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

Enhanced polyglucan contents in divergent cyanobacteria under nutrient-deprived photoautotrophy: transcriptional and metabolic changes in response to increased glycogen accumulation in nitrogen-deprived Synechocystis sp. PCC 6803

Sun, 27/11/2022 - 12:00
World J Microbiol Biotechnol. 2022 Nov 28;39(1):27. doi: 10.1007/s11274-022-03476-1.ABSTRACTCyanobacteria accumulate polyglucan as main carbohydrate storage. Here, the cellular polyglucan content was determined in 27 cyanobacterial strains from 25 genera. The polyglucan contents were significantly enhanced in 20 and 23 strains under nitrogen (-N) and phosphate (-P) deprivation, respectively. High polyglucan accumulation was not associated with particular evolutionary groups but was strain specific. The highest polyglucan accumulations of 46.2% and 52.5% (w/w dry weight; DW) were obtained under -N in Synechocystis sp. PCC 6803 (hereafter Synechocystis) and Chroococcus limneticus, respectively. In Synechocystis, 80-97% (w/w) of the polyglucan was glycogen. Transcriptome and metabolome analyses during glycogen accumulation under -N were determined in Synechocystis. The genes responsible for the supply of the substrates for glycogen synthesis: glycerate-1,3-phosphate and fructose-1,6-phosphate, were significantly up-regulated. The genes encoding the enzymes converting succinate to malate in TCA cycle, were significantly down-regulated. The genes encoding the regulator proteins which inhibits metabolism at lower part of glycolysis pathway, were also significantly up-regulated. The transcript levels of PII protein and the level of 2-oxoglutarate, which form a complex that inhibits lower part of glycolysis pathway, were significantly increased. Thus, the increased Synechocystis glycogen accumulation under -N was likely to be mediated by the increased supply of glycogen synthesis substrates and metabolic inhibitions at lower part of glycolysis pathway and TCA cycle.PMID:36437374 | DOI:10.1007/s11274-022-03476-1

Food Metabolomics

Sun, 27/11/2022 - 12:00
J Nutr Sci Vitaminol (Tokyo). 2022;68(Supplement):S128-S130. doi: 10.3177/jnsv.68.S128.ABSTRACTFoods contain not only nutrients but also a wide variety of components related to flavor and functionality. Many studies have been conducted on the components of foods. Quantitative analysis has been used to assess compounds in food such as sugars, amino acids, and organic acids for food flavor; carotenoids and anthocyanins for appearance and color; and vitamins related to functionality for human health. Plants and animals that are food materials are thought to contain hundreds to thousands of compounds. Recent improvements in analytical technologies have made it possible to detect a large number of compounds simultaneously using metabolomics, a comprehensive analysis technology for low-molecular-weight compounds, and its application to food analysis has been reported. Food metabolomics has the potential to identify compounds related to flavor and functionality that have not been reported in previous studies; moreover, it is expected to add value to the target foods. By integrating the results of sensory evaluation, animal experiments, and other experiments with metabolomic data and providing them for analysis using informatics, such as artificial intelligence, it may be possible to derive more accurate evaluations of food quality.PMID:36436994 | DOI:10.3177/jnsv.68.S128

Longitudinal spatial mapping of lipid metabolites reveals pre-symptomatic changes in the hippocampi of Huntington's disease transgenic mice

Sun, 27/11/2022 - 12:00
Neurobiol Dis. 2022 Nov 24:105933. doi: 10.1016/j.nbd.2022.105933. Online ahead of print.ABSTRACTIn Huntington's disease (HD), a key pathological feature includes the development of inclusion-bodies of fragments of the mutant huntingtin protein in the neurons of the striatum and hippocampus. To examine the molecular changes associated with inclusion-body formation, we applied MALDI-mass spectrometry imaging and deuterium pulse labelling to determine lipid levels and synthesis rates in the hippocampus of a transgenic mouse model of HD (R6/1 line). The R6/1 HD mice lacked inclusions in the hippocampus at 6 weeks of age (pre-symptomatic), whereas inclusions were pervasive by 16 weeks of age (symptomatic). Hippocampal subfields (CA1, CA3 and DG), which formed the highest density of inclusion formation in the mouse brain showed a reduction in the relative abundance of neuron-enriched lipids that have roles in neurotransmission, synaptic plasticity, neurogenesis, and ER-stress protection. Lipids involved in the adaptive response to ER stress (phosphatidylinositol, phosphatidic acid, and ganglioside classes) displayed increased rates of synthesis in HD mice relative to WT mice at all the ages examined, including prior to the formation of the inclusion bodies. Our findings, therefore, support a role for ER stress occurring pre-symptomatically and potentially contributing to pathological mechanisms underlying HD.PMID:36436748 | DOI:10.1016/j.nbd.2022.105933

Transcriptome and metabolome analyses reveal the regulatory effects of compound probiotics on cecal metabolism in heat-stressed broilers

Sun, 27/11/2022 - 12:00
Poult Sci. 2022 Nov 5;102(1):102323. doi: 10.1016/j.psj.2022.102323. Online ahead of print.ABSTRACTThe effect of compound probiotics on the caecum of broilers under heat stress was assessed in this study. A total of 400 twenty-eight-day-old AA male broilers were randomly divided into 4 treatment groups, where each group had 5 replicates of 20 broilers. The 4 treatment groups were a heat stress control group (broilers receiving a normal diet) and groups HP I, HP II, and HP Ⅲ, consisting of broilers receiving 1, 5, and 10 g of compound probiotics added to each kilogram of feed, respectively. Compound probiotics (L. casei, L. acidophilus, and B. lactis at a ratio of 1:1:2) were used to formulate a compound probiotic powder, with 1 × 1010 CFU/g of effective viable bacteria. Heat stress treatment was performed at 32 ± 1°C from 9:00 to 17:00 every day from 28 d to 42 d. In d 28 to 42, compared with the HC group, the ADG of broilers in the HP II and III groups was significantly increased (P < 0.05); the ADFI difference between groups was not significant (P > 0.05); the FCR of HP II and III broilers was significantly decreased (P < 0.05); and the FCR of the HP I group increased, but the difference was not significant (P > 0.05). Transcriptome results demonstrate that 665 differential genes were screened (DEGs; upregulated: 366, downregulated: 299). The DEGs were enriched in the B cell receptor signaling pathway, the intestinal immune network for IgA synthesis, the Fc epsilon RI signaling pathway, and other signaling pathways, according to KEGG enrichment analysis. Metabolome analysis identified 92 differential metabolites (DAMs; upregulated: 48, downregulated: 44). KEGG enrichment analysis indicated significant enrichment of Pantothenate and CoA biosynthesis and beta-Alanine metabolism. The combined transcriptome and metabolome analysis revealed that the DAMs and DEGs were mostly involved in beta-alanine metabolism, arginine biosynthesis, amino sugar and nucleotide sugar, and alanine, aspartate, and glutamate metabolism. The results of this study suggest that the addition of compound probiotics has a positive effect on intestinal metabolites, improving the growth performance and contributing to the overall health of broilers under heat stress.PMID:36436366 | DOI:10.1016/j.psj.2022.102323

Effects of different cooking treatments on the sensory qualities and pigmented phytochemicals of carrots

Sun, 27/11/2022 - 12:00
Food Chem. 2022 Nov 21;405(Pt B):135015. doi: 10.1016/j.foodchem.2022.135015. Online ahead of print.ABSTRACTEffects of different cooking treatments including steaming (S), boiling (B), stir-frying (SF) and frying (F) on the sensory qualities and pigmented phytochemicals of "Guanghong" carrot were studied based on intelligent sensory technology and targeted metabolomics, with fresh carrot slices (R) as control. Results showed cooking treatments reduced the brightness, redness, yellowness, and color saturation, and h° was the core index reflecting consumers' preference for the color characteristics of cooked carrots. The overall acceptability of cooked carrots was higher than R, and S gave carrots the best taste. (E/Z)-phytoene, α-carotene and β-carotene were the most dominant carotenoids monomers. None of the four cooking methods resulted in a loss of total monomer carotenoids content (TMCC) in carrots. B and SF increased the contents of xanthophyll and carotene, respectively, while the carotenoid esters's content remained stable during cooking. SF significantly increased TMCC and the contents of γ-carotene, α-carotene and (E/Z)-phytoene (p < 0.05). Pel-3-O-glu was the most important anthocyanins monomer in "Guanghong" carrot.PMID:36436237 | DOI:10.1016/j.foodchem.2022.135015

Critical assessment of chromatographic metadata in publicly available metabolomics data repositories

Sun, 27/11/2022 - 12:00
Metabolomics. 2022 Nov 27;18(12):97. doi: 10.1007/s11306-022-01956-x.ABSTRACTINTRODUCTION: The structural identification of metabolites represents one of the current bottlenecks in non-targeted liquid chromatography-mass spectrometry (LC-MS) based metabolomics. The Metabolomics Standard Initiative has developed a multilevel system to report confidence in metabolite identification, which involves the use of MS, MS/MS and orthogonal data. Limitations due to similar or same fragmentation pattern (e.g. isomeric compounds) can be overcome by the additional orthogonal information of the retention time (RT), since it is a system property that is different for each chromatographic setup.OBJECTIVES: In contrast to MS data, sharing of RT data is not as widespread. The quality of data and its (re-)useability depend very much on the quality of the metadata. We aimed to evaluate the coverage and quality of this metadata from public metabolomics repositories.METHODS: We acquired an overview on the current reporting of chromatographic separation conditions. For this purpose, we defined the following information as important details that have to be provided: column name and dimension, flow rate, temperature, composition of eluents and gradient.RESULTS: We found that 70% of descriptions of the chromatographic setups are incomplete (according to our definition) and an additional 10% of the descriptions contained ambiguous and/or incorrect information. Accordingly, only about 20% of the descriptions allow further (re-)use of the data, e.g. for RT prediction. Therefore, we have started to develop a unified and standardized notation for chromatographic metadata with detailed and specific description of eluents, columns and gradients.CONCLUSION: Reporting of chromatographic metadata is currently not unified. Our recommended suggestions for metadata reporting will enable more standardization and automatization in future reporting.PMID:36436113 | DOI:10.1007/s11306-022-01956-x

Metabolic regulation of cholestatic liver injury by D-2-hydroxyglutarate with the modulation of hepatic microenvironment and the mammalian target of rapamycin signaling

Sat, 26/11/2022 - 12:00
Cell Death Dis. 2022 Nov 26;13(11):1001. doi: 10.1038/s41419-022-05450-z.ABSTRACTBiliary atresia (BA) is a cholestatic liver disease in neonates with devastating obstructive intrahepatic and extrahepatic biliary ducts. Owing to the lack of an early diagnostic marker and limited understanding of its pathogenesis, BA often leads to death within 2 years. Therefore, this study aimed to develop early diagnostic methods and investigate the underlying pathogenesis of liver injury in BA using metabolomics. Metabolomics and organoid combined energy metabolism analysis was used to obtain new insights into BA diagnosis and pathobiology using patient samples, mice liver organoids, and a zebrafish model. Metabolomics revealed that D-2-hydroxyglutarate (D-2-HG) levels were significantly elevated in the plasma and liver of patients with BA and closely correlated with liver injuries and impaired liver regeneration. D-2-HG suppressed the growth and expansion of liver organoids derived from the intrahepatic biliary ducts. The energy metabolism analysis demonstrated that D-2-HG inhibited mitochondrial respiration and ATP synthase; however, it increased aerobic glycolysis in organoids. In addition, D-2-HG exposure caused liver degeneration in zebrafish larvae. Mechanistically, D-2-HG inhibited the activation of protein kinase B and the mammalian target of rapamycin signaling. These findings reveal that D-2-HG may represent a novel noninvasive diagnostic biomarker and a potential therapeutic target for infants with BA.PMID:36435860 | DOI:10.1038/s41419-022-05450-z

Dynamics of quality attributes, flavor compounds, and microbial communities during multi-driven-levels chili fermentation: Interactions between the metabolome and microbiome

Sat, 26/11/2022 - 12:00
Food Chem. 2022 Nov 12;405(Pt B):134936. doi: 10.1016/j.foodchem.2022.134936. Online ahead of print.ABSTRACTDynamics and correlations of quality attributes, microbial profiles, and flavor metabolites were systematically investigated during chili fermentation on multi-salinity-driven levels (8/13/18 %). Metabolomic analysis revealed that pre-fermentation contributed to acetic acid (10.16 mg/kg, 65.01 %) and biogenic amines (53.70 mg/kg, 70.43 %). While main- and post-fermentation accumulated lactic acid (48.33 mg/kg, 76.49 %). Metabolome-microbiome interactions revealed that dominant genera mediated by salt levels affected the distribution of 24 differential odorants in 54 aromatic compounds. Enterobacter, Klebsiella, Cronobacter, and Acinetobacter triggered the production of 121 mg/kg biogenic amines and 7 unpleasant flavors. 7 dominant genera including Leuconostoc, Lactococcus, Weissella, Lactobacillus, Candida, Pichia, and Kazachstania were correlated with spicy, fruity, and floral aromas. Interestingly, salt-acid alternation drove succession from Leuconostoc, Weissella, and Lactococcus to Lactobacillus and Pediococcus. Overall, microbial composition and function were metabolism-dependent patterns. These results provide insight into microbial succession and flavor formation during staged fermentation and promote to optimize quality of fermented chili.PMID:36435118 | DOI:10.1016/j.foodchem.2022.134936

Polarity-extended composition profiling via LC-MS-based metabolomics approaches: A key to functional investigation of Citrus aurantium L

Sat, 26/11/2022 - 12:00
Food Chem. 2022 Nov 17;405(Pt B):134988. doi: 10.1016/j.foodchem.2022.134988. Online ahead of print.ABSTRACTCitrus is a genus containing diverse edible species, among them Citrus aurantium L. is widely utilized while short of composition research. Herein, utilizing multiple liquid chromatography-mass spectrometry (LC-MS)-based metabolomics approaches, we comprehensively characterized its components. We first systematized both LC and MS characteristics of polymethoxyflavones (PMFs), by which 13 PMFs were identified in C. aurantium, and their biosynthesis pathway was further established. Using derivatization-LC-MS targeted metabolomics approaches, 28 carbohydrates and 18 carboxylic acids were firstly found in C. aurantium. Combined with untargeted metabolomics method, total 147 compositions were characterized, among which 92 were firstly reported in C. aurantium. We further obtained their geographical features and sought out principal discriminative compounds. Moreover, typical biofunctions of C. aurantium from diverse regions were speculated using pharmacological platform and partly verified by experiments. The present study provided systematic component information for C. aurantium, which laid the foundation for its further exploitation as functional food.PMID:36435109 | DOI:10.1016/j.foodchem.2022.134988

Combined transcriptome and metabolome analyses reveal the mechanisms of ultrasonication improvement of brown rice germination

Sat, 26/11/2022 - 12:00
Ultrason Sonochem. 2022 Nov 23;91:106239. doi: 10.1016/j.ultsonch.2022.106239. Online ahead of print.ABSTRACTThis study investigated the effects of ultrasonication treatment on the germination rate of brown rice. Brown rice grains were subjected to ultrasound (40 kHz/30 min) and then incubated for 36 h at 37 °C to germinate the seeds. Ultrasonic treatment increased the germination rate of brown rice by up to ∼28 % at 30 h. Transcriptomic and metabolomic analyses were performed to explore the mechanisms underlying the effect of ultrasonic treatment on the brown rice germination rate. Comparing the treated and control check samples, 867 differentially expressed genes (DEGs) were identified, including 638 upregulated and 229 downregulated), as well as 498 differentially accumulated metabolites (DAMs), including 422 up accumulated and 76 down accumulated. Multi-omics analysis revealed that the germination rate of brown rice was promoted by increased concentrations of low-molecular metabolites (carbohydrates and carbohydrate conjugates, fatty acids, amino acids, peptides, and analogues), and transcription factors (ARR-B, NAC, bHLH and AP2/EREBP families) as well as increased carbon metabolism. These findings provide new insights into the mechanisms of action of ultrasound in improving the brown rice germination rate and candidate DEGs and DAMs responsible for germination have been identified.PMID:36435087 | DOI:10.1016/j.ultsonch.2022.106239

Metabolomics window into the diagnosis and treatment of inflammatory bowel disease in recent 5 years

Sat, 26/11/2022 - 12:00
Int Immunopharmacol. 2022 Nov 23;113(Pt B):109472. doi: 10.1016/j.intimp.2022.109472. Online ahead of print.ABSTRACTInflammatory bowel disease (IBD) is a kind of chronic inflammation that occurs in gastrointestinal tract, including Ulcerative colitis (UC) and Crohn's disease (CD). Although UC and CD are associated with intestinal inflammation and epithelial damage, they are quite different. The etiology of IBD has not been fully determined, but there is extensive evidence that its pathogenesis involves environmental, genetic, immune and microbial factors. The diagnosis and treatment of IBD is challenging due to its recurrent episodes and complex evolution. Metabolomics, as a new developing technology, can be used to qualitatively and quantitatively study small metabolic molecules in samples of patients, which include stool, urine, serum, plasma and tissues, and is increasingly valued in the diagnosis and treatment of IBD. This article sums up the recent progress of metabolomics in helping to diagnose and treat IBD diseases, hoping to provide biomarkers and new targets for the diagnosis and treatment of IBD. In addition, we present the limitations of the current study of metabolomics and highlight some solutions.PMID:36435058 | DOI:10.1016/j.intimp.2022.109472

Abnormal fatty acid metabolism and ceramide expression may discriminate myocardial infarction from strangulation death: A pilot study

Sat, 26/11/2022 - 12:00
Tissue Cell. 2022 Nov 21;80:101984. doi: 10.1016/j.tice.2022.101984. Online ahead of print.ABSTRACTDetermining myocardial infarction (MI) and mechanical asphyxia (MA) was one of the most challenging tasks in forensic practice. The present study aimed to investigate the potential of fatty acid (FAs) metabolism, and lipid alterations in determining MI and MA. MA and MI mouse models were constructed, and metabolic profiles were obtained by LC-MS-based untargeted metabolomics. The metabolic alterations were explored using the PCA, OPLS-DA, the Wilcoxon test, and fold change analysis. The contents of lipid droplets (LDs) were detected by the transmission scanning electron microscope and Oil red O staining. The immunohistochemical assay was performed to detect CD36 and dysferlin. The ceramide was assessed by LC-MS. PCA showed considerable differences in the metabolite profiles, and the well-fitting OPLS-DA model was developed to screen differential metabolites. Thereinto, 9 metabolites in the MA were reduced, while metabolites were up- and down-regulated in MI. The increased CD36 suggested that MI and MA could enhance the intake of FAs and disturb energy metabolism. The increased LDs, decreased dysferlin, and increased ceramide (C18:0, C22:0, and C24:0) were observed in MI groups, confirming the lipid deposition. The present study indicated significant differences in myocardial FAs metabolism and lipid alterations between MI and MA, suggesting that FAs metabolism and related proteins, certain ceramide may harbor the potential as biomarkers for discrimination of MI and MA.PMID:36434828 | DOI:10.1016/j.tice.2022.101984

Integrated metabolomics, network pharmacology and biological verification to reveal the mechanisms of Nauclea officinalis treatment of LPS-induced acute lung injury

Sat, 26/11/2022 - 12:00
Chin Med. 2022 Nov 24;17(1):131. doi: 10.1186/s13020-022-00685-6.ABSTRACTBACKGROUND: Acute lung injury (ALI) is a severe inflammatory disease, underscoring the urgent need for novel treatments. Nauclea officinalis Pierre ex Pitard (Danmu in Chinese, DM) is effective in treating inflammatory respiratory diseases. However, there is still no evidence of its protective effect against ALI.METHODS: Metabolomics was applied to identify the potential biomarkers and pathways in ALI treated with DM. Further, network pharmacology was introduced to predict the key targets of DM against ALI. Then, the potential pathways and key targets were further verified by immunohistochemistry and western blot assays.RESULTS: DM significantly improved lung histopathological characteristics and inflammatory response in LPS-induced ALI. Metabolomics analysis showed that 16 and 19 differential metabolites were identified in plasma and lung tissue, respectively, and most of these metabolites tended to recover after DM treatment. Network pharmacology analysis revealed that the PI3K/Akt pathway may be the main signaling pathway of DM against ALI. The integrated analysis of metabolomics and network pharmacology identified 10 key genes. These genes are closely related to inflammatory response and cell apoptosis of lipopolysaccharide (LPS)-induced ALI in mice. Furthermore, immunohistochemistry and western blot verified that DM could regulate inflammatory response and cell apoptosis by affecting the PI3K/Akt pathway, and expression changes in Bax and Bcl-2 were also triggered.CONCLUSION: This study first integrated metabolomics, network pharmacology and biological verification to investigate the potential mechanism of DM in treating ALI, which is related to the regulation of inflammatory response and cell apoptosis. And the integrated analysis can provide new strategies and ideas for the study of traditional Chinese medicines in the treatment of ALI.PMID:36434729 | DOI:10.1186/s13020-022-00685-6

Lipid and metabolic alteration involvement in physiotherapy for chronic nonspecific low back pain

Sat, 26/11/2022 - 12:00
Lipids Health Dis. 2022 Nov 25;21(1):125. doi: 10.1186/s12944-022-01737-4.ABSTRACTBACKGROUND: Chronic nonspecific low back pain (cNLBP) is a common health problem worldwide, affecting 65-80% of the population and greatly affecting people's quality of life and productivity. It also causes huge economic losses. Manual therapy (MT) and therapeutic exercise (TE) are effective treatment options for cNLBP physiotherapy-based treatment. However, the underlying mechanisms that promote cNLBP amelioration by MT or TE are incompletely understood.METHODS: Seventeen recruited subjects were randomly divided into an MT group and a TE group. Subjects in the MT group performed muscular relaxation, myofascial release, and mobilization for 20 min during each treatment session. The treatment lasted for a total of six sessions, once every two days. Subjects in the TE group completed motor control and core stability exercises for 30 min during each treatment session. The motor control exercise included stretching of the trunk and extremity muscles through trunk and hip rotation and flexion training. Stabilization exercises consisted of the (1) bridge exercise, (2) single-leg-lift bridge exercise, (3) side bridge exercise, (4) two-point bird-dog position with an elevated contralateral leg and arm, (5) bear crawl exercise, and (6) dead bug exercise. The treatment lasted for a total of six sessions, with one session every two days. Serum samples were collected from subjects before and after physiotherapy-based treatment for lipidomic and metabolomic measurements.RESULTS: Through lipidomic analysis, we found that the phosphatidylcholine/phosphatidylethanolamine (PC/PE) ratio decreased and the sphingomyelin/ceramide (SM/Cer) ratio increased in cNLBP patients after MT or TE treatment. In addition, eight metabolites enriched in pyrimidine and purine differed significantly in cNLBP patients who received MT treatment. A total of nine metabolites enriched in pyrimidine, tyrosine, and galactose pathways differed significantly in cNLBP patients after TE treatment during metabolomics analysis.CONCLUSION: Our study was the first to elucidate the alterations in the lipidomics and metabolomics of cNLBP physiotherapy-based treatment and can expand our knowledge of cNLBP physiotherapy-based treatment.PMID:36434687 | DOI:10.1186/s12944-022-01737-4

Molecular characterization of gut microbiome in weaning pigs supplemented with multi-strain probiotics using metagenomic, culturomic, and metabolomic approaches

Sat, 26/11/2022 - 12:00
Anim Microbiome. 2022 Nov 24;4(1):60. doi: 10.1186/s42523-022-00212-w.ABSTRACTBACKGROUND: Probiotics have been reported to exhibit positive effects on host health, including improved intestinal barrier function, preventing pathogenic infection, and promoting nutrient digestion efficiency. These internal changes are reflected to the fecal microbiota composition and, bacterial metabolites production. In accordance, the application of probiotics has been broadened to industrial animals, including swine, which makes people to pursue better knowledge of the correlation between changes in the fecal microbiota and metabolites. Therefore, this study evaluated the effect of multi-strain probiotics (MSP) supplementation to piglets utilizing multiomics analytical approaches including metagenomics, culturomics, and metabolomics.RESULTS: Six-week-old piglets were supplemented with MSP composed of Lactobacillus isolated from the feces of healthy piglets. To examine the effect of MSP supplement, piglets of the same age were selected and divided into two groups; one with MSP supplement (MSP group) and the other one without MSP supplement (Control group). MSP feeding altered the composition of the fecal microbiota, as demonstrated by metagenomics analysis. The abundance of commensal Lactobacillus was increased by 2.39%, while Clostridium was decreased, which revealed the similar pattern to the culturomic approach. Next, we investigated the microbial metabolite profiles, specifically SCFAs using HPLC-MS/MS and others using GC-MS, respectively. MSP supplement elevated the abundance of amino acids, including valine, isoleucine and proline as well as the concentration of acetic acid. According to the correlation analyses, these alterations were found out to be crucial in energy synthesizing metabolism, such as branched-chain amino acid (BCAA) metabolism and coenzyme A biosynthesis. Furthermore, we isolated commensal Lactobacillus strains enriched by MSP supplement, and analyzed the metabolites and evaluated the functional improvement, related to tight junction from intestinal porcine enterocyte cell line (IPEC-J2).CONCLUSIONS: In conclusion, MSP administration to piglets altered their fecal microbiota, by enriching commensal Lactobacillus strains. This change contributed amino acid, acetic acid, and BCAA concentrations to be increased, and energy metabolism pathway was also increased at in vivo and in vitro. These changes produced by MSP supplement suggests the correlation between the various physiological energy metabolism functions induced by health-promoting Lactobacillus and the growth performance of piglets.PMID:36434671 | DOI:10.1186/s42523-022-00212-w

Metabolic changes during exclusive enteral nutrition in pediatric Crohn's disease patients

Sat, 26/11/2022 - 12:00
Metabolomics. 2022 Nov 25;18(12):96. doi: 10.1007/s11306-022-01953-0.ABSTRACTBACKGROUND AND AIMS: Exclusive enteral nutrition is recommended as a first-line treatment in active pediatric Crohn's Disease, but its mechanism of action is still not clear. We aimed to assess alterations in the metabolic profile of newly diagnosed pediatric Crohn's Disease patients before and during exclusive enteral nutrition therapy.METHODS: Plasma samples from 14 pediatric Crohn's Disease patients before and after 3-4 weeks on exclusive enteral nutrition were analyzed using mass spectrometry. T-test, fold change and orthogonal partial least squares discriminant analysis were used for mining significant features. Correlation analysis was performed between the annotated features and the weighted pediatric Crohn's disease activity index using Pearson r distance.RESULTS: Among the 13 compounds which decreased during exclusive enteral nutrition, most are related to diet, while one is a bacterial metabolite, Bacteriohopane-32,33,34,35-tetrol. The phosphatidic acid metabolite PA(15:1/18:0) was significantly reduced and correlated with the weighted pediatric Crohn's disease activity index. Lipids increased during exclusive enteral nutrition therapy included phosphatidylethanolamines; PE(24:1/24:1), PE(17:2/20:2) and one lactosylceramide; LacCer(d18:1/14:0).CONCLUSION: Food additives and other phytochemicals were the major metabolites, which decreased following the exclusion of a regular diet during exclusive enteral nutrition. An alteration in bacterial biomarkers may reflect changes in intestinal microbiota composition and metabolism. Thus, metabolomics provides an opportunity to characterize the molecular mechanisms of dietary factors triggering Crohn's Disease activity, and the mechanisms of action of exclusive enteral nutrition, thereby providing the basis for the development and evaluation of improved intervention strategies for prevention and treatment.PMID:36434414 | DOI:10.1007/s11306-022-01953-0

Glutamatergic synapse in autism: a complex story for a complex disorder

Sat, 26/11/2022 - 12:00
Mol Psychiatry. 2022 Nov 25. doi: 10.1038/s41380-022-01860-9. Online ahead of print.ABSTRACTAutism spectrum disorder (ASD) is a neurodevelopmental disorder whose pathophysiological mechanisms are still unclear. Hypotheses suggest a role for glutamate dysfunctions in ASD development, but clinical studies investigating brain and peripheral glutamate levels showed heterogenous results leading to hypo- and hyper-glutamatergic hypotheses of ASD. Recently, studies proposed the implication of elevated mGluR5 densities in brain areas in the pathophysiology of ASD. Thus, our objective was to characterize glutamate dysfunctions in adult subjects with ASD by quantifying (1) glutamate levels in the cingulate cortex and periphery using proton magnetic resonance spectroscopy and metabolomics, and (2) mGluR5 brain density in this population and in a validated animal model of ASD (prenatal exposure to valproate) at developmental stages corresponding to childhood and adolescence in humans using positron emission tomography. No modifications in cingulate Glu levels were observed between individuals with ASD and controls further supporting the difficulty to evaluate modifications in excitatory transmission using spectroscopy in this population, and the complexity of its glutamate-related changes. Our imaging results showed an overall increased density in mGluR5 in adults with ASD, that was only observed mostly subcortically in adolescent male rats prenatally exposed to valproic acid, and not detected in the stage corresponding to childhood in the same animals. This suggest that clinical changes in mGluR5 density could reflect the adaptation of the glutamatergic dysfunctions occurring earlier rather than being key to the pathophysiology of ASD.PMID:36434055 | DOI:10.1038/s41380-022-01860-9

MaHPIC malaria systems biology data from Plasmodium cynomolgi sporozoite longitudinal infections in macaques

Sat, 26/11/2022 - 12:00
Sci Data. 2022 Nov 24;9(1):722. doi: 10.1038/s41597-022-01755-y.ABSTRACTPlasmodium cynomolgi causes zoonotic malarial infections in Southeast Asia and this parasite species is important as a model for Plasmodium vivax and Plasmodium ovale. Each of these species produces hypnozoites in the liver, which can cause relapsing infections in the blood. Here we present methods and data generated from iterative longitudinal systems biology infection experiments designed and performed by the Malaria Host-Pathogen Interaction Center (MaHPIC) to delve deeper into the biology, pathogenesis, and immune responses of P. cynomolgi in the Macaca mulatta host. Infections were initiated by sporozoite inoculation. Blood and bone marrow samples were collected at defined timepoints for biological and computational experiments and integrative analyses revolving around primary illness, relapse illness, and subsequent disease and immune response patterns. Parasitological, clinical, haematological, immune response, and -omic datasets (transcriptomics, proteomics, metabolomics, and lipidomics) including metadata and computational results have been deposited in public repositories. The scope and depth of these datasets are unprecedented in studies of malaria, and they are projected to be a F.A.I.R., reliable data resource for decades.PMID:36433985 | DOI:10.1038/s41597-022-01755-y

The nearly complete genome sequence of Jasminum sambac reveals the molecular mechanism underlying the accumulation of jasmonates

Sat, 26/11/2022 - 12:00
J Exp Bot. 2022 Nov 26:erac464. doi: 10.1093/jxb/erac464. Online ahead of print.ABSTRACTJasminum sambac is a well-known plant for its attractive and exceptional flower fragrance, and the flowers are used to produce scented tea. Jasmonate (JA), an important plant hormone was first identified in Jasminum species. Jasmine plants contain abundant JA naturally, of which the molecular mechanisms of synthesis and accumulation are not clearly understood. Here, we report a telomere-to-telomere consensus assembly of double-petal J. sambac genome along with two haplotype-resolved genomes. We found that gain-and-loss, positive selection, and allelic specific expression of aromatic votatile related genes contributed to the stronger flower fragrance in double-petal J. sambac compared with single- and multi-petal jasmines. Through comprehensive comparative genomic, transcriptomic, and metabolomic analyses of double-petal J. sambac, we revealed the genetic basis of the production of aromatic volatiles, salicylic acid (SA) and the accumulation of JA under non-stress conditions. We identified several key genes associated with JA biosynthesis, and their non-stress related activities lead to extraordinarily high concentrations of JA in tissues. High JA synthesis coupled with low degradation in J. sambac results in the accumulation of plentiful JA under typical environmental conditions, similar accumulation mechanism of SA. This study offers important insights into the biology of J. sambac, and provides valuable genomic resources for further utilization of natural products.PMID:36433929 | DOI:10.1093/jxb/erac464

β-glucan alleviates mice with ulcerative colitis through interactions between gut microbes and amino acids metabolism

Sat, 26/11/2022 - 12:00
J Sci Food Agric. 2022 Nov 26. doi: 10.1002/jsfa.12357. Online ahead of print.ABSTRACTBACKGROUND: Food polysaccharide 1,3-β-D-glucan (OBG) has been shown to alleviate ulcerative colitis (UC) in a mouse model, but the underlying mechanisms remain unclear. Here, we aimed to study potential mechanisms involving interactions among gut microbiota, microbial metabolites, and host metabolic function.RESULTS: OBG alleviated colonic inflammation, barrier dysfunction, intestinal concentrations of short-chain fatty acids in mice with UC. In addition, the relative abundances of Muribaculaceae, Alistipes, Erysipelatoclostridium, and Blautia increased, while the abundances of Proteus, Lachnospiraceae, and Ruminococcus decreased within the gut microbiota upon OBG treatment. KEGG analyzes showed that intestinal enzymes altered upon OBG treatment were mainly enriched in sub-pathways of amino acid biosynthesis. Metabolomics analyses showed that L-tryptophan, L-tyrosine, L-phenylalanine and L-alanine increased, which were consistent with the predictive metabolism of gut microbiota. Correlation analysis and interaction networks highlighted gut microbiota (especially Lactobacillus, Parabacteroides, Proteus, and Blautia), metabolites (especially L-phenylalanine, L-tryptophan, L-tyrosine, and acetic acid), and metabolism (phenylalanine, tyrosine and tryptophan biosynthesis) that may be key targets of OBG.CONCLUSION: OBG is beneficial to the gut microecological balance in mice with colitis, mainly due to its impact on the interactions between gut microbes and amino acids metabolism (especially tyrosine and tryptophan metabolism). This article is protected by copyright. All rights reserved.PMID:36433918 | DOI:10.1002/jsfa.12357

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