PubMed

Int J Mol Sci. 2024 Mar 18;25(6):3416. doi: 10.3390/ijms25063416.ABSTRACTIn arterial hypertension, the dysregulation of several metabolic pathways is closely associated with chronic immune imbalance and inflammation progression. With time, these disturbances lead to the development of progressive disease and end-organ involvement. However, the influence of cholecalciferol on metabolic pathways as a possible mechanism of its immunomodulatory activity in obesity-related hypertension is not known. In a phase 2, randomized, single-center, 24-week trial, we evaluated, as a secondary outcome, the serum metabolome of 36 age- and gender-matched adults with obesity-related hypertension and vitamin D deficiency, before and after supplementation with cholecalciferol therapy along with routine medication. The defined endpoint was the assessment of circulating metabolites using a nuclear magnetic resonance-based metabolomics approach. Univariate and multivariate analyses were used to evaluate the systemic metabolic alterations caused by cholecalciferol. In comparison with normotensive controls, hypertensive patients presented overall decreased expression of several amino acids (p < 0.05), including amino acids with ketogenic and glucogenic properties as well as aromatic amino acids. Following cholecalciferol supplementation, increases were observed in glutamine (p < 0.001) and histidine levels (p < 0.05), with several other amino acids remaining unaffected. Glucose (p < 0.05) and acetate (p < 0.05) decreased after 24 weeks in the group taking the supplement, and changes in the saturation of fatty acids (p < 0.05) were also observed, suggesting a role of liposoluble vitamin D in lipid metabolism. Long-term cholecalciferol supplementation in chronically obese and overweight hypertensives induced changes in the blood serum metabolome, which reflected systemic metabolism and may have fostered a new microenvironment for cell proliferation and biology. Of note, the increased availability of glutamine may be relevant for the proliferation of different T-cell subsets.PMID:38542390 | DOI:10.3390/ijms25063416

Int J Mol Sci. 2024 Mar 16;25(6):3366. doi: 10.3390/ijms25063366.ABSTRACTAuxin plays a crucial role in regulating root growth and development, and its distribution pattern under environmental stimuli significantly influences root plasticity. Under K deficiency, the interaction between K+ transporters and auxin can modulate root development. This study compared the differences in root morphology and physiological mechanisms of the low-K-tolerant maize inbred line 90-21-3 and K-sensitive maize inbred line D937 under K-deficiency (K+ = 0.2 mM) with exogenous NAA (1-naphthaleneacetic acid, NAA = 0.01 mM) treatment. Root systems of 90-21-3 exhibited higher K+ absorption efficiency. Conversely, D937 seedling roots demonstrated greater plasticity and higher K+ content. In-depth analysis through transcriptomics and metabolomics revealed that 90-21-3 and D937 seedling roots showed differential responses to exogenous NAA under K-deficiency. In 90-21-3, upregulation of the expression of K+ absorption and transport-related proteins (proton-exporting ATPase and potassium transporter) and the enrichment of antioxidant-related functional genes were observed. In D937, exogenous NAA promoted the responses of genes related to intercellular ethylene and cation transport to K-deficiency. Differential metabolite enrichment analysis primarily revealed significant enrichment in flavonoid biosynthesis, tryptophan metabolism, and hormone signaling pathways. Integrated transcriptomic and metabolomic analyses revealed that phenylpropanoid biosynthesis is a crucial pathway, with core genes (related to peroxidase enzyme) and core metabolites upregulated in 90-21-3. The findings suggest that under K-deficiency, exogenous NAA induces substantial changes in maize roots, with the phenylpropanoid biosynthesis pathway playing a crucial role in the maize root's response to exogenous NAA regulation under K-deficiency.PMID:38542340 | DOI:10.3390/ijms25063366

Int J Mol Sci. 2024 Mar 15;25(6):3347. doi: 10.3390/ijms25063347.ABSTRACTBladder cancer (BCa) research relying on Omics approaches has increased over the last few decades, improving the understanding of BCa pathology and contributing to a better molecular classification of BCa subtypes. To gain further insight into the molecular profile underlying the development of BCa, a systematic literature search was performed in PubMed until November 2023, following the PRISMA guidelines. This search enabled the identification of 25 experimental studies using mass spectrometry or nuclear magnetic resonance-based approaches to characterize the metabolite signature associated with BCa. A total of 1562 metabolites were identified to be altered by BCa in different types of samples. Urine samples displayed a higher likelihood of containing metabolites that are also present in bladder tumor tissue and cell line cultures. The data from these comparisons suggest that increased concentrations of L-isoleucine, L-carnitine, oleamide, palmitamide, arachidonic acid and glycoursodeoxycholic acid and decreased content of deoxycytidine, 5-aminolevulinic acid and pantothenic acid should be considered components of a BCa metabolome signature. Overall, molecular profiling of biological samples by metabolomics is a promising approach to identifying potential biomarkers for early diagnosis of different BCa subtypes. However, future studies are needed to understand its biological significance in the context of BCa and to validate its clinical application.PMID:38542319 | DOI:10.3390/ijms25063347

Int J Mol Sci. 2024 Mar 14;25(6):3295. doi: 10.3390/ijms25063295.ABSTRACTInflammatory bowel diseases are extremely common throughout the world. However, in most cases, it is asymptomatic at the initial stage. Therefore, it is important to develop non-invasive diagnostic methods that allow identification of the IBD risks in a timely manner. It is well known that gastrointestinal microbiota secrete volatile compounds (VOCs) and their composition may change in IBD. We propose a non-invasive method to identify the dynamics of IBD development in the acute and remission stage at the level of VOCs in model of dextran sulfate sodium (DSS) with chemically induced colitis measured by headspace GC/MS (HS GC/MS). Methods: VOCs profile was identified using a headspace GC/MS (HS GC/MS). GC/MS data were processed using MetaboAnalyst 5.0 and GraphPad Prism 8.0.1 software. The disease activity index (DAI) and histological method were used to assess intestinal inflammation. The peak of intestinal inflammation activity was reached on day 7, according to the disease activity index. Histological examination data showed changes in the intestine due to different stages of inflammation. As the acute inflammation stage was reached, the metabolomic profile also underwent changes, especially at the short-fatty acids level. A higher relative amounts of acetic acid (p value < 0.025) and lower relative amounts of propanoic acid (p value < 0.0005), butanoic acid (p value < 0.005) and phenol 4-methyl- (p value = 0.053) were observed in DSS7 group on day 7 compared to the control group. In remission stage, disease activity indexes decreased, and the histological picture also improved. But metabolome changes continued despite the withdrawal of the DSS examination. A lower relative amounts of propanoic acid (p value < 0.025), butanoic acid (p value < 0.0005), pentanoic acid (p value < 0.0005), and a significant de-crease of hexanoic acid (p value < 0.0005) relative amounts were observed in the DSS14 group compared to the control group on day 14. A model of DSS-induced colitis in rats was successfully implemented for metabolomic assessment of different stages of inflammation. We demonstrated that the ratios of volatile compounds change in response to DSS before the appearance of standard signs of inflammation, determined by DAI and histological examination. Changes in the volatile metabolome persisted even after visual intestine repair and it confirms the high sensitivity of the microbiota to the damaging effects of DSS. The use of HS GC/MS may be an important addition to existing methods for assessing inflammation at early stages.PMID:38542269 | DOI:10.3390/ijms25063295

Int J Mol Sci. 2024 Mar 11;25(6):3201. doi: 10.3390/ijms25063201.ABSTRACTChronic rhinosinusitis (CRS) is a significant public health problem. Bacterial colonization and impaired mucociliary clearance play a significant role in the inflammatory process. Several inflammatory pathways and host defense elements are altered in CRS, which may contribute to observed differences in the microbiome. To date, researching CRS has been difficult due to limited access to the studied tissue and a lack of available biomarkers. Ongoing scientific research is increasingly based on simple and objective analytical methods, including sensors, detection with PCR, and sequencing. Future research on microbiota and human factors should also include genomics, transcriptomics, and metabolomics approaches. This report analyzes the changes that occur in the paranasal sinuses of people with acute and chronic rhinosinusitis, the composition of the microbiota, the human genetic markers that may shed light on the predisposition to CRS, and the advantages and disadvantages of classical and molecular diagnostic methods, as well as addressing the difficulties of sinusitis treatment.PMID:38542175 | DOI:10.3390/ijms25063201

Int J Mol Sci. 2024 Mar 9;25(6):3158. doi: 10.3390/ijms25063158.ABSTRACTOsteoarthritis (OA) is a pathology of great impact worldwide. Its physiopathology is not completely known, and it is usually diagnosed by imaging techniques performed at advanced stages of the disease. The aim of this study was to evaluate early serum metabolome changes and identify the main metabolites involved in an inflammatory OA animal model. This study was performed on thirty rats. OA was induced in all animals by intra-articular injection of monoiodoacetate into the knee joint. Blood samples were taken from all animals and analyzed by mass spectrometry before OA induction and 28, 56, and 84 days following induction. Histological evaluation confirmed OA in all samples. The results of this study allow the identification of several changes in 18 metabolites over time, including organic acids, benzenoids, heterocyclic compounds, and lipids after 28 days, organic acids after 56 days, and lipid classes after 84 days. We conclude that OA induces serological changes in the serum metabolome, which could serve as potential biomarkers. However, it was not possible to establish a relationship between the identified metabolites and the time at which the samples were taken. Therefore, these findings should be confirmed in future OA studies.PMID:38542132 | DOI:10.3390/ijms25063158

Int J Mol Sci. 2024 Mar 8;25(6):3134. doi: 10.3390/ijms25063134.ABSTRACTOne of the common illnesses that affect women's physical and mental health is urinary tract infection (UTI). The disappointing results of empirical anti-infective treatment and the lengthy time required for urine bacterial culture are two issues. Antibiotic misuse is common, especially in females who experience recurrent UTI (rUTI). This leads to a higher prevalence of antibiotic resistance in the microorganisms that cause the infection. Antibiotic therapy will face major challenges in the future, prompting clinicians to update their practices. New testing techniques are making the potential association between the urogenital microbiota and UTIs increasingly apparent. Monitoring changes in female urinary tract (UT) microbiota, as well as metabolites, may be useful in exploring newer preventive treatments for UTIs. This review focuses on advances in urogenital microbiology and organismal metabolites relevant to the identification and handling of UTIs in an attempt to provide novel methods for the identification and management of infections of the UT. Particular attention is paid to the microbiota and metabolites in the patient's urine in relation to their role in supporting host health.PMID:38542107 | DOI:10.3390/ijms25063134

J Pers Med. 2024 Feb 28;14(3):262. doi: 10.3390/jpm14030262.ABSTRACTBACKGROUND: Primary liver cancer (PLC) ranks third in terms of fatality rate among all malignant tumors worldwide. Proteomics and metabolomics have become widely utilized in identifying causes and diagnostic indicators of PLC. Nevertheless, in studies aiming to identify proteins/metabolites that experienced significant changes before PLC, the potential impact of reverse causation and confounding variables still needs to be fully addressed.METHODS: This study thoroughly investigated the causal relationship between 4719 blood proteins, 21 amino acids, and the risk of PLC using the Mendelian randomization (MR) method. In addition, through a comprehensive analysis of the TCGA-LIHC cohort and GEO databases, we evaluated the differentially expressed genes (DEGs) related to serine metabolism in diagnosing and predicting the prognosis of patients with PLC.RESULTS: A total of 63 proteins have been identified as connected to the risk of PLC. Additionally, there has been confirmation of a positive cause-effect between PLC and the concentration of serine. The integration of findings from both MR analyses determined that the protein associated with PLC risk exhibited a significant correlation with serine metabolism. Upon careful analysis of the TCGA-LIHC cohort, it was found that eight DEGs are linked to serine metabolism. After thoroughly validating the GEO database, two DEGs, TDO2 and MICB, emerged as potential biomarkers for diagnosing PLC.CONCLUSIONS: Two proteins involved in serine metabolism, MICB and TDO2, are causally linked to the risk of PLC and could potentially be used as diagnostic indicators.PMID:38541004 | DOI:10.3390/jpm14030262

J Pers Med. 2024 Feb 20;14(3):225. doi: 10.3390/jpm14030225.ABSTRACTSepsis is one of the most common causes of morbidity and mortality worldwide. Despite the remarkable advances in modern medicine throughout the last century, the mortality rates associated with sepsis have remained significantly elevated, both in high- and low-income countries. The main difficulty in the diagnosis and treatment of septic patients is the tremendous heterogeneity of this condition. The vast heterogeneity that characterizes sepsis ranges from the clinical presentation to the biological aspects of the disease. Evidence-based medicine approaches sepsis as a homogenous syndrome and does not consider the individual discrepancies between septic patients. This approach may contribute to the poor outcomes of septic patients. In recent years, personalized medicine has gained significant interest. This novel form of medicine underlines the importance of understanding the genetic, epigenetic, and molecular basis of a disease in order to provide a more tailored approach for the patient. The study of "omics", such as cytomics, genomics, epigenomics, transcriptomics, proteomics, and metabolomics, provides a deeper comprehension of the complex interactions between the host, the disease, and the environment. The aim of this review is to summarize the potential role of a personalized approach in sepsis management, considering the interactions between various "omics".PMID:38540968 | DOI:10.3390/jpm14030225

Foods. 2024 Mar 21;13(6):956. doi: 10.3390/foods13060956.ABSTRACTWith increasing interest in Korean foods and beverages, Korean traditional alcoholic beverages need to be studied. To characterize Korean traditional alcoholic beverages, we analyzed the metabolites of Takju, Yakju, and Traditional-Soju using 48 commercial products. We performed non-targeted metabolite profiling using gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) and identified 33 significantly discriminant metabolites, including nine organic acids, three amino acids, and seven fatty acids, in the three types of alcoholic beverage. Subsequently, we quantified the profiled metabolites in each product and compared their contents to identify alcoholic beverage type-specific metabolites. Thus, we figured out seven metabolites using receiver operating characteristic (ROC) curves. The results revealed that octadecanoic acid (limit of detection (LOD) to 168.72 mg/L), nonanoic acid (LOD to 112.54 mg/L), and octanoic acid (8.00 to 145.08 mg/L) in Takju; succinic acid (LOD to 1.90 mg/mL), heptanoic acid (LOD to 343.23 mg/L), and hexadecanoic acid (20.28 to 126.45 mg/L) in Yakju; and malonic acid (LOD to 19.13 mg/mL) in Traditional-Soju, with an area under the curve (AUC) > 0.7, are important metabolites that can distinguish the type of alcoholic beverage. Our results provide qualitative and quantitative metabolite information about Korean traditional alcoholic beverages that can be used by consumers and manufacturers.PMID:38540946 | DOI:10.3390/foods13060956

Foods. 2024 Mar 19;13(6):926. doi: 10.3390/foods13060926.ABSTRACTElaeagnus moorcroftii Wall.ex Schlecht. (EWS) has extensive nutrients and functional active ingredients, which makes it an excellent potential substrate for fermentation. The improvement in the antioxidant activity of Elaeagnus moorcroftii Wall.ex Schlecht. juice (EWSJ) fermented by Bifidobacterium animalis subsp. lactis HN-3 (B.an3) could be attributed to the metabolism and biotransformation of plant-based products by the bacterial strain. To reveal the underlying mechanism, non-targeted metabolomics was applied in this study. After fermentation, the structure of downregulated carbohydrates, amino acids, fatty acids, and flavonoids was changed by Bifidobacterium biotransformation (included four reductions, three hydrolyses, four isomerizations, three deglycosidations, and five other reactions). The structure of these converted upregulated products has a higher antioxidant ability to reduce free radicals than their precursors, such as the flavonoids in the form of hydrolyzed conjugates, amino acids with multiple sulfhydryls or hydroxys, carbohydrates with reactive oxygen on benzene rings and fatty acids with unsaturated bonds, short chains, and glycosides. These findings shed light on the mechanism of the metabolism and biotransformation of EWSJ by B.an3, facilitate the study of the interaction between probiotics and fermented plant-based products, and provide a theoretical basis for the development of Bifidobacterium-fermented plant products with stronger functional activities.PMID:38540916 | DOI:10.3390/foods13060926

Foods. 2024 Mar 17;13(6):913. doi: 10.3390/foods13060913.ABSTRACTINTRODUCTION: Goat milk has poorer fermentation characteristics due to the absence or only traces of αs1-casein, due to which goat yoghurt contains a less dense gel structure. Moreover, the fermentation characteristics of the milk vary between the breeds of the same species. Therefore, it becomes imperative to explore a few metabolites which could regulate the techno-functional properties of goat yoghurt.OBJECTIVES: This study was aimed at relating the metabolite profile of yoghurt prepared from milk of Barbari, an indigenous goat breed of India, and its techno-functional properties (firmness, whey syneresis, and flow behaviour) using multivariate data analysis and regression models.RESULTS: Goat yoghurt was prepared with two different total solids (TS) levels (12 and 16%) and cultures, namely, commercial culture comprising a thermophilic yoghurt culture (A) and NCDC-263 comprising a mixed yoghurt culture (B). Results demonstrated a significant difference (p < 0.05) in whey syneresis with the increase in the TS level. Flow behaviour of all yoghurt samples showed a decrease in viscosity with an increase in shear rate, which confirmed its non-Newtonian behaviour and shear thinning nature, whereas frequency sweep confirmed its viscoelastic nature. Firmness was the most affected under the influence of different TS and culture levels. It was higher (p < 0.05) for 16-A, followed by 16-3B, and minimum for 12-2B. GC-MS-based metabolomics of the yoghurt revealed a total of 102 metabolites, out of which 15 metabolites were differentially expressed (p < 0.05), including 2-hydroxyethyl palmitate, alpha-mannobiose, and myo-inositol. Multivariate data analysis revealed clear separation among groups using principal component analysis and several correlations using a correlation heat map. Further, regression analysis exhibited methylamine (0.669) and myo-inositol (0.947) with higher regression coefficients (R2 values) exceeding 0.6, thus demonstrating their significant influence on the techno-functional properties, mainly firmness, of the yogurt.CONCLUSION: In conclusion, A gas chromatography-based metabolomics approach could successfully establish a relationship between the metabolome and the techno-functional properties of the yoghurt.PMID:38540903 | DOI:10.3390/foods13060913

Foods. 2024 Mar 15;13(6):895. doi: 10.3390/foods13060895.ABSTRACTLigilactobacillus salivarius (basonym: Lactobacillus salivarius, L. salivarius) is a type of lactic acid bacteria (LAB) commonly found in the oropharyngeal-gastrointestinal tract (OGT). It has gained significant attention due to its probiotic and functional properties as well as its various health-promoting roles. L. salivarius strains exhibit strong resistance and adhesion in the OGT along with outstanding antioxidant and antimicrobial properties. Additionally, numerous L. salivarius strains have the ability to produce bacteriocins with antagonistic activity. These probiotic characteristics of L. salivarius indicate its remarkable potential in promoting favorable effects on human health. It has also been observed that L. salivarius has a positive effect on the composition of intestinal microbiota, thereby improving the metabolic profiling of intestinal microbiota, promoting a healthy and balanced internal environment. In recent years, multi-omics technologies such as genomics, transcriptomics, proteomics and metabolomics have been employed to gain a deeper understanding of the roles and mechanisms of L. salivarius associated with its functional properties. This review aims to provide an overview of the probiotic characteristics of L. salivarius, containing its specific interactions with the host microflora, as well as insights from omics studies.PMID:38540885 | DOI:10.3390/foods13060895

Foods. 2024 Mar 13;13(6):867. doi: 10.3390/foods13060867.ABSTRACTThe composition of culture substrate is an important environmental factor that affects the growth and metabolism of Hypsizygus marmoreus, and sawdust is commonly used as the substrate for cultivating mushrooms. However, the influences of sawdust on metabolic level of H. marmoreus in mycelial growth is little reported. In this study, the effect of sawdust addition on mycelial growth rate, morphological characteristics and nutrient content of H. marmoreus was explored, and the metabolic response was analyzed based on LC-MS/MS. The results showed the mycelial growth rates and the number of mycelial clamp connections in sawdust medium A and sawdust medium B were significantly higher than that of the basic medium (Control). The mycelial morphology in sawdust medium A was denser, with higher edge trimness and stronger aerial mycelia. The contents of crude fiber, crude protein and polysaccharide of the mycelia from sawdust medium A increased by 85.15%, 90.65% and 92.61%, respectively, compared to that in the basic medium. A total of 551 metabolites were identified and obtained. The differential accumulated metabolites (DAMs) were mainly amino acids, lipids compounds and carbohydrates. It was speculated that the addition of sawdust played a vital role in promoting the cell division and, thus, the formation of clamp connections in H. marmoreus mycelia. Regarding amino acids, the metabolism of glycine, serine and ABC transporters was active with the increase in sawdust, thereby increasing the protein content. And some valuable bioactive molecules were found, such as docosahexaenoic acid (DHA). This study will lay the foundation for further research on the substance transformation and quality improvement of cultivation substrate for mushrooms.PMID:38540857 | DOI:10.3390/foods13060867

Foods. 2024 Mar 8;13(6):835. doi: 10.3390/foods13060835.ABSTRACTEdible plant and fruit-derived nanovesicles (NVs) are membrane-enclosed particles with round-shape morphology and signaling functions, which resemble mammalian cell-derived extracellular vesicles. These NVs can transmit cross-kingdom signals as they contain bioactive molecules and exert biological effects on mammalian cells. Their properties and stability in the gastrointestinal tract suggest NVs as a promising nutraceutical tool. In this study, we have demonstrated for the first time the presence of NVs in olive vegetation water (OVW), a waste by-product generated during olive oil production. Biophysical characterization by scanning electron microscopy, cryo-transmission electron microscopy, and nanoparticle tracking analysis revealed the presence in OVW of NVs having size and morphology similar to that of vesicles isolated from edible plants. Integrated lipidomic, metabolomic, and proteomic analyses showed that OVW-NVs carry a set of lipids, metabolites and proteins which have recognized antioxidant and anti-inflammatory activities. The nature of biomolecules identified in OVW-NVs suggests that these vesicles could exert beneficial effects on mammalian cells and could be used in the nutraceutical and food industries. The successful isolation of OVW-NVs and the characterization of their features strengthen the idea that agricultural waste might represent a source of NVs having features similar to NVs isolated from edible plants/fruits.PMID:38540825 | DOI:10.3390/foods13060835

Foods. 2024 Mar 8;13(6):827. doi: 10.3390/foods13060827.ABSTRACTCitri Reticulatae Pericarpium, especially the pericarp of Citrus reticulata Blanco cv. Chachiensis (PCRC), is an important edible and medicinal ingredient for health and pharmacological properties. Citrus Huanglongbing, a devastating disease that currently threatens the citrus industry worldwide, is caused by a phloem-limited alpha-proteobacterium, "Candidatus Liberibacter asiaticus" (CLas). The industry of cultivar Chachiensis has been suffering from HLB. Although HLB affected the quality of citrus fruit, whether the quality of PCRC was affected by HLB remains unclear. In this study, we compared the metabolite profiles between HLB-affected and healthy PCRC from three sources: fresh, 6-month-old, and 9-year-old PCRC, through the untargeted LC-MS method. Compared to healthy controls, various types of bioactive compounds, mainly flavonoids, terpenoids, alkaloids, coumarins, polysaccharides, and phenolic acids, accumulated in HLB-affected PCRC, especially in the HLB-affected 9-year PCRC. In particular, isorhamnetin, isoliquiritigenin, luteolin 7-O-beta-D-glucoside, limonin, geniposide, pyrimidodiazepine, scoparone, chitobiose, m-coumaric acid, malonate, and pantothenic acid, which contributed to the pharmacological activity and health care effects of PCRC, were highly accumulated in HLB-affected 9-year-old PCRC compared to the healthy control. Multibioassay analyses revealed that HLB-affected 9-year-old PCRC had a higher content of total flavonoids and total polyphenols and exhibited similar antioxidant capacity as compared to healthy controls. The results of this study provided detailed information on the quality of HLB-affected PCRC.PMID:38540817 | DOI:10.3390/foods13060827

Biomolecules. 2024 Mar 13;14(3):344. doi: 10.3390/biom14030344.ABSTRACTThe eubiotic state of the gut microbiota is primarily brought about by various probiotic species that colonize the gut. It is becoming very clear that the probiotic-metabolite mixtures in the gut luminal milieu is central in establishing cross-kingdom signalling networks to maintain gut-multi-organ axes health. Culturally, different fermented foods and beverages have been regional staples since ancient times, and are known to be enriched with probiotics. However, regional variations including the environment, the staple food source (prebiotics), and fermentation methods, among other factors, influence the fermenting probiotic species. Fermented rice water (FRW), an economical, easy to make, simple beverage is a rich source of synbiotics. Therefore, consumption of fermented rice water allows for the intake of a variety of region-specific live probiotics. The secondary metabolites (postbiotics) present in such symbiotic mixtures may also contribute toward maintaining normal intestinal cellular functions. In this study, we highlight that regional staples such as rice consumed in their fermented form may hold promise in alleviating gut-related diseases. Our results show that simple overnight fermentation of cooked edible rice enables the growth of probiotic bacterial species belonging to the Lactic Acid Bacteria group (Leuconostoc lactis, Weisella confusa, Weisella cibacria, Lactococcus lactis, lactococcus taiwanensis, Lactobacillus fermentum, Lactobacillus nagelii, and Lactobacillus delbrueckii ssp. indicus). Metabolomic analysis of the overnight fermented and over two-nights fermented rice water identified more than 200 postbiotic metabolites. Our results show that postbiotics contributing to energy metabolism, gut-multiorgan axes, and microbial paraprobiotics are enriched in the overnight (~10 h) fermented rice water as compared to the over two-nights fermented rice water. Functional analysis via gene expression studies for nutrient absorption (mct-1 and mct-2) and barrier integrity (occludin and zo-1) reveals significant upregulation of these genes upon FRW treatment of HT29 colon cells. This study is a first-of-its-kind to demonstrate the proof-of-principle that postbiotics of naturally fermented rice water positively modulates colonocyte health.PMID:38540763 | DOI:10.3390/biom14030344

Biomolecules. 2024 Mar 7;14(3):319. doi: 10.3390/biom14030319.ABSTRACTICT1 is an Arabidopsis thaliana line that overexpresses the gene encoding the S30 ribosomal subunit, leading to tolerance to exogenous indole-3-carbinol. Indole-3-carbinol (I3C) is a protective chemical formed as a breakdown of I3M in cruciferous vegetables. The overexpression of S30 in ICT1 results in transcriptional changes that prime the plant for the I3C, or biotic insult. Emerging evidence suggests that ribosomal proteins play important extra-ribosomal roles in various biochemical and developmental processes, such as transcription and stress resistance. In an attempt to elucidate the mechanism leading to I3C and stress resistance in ICT1, and using a multi-pronged approach employing transcriptomics, metabolomics, phenomics, and physiological studies, we show that overexpression of S30 leads to specific transcriptional alterations, which lead to both changes in metabolites connected to biotic and oxidative stress tolerance and, surprisingly, to photomorphogenesis.PMID:38540739 | DOI:10.3390/biom14030319

Biomolecules. 2024 Mar 5;14(3):307. doi: 10.3390/biom14030307.ABSTRACTPurpose: to determine the metabolomics profiles in the plasma samples of primary open-angle glaucoma (POAG) patients. Methods: The plasma samples from 20 POAG patients under intraocular pressure (IOP)-lowering medication treatment and 20 control subjects were subjected to the untargeted metabolomics analysis, among which 10 POAG patients and 10 control subjects were further subjected to the oxylipin-targeted metabolomics analysis by liquid chromatography-mass spectrometry analysis. The prediction accuracy of the differentially abundant metabolites was assessed by the receiver operating characteristic curves. Pathway analysis and correlation analysis on the differentially abundant metabolites and clinical and biochemical parameters were also conducted. Results: Untargeted metabolomics profiling identified 33 differentially abundant metabolites in the POAG patients, in which the metabolism of linoleic acid, α-linolenic acid, phenylalanine, and tricarboxylic acid cycle were enriched. The correlation analysis indicated that the differentially abundant metabolites were associated with central corneal thickness, peripapillary retinal nerve fiber layer thickness, visual field defects, and lymphocytes. The oxylipin-targeted metabolomics analysis identified 15-keto-Prostaglandin F2 alpha, 13,14-Dihydro-15-keto-prostaglandin D2, 11-Dehydro-thromboxane B2, 8,9-Epoxyeicosatrienoic acid, and arachidonic acid to be significantly decreased in the POAG patients and enriched in the arachidonic acid (AA) pathway. Conclusions: This study revealed that the metabolites in the arachidonic acid metabolism pathway are differentially abundant, suggesting high IOP may not be the only detrimental factor for optic nerve cell damage in this group of POAG patients. Lipid metabolism instability-mediated alterations in oxylipins and AA pathways may be important in POAG, suggesting that oxidative stress and immune-related inflammation could be valuable directions for future therapeutic strategies.PMID:38540727 | DOI:10.3390/biom14030307

Biomolecules. 2024 Mar 1;14(3):296. doi: 10.3390/biom14030296.ABSTRACTThe severity of COVID-19 is linked to an imbalanced immune response. The dysregulated metabolism of small molecules and bioactive lipids has also been associated with disease severity. To promote understanding of the disease biochemistry and provide targets for intervention, we applied a range of LC-MS platforms to analyze over 100 plasma samples from patients with varying COVID-19 severity and with detailed clinical information on inflammatory responses (>30 immune markers). This is the third publication in a series, and it reports the results of comprehensive lipidome profiling using targeted LC-MS/MS. We identified 1076 lipid features across 25 subclasses, including glycerophospholipids, sterols, glycerolipids, and sphingolipids, among which 531 lipid features were dramatically changed in the plasma of intensive care unit (ICU) patients compared to patients in the ward. Patients in the ICU showed 1.3-57-fold increases in ceramides, (lyso-)glycerophospholipids, diglycerides, triglycerides, and plasmagen phosphoethanolamines, and 1.3-2-fold lower levels of a cyclic lysophosphatidic acid, sphingosine-1-phosphates, sphingomyelins, arachidonic acid-containing phospholipids, lactosylceramide, and cholesterol esters compared to patients in the ward. Specifically, phosphatidylinositols (PIs) showed strong fatty acid saturation-dependent behavior, with saturated fatty acid (SFA)- and monosaturated fatty acid (MUFA)-derived PI decreasing and polystaturated (PUFA)-derived PI increasing. We also found ~4000 significant Spearman correlations between lipids and multiple clinical markers of immune response with |R| ≥ 0.35 and FDR corrected Q < 0.05. Except for lysophosphatidic acid, lysophospholipids were positively associated with the CD4 fraction of T cells, and the cytokines IL-8 and IL-18. In contrast, sphingosine-1-phosphates were negatively correlated with innate immune markers such as CRP and IL-6. Further indications of metabolic changes in moderate COVID-19 disease were demonstrated in recovering ward patients compared to those at the start of hospitalization, where 99 lipid species were altered (6 increased by 30-62%; 93 decreased by 1.3-2.8-fold). Overall, these findings support and expand on early reports that dysregulated lipid metabolism is involved in COVID-19.PMID:38540716 | DOI:10.3390/biom14030296