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

Metabolite Profiling to Evaluate Metabolic Changes in Genetically Modified Protopanaxadiol-Enriched Rice

Sat, 25/02/2023 - 12:00
Plants (Basel). 2023 Feb 8;12(4):758. doi: 10.3390/plants12040758.ABSTRACTEvent DS rice producing protopanaxadiol (PPD) has been previously developed by inserting Panax ginseng dammarenediol-II synthase gene (PgDDS) and PPD synthase gene (CYP716A47). We performed a gas chromatography-mass spectrometry (GC-MS)-based metabolomics of the DS rice to identify metabolic alterations as the effects of genetic engineering by measuring the contents of 65 metabolites in seeds and 63 metabolites in leaves. Multivariate analysis and one-way analysis of variance between DS and non-genetically modified (GM) rice showed that DS rice accumulated fewer tocotrienols, tocopherols, and phytosterols than non-GM rice. These results may be due to competition for the same precursors because PPDs in DS rice are synthesized from the same precursors as those of phytosterols. In addition, multivariate analysis of metabolic data from rice leaves revealed that composition differed by growth stage rather than genetic modifications. Our results demonstrate the potential of metabolomics for identifying metabolic alterations in response to genetic modifications.PMID:36840106 | DOI:10.3390/plants12040758

The Combination of Both Heat and Water Stresses May Worsen Botryosphaeria Dieback Symptoms in Grapevine

Sat, 25/02/2023 - 12:00
Plants (Basel). 2023 Feb 8;12(4):753. doi: 10.3390/plants12040753.ABSTRACT(1) Background: Grapevine trunk diseases (GTDs) have become a global threat to vineyards worldwide. These diseases share three main common features. First, they are caused by multiple pathogenic micro-organisms. Second, these pathogens often maintain a long latent phase, which makes any research in pathology and symptomatology challenging. Third, a consensus is raising to pinpoint combined abiotic stresses as a key factor contributing to disease symptom expression. (2) Methods: We analyzed the impact of combined abiotic stresses in grapevine cuttings artificially infected by two fungi involved in Botryosphaeria dieback (one of the major GTDs), Neofusicoccum parvum and Diplodia seriata. Fungal-infected and control plants were subjected to single or combined abiotic stresses (heat stress, drought stress or both). Disease intensity was monitored thanks to the measurement of necrosis area size. (3) Results and conclusions: Overall, our results suggest that combined stresses might have a stronger impact on disease intensity upon infection by the less virulent pathogen Diplodia seriata. This conclusion is discussed through the impact on plant physiology using metabolomic and transcriptomic analyses of leaves sampled for the different conditions.PMID:36840101 | DOI:10.3390/plants12040753

Modulation of Morpho-Physiological and Metabolic Profiles of Lettuce Subjected to Salt Stress and Treated with Two Vegetal-Derived Biostimulants

Sat, 25/02/2023 - 12:00
Plants (Basel). 2023 Feb 6;12(4):709. doi: 10.3390/plants12040709.ABSTRACTSalinity in water and soil is a critical issue for food production. Using biostimulants provides an effective strategy to protect crops from salinity-derived yield losses. The research supports the effectiveness of protein hydrolysate (PH) biostimulants based on their source material. A greenhouse experiment was performed on lettuce plants under control (0 mM NaCl) and high salinity conditions (30 mM NaCl) using the Trainer (T) and Vegamin (V) PH biostimulants. The recorded data included yield parameters, mineral contents, auxiliary pigments, and polyphenolics. The plant sample material was further analyzed to uncover the unique metabolomic trace of the two biostimulants. The results showed an increased yield (8.9/4.6%, T/V) and higher photosynthetic performance (14%) compared to control and salinity treatments. Increased yield in salinity condition by T compared to V was deemed significant due to the positive modulation in stress-protecting molecules having an oxidative stress relief effect such as lutein (39.9% 0 × T vs. 30 × V), β-carotene (23.4% vs. V overall), and flavonoids (27.7% vs. V). The effects of PH biostimulants on the physio-chemical and metabolic performance of lettuce plants are formulation dependent. However, they increased plant growth under stress conditions, which can prove profitable.PMID:36840057 | DOI:10.3390/plants12040709

Metabolomics Profiling Reveals the Role of PEDF in Triple-Negative Breast Cancer Cell MDA-MB-231 under Glycaemic Loading

Sat, 25/02/2023 - 12:00
Pharmaceutics. 2023 Feb 6;15(2):543. doi: 10.3390/pharmaceutics15020543.ABSTRACTPigment epithelium-derived factor (PEDF) is a secreted glycoprotein that belongs to the serine protease inhibitor (serpin) family. An increase in PEDF activity has been shown to be a potent inhibitor of tumour progression and proliferation, suggesting a possible therapeutic target. There is still a great deal to learn about how PEDF controls metabolic pathways in breast cancer and its metastatic form. Given this, the primary purpose of this study was to use a metabolomics approach to gain a better understanding of the mechanisms driving the reprogramming of metabolic events involved in breast cancer pertaining to PEDF under various glycaemic loads. We employed gas chromatography-quadrupole mass spectrometry (GC-Q-MS) to investigate metabolic changes in the triple-negative breast cancer (TNBC) cell line MDA-MB-231 treated with PEDF under glycaemic loading. Multivariate and univariate analyses were carried out as indicative tools via MetaboAnalyst (V.5.0) and R packages to identify the significantly altered metabolites in the MDA-MB-231 cell line after PEDF exposure under glycaemic loading. A total of 61 metabolites were found, of which nine were selected to be distinctively expressed in MDA-MB-231 cells under glycaemic conditions and exhibited differential responses to PEDF (p < 0.05, VIP > 1). Abnormalities in amino acid metabolism pathways were observed. In particular, glutamic acid, glutamine, and phenylalanine showed different levels of expression across different treatment groups. The lactate and glucose-6-phosphate production significantly increased in high-glucose vs. normal conditions while it decreased when the cells were exposed to PEDF, confirming the positive influence on the Warburg effect. The TCA cycle intermediates, including malate and citric acid, showed different patterns of expression. This is an important finding in understanding the link of PEDF with metabolic perturbation in TNBC cells in response to glycaemic conditions. Our findings suggest that PEDF significantly influenced the Warburg effect (as evidenced by the significantly lower levels of lactate), one of the well-known metabolic reprogramming pathways in cancer cells that may be responsive to metabolic-targeted therapeutic strategies. Moreover, our results demonstrated that GC-MS-based metabolomics is an effective tool for identifying metabolic changes in breast cancer cells after glycaemic stress or in response to PEDF treatment.PMID:36839865 | DOI:10.3390/pharmaceutics15020543

Sonoporation of the Round Window Membrane on a Sheep Model: A Safety Study

Sat, 25/02/2023 - 12:00
Pharmaceutics. 2023 Jan 29;15(2):442. doi: 10.3390/pharmaceutics15020442.ABSTRACTSonoporation using microbubble-assisted ultrasound increases the permeability of a biological barrier to therapeutic molecules. Application of this method to the round window membrane could improve the delivery of therapeutics to the inner ear. The aim of this study was to assess the safety of sonoporation of the round window membrane in a sheep model. To achieve this objective, we assessed auditory function and cochlear heating, and analysed the metabolomics profiles of perilymph collected after sonoporation, comparing them with those of the control ear in the same animal. Six normal-hearing ewes were studied, with one sonoporation ear and one control ear for each. A mastoidectomy was performed on both ears. On the sonoporation side, Vevo MicroMarker® microbubbles (MBs; VisualSonics-Fujifilm, Amsterdam, The Netherlands) at a concentration of 2 × 108 MB/mL were locally injected into the middle ear and exposed to 1.1 MHz sinusoidal ultrasonic waves at 0.3 MPa negative peak pressure with 40% duty cycle and 100 μs interpulse period for 1 min; this was repeated three times with 1 min between applications. The sonoporation protocol did not induce any hearing impairment or toxic overheating compared with the control condition. The metabolomic analysis did not reveal any significant metabolic difference between perilymph samples from the sonoporation and control ears. The results suggest that sonoporation of the round window membrane does not cause damage to the inner ear in a sheep model.PMID:36839763 | DOI:10.3390/pharmaceutics15020442

Integrating Transcriptomics and Metabolomics to Explore the Novel Pathway of <em>Fusobacterium nucleatum</em> Invading Colon Cancer Cells

Sat, 25/02/2023 - 12:00
Pathogens. 2023 Jan 28;12(2):201. doi: 10.3390/pathogens12020201.ABSTRACTColorectal cancer (CRC) is a malignancy with a very high incidence and mortality rate worldwide. Fusobacterium nucleatum bacteria and their metabolites play a role in inducing and promoting CRC; however, no studies on the exchange of information between Fusobacterium nucleatum extracellular vesicles (Fnevs) and CRC cells have been reported. Our research shows that Fusobacterium nucleatum ATCC25586 secretes extracellular vesicles carrying active substances from parental bacteria which are endocytosed by colon cancer cells. Moreover, Fnevs promote the proliferation, migration, and invasion of CRC cells and inhibit apoptosis; they also improve the ability of CRC cells to resist oxidative stress and SOD enzyme activity. The genes differentially expressed after transcriptome sequencing are mostly involved in the positive regulation of tumor cell proliferation. After detecting differential metabolites using liquid chromatography-tandem mass spectrometry, Fnevs were found to promote cell proliferation by regulating amino acid biosynthesis in CRC cells and metabolic pathways such as central carbon metabolism, protein digestion, and uptake in cancer. In summary, this study not only found new evidence of the synergistic effect of pathogenic bacteria and colon cancer tumor cells, but also provides a new direction for the early diagnosis and targeted treatment of colon cancer.PMID:36839472 | DOI:10.3390/pathogens12020201

Anti-Hyperuricemic Effect of Anserine Based on the Gut-Kidney Axis: Integrated Analysis of Metagenomics and Metabolomics

Sat, 25/02/2023 - 12:00
Nutrients. 2023 Feb 15;15(4):969. doi: 10.3390/nu15040969.ABSTRACTNowadays, developing effective intervention substances for hyperuricemia has become a public health issue. Herein, the therapeutic ability of anserine, a bioactive peptide, was validated through a comprehensive multiomics analysis of a rat model of hyperuricemia. Anserine was observed to improve liver and kidney function and modulate urate-related transporter expressions in the kidneys. Urine metabolomics showed that 15 and 9 metabolites were significantly increased and decreased, respectively, in hyperuricemic rats after the anserine intervention. Key metabolites such as fructose, xylose, methionine, erythronic acid, glucaric acid, pipecolic acid and trans-ferulic acid were associated with ameliorating kidney injury. Additionally, anserine regularly changed the gut microbiota, thereby ameliorating purine metabolism abnormalities and alleviating inflammatory responses. The integrated multiomics analysis indicated that Saccharomyces, Parasutterella excrementihominis and Emergencia timonensis were strongly associated with key differential metabolites. Therefore, we propose that anserine improved hyperuricemia via the gut-kidney axis, highlighting its potential in preventing and treating hyperuricemia.PMID:36839325 | DOI:10.3390/nu15040969

A Novel Symbiotic Formulation Reduces Obesity and Concomitant Metabolic Syndrome in Rats by Raising the Relative Abundance of Blautia

Sat, 25/02/2023 - 12:00
Nutrients. 2023 Feb 14;15(4):956. doi: 10.3390/nu15040956.ABSTRACTObesity is regarded as an abnormal or excessive buildup of fat that may be bad for health and is influenced by a combination of intestinal flora, genetic background, physical activity level and environment. Symbiotic supplementation may be a realistic and easy therapy for the reversal of obesity and associated metabolic problems. In this study, we chose two Bifidobacterium species, three Lactobacilli species and four prebiotics to make a new symbiotic formulation. High or low doses of the symbiotic were administered to rats, and biochemical indicators were recorded to assess the biological effects in a high-fat-diet-induced rat model. The underlying mechanisms were explored by integrating 16S rRNA sequencing with an extensively targeted metabolome. High-dose symbiotic supplementation was effective in reducing obesity and concomitant metabolic syndrome. The high-dose symbiotic also significantly increased the abundance of Blautia, which was negatively correlated with taurocholic acid and the main differential metabolites involved in amino acid and bile acid metabolism. While the low-dose symbiotic had some therapeutic effects, they were not as strong as those at the high dose, demonstrating that the effects were dose-dependent. Overall, our novel symbiotic combination improved plasma glucose and lipid levels, shrunk adipocyte size, restored liver function, increased the abundance of Blautia and adjusted bile acid and amino acid metabolism.PMID:36839314 | DOI:10.3390/nu15040956

An Oxylipin-Related Nutrient Pattern and Risk of Type 1 Diabetes in the Diabetes Autoimmunity Study in the Young (DAISY)

Sat, 25/02/2023 - 12:00
Nutrients. 2023 Feb 14;15(4):945. doi: 10.3390/nu15040945.ABSTRACTOxylipins, pro-inflammatory and pro-resolving lipid mediators, are associated with the risk of type 1 diabetes (T1D) and may be influenced by diet. This study aimed to develop a nutrient pattern related to oxylipin profiles and test their associations with the risk of T1D among youth. The nutrient patterns were developed with a reduced rank regression in a nested case-control study (n = 335) within the Diabetes Autoimmunity Study in the Young (DAISY), a longitudinal cohort of children at risk of T1D. The oxylipin profiles (adjusted for genetic predictors) were the response variables. The nutrient patterns were tested in the case-control study (n = 69 T1D cases, 69 controls), then validated in the DAISY cohort using a joint Cox proportional hazards model (n = 1933, including 81 T1D cases). The first nutrient pattern (NP1) was characterized by low beta cryptoxanthin, flavanone, vitamin C, total sugars and iron, and high lycopene, anthocyanidins, linoleic acid and sodium. After adjusting for T1D family history, the HLA genotype, sex and race/ethnicity, NP1 was associated with a lower risk of T1D in the nested case-control study (OR: 0.44, p = 0.0126). NP1 was not associated with the risk of T1D (HR: 0.54, p-value = 0.1829) in the full DAISY cohort. Future studies are needed to confirm the nested case-control findings and investigate the modifiable factors for oxylipins.PMID:36839302 | DOI:10.3390/nu15040945

Demand for Water-Soluble Vitamins in a Group of Patients with CKD versus Interventions and Supplementation-A Systematic Review

Sat, 25/02/2023 - 12:00
Nutrients. 2023 Feb 8;15(4):860. doi: 10.3390/nu15040860.ABSTRACTBACKGROUND: Increasingly, chronic kidney disease (CKD) is becoming an inevitable consequence of obesity, metabolic syndrome, and diabetes. As the disease progresses, and through dialysis, the need for and loss of water-soluble vitamins both increase. This review article looks at the benefits and possible risks of supplementing these vitamins with the treatment of CKD.METHODS: Data in the PubMed and Embase databases were analyzed. The keywords "chronic kidney disease", in various combinations, are associated with thiamin, riboflavin, pyridoxine, pantothenic acid, folates, niacin, cobalamin, and vitamin C. This review focuses on the possible use of water-soluble vitamin supplementation to improve pharmacological responses and the overall clinical condition of patients.RESULTS: The mechanism of supportive supplementation is based on reducing oxidative stress, covering the increased demand and losses resulting from the treatment method. In the initial period of failure (G2-G3a), it does not require intervention, but later, especially in the case of inadequate nutrition, the inclusion of supplementation with folate and cobalamin may bring benefits. Such supplementation seems to be a necessity in patients with stage G4 or G5 (uremia). Conversely, the inclusion of additional B6 supplementation to reduce CV risk may be considered. At stage 3b and beyond (stages 4-5), the inclusion of niacin at a dose of 400-1000 mg, depending on the patient's tolerance, is required to lower the phosphate level. The inclusion of supplementation with thiamine and other water-soluble vitamins, especially in peritoneal dialysis and hemodialysis patients, is necessary for reducing dialysis losses. Allowing hemodialysis patients to take low doses of oral vitamin C effectively reduces erythropoietin dose requirements and improves anemia in functional iron-deficient patients. However, it should be considered that doses of B vitamins that are several times higher than the recommended dietary allowance of consumption may exacerbate left ventricular diastolic dysfunction in CKD patients.CONCLUSIONS: Taking into account the research conducted so far, it seems that the use of vitamin supplementation in CKD patients may have a positive impact on the treatment process and maintaining a disease-free condition.PMID:36839219 | DOI:10.3390/nu15040860

Untargeted Metabolomics Analysis Using UHPLC-Q-TOF/MS Reveals Metabolic Changes Associated with Hypertension in Children

Sat, 25/02/2023 - 12:00
Nutrients. 2023 Feb 6;15(4):836. doi: 10.3390/nu15040836.ABSTRACTThe mechanism of hypertension in children remains elusive. The objective of this study was to analyze plasma metabolomics characteristics to explore the potential mechanism of hypertension in children. Serum samples from 29 control children, 38 children with normal body mass index and simple hypertension (NBp), 8 children overweight with simple hypertension (OBp), 37 children with normal body mass index and H-type hypertension (NH) and 19 children overweight with H-type hypertension (OH) were analyzed by non-targeted metabolomics. A total of 1235 differential metabolites were identified between children with hypertension and normal controls, of which 193 metabolites including various lipids were significantly expressed. Compared with the control group, 3-dehydroepiandrosterone sulfate, oleic acid and linoleic acid were up-regulated, and gamma-muricholic acid was down-regulated in the NBp group; 3-dehydroepiandrosterone sulfate, 4-acetamidobutanoate and 1-hexadecanoyl-2-octadecadienoyl-sn-glyero-3-phosphocholine were up-regulated in the OBp group, whereas adenosine and 1-myristoyl-sn-glyero-3-phosphocholine were down-regulated; in the NH group, 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphocholine, phenol and 3-methoxytyramine were up-regulated, while pentadecanoic acid was down-regulated; in the OH group, NG,NG-dimethyl-L-arginine, 1-palmitoyl-sn-glycero-3-phosphocholine and monoethyl phthalate were up-regulated, while phloretin and glycine were down-regulated. The results showed that the children with hypertension had obvious disorders of lipid metabolism (especially in the overweight hypertension group), which led to the occurrence of hypertension. Additionally, the concentration of NO production-related NG, NG-dimethyl-L-arginine, was significantly increased, which may play an important role in H-type hypertension in children.PMID:36839194 | DOI:10.3390/nu15040836

Physiological and Metabolic Changes in Tamarillo (<em>Solanum betaceum</em>) during Fruit Ripening

Sat, 25/02/2023 - 12:00
Molecules. 2023 Feb 14;28(4):1800. doi: 10.3390/molecules28041800.ABSTRACTPhysiological and metabolic profiles in tamarillo were investigated to reveal the molecular changes during fruit maturation. The firmness, ethylene production, soluble sugar contents, and metabolomic analysis were determined in tamarillo fruit at different maturity stages. The firmness of tamarillo fruit gradually decreased during fruit ripening with increasing fructose and glucose accumulation. The rapid increase in ethylene production was found in mature fruit. Based on the untargeted metabolomic analysis, we found that amino acids, phospholipids, monosaccharides, and vitamin-related metabolites were identified as being changed during ripening. The contents of malic acid and citric acid were significantly decreased in mature fruits. Metabolites involved in phenylpropanoid biosynthesis, phenylalanine metabolism, caffeine metabolism, monoterpenoid biosynthesis, and thiamine metabolism pathways showed high abundance in mature fruits. However, we also found that most of the mature-enhanced metabolites showed reduced abundance in over-mature fruits. These results reveal the molecular profiles during tamarillo fruit maturing and suggest tamarillos have potential benefits with high nutrition and health function.PMID:36838788 | DOI:10.3390/molecules28041800

NMR-Based Metabolomics: A New Paradigm to Unravel Defense-Related Metabolites in Insect-Resistant Cotton Variety through Different Multivariate Data Analysis Approaches

Sat, 25/02/2023 - 12:00
Molecules. 2023 Feb 13;28(4):1763. doi: 10.3390/molecules28041763.ABSTRACTCotton (Gossypium hirsutum) is an economically important crop and is widely cultivated around the globe. However, the major problem of cotton is its high vulnerability to biotic and abiotic stresses. It has been around three decades since the cotton plant was genetically engineered with genes encoding insecticidal proteins (mainly Cry proteins) with an aim to protect it against insect attack. Several studies have been reported on the impact of these genes on cotton production and fiber quality. However, the metabolites responsible for conferring resistance in genetically modified cotton need to be explored. The current work aims to unveil the key metabolites responsible for insect resistance in Bt cotton and also compare the conventional multivariate analysis methods with deep learning approaches to perform clustering analysis. We aim to unveil the marker compounds which are responsible for inducing insect resistance in cotton plants. For this purpose, we employed 1H-NMR spectroscopy to perform metabolite profiling of Bt and non-Bt cotton varieties, and a total of 42 different metabolites were identified in cotton plants. In cluster analysis, deep learning approaches (linear discriminant analysis (LDA) and neural networks) showed better separation among cotton varieties compared to conventional methods (principal component analysis (PCA) and orthogonal partial least square discriminant analysis (OPLSDA)). The key metabolites responsible for inter-class separation were terpinolene, α-ketoglutaric acid, aspartic acid, stigmasterol, fructose, maltose, arabinose, xylulose, cinnamic acid, malic acid, valine, nonanoic acid, citrulline, and shikimic acid. The metabolites which regulated differently with the level of significance p < 0.001 amongst different cotton varieties belonged to the tricarboxylic acid cycle (TCA), Shikimic acid, and phenylpropanoid pathways. Our analyses underscore a biosignature of metabolites that might involve in inducing insect resistance in Bt cotton. Moreover, novel evidence from our study could be used in the metabolic engineering of these biological pathways to improve the resilience of Bt cotton against insect/pest attacks. Lastly, our findings are also in complete support of employing deep machine learning algorithms as a useful tool in metabolomics studies.PMID:36838756 | DOI:10.3390/molecules28041763

An In Vitro Catalysis of Tea Polyphenols by Polyphenol Oxidase

Sat, 25/02/2023 - 12:00
Molecules. 2023 Feb 10;28(4):1722. doi: 10.3390/molecules28041722.ABSTRACTTea polyphenol (TPs) oxidation caused by polyphenol oxidase (PPO) in manufacturing is responsible for the sensory characteristics and health function of fermented tea, therefore, this subject is rich in scientific and commercial interests. In this work, an in vitro catalysis of TPs in liquid nitrogen grinding of sun-dried green tea leaves by PPO was developed, and the changes in metabolites were analyzed by metabolomics. A total of 441 metabolites were identified in the catalyzed tea powder and control check samples, which were classified into 11 classes, including flavonoids (125 metabolites), phenolic acids (67 metabolites), and lipids (55 metabolites). The relative levels of 28 metabolites after catalysis were decreased significantly (variable importance in projection (VIP) > 1.0, p < 0.05, and fold change (FC) < 0.5)), while the relative levels of 45 metabolites, including theaflavin, theaflavin-3'-gallate, theaflavin-3-gallate, and theaflavin 3,3'-digallate were increased significantly (VIP > 1.0, p < 0.05, and FC > 2). The increase in theaflavins was associated with the polymerization of catechins catalyzed by PPO. This work provided an in vitro method for the study of the catalysis of enzymes in tea leaves.PMID:36838710 | DOI:10.3390/molecules28041722

Study on the Comprehensive Phytochemicals and the Anti-Ulcerative Colitis Effect of <em>Saussurea pulchella</em>

Sat, 25/02/2023 - 12:00
Molecules. 2023 Feb 4;28(4):1526. doi: 10.3390/molecules28041526.ABSTRACTBACKGROUND: Saussurea pulchella (SP) is a traditional medicinal plant that is widely used in folk medicine because of its diverse biological activities, particularly its anti-inflammatory effects. However, the alleviation effect of SP on ulcerative colitis (UC) has not yet been realized.PURPOSE: To investigate the chemical composition and therapeutic effect of SP extract against UC.METHODS: First, qualitative and quantitative analysis of SP 75% ethanol extract was performed by UPLC-Q/TOF-MS. Second, a dextran sodium sulfate (DSS) model of UC mice was developed to study the effects of SP on the symptoms, inflammatory factors, oxidative stress indexes and colon histopathology. Third, an integration of network pharmacology with metabolomics was performed to investigate the key metabolites, biological targets and metabolisms closely related to the effect of SP.RESULTS: From the SP ethanol extract, 149 compounds were identified qualitatively and 20 were determined quantitatively. The SP could dose-dependently decrease the DAI score, spleen coefficient and the levels of TNF-α, IL-6, iNOS, MPO and MDA; increase the colon length, GSH level and SOD activity; and protect the intestinal barrier in the UC mice. Moreover, 10 metabolite biomarkers,18 targets and 5 metabolisms were found to play crucial roles in the treatment of UC with SP.CONCLUSIONS: SP 75% ethanol extract could effectively alleviate the progression of UC and, therefore, could be classified as a novel natural treatment for UC.PMID:36838515 | DOI:10.3390/molecules28041526

Gut Microbiota as Well as Metabolomes of Wistar Rats Recover within Two Weeks after Doripenem Antibiotic Treatment

Sat, 25/02/2023 - 12:00
Microorganisms. 2023 Feb 20;11(2):533. doi: 10.3390/microorganisms11020533.ABSTRACTAn understanding of the changes in gut microbiome composition and its associated metabolic functions is important to assess the potential implications thereof on host health. Thus, to elucidate the connection between the gut microbiome and the fecal and plasma metabolomes, two poorly bioavailable carbapenem antibiotics (doripenem and meropenem), were administered in a 28-day oral study to male and female Wistar rats. Additionally, the recovery of the gut microbiome and metabolomes in doripenem-exposed rats were studied one and two weeks after antibiotic treatment (i.e., doripenem-recovery groups). The 16S bacterial community analysis revealed an altered microbial population in all antibiotic treatments and a recovery of bacterial diversity in the doripenem-recovery groups. A similar pattern was observed in the fecal metabolomes of treated animals. In the recovery group, particularly after one week, an over-compensation was observed in fecal metabolites, as they were significantly changed in the opposite direction compared to previously changed metabolites upon 28 days of antibiotic exposure. Key plasma metabolites known to be diagnostic of antibiotic-induced microbial shifts, including indole derivatives, hippuric acid, and bile acids were also affected by the two carbapenems. Moreover, a unique increase in the levels of indole-3-acetic acid in plasma following meropenem treatment was observed. As was observed for the fecal metabolome, an overcompensation of plasma metabolites was observed in the recovery group. The data from this study provides insights into the connectivity of the microbiome and fecal and plasma metabolomes and demonstrates restoration post-antibiotic treatment not only for the microbiome but also for the metabolomes. The importance of overcompensation reactions for health needs further studies.PMID:36838498 | DOI:10.3390/microorganisms11020533

Gut Microbiota and Metabolome Changes in Three Pulmonary Hypertension Rat Models

Sat, 25/02/2023 - 12:00
Microorganisms. 2023 Feb 13;11(2):472. doi: 10.3390/microorganisms11020472.ABSTRACTDysbiosis of the gut microbiota and metabolites is found in both pulmonary hypertension patients and pulmonary hypertension rodent models. However, the exact changes in gut microbiota during the development of pulmonary hypertension is unclear. The function of the gut microbiota is also ambiguous. Here, this study showed that the gut microbiota was disrupted in rats with hypoxia (Hyp)-, hypoxia/Sugen5416 (HySu)-, and monocrotaline (MCT)-induced pulmonary hypertension. The gut microbiota is dynamically changed during the development of Hyp-, HySu-, and MCT-induced rat pulmonary hypertension. The variation in the α diversity of the gut microbiota in Hyp-induced pulmonary hypertension rats was similar to that in rats with MCT-induced pulmonary hypertension and different from that in rats with HySu-induced pulmonary hypertension. In addition, six plasma biomarkers, His, Ala, Ser, ADMA, 2-hydroxybutyric acid, and cystathionine, were identified in Hyp-induced pulmonary hypertension rats. Furthermore, a disease-associated network connecting Streptococcus with Hyp-induced pulmonary hypertension-associated metabolites was described here, including trimethylamine N-oxide, Asp, Asn, Lys, His, Ser, Pro, and Ile.PMID:36838437 | DOI:10.3390/microorganisms11020472

Gut Microbiota and Metabolites May Play a Crucial Role in Sea Cucumber <em>Apostichopus japonicus</em> Aestivation

Sat, 25/02/2023 - 12:00
Microorganisms. 2023 Feb 7;11(2):416. doi: 10.3390/microorganisms11020416.ABSTRACTThe constant increase in temperatures under global warming has led to a prolonged aestivation period for Apostichopus japonicus, resulting in considerable losses in production and economic benefits. However, the specific mechanism of aestivation has not been fully elucidated. In this study, we first tried to illustrate the biological mechanisms of aestivation from the perspective of the gut microbiota and metabolites. Significant differences were found in the gut microbiota of aestivating adult A. japonicus (AAJSD group) compared with nonaestivating adult A. japonicus (AAJRT group) and young A. japonicus (YAJRT and YAJSD groups) based on 16S rRNA gene high-throughput sequencing analysis. The abundances of Desulfobacterota, Myxococcota, Bdellovibrionota, and Firmicutes (4 phyla) in the AAJSD group significantly increased. Moreover, the levels of Pseudoalteromonas, Fusibacter, Labilibacter, Litorilituus, Flammeovirga, Polaribacter, Ferrimonas, PB19, and Blfdi19 genera were significantly higher in the AAJSD group than in the other three groups. Further analysis of the LDA effect size showed that species with significant variation in abundance in the AAJSD group, including the phylum Firmicutes and the genera Litorilituus, Fusibacter, and Abilibacter, might be important biomarkers for aestivating adult A. japonicus. In addition, the results of metabolomics analysis showed that there were three distinct metabolic pathways, namely biosynthesis of secondary metabolites, tryptophan metabolism, and sesquiterpenoid and triterpenoid biosynthesis in the AAJSD group compared with the other three groups. Notably, 5-hydroxytryptophan was significantly upregulated in the AAJSD group in the tryptophan metabolism pathway. Moreover, the genera Labilibacter, Litorilituus, Ferrimonas, Flammeovirga, Blfdi19, Fusibacter, Pseudoalteromonas, and PB19 with high abundance in the gut of aestivating adult A. japonicus were positively correlated with the metabolite 5-HTP. These findings suggest that there may be potential biological associations among the gut microbiota, metabolites, and aestivation in A. japonicus. This work may provide a new perspective for further understanding the aestivation mechanism of A. japonicus.PMID:36838381 | DOI:10.3390/microorganisms11020416

New Insights on Endophytic <em>Microbacterium</em>-Assisted Blast Disease Suppression and Growth Promotion in Rice: Revelation by Polyphasic Functional Characterization and Transcriptomics

Sat, 25/02/2023 - 12:00
Microorganisms. 2023 Jan 31;11(2):362. doi: 10.3390/microorganisms11020362.ABSTRACTPlant growth-promoting endophytic microbes have drawn the attention of researchers owing to their ability to confer fitness benefits in many plant species. Here, we report agriculturally beneficial traits of rice-leaf-adapted endophytic Microbacterium testaceum. Our polyphasic taxonomic investigations revealed its identity as M. testaceum. The bacterium displayed typical endophytism in rice leaves, indicated by the green fluorescence of GFP-tagged M. testaceum in confocal laser scanning microscopy. Furthermore, the bacterium showed mineral solubilization and production of IAA, ammonia, and hydrolytic enzymes. Tobacco leaf infiltration assay confirmed its non-pathogenic nature on plants. The bacterium showed antifungal activity on Magnaporthe oryzae, as exemplified by secreted and volatile organic metabolome-mediated mycelial growth inhibition. GC-MS analysis of the volatilome of M. testaceum indicated the abundance of antimicrobial compounds. Bacterization of rice seedlings showed phenotypic traits of MAMP-triggered immunity (MTI), over-expression of OsNPR1 and OsCERK, and the consequent blast suppressive activity. Strikingly, M. testaceum induced the transcriptional tradeoff between physiological growth and host defense pathways as indicated by up- and downregulated DEGs. Coupled with its plant probiotic features and the defense elicitation activity, the present study paves the way for developing Microbacterium testaceum-mediated bioformulation for sustainably managing rice blast disease.PMID:36838327 | DOI:10.3390/microorganisms11020362

Dietary Supplementation with Botanical Blends Modified Intestinal Microbiota and Metabolomics of Weaned Pigs Experimentally Infected with Enterotoxigenic <em>Escherichia coli</em>

Sat, 25/02/2023 - 12:00
Microorganisms. 2023 Jan 27;11(2):320. doi: 10.3390/microorganisms11020320.ABSTRACTThe objective of this study was to investigate supplementation of botanical blends (BB) comprised of 0.3% capsicum oleoresin and 12% garlic oil on gut microbiota and metabolomic profiles in serum and ileal mucosa of Escherichia coli infected pigs. Sixty weaned pigs were assigned to one of five treatments: negative control (CON-), positive control (CON+), dietary supplementation of 100 ppm BB1, 50 or 100 ppm BB2. All pigs, except CON-, were orally inoculated with 1010 CFU F18 ETEC/3-mL dose for 3 consecutive days after 7 d adaption. Feces, ileal digesta and cecal content were collected for 16S rRNA amplicon sequencing. Serum and ileal mucosa underwent primary metabolomics analysis. Supplementing 100 ppm BB1 increased (p < 0.05) relative abundances of Enterobacteriaceae and Escherichia-Shigella in ileum, and the relative abundances of Bacteroidota and Prevotellaceae in cecum than CON+ on d 5 post-inoculation (PI). Supplementing 100 ppm BB2 upregulated serum pinitol on d 4 PI and serum cholesterol and aminomalonic acids on d 21 PI, while supplementing 50 ppm BB2 reduced asparagine in ileal mucosa on d 5 PI than CON+. Supplementation with botanical blends modulated ileal and cecal microbiota and serum metabolomics profiles in weaned pigs under Escherichia coli challenge.PMID:36838285 | DOI:10.3390/microorganisms11020320

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