ± 1.4 mg L-1 to 331.45 ± 2.3 mg L-1), LPC (ranged from 13.1 ± 0.08 mg L-1 to 10.2 ± 0.1 mg L-1) and Cho (ranged from 9.0 ± 0.3 mg L-1 to 5.7 ± 0.2 mg L-1) in intestinal digestive products were significantly decreased, indicating that the digestion of lipid was inhibited. 8-C-glucosylorobol, from Lactobacillus casei, was confirmed from quantitative results and molecular simulation calculations to inhibit the transformation of TG, DG, and ChE through weakening hydrogen bonds between enzymes and substrates and reducing the binding energy. Pristimerin and 2,4-quinolinediol can effectively reduce the hydrogen bonding force between PC and phospholipase A2, which were related to the obstruction of phosphatidylcholine digestion. This research deepened the understanding of the mechanism underlying the inactivated probiotics affecting lipid digestion, establishing the critical groundwork for clinical application of probiotics in inhibiting obesity.PMID:37486034 | DOI:10.1039/d3fo00809f

Mol Syst Biol. 2023 Jul 24:e11525. doi: 10.15252/msb.202311525. Online ahead of print.ABSTRACTMulti-omics analyses are used in microbiome studies to understand molecular changes in microbial communities exposed to different conditions. However, it is not always clear how much each omics data type contributes to our understanding and whether they are concordant with each other. Here, we map the molecular response of a synthetic community of 32 human gut bacteria to three non-antibiotic drugs by using five omics layers (16S rRNA gene profiling, metagenomics, metatranscriptomics, metaproteomics and metabolomics). We find that all the omics methods with species resolution are highly consistent in estimating relative species abundances. Furthermore, different omics methods complement each other for capturing functional changes. For example, while nearly all the omics data types captured that the antipsychotic drug chlorpromazine selectively inhibits Bacteroidota representatives in the community, the metatranscriptome and metaproteome suggested that the drug induces stress responses related to protein quality control. Metabolomics revealed a decrease in oligosaccharide uptake, likely caused by Bacteroidota depletion. Our study highlights how multi-omics datasets can be utilized to reveal complex molecular responses to external perturbations in microbial communities.PMID:37485738 | DOI:10.15252/msb.202311525

Photochem Photobiol. 2023 Jul 24. doi: 10.1111/php.13841. Online ahead of print.ABSTRACTA reconstructed human epidermal model (RHE) colonized with human microbiota and sebum was developed to reproduce the complexity of the skin ecosystem in vitro. The RHE model was exposed to simulated solar radiation (SSR) with or without SPF50+ sunscreen (with UVB, UVA, long-UVA, and visible light protection). Structural identification of discriminant metabolites was acquired by nuclear magnetic resonance and metabolomic fingerprints were identified using reverse phase-ultra high-performance liquid chromatography-high resolution mass spectrometry, followed by pathway enrichment analysis. Over 50 metabolites were significantly altered by SSR (p < 0.05, log2 values), showing high skin oxidative stress (glutathione and purine pathways, urea cycle) and altered skin microbiota (branched-chain amino acid cycle and tryptophan pathway). 16S and internal transcribed spacer rRNA sequencing showed the relative abundance of various bacteria and fungi altered by SSR. This study identified highly accurate metabolomic fingerprints and metagenomic modifications of sun-exposed skin to help elucidate the interactions between the skin and its microbiota. Application of SPF50+ sunscreen protected the skin ecosystem model from the deleterious effects of SSR and preserved the physiological interactions within the skin ecosystem. These innovative technologies could thus be used to evaluate the effectiveness of sunscreen.PMID:37485720 | DOI:10.1111/php.13841

Front Microbiol. 2023 Jul 7;14:1179534. doi: 10.3389/fmicb.2023.1179534. eCollection 2023.ABSTRACTIrritable bowel syndrome (IBS) has no clinically accepted biomarkers even though it affects a large number of individuals worldwide. To address this lack of understanding, we evaluated peptidase activity in fecal samples from 35 patients with diarrheal IBS without symptom exacerbation (IBS-n) and 35 healthy subjects using a library of 384 fluorescent enzymatic substrate probes. IBS-n patients had high trypsin-like peptidase activity for cleavage of C-terminal lysine and arginine residues and low elastase-like activity for cleavage of C-terminal serine and glycine residues. These fluorescent probe library data, together with diagnostic machine-learning techniques, were able to accurately predict IBS-n. This approach can be used to diagnose diseases where no clinically accepted biomarkers exist, in which fecal enzyme activity is altered and also suggests that the development of new therapies targeting enzyme activities is possible.PMID:37485510 | PMC:PMC10361618 | DOI:10.3389/fmicb.2023.1179534

Front Microbiol. 2023 Jul 6;14:1197981. doi: 10.3389/fmicb.2023.1197981. eCollection 2023.ABSTRACTOBJECTIVE: Host genetics and environment participate in the shaping of gut microbiota. Diannan small ear pigs and Diqing Tibetan pigs are excellent native pig breeds in China and live in different environments. However, the gut microbiota of Diannan small ear pigs and Diqing Tibetan pigs were still rarely understood. Therefore, this study aimed to analyze the composition characteristics of gut microbiota and metabolites in Diannan small ear pigs and Diqing Tibetan pigs.METHODS: Fresh feces of 6 pigs were randomly collected from 20 4-month-old Diannan small ear pigs (DA group) and 20 4-month-old Diqing Tibetan pigs (TA group) for high-throughput 16S rRNA sequencing and liquid chromatography-mass spectrometry (LC-MS) non-targeted metabolome analysis.RESULTS: The results revealed that Firmicutes and Bacteroidetes were the dominant phyla in the two groups. Chao1 and ACE indices differed substantially between DA and TA groups. Compared with the DA group, the relative abundance of Prevotellaceae, and Ruminococcus was significantly enriched in the TA group, while the relative abundance of Lachnospiraceae, Actinomyces, and Butyricicoccus was significantly reduced. Cholecalciferol, 5-dehydroepisterol, stigmasterol, adrenic acid, and docosahexaenoic acid were significantly enriched in DA group, which was involved in the steroid biosynthesis and biosynthesis of unsaturated fatty acids. 3-phenylpropanoic acid, L-tyrosine, phedrine, rhizoctin B, and rhizoctin D were significantly enriched in TA group, which was involved in the phenylalanine metabolism and phosphonate and phosphinate metabolism.CONCLUSION: We found that significant differences in gut microbiota composition and metabolite between Diannan small ear pigs and Diqing Tibetan pigs, which provide a theoretical basis for exploring the relationship between gut microbiota and pig breeds.PMID:37485506 | PMC:PMC10359432 | DOI:10.3389/fmicb.2023.1197981

Front Microbiol. 2023 Jul 6;14:1183598. doi: 10.3389/fmicb.2023.1183598. eCollection 2023.ABSTRACTObesity has been regarded as one of the major health problems worldwide. Studies demonstrated that ursolic acid (UA) can significantly ameliorate the progress of obesity. However, whether the effect of UA on obesity depends on the regulation of gut microbiota and metabolism is uncertain. To investigate the regulatory role of UA in obese mice from the perspective of intestinal microbiome and metabolomics analyses, an obese mice model was established with a high-fat diet, and the effect of UA on obesity was evaluated. The alterations of gut microbiota and metabolism related to obesity were evaluated by bioinformatic analysis. The results of the gut microbiota analysis showed that UA intervention could shift the Firmicutes to Bacteroidetes ratio at the phylum level and increase in the genera of Lactobacillus, Bacteroides, and Akkermansia. Additionally, metabolomics analysis showed that the beneficial influence of UA on obesity partly depended on amino acid metabolism. The current study demonstrated the roles of UA in the anti-obesity process, which depends in part on alterations in the gut microbiota and metabolism. Therefore, our findings highlight the potential therapeutic effect of UA on the improvement of diet-induced obesity in humans.PMID:37485499 | PMC:PMC10359042 | DOI:10.3389/fmicb.2023.1183598

Future Sci OA. 2023 May 16;9(7):FSO868. doi: 10.2144/fsoa-2023-0060. eCollection 2023 Aug.ABSTRACTIt is proposed that gut microbiome of species like cockroaches may offer a potential source of novel mechanisms/molecules that can be translated into humans to safeguard astronauts against stressors of the space environment during deep space exploration missions.PMID:37485442 | PMC:PMC10357397 | DOI:10.2144/fsoa-2023-0060

RSC Adv. 2023 Jul 20;13(31):21471-21493. doi: 10.1039/d3ra03141a. eCollection 2023 Jul 12.ABSTRACTBalanites aegyptiaca (L.) Delile (Zygophyllaceae), also known as the desert date, is an edible fruit-producing tree popular for its nutritional and several health benefits. In this study, multi-targeted comparative metabolic profiling and fingerprinting approaches were conducted for the assessment of the nutrient primary and secondary metabolite heterogeneity in different parts, such as leaves, stems, seeds, unripe, and ripe fruits of B. aegyptiaca using nuclear magnetic resonance (NMR), ultra-performance liquid chromatography (UPLC-MS), and gas chromatography mass-spectrometry (GC-MS) based metabolomics coupled to multivariate analyses and in relation to its cytotoxic activities. NMR-based metabolomic study identified and quantified 15 major primary and secondary metabolites belonging to alkaloids, saponins, flavonoids, sugars, and amino and fatty acids. Principal component analysis (PCA) of the NMR dataset revealed α-glucose, sucrose, and isorhamnetin as markers for fruit and stem and unsaturated fatty acids for predominated seeds. Orthogonal projections to latent structure discriminant analysis (OPLS-DA) revealed trigonelline as a major distinctive metabolite in the immature fruit and isorhamnetin as a major distinct marker in the mature fruit. UPLC-MS/MS analysis using feature-based molecular networks revealed diverse chemical classes viz. steroidal saponins, N-containing metabolites, phenolics, fatty acids, and lipids as the constitutive metabolome in Balanites. Gas chromatography-mass spectroscopy (GC-MS) profiling of primary metabolites led to the detection of 135 peaks belonging to sugars, fatty acids/esters, amino acids, nitrogenous, and organic acids. Monosaccharides were detected at much higher levels in ripe fruit and disaccharides in predominate unripe fruits, whereas B. aegyptiaca vegetative parts (leaves and stem) were rich in amino acids and fatty acids. The antidiabetic compounds, viz, nicotinic acid, and trigonelline, were detected in all parts especially unripe fruit in addition to the sugar alcohol d-pinitol for the first time providing novel evidence for B. aegyptiaca use in diabetes. In vitro cytotoxic activity revealed the potential efficacy of immature fruit and seeds as cytotoxic agents against human prostate cancer (PC3) and human colorectal cancer (HCT-116) cell lines. Collectively, such detailed profiling of parts provides novel evidence for B. aegyptiaca medicinal uses.PMID:37485437 | PMC:PMC10359763 | DOI:10.1039/d3ra03141a

Front Nutr. 2023 Jul 6;10:1183963. doi: 10.3389/fnut.2023.1183963. eCollection 2023.ABSTRACTINTRODUCTION: Coeliac disease is a lifelong immune-mediated enteropathy manifested as gluten intolerance in individuals carrying specific human leukocyte antigen (HLA) molecules. Other factors than genetics and gluten intake, however, may play a role in triggering the disease. The gut internal environment is thought to be one of these potential contributing factors, and it can be influenced throughout life.METHODS: We examine the impact of Lactiplantibacillus plantarum HEAL9 and Lacticaseibacillus paracasei 8700:2 supplementation on the faecal metabolome in genetically predisposed children having tissue transglutaminase autoantibodies, i.e., coeliac disease autoimmunity. Probiotic strains were selected based on their beneficial properties, including mucosal permeability and immune modulation effects. The intervention group (n = 40) and control group (n = 38) took the probiotics or placebo daily for 6 months in a double-blinded randomised trial. Faecal samples were collected at baseline and after 3 and 6 months and analysed using the 1H NMR for metabolome. The incorporation of 16S rRNA sequencing as a supportive dataset complemented the analysis of the metabolome data.RESULTS: During the 6 months of intervention, the stool concentrations of 4-hydroxyphenylacetate increased in the intervention group as compared to controls, whereas concentrations of threonine, valine, leucine, isoleucine, methionine, phenylalanine, aspartate, and fumarate decreased. Additionally, a noteworthy effect on the glycine, serine, and threonine metabolic pathway has been observed.CONCLUSION: The findings suggest a modest yet significant impact of the probiotics on the faecal metabolome, primarily influencing proteolytic processes in the gut.CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT03176095.PMID:37485388 | PMC:PMC10359497 | DOI:10.3389/fnut.2023.1183963