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

Study on the Mechanism of Qing-Fei-Shen-Shi Decoction on Asthma Based on Integrated 16S rRNA Sequencing and Untargeted Metabolomics

Mon, 27/02/2023 - 12:00
Evid Based Complement Alternat Med. 2023 Feb 15;2023:1456844. doi: 10.1155/2023/1456844. eCollection 2023.ABSTRACTQing-Fei-Shen-Shi decoction (QFSS) consists of Prunus armeniaca L., Gypsum Fibrosum, Smilax glabra Roxb., Coix lacryma-jobi L., Benincasa hispida (Thunb.) Cogn., Plantago asiatica L., Pyrrosia lingua (Thunb.) Farw., Houttuynia cordata Thunb., Fritillaria thunbergii Miq., Cicadae Periostracum, and Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle. QFSS shows significant clinical efficacy in the treatment of asthma. However, the specific mechanism of QFSS on asthma remains unclear. Recently, multiomics techniques are widely used in elucidating the mechanisms of Chinese herbal formulas. The use of multiomics techniques can better illuminate the multicomponents and multitargets of Chinese herbal formulas. In this study, ovalbumin (OVA) was first employed to induce an asthmatic mouse model, followed by a gavage of QFSS. First, we evaluated the therapeutic effects of QFSS on the asthmatic model mice. Second, we investigated the mechanism of QFSS in treating asthma by using an integrated 16S rRNA sequencing technology and untargeted metabolomics. Our results showed that QFSS treatment ameliorated asthma in mice. In addition, QFSS treatment affected the relative abundances of gut microbiota including Lactobacillus, Dubosiella, Lachnospiraceae_NK4A136_group, and Helicobacter. Untargeted metabolomics results showed that QFSS treatment regulated the metabolites such as 2-(acetylamino)-3-[4-(acetylamino) phenyl] acrylic acid, D-raffinose, LysoPC (15 : 1), methyl 10-undecenoate, PE (18 : 1/20 : 4), and D-glucose6-phosphate. These metabolites are associated with arginine and proline metabolism, arginine biosynthesis, pyrimidine metabolism, and glycerophospholipid metabolism. Correlation analysis indicated that arginine and proline metabolism and pyrimidine metabolism metabolic pathways were identified as the common metabolic pathways of 16s rRNA sequencing and untargeted metabolomics. In conclusion, our results showed that QFSS could ameliorate asthma in mice. The possible mechanism of QFSS on asthma may be associated with regulating the gut microbiota and arginine and proline metabolism and pyrimidine metabolism. Our study may be useful for researchers to study the integrative mechanisms of Chinese herbal formulas based on modulating gut microbiota and metabolism.PMID:36846048 | PMC:PMC9946754 | DOI:10.1155/2023/1456844

Propanol and 1, 3-propanediol enhance fatty acid accumulation synergistically in <em>Schizochytrium</em> ATCC 20888

Mon, 27/02/2023 - 12:00
Front Microbiol. 2023 Feb 9;13:1106265. doi: 10.3389/fmicb.2022.1106265. eCollection 2022.ABSTRACTThe effects of propanol and 1, 3-propanediol on fatty acid and biomass accumulation in Schizochytrium ATCC 20888 were explored. Propanol increased the contents of saturated fatty acids and total fatty acids by 55.4 and15.3%, while 1, 3-propanediol elevated the polyunsaturated fatty acids, total fatty acids and biomass contents by 30.7, 17.0, and 6.89%. Although both of them quench ROS to increase fatty acids biosynthesis, the mechanisms are different. The effect of propanol did not reflect on metabolic level while 1, 3-propanediol elevated osmoregulators contents and activated triacylglycerol biosynthetic pathway. The triacylglycerol content and the ratio of polyunsaturated fatty acids to saturated fatty acids were significantly increased by 2.53-fold, which explained the higher PUFA accumulation in Schizochytrium after adding 1, 3- propanediol. At last, the combination of propanol and 1, 3-propanediol further elevated total fatty acids by approximately 1.2-fold without compromising cell growth. These findings are valuable for scale-up production of designed Schizochytrium oil for various application purposes.PMID:36845976 | PMC:PMC9947470 | DOI:10.3389/fmicb.2022.1106265

Expanding the diversity of Chardonnay aroma through the metabolic interactions of <em>Saccharomyces cerevisiae</em> cocultures

Mon, 27/02/2023 - 12:00
Front Microbiol. 2023 Feb 9;13:1032842. doi: 10.3389/fmicb.2022.1032842. eCollection 2022.ABSTRACTYeast co-inoculations in winemaking are often studied in the framework of modulating the aromatic profiles of wines. Our study aimed to investigate the impact of three cocultures and corresponding pure cultures of Saccharomyces cerevisiae on the chemical composition and the sensory profile of Chardonnay wine. Coculture makes it possible to obtain completely new aromatic expressions that do not exist in the original pure cultures attributed to yeast interactions. Esters, fatty acids and phenol families were identified as affected. The sensory profiles and metabolome of the cocultures, corresponding pure cultures and associated wine blends from both pure cultures were found to be different. The coculture did not turn out to be the addition of the two pure culture wines, indicating the impact of interaction. High resolution mass spectrometry revealed thousands of cocultures biomarkers. The metabolic pathways involved in these wine composition changes were highlighted, most of them belonging to nitrogen metabolism.PMID:36845971 | PMC:PMC9947296 | DOI:10.3389/fmicb.2022.1032842

Metabolomic biomarkers for the diagnosis and post-transplant outcomes of AFP negative hepatocellular carcinoma

Mon, 27/02/2023 - 12:00
Front Oncol. 2023 Feb 9;13:1072775. doi: 10.3389/fonc.2023.1072775. eCollection 2023.ABSTRACTBACKGROUND: Early diagnosis for α-fetoprotein (AFP) negative hepatocellular carcinoma (HCC) remains a critical problem. Metabolomics is prevalently involved in the identification of novel biomarkers. This study aims to identify new and effective markers for AFP negative HCC.METHODS: In total, 147 patients undergoing liver transplantation were enrolled from our hospital, including liver cirrhosis patients (LC, n=25), AFP negative HCC patients (NEG, n=44) and HCC patients with AFP over 20 ng/mL (POS, n=78). 52 Healthy volunteers (HC) were also recruited in this study. Metabolomic profiling was performed on the plasma of those patients and healthy volunteers to select candidate metabolomic biomarkers. A novel diagnostic model for AFP negative HCC was established based on Random forest analysis, and prognostic biomarkers were also identified.RESULTS: 15 differential metabolites were identified being able to distinguish NEG group from both LC and HC group. Random forest analysis and subsequent Logistic regression analysis showed that PC(16:0/16:0), PC(18:2/18:2) and SM(d18:1/18:1) are independent risk factor for AFP negative HCC. A three-marker model of Metabolites-Score was established for the diagnosis of AFP negative HCC patients with an area under the time-dependent receiver operating characteristic curve (AUROC) of 0.913, and a nomogram was then established as well. When the cut-off value of the score was set at 1.2895, the sensitivity and specificity for the model were 0.727 and 0.92, respectively. This model was also applicable to distinguish HCC from cirrhosis. Notably, the Metabolites-Score was not correlated to tumor or body nutrition parameters, but difference of the score was statistically significant between different neutrophil-lymphocyte ratio (NLR) groups (≤5 vs. >5, P=0.012). Moreover, MG(18:2/0:0/0:0) was the only prognostic biomarker among 15 metabolites, which is significantly associated with tumor-free survival of AFP negative HCC patients (HR=1.160, 95%CI 1.012-1.330, P=0.033).CONCLUSION: The established three-marker model and nomogram based on metabolomic profiling can be potential non-invasive tool for the diagnosis of AFP negative HCC. The level of MG(18:2/0:0/0:0) exhibits good prognosis prediction performance for AFP negative HCC.PMID:36845695 | PMC:PMC9947281 | DOI:10.3389/fonc.2023.1072775

Editorial: Advances and challenges in untargeted metabolomics

Mon, 27/02/2023 - 12:00
Front Mol Biosci. 2023 Feb 10;10:1097443. doi: 10.3389/fmolb.2023.1097443. eCollection 2023.NO ABSTRACTPMID:36845548 | PMC:PMC9951091 | DOI:10.3389/fmolb.2023.1097443

Metabolomics investigation on the volatile and non-volatile composition in enzymatic hydrolysates of Pacific oyster (<em>Crassostrea gigas</em>)

Mon, 27/02/2023 - 12:00
Food Chem X. 2023 Jan 9;17:100569. doi: 10.1016/j.fochx.2023.100569. eCollection 2023 Mar 30.ABSTRACTTo investigate the differences of volatile and non-volatile metabolites between oyster enzymatic hydrolysates and boiling concentrates, molecular sensory analysis and untargeted metabolomics were employed. "Grassy," "fruity," "oily/fatty," "fishy," and "metallic" were identified as sensory attributes used to evaluate different processed oyster homogenates. Sixty-nine and 42 volatiles were identified by gas chromatography-ion mobility spectrometry and gas chromatography-mass spectrometry, respectively. Pentanal, 1-penten-3-ol, hexanal, (E)-2-pentenal, heptanal, (E)-2-hexenal, 4-octanone, (E)-4-heptenal, 3-octanone, octanal, nonanal, 1-octen-3-ol, benzaldehyde, (E)-2-nonenal, and (E, Z)-2,6-nonadienal were detected as the key odorants (OAV > 1) after enzymatic hydrolysis. Hexanal, (E)-4-heptenal, and (E)-2-pentenal were significantly associated with off-odor, and 177 differential metabolites were classified. Aspartate, glutamine, alanine, and arginine were the key precursors affecting the flavor profile. Linking sensory descriptors to volatile and nonvolatile components of different processed oyster homogenates will provide information for the process and quality improvement of oyster products.PMID:36845524 | PMC:PMC9945435 | DOI:10.1016/j.fochx.2023.100569

Comparative nutritional and metabolic analysis reveals the taste variations during yellow rambutan fruit maturation

Mon, 27/02/2023 - 12:00
Food Chem X. 2023 Jan 19;17:100580. doi: 10.1016/j.fochx.2023.100580. eCollection 2023 Mar 30.ABSTRACTThe metabolic reasons for rambutan taste variations during maturity are unknown. Here, we obtained a unique rambutan cultivar Baoyan No.2 (BY2) with a strong yellow pericarp and excellent taste, the sugar-acid ratios of which ranged from 21.7 to 94.5 during maturation. Widely targeted metabolomics analysis was performed to reveal the metabolic reasons behind these taste variations. The results showed that 51 metabolites were identified as common different metabolites (DMs), including 16 lipids, 12 amino acids and others. Among them, the abundance level of 3,4-digalloylshikimic acid exhibited a positive correlation with the titratable acids (R2 = 0.9996) and a negative correlation with the sugar-acid ratio (R2 = 0.9999). Therefore, it could be a taste biomarker of BY2 rambutan. Moreover, all DMs were enriched in "galactose metabolism", "fructose and mannose metabolism" and "biosynthesis of amino acids" pathways, which predominantly accounted for the taste variation. Our findings provided new metabolic evidence for the taste variation of rambutan.PMID:36845499 | PMC:PMC9944575 | DOI:10.1016/j.fochx.2023.100580

Metabolomics analysis reveals the accumulation patterns of flavonoids and phenolic acids in quinoa (<em>Chenopodium quinoa</em> Willd.) grains of different colors

Mon, 27/02/2023 - 12:00
Food Chem X. 2023 Feb 6;17:100594. doi: 10.1016/j.fochx.2023.100594. eCollection 2023 Mar 30.ABSTRACTQuinoa grains are gaining increasing popularity owing to their high nutritional merits. However, only limited information is available on the metabolic profiles of quinoa grains. In this study, we determined the metabolic profiles of black, red, and white quinoa grains via an ultraperformance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS)-based metabolomics. A total of 689 metabolites were identified, among which 251, 182, and 317 metabolites displayed different accumulation patterns in the three comparison groups (Black vs Red, Black vs White, and Red vs White), respectively. In particular, flavonoid and phenolic acid contents displayed considerable differences, with 22 flavonoids, 5 phenolic acids, and 1 betacyanin being differentially accumulated among the three quinoa cultivars. Additionally, correlation analysis showed that flavonoids and phenolic acids could act as betanin co-pigments in quinoa grains. In conclusion, this study provides comprehensive insights into the adequate utilization and development of novel quinoa-based functional foods.PMID:36845489 | PMC:PMC9945449 | DOI:10.1016/j.fochx.2023.100594

HS-SPME-GC × GC/MS combined with multivariate statistics analysis to investigate the flavor formation mechanism of tank-fermented broad bean paste

Mon, 27/02/2023 - 12:00
Food Chem X. 2022 Dec 27;17:100556. doi: 10.1016/j.fochx.2022.100556. eCollection 2023 Mar 30.ABSTRACTWith the advancement of industrialization, tank fermentation technology is promising for Pixian broad bean paste. This study identified and analyzed the general physicochemical factors and volatile metabolites of fermented broad beans in a thermostatic fermenter. Headspace solid-phase microextraction (HS-SPME)-two-dimensional gas chromatography-mass spectrometry (GC × GC-MS) was applied to detect the volatile compounds in fermented broad beans, while metabolomics was used to explore their physicochemical characteristics and analyze the possible metabolic mechanism. A total of 184 different metabolites were detected, including 36 alcohols, 29 aldehydes, 26 esters, 21 ketones, 14 acids, 14 aromatic compounds, ten heterocycles, nine phenols, nine organonitrogen compounds, seven hydrocarbons, two ethers, and seven other types, which were annotated to various branch metabolic pathways of carbohydrate and amino acid metabolism. This study provides references for subsequent functional microorganism mining to improve the quality of the tank-fermented broad beans and upgrade the Pixian broad bean paste industry.PMID:36845488 | PMC:PMC9943836 | DOI:10.1016/j.fochx.2022.100556

HPLC-QTRAP-MS-based metabolomics approach investigates the formation mechanisms of meat quality and flavor of Beijing You chicken

Mon, 27/02/2023 - 12:00
Food Chem X. 2022 Dec 21;17:100550. doi: 10.1016/j.fochx.2022.100550. eCollection 2023 Mar 30.ABSTRACTChicken meat quality and flavor are determined by abundant metabolites. In this study, HPLC-QTRAP-MS-based metabolomic analysis was used to evaluate the characteristic metabolites in the breast muscle of Beijing You chickens aged 56, 98, and 120 days. A total of 544 metabolites in 32 categories were identified, among which amino acids and organic acids were the most abundant. 60 and 55 differential metabolites were identified between 56 and 98 days of age, 98 and 120 days of age, respectively. The content of l-carnitine, l-methionine and 3-hydroxybutyrate increased significantly at 98 or 120 days of age. Arginine biosynthesis, purine metabolism, alanine, aspartic acid, and glutamic acid metabolism were important metabolic pathways that affect chicken meat flavor. This study can help to elucidate the metabolic mechanism of breast muscle during Beijing You chicken development and provide a theoretical reference for the improvement of chicken meat quality and flavor.PMID:36845483 | PMC:PMC9943843 | DOI:10.1016/j.fochx.2022.100550

Metabonomic analysis of human and 12 kinds of livestock mature milk

Mon, 27/02/2023 - 12:00
Food Chem X. 2023 Jan 20;17:100581. doi: 10.1016/j.fochx.2023.100581. eCollection 2023 Mar 30.ABSTRACTMature milk, as a nutrient-rich endogenous metabolite, has various beneficial effects on the human body. In order to investigate the specific nutrients provided by different dairy products to humans, we used UHPLC-Q-TOF MS to analyze the highly significantly differentially expressed metabolites in 13 species of mammalian mature milk, which were grouped into 17 major metabolite classes with 1992 metabolites based on chemical classification. KEGG shows that 5 pathways in which differentially significant metabolites are actively involved are ABC transporters, Purine metabolism, Pyrimidine metabolism, Phosphotransferase system, Galactose metabolism. The study found that pig milk and goat milk are closer to human milk and contain more nutrients that are beneficial to human health, followed by camel milk and cow milk. In the context of dairy production, the development of goat milk is more likely to meet human needs and health.PMID:36845482 | PMC:PMC9944509 | DOI:10.1016/j.fochx.2023.100581

Short communication: unique metabolic signature of proliferative retinopathy in the tear fluid of diabetic patients with comorbidities - preliminary data for PPPM validation

Mon, 27/02/2023 - 12:00
EPMA J. 2023 Feb 22:1-9. doi: 10.1007/s13167-023-00318-4. Online ahead of print.ABSTRACTType 2 diabetes (T2DM) defined as the adult-onset type that is primarily not insulin-dependent, comprises over 95% of all diabetes mellitus (DM) cases. According to global records, 537 million adults aged 20-79 years are affected by DM that means at least 1 out of 15 persons. This number is projected to grow by 51% by the year 2045. One of the most common complications of T2DM is diabetic retinopathy (DR) with an overall prevalence over 30%. The total number of the DR-related visual impairments is on the rise, due to the growing T2DM population. Proliferative diabetic retinopathy (PDR) is the progressing DR and leading cause of preventable blindness in working-age adults. Moreover, PDR with characteristic systemic attributes including mitochondrial impairment, increased cell death and chronic inflammation, is an independent predictor of the cascading DM-complications such as ischemic stroke. Therefore, early DR is a reliable predictor appearing upstream of this "domino effect". Global screening, leading to timely identification of DM-related complications, is insufficiently implemented by currently applied reactive medicine. A personalised predictive approach and cost-effective targeted prevention shortly - predictive, preventive and personalised medicine (PPPM / 3PM) could make a good use of the accumulated knowledge, preventing blindness and other severe DM complications. In order to reach this goal, reliable stage- and disease-specific biomarker panels are needed characterised by an easy way of the sample collection, high sensitivity and specificity of analyses. In the current study, we tested the hypothesis that non-invasively collected tear fluid is a robust source for the analysis of ocular and systemic (DM-related complications) biomarker patterns suitable for differential diagnosis of stable DR versus PDR. Here, we report the first results of the comprehensive ongoing study, in which we correlate individualised patient profiles (healthy controls versus patients with stable D as well as patients with PDR with and without co-morbidities) with their metabolic profiles in the tear fluid. Comparative mass spectrometric analysis performed has identified following metabolic clusters which are differentially expressed in the groups of comparison: acylcarnitines, amino acid & related compounds, bile acids, ceramides, lysophosphatidyl-choline, nucleobases & related compounds, phosphatidyl-cholines, triglycerides, cholesterol esters, and fatty acids. Our preliminary data strongly support potential clinical utility of metabolic patterns in the tear fluid indicating a unique metabolic signature characteristic for the DR stages and PDR progression. This pilot study creates a platform for validating the tear fluid biomarker patterns to stratify T2DM-patients predisposed to the PDR. Moreover, since PDR is an independent predictor of severe T2DM-related complications such as ischemic stroke, our international project aims to create an analytical prototype for the "diagnostic tree" (yes/no) applicable to healthrisk assessment in diabetes care.PMID:36845280 | PMC:PMC9944425 | DOI:10.1007/s13167-023-00318-4

Quiescence preconditioned nucleus pulposus stem cells alleviate intervertebral disc degeneration by enhancing cell survival <em>via</em> adaptive metabolism pattern in rats

Mon, 27/02/2023 - 12:00
Front Bioeng Biotechnol. 2023 Feb 10;11:1073238. doi: 10.3389/fbioe.2023.1073238. eCollection 2023.ABSTRACTQuiescence is a cellular state of reversible growth arrest required to maintain homeostasis and self-renewal. Entering quiescence allows the cells to remain in the non-dividing stage for an extended period of time and enact mechanisms to protect themselves from damage. Due to the extreme nutrient-deficient microenvironment in the intervertebral disc (IVD), the therapeutic effect of cell transplantation is limited. In this study, nucleus pulposus stem cells (NPSCs) were preconditioned into quiescence through serum starvation in vitro and transplanted to repair intervertebral disc degeneration (IDD). In vitro, we investigated apoptosis and survival of quiescent NPSCs in a glucose-free medium without fetal bovine serum. Non-preconditioned proliferating NPSCs served as controls. In vivo, the cells were transplanted into a rat model of IDD induced by acupuncture, and the intervertebral disc height, histological changes, and extracellular matrix synthesis were observed. Finally, to elucidate the mechanisms underlying the quiescent state of NPSCs, the metabolic patterns of the cells were investigated through metabolomics. The results revealed that quiescent NPSCs decreased apoptosis and increased cell survival when compared to proliferating NPSCs both in vitro and in vivo, as well as maintained the disc height and histological structure significantly better than that by proliferating NPSCs. Furthermore, quiescent NPSCs have generally downregulated metabolism and reduced energy requirements in response to a switch to a nutrient-deficient environment. These findings support that quiescence preconditioning maintains the proliferation and biological function potential of NPSCs, increases cell survival under the extreme environment of IVD, and further alleviates IDD via adaptive metabolic patterns.PMID:36845177 | PMC:PMC9950514 | DOI:10.3389/fbioe.2023.1073238

Bacterial volatile organic compounds (VOCs) promote growth and induce metabolic changes in rice

Mon, 27/02/2023 - 12:00
Front Plant Sci. 2023 Feb 9;13:1056082. doi: 10.3389/fpls.2022.1056082. eCollection 2022.ABSTRACTPlant growth-promoting bacteria (PGPB) represent an eco-friendly alternative to reduce the use of chemical products while increasing the productivity of economically important crops. The emission of small gaseous signaling molecules from PGPB named volatile organic compounds (VOCs) has emerged as a promising biotechnological tool to promote biomass accumulation in model plants (especially Arabidopsis thaliana) and a few crops, such as tomato, lettuce, and cucumber. Rice (Oryza sativa) is the most essential food crop for more than half of the world's population. However, the use of VOCs to improve this crop performance has not yet been investigated. Here, we evaluated the composition and effects of bacterial VOCs on the growth and metabolism of rice. First, we selected bacterial isolates (IAT P4F9 and E.1b) that increased rice dry shoot biomass by up to 83% in co-cultivation assays performed with different durations of time (7 and 12 days). Metabolic profiles of the plants co-cultivated with these isolates and controls (without bacteria and non-promoter bacteria-1003-S-C1) were investigated via 1H nuclear magnetic resonance. The analysis identified metabolites (e.g., amino acids, sugars, and others) with differential abundance between treatments that might play a role in metabolic pathways, such as protein synthesis, signaling, photosynthesis, energy metabolism, and nitrogen assimilation, involved in rice growth promotion. Interestingly, VOCs from IAT P4F9 displayed a more consistent promotion activity and were also able to increase rice dry shoot biomass in vivo. Molecular identification by sequencing the 16S rRNA gene of the isolates IAT P4F9 and E.1b showed a higher identity with Serratia and Achromobacter species, respectively. Lastly, volatilomes of these and two other non-promoter bacteria (1003-S-C1 and Escherichia coli DH5α) were evaluated through headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry. Compounds belonging to different chemical classes, such as benzenoids, ketones, alcohols, sulfide, alkanes, and pyrazines, were identified. One of these VOCs, nonan-2-one, was validated in vitro as a bioactive compound capable of promoting rice growth. Although further analyses are necessary to properly elucidate the molecular mechanisms, our results suggest that these two bacterial isolates are potential candidates as sources for bioproducts, contributing to a more sustainable agriculture.PMID:36844905 | PMC:PMC9948655 | DOI:10.3389/fpls.2022.1056082

A Brief History of Microbial Study and Techniques for Exploring the Gastrointestinal Microbiome

Mon, 27/02/2023 - 12:00
Clin Colon Rectal Surg. 2023 Jan 25;36(2):98-104. doi: 10.1055/s-0042-1760678. eCollection 2023 Mar.ABSTRACTOver the past 20 years, the study of microbial communities has benefited from simultaneous advancements across several fields resulting in a high-resolution view of human consortia. Although the first bacterium was described in the mid-1600s, the interest in community membership and function has not been a focus or feasible until recent decades. With strategies such as shotgun sequencing, microbes can be taxonomically profiled without culturing and their unique variants defined and compared across phenotypes. Approaches such as metatranscriptomics, metaproteomics, and metabolomics can define the current functional state of a population through the identification of bioactive compounds and significant pathways. Prior to sample collection in microbiome-based studies it is critical to evaluate the requirements of downstream analyses to ensure accurate processing and storage for generation of high data quality. A common pipeline for the analysis of human samples includes approval of collection protocols and method finalization, patient sample collection, sample processing, data analysis, and visualization. Human-based microbiome studies are inherently challenging but with the application of complementary multi-omic strategies there is an unbounded potential for discovery.PMID:36844714 | PMC:PMC9946713 | DOI:10.1055/s-0042-1760678

The Role of the Microbiome in the Etiology of Inflammatory Bowel Diseases

Mon, 27/02/2023 - 12:00
Clin Colon Rectal Surg. 2023 Jan 25;36(2):120-126. doi: 10.1055/s-0042-1760680. eCollection 2023 Mar.ABSTRACTInflammatory bowel diseases (IBDs) result from dysregulated immune responses to environmental and microbial triggers in genetically susceptible hosts. Many clinical observations and animal studies support the role of the microbiome in the pathogenesis of IBD. Restoration of the fecal stream leads to postoperative Crohn's recurrence, while diversion can treat active inflammation. Antibiotics can be effective in prevention of postoperative Crohn's recurrence and in pouch inflammation. Several gene mutations associated with Crohn's risk lead to functional changes in microbial sensing and handling. However, the evidence linking the microbiome to the IBD is largely correlative, given the difficulty in studying the microbiome before disease occurs. Attempts to modify the microbial triggers of inflammation have had modest success to date. Exclusive enteral nutrition can treat Crohn's inflammation though no whole food diet to date has been shown to treat inflammation. Manipulation of the microbiome through fecal microbiota transplant and probiotics have had limited success. Further focus on early changes in the microbiome and functional consequences of microbial changes through the study of metabolomics are needed to help advance the field.PMID:36844713 | PMC:PMC9946717 | DOI:10.1055/s-0042-1760680

Maximizing light-driven CO<sub>2</sub> and N<sub>2</sub> fixation efficiency in quantum dot-bacteria hybrids

Mon, 27/02/2023 - 12:00
Nat Catal. 2022 Nov;5(11):1019-1029. doi: 10.1038/s41929-022-00867-3. Epub 2022 Nov 10.ABSTRACTIntegrating light-harvesting materials with microbial biochemistry is a viable approach to produce chemicals with high efficiency from the air, water, and sunlight. Yet it remains unclear whether all absorbed photons in the materials can be transferred through the material-biology interface for solar-to-chemical production and whether the presence of materials beneficially affect the microbial metabolism. Here we report a microbe-semiconductor hybrid by interfacing CO2/N2-fixing bacterium Xanthobacter autotrophicus with CdTe quantum dots for light-driven CO2 and N2 fixation with internal quantum efficiencies of 47.2 ± 7.3% and 7.1 ± 1.1%, respectively, reaching the biochemical limits of 46.1% and 6.9% imposed by the stoichiometry in biochemical pathways. Photophysical studies suggest fast charge-transfer kinetics at the microbe-semiconductor interfaces, while proteomics and metabolomics indicate a material-induced regulation of microbial metabolism favoring higher quantum efficiencies compared to the biological counterparts alone.PMID:36844635 | PMC:PMC9956923 | DOI:10.1038/s41929-022-00867-3

The Efficacy and Mechanism of Qinghua Jianpi Recipe in Inhibiting Canceration of Colorectal Adenoma Based on Inflammatory Cancer Transformation

Mon, 27/02/2023 - 12:00
J Immunol Res. 2023 Feb 15;2023:4319551. doi: 10.1155/2023/4319551. eCollection 2023.ABSTRACTOBJECTIVE: This study is aimed at exploring the effect of Qinghua Jianpi Recipe on preventing colon polyp recurrence and inhibiting the progress of "inflammatory cancer transformation." And another goal is to explore the changes of intestinal flora structure and intestinal inflammatory (immune) microenvironment of mice with colon polyps treated by Qinghua Jianpi Recipe and to clarify its mechanism.METHODS: Clinical trials were conducted to confirm the therapeutic effect of Qinghua Jianpi Recipe on patients with inflammatory bowel disease. The inhibitory effect of Qinghua Jianpi Recipe on "inflammatory cancer transformation" of colon cancer was confirmed by an adenoma canceration mouse model. Histopathological examination was used to evaluate the effects of Qinghua Jianpi Recipe on intestinal inflammatory state, adenoma number, and pathological changes of adenoma model mice. The changes of inflammatory indexes in intestinal tissue were tested by ELISA. Intestinal flora was detected by 16S rRNA high-throughput sequencing. Short-chain fatty acid metabolism in the intestine was analyzed by targeted metabolomics. Network pharmacology analysis of possible mechanism of Qinghua Jianpi Recipe on colorectal cancer was performed. Western blot was used to detect the protein expression of the related signaling pathways.RESULTS: Qinghua Jianpi Recipe can significantly improve intestinal inflammation status and function in patients with inflammatory bowel disease. Qinghua Jianpi Recipe could significantly improve the intestinal inflammatory activity and pathological damage of adenoma model mice and reduce the number of adenoma. Qinghua Jianpi Recipe significantly increased the levels of Peptostreptococcales_Tissierellales, NK4A214_group, Romboutsia, and other intestinal flora after intervention. Meanwhile, the treatment group of Qinghua Jianpi Recipe could reverse the changes of short-chain fatty acids. Network pharmacology analysis and experimental studies showed that Qinghua Jianpi Recipe inhibited the "inflammatory cancer transformation" of colon cancer by regulating intestinal barrier function-related proteins, inflammatory and immune-related signaling pathways, and free fatty acid receptor 2 (FFAR2).CONCLUSION: Qinghua Jianpi Recipe can improve the intestinal inflammatory activity and pathological damage of patient and adenoma cancer model mice. And its mechanism is related to the regulation of intestinal flora structure and abundance, short-chain fatty acid metabolism, intestinal barrier function, and inflammatory pathways.PMID:36844438 | PMC:PMC9946765 | DOI:10.1155/2023/4319551

Integrative analysis of sensory evaluation and non-targeted metabolomics to unravel tobacco leaf metabolites associated with sensory quality of heated tobacco

Mon, 27/02/2023 - 12:00
Front Plant Sci. 2023 Feb 8;14:1123100. doi: 10.3389/fpls.2023.1123100. eCollection 2023.ABSTRACTINTRODUCTION: Heated tobacco (Nicotiana tabacum L.) products are heating tobacco plug at a temperature of 350°C and produce different emissions in aerosol and sensory perceptions of tobacco leaf compared with combustible tobacco. Previous study assessed different tobacco varieties in heated tobacco for sensory quality and analyzed the links between sensory scores of the final products and certain chemical classes in tobacco leaf. However, contribution of individual metabolites to sensory quality of heated tobacco remains largely open for investigation.METHODS: In present study, five tobacco varieties were evaluated as heated tobacco for sensory quality by an expert panel and the volatile and non-volatile metabolites were analyzed by non-targeted metabolomics profiling.RESULTS: The five tobacco varieties had distinct sensory qualities and can be classified into higher and lower sensory rating classes. Principle component analysis and hierarchical cluster analysis showed that leaf volatile and non-volatile metabolome annotated were grouped and clustered by sensory ratings of heated tobacco. Orthogonal projections to latent structures discriminant analysis followed by variable importance in projection and fold-change analysis revealed 13 volatiles and 345 non-volatiles able to discriminate the tobacco varieties with higher and lower sensory ratings. Some compounds such as β-damascenone, scopoletin, chlorogenic acids, neochlorogenic acids, and flavonol glycosyl derivatives had strong contribution to the prediction of sensory quality of heated tobacco. Several lyso-phosphatidylcholine and lyso-phosphatidylethanolamine lipid species, and reducing and non-reducing sugar molecules were also positively related to sensory quality.DISCUSSION: Taken together, these discriminating volatile and non-volatile metabolites support the role of leaf metabolites in affecting the sensory quality of heated tobacco and provide new information on the types of leaf metabolites that can be used to predict applicability of tobacco varieties for heated tobacco products.PMID:36844088 | PMC:PMC9944805 | DOI:10.3389/fpls.2023.1123100

Mellein: Production in culture by <em>Macrophomina phaseolina</em> isolates from soybean plants exhibiting symptoms of charcoal rot and its role in pathology

Mon, 27/02/2023 - 12:00
Front Plant Sci. 2023 Feb 8;14:1105590. doi: 10.3389/fpls.2023.1105590. eCollection 2023.ABSTRACTMacrophomina phaseolina (Mp) is a fungal pathogen proposed to enter host roots by releasing toxins that induce local necrosis in roots allowing entry of hyphae. Mp is reported to produce several potent phytotoxins, including (-)-botryodiplodin and phaseolinone, but isolates that do not produce these phytotoxins retain virulence. One hypothesis explaining these observations is that some Mp isolates may produce other unidentified phytotoxin(s) responsible for virulence. A previous study of Mp isolates from soybean found 14 previously unreported secondary metabolites using LC-MS/MS, including mellein, which has various reported biological activities. This study was conducted to investigate the frequency and amounts of mellein produced in culture by Mp isolates from soybean plants exhibiting symptoms of charcoal rot and to investigate the role of mellein in any observed phytotoxicity. LC-MS/MS analysis of cell-free culture filtrates (CCFs) from 89 Mp isolates revealed that 28.1% produced mellein (49-2,203 µg/L). In soybean seedlings in hydroponic culture, Mp CCFs diluted to 25% (vol/vol) in hydroponic growth medium induced phytotoxic symptoms with frequencies of 73% chlorosis, 78% necrosis, 7% wilting, and 16% death, and at 50% (vol/vol) induced phytotoxicity with frequencies of 61% chlorosis, 82% necrosis, 9% wilting, and 26% death. Commercially-available mellein (40-100 µg/mL) in hydroponic culture medium induced wilting. However, mellein concentrations in CCFs exhibited only weak, negative, insignificant correlations with phytotoxicity measures in soybean seedlings, suggesting that mellein does not contribute substantially to observed phytotoxic effects. Further investigation is needed to determine if mellein plays any role in root infection.PMID:36844080 | PMC:PMC9944435 | DOI:10.3389/fpls.2023.1105590

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