Important Metabolites Research Articles

Exogenous of different elicitors: proline and ornithine on Sansevieria trifasciata under particulate matter (PM) and volatile organic compounds (VOC).

Phytoremediation has become famous for removing particulate matter (PM) and volatile organic compounds (VOC) in situ. Plants for removing PM and VOC were associated with botanical biofilters to attract pollution to the plant. On the other hand, persistent pollution exposure can lower plant health and phytoremediation effectiveness; therefore, improving plant tolerance against stress is necessary. Various elicitors can enhance plant tolerance to certain stressors. This study aims to investigate different elicitors to maintain plant health and improve the use of plants in phytoremediation for PM and VOC pollution. This experiment used Sansevieria trifasciata hort. ex Prain under PM and VOC stress. Exogenous elicitors, such as proline, ornithine, and a commercial product, were applied to the leaf parts before exposure to PM and VOC stress. The initial concentrations of PM1, PM2.5, and PM10 were 300-350, 350-450, and 400-500µgm-3, respectively, while the VOC concentration was 2.5-3.0mgm-3. The plant was stressed for 7days. The result indicated that ornithine 10mM is vital in improving plant tolerance and inducing antioxidant enzymes against PM and VOC, while proline 50mM and a commercial product could not reduce plant stress. This study suggests that ornithine might be an important metabolite to improve plant tolerance to PM and VOC.

Selective and sensitive detection of hypochlorite in living cells using reduced iodine-doped carbon dots

Hypochlorite (ClO−) is an important metabolite that participates a series of intracellular signal communications, which is closely related with the generation and development of various diseases. Herein, we design and prepare reduced iodine-doped carbon dots (I-CDs) that are highly sensitive to ClO−. The proposed I-CDs show bright green fluorescence (FL), which can be efficiently quenched upon treatment with ClO− because of the destroy of I-CDs structure caused by oxidation of iodine by ClO−. This sensing platform displays a good linear response range of 1 − 60 μM with a low detection limit of 95.1 nM. Importantly, monitoring ClO− level in living cells is further realized, demonstrating the capability of this strategy to determine the content of intracellular ClO−. This work provides a promising tool for visual sensing ClO−, which is of great significance for early diagnosis of ClO− related diseases.

Chitosan Oligosaccharides Mitigate Flooding Stress Damage in Rice by Affecting Antioxidants, Osmoregulation, and Hormones

Rice (Oryza sativa L.) is one of the most important food crops worldwide. However, during direct seeding, rice is extremely vulnerable to flooding stress, which impairs rice’s emergence and seedling growth and results in a significant yield loss. According to our research, chitosan oligosaccharides have the potential to be a chemical seed-soaking agent that greatly increases rice’s resistance to flooding. Chitosan oligosaccharides were able to enhance seed energy supply, osmoregulation, and antioxidant capacity, according to physiological index assessments. Using transcriptome and metabolomic analysis, we discovered that important differential metabolites and genes were involved in the signaling pathway for hormone synthesis and antioxidant capacity. Exogenous chitosan oligosaccharides specifically and significantly inhibit genes linked to auxin, jasmonic acid, and abscisic acid. This suggested that applying chitosan oligosaccharides could stabilize seedling growth and development by controlling associated hormones and reducing flooding stress by enhancing membrane stability and antioxidant capacity. Finally, we verified the effectiveness of exogenous chitosan oligosaccharides imbibed in seeds by field validation, demonstrating that they can enhance rice seedling emergence and growth under flooding stress.

Enrichment and Evaluation of Antitumor Properties of Total Flavonoids from Juglans mandshurica Maxim

Flavonoids are important secondary metabolites found in Juglans mandshurica Maxim., which is a precious reservoir of bioactive substances in China. To explore the antitumor actions of flavonoids (JMFs) from the waste branches of J. mandshurica, the following optimized purification parameters of JMFs by macroporous resins were first obtained. The loading concentration, flow rate, and loading volume of raw flavonoid extracts were 1.4 mg/mL, 2.4 BV/h, and 5 BV, respectively, and for desorption, 60% ethanol (4 BV) was selected to elute JMFs-loaded AB-8 resin at a flow rate of 2.4 BV/h. This adsorption behavior can be explained by the pseudo-second-order kinetic model and Langmuir isotherm model. Subsequently, JMFs were identified using Fourier transform infrared combined with high-performance liquid chromatography and tandem mass spectrometry, and a total of 156 flavonoids were identified. Furthermore, the inhibitory potential of JMFs on the proliferation, migration, and invasion of HepG2 cells was demonstrated. The results also show that exposure to JMFs induced apoptotic cell death, which might be associated with extrinsic and intrinsic pathways. Additionally, flow cytometry detection found that JMFs exposure triggered S phase arrest and the generation of reactive oxygen species in HepG2 cells. These findings suggest that the JMFs purified in this study represent great potential for the treatment of liver cancer.

Cell-Free Supernatant of Lactobacillus rhamnosus and Bifidobacterium breve Ameliorates Ischemic Stroke-Generated Neurological Deficits in Rats.

The beneficial effects of probiotics, postbiotics, and paraprobiotics have already been registered in managing ischemic stroke-generated neuroinflammation and gut dysbiosis. Herein, we examined the impact of cell-free supernatant (CFS) obtained from probiotics (Lactobacillus rhamnosus UBLR-58 and Bifidobacterium breve UBBr-01) in a rat transient middle cerebral artery occlusion (MCAO) model of focal cerebral injury. Pre-MCAO supplementation of probiotics (2 × 109CFU/mL) for 21days or CFS (1mL/rat) for 7days protect the MCAO-induced somatosensory and motor impairments recorded at 24h and 72h after reperfusion in foot-fault, rotarod, adhesive removal, and vibrissae-evoked forelimb placing tests. We also noted the reduced infarct area and neuronal degradation in the right hemisphere of probiotics- and CFS-recipient MCAO-operated animals. Moreover, MCAO-induced altered concentrations of glial-fibrillary acidic protein, NeuN, zonula occludens-1 (ZO-1), TLR4, IL-1β, IL-6, and TNF-α, as well as matrix metalloproteinase-9 (MMP9) were reversed in the treatment groups. Probiotics and CFS treatment ameliorated the elevated levels of IL-6, IL-1β, and MMP9 in the blood plasma of rats. The disrupted microbial phyla, Firmicutes-to-Bacteroides ratio, villi/crypt ratio, and decreased mucin-producing goblet cells, ZO-1, and occludin in the colon of MCAO-operated rats were recovered following probiotics and CFS treatment. NMR characterization of CFS and rat blood plasma revealed the presence of several important bacterial metabolites. These findings suggest that the CFS obtained from Lactobacillus rhamnosus UBLR-58 and Bifidobacterium breve UBBr-01 has the propensity to improve MCAO-generated neurological dysfunctions in rats by dampening neuroinflammation and modulating the gut-brain axis modulators.

Bile Salt Hydrolase Activity-Based Probes for Monitoring Gut Microbial Bile Acid Metabolism.

Bile acids are bioactive metabolites that are biotransformed into secondary bile acids by the gut microbiota, a vast consortium of microbes that inhabit the intestines. The first step in intestinal secondary bile acid metabolism is carried out by a critical enzyme, bile salt hydrolase (BSH), that catalyzes the gateway reaction that precedes all subsequent microbial metabolism of these important metabolites. As gut microbial metabolic activity is difficult to probe due to the complex nature of the gut microbiome, approaches are needed to profile gut microbiota-associated enzymes such as BSH. Here, we develop a panel of BSH activity-based probes (ABPs) to determine how changes in diurnal rhythmicity of gut microbiota-associated metabolism affects BSH activity and substrate preference. This panel of covalent probes enables determination of BSH activity and substrate specificity from multiple gut anerobic bacteria derived from the human and mouse gut microbiome. We found that both gut microbiota-associated BSH activity and substrate preference is rhythmic, likely due to feeding patterns of the mice. These results indicate that this ABP-based approach can be used to profile changes in BSH activity in physiological and disease states that are regulated by circadian rhythms.

Navigating Amaryllidaceae Alkaloids: Bridging Gaps and Charting Biosynthetic Territories - A Comprehensive Review.

Amaryllidaceae alkaloid (AAs) biosynthesis has garnered significant attention in recent years, particularly with the commercialisation of galanthamine as a treatment for the symptoms of Alzheimer's disease. A significant amount of research work over the last 8 decades has focused on the understanding of AA biosynthesis, starting from early radiolabelling studies to recent multi-omics analysis with modern biotechnological advancements. Those studies enabled the identification of hundreds of metabolites, the characterisation of biochemical pathway, an understanding of the environmental stimuli, and of the molecular regulation of these pharmaceutically and agriculturally important metabolites. Despite the numerous works there remain significant gaps in understanding their biosynthesis in Amaryllidaceae plants. As such, further research is needed to fully elucidate the metabolic pathway and facilitate their production. This review aims to provide a comprehensive overall summary of the current state of knowledge on AAs biosynthesis, from elicitation of transcription factors expression in the cell nucleus to alkaloid transport in the apoplast, and to highlight the challenges that need to be overcome for further advancement.

Functional Characterization of PmDXR, a Critical Rate-Limiting Enzyme, for Turpentine Biosynthesis in Masson Pine (Pinus massoniana Lamb.).

As one of the largest and most diverse classes of specialized metabolites in plants, terpenoids (oprenoid compounds, a type of bio-based material) are widely used in the fields of medicine and light chemical products. They are the most important secondary metabolites in coniferous species and play an important role in the defense system of conifers. Terpene synthesis can be promoted by regulating the expressions of terpene synthase genes, and the terpene biosynthesis pathway has basically been clarified in Pinus massoniana, in which there are multiple rate-limiting enzymes and the rate-limiting steps are difficult to determine, so the terpene synthase gene regulation mechanism has become a hot spot in research. Herein, we amplified a PmDXR gene (GenBank accession no. MK969119.1) of the MEP pathway (methyl-erythritol 4-phosphate) from Pinus massoniana. The DXR enzyme activity and chlorophyll a, chlorophyll b and carotenoid contents of overexpressed Arabidopsis showed positive regulation. The PmDXR gene promoter was a tissue-specific promoter and can respond to ABA, MeJA and GA stresses to drive the expression of the GUS reporter gene in N. benthamiana. The DXR enzyme was identified as a key rate-limiting enzyme in the MEP pathway and an effective target for terpene synthesis regulation in coniferous species, which can further lay the theoretical foundation for the molecularly assisted selection of high-yielding lipid germplasm of P. massoniana, as well as provide help in the pathogenesis of pine wood nematode disease.

Growth conditions trigger genotype-specific metabolic responses that affect the nutritional quality of kale cultivars.

Kales (Brassica oleracea convar acephala) are fast-growing, nutritious leafy vegetables ideal for year-round indoor farming. However, selection of best cultivars for growth under artificial lighting necessitates a deeper understanding of leaf metabolism in different kale types. Here we examined a curly leaved cultivar Half Tall and a lacinato type cultivar Black Magic under moderate growth light (130 µmol photons m-1s-1/22°C) and high light (800 µmol photons m-1s-1/26°C) conditions. These conditions induced genotype-dependent differences in nutritionally important metabolites, especially anthocyanins and glucosinolates (GSLs), in the kale cultivars. In the pale green Half Tall, growth under high light conditions did not induce changes in either pigmentation or total GSL content. In contrast, the purple pigmentation of Black Magic intensified due to increased anthocyanin accumulation. Black Magic showed reduced amounts of indole GSLs and increased amounts of aliphatic GSLs under high light conditions, with notable cultivar-specific adjustments in individual GSL species. Correlation analysis of metabolite profiles suggested cultivar-specific metabolic interplay between serine biosynthesis and the production of indole GSLs. RNA sequencing identified candidate genes encoding metabolic enzymes and regulatory components behind anthocyanin and GSL biosynthesis. These findings improve the understanding of leaf metabolism and its effects on the nutritional quality of kale cultivars.

Validation of a commercial ELISA kit to measure 11-oxoetiocholanolone in equine and bovine feces.

Feces are a noninvasive and easily collectible matrix that may help determine cumulative hormone metabolite concentrations over medium-to-long times. To date, 11-oxoetiocholanolone, an important metabolite of cortisol, has been measured in equine and bovine feces solely by an in-house enzyme immunoassay (EIA). Therefore, we validated the use of a commercial ELISA kit (11-oxoetiocholanolone ELISA kit; Cayman Chemical), which had been validated on sheep feces and human urine, to measure 11-oxoetiocholanolone in feces from 42 horses and 32 bulls. The ELISA kit had good precision (intra- and inter-assay CVs: 5.8% and 11.2% for equine feces; 9.9% and 11.2% for bovine feces, respectively), analytical sensitivity (0.186 ng/mL for both equine and bovine feces), and accuracy (parallelism and recovery tests) in determining 11-oxoetiocholanolone concentrations in feces from both species. We found ranges of 11-oxoetiocholanolone concentrations of 1-109 ng/g in equine feces and 40-302 ng/g in feces of bulls. The Cayman Chemical ELISA kit offers a simple and accessible means of analysis of 11-oxoetiocholanolone in equine and bovine fecal samples.

Combining association with linkage mapping to dissect the phenolamides metabolism of the maize kernel.

Phenolamides are important secondary metabolites in plant species. They play important roles in plant defense responses against pathogens and insect herbivores, protection against UV irradiation and floral induction and development. However, the accumulation and variation in phenolamides content in diverse maize lines and the genes responsible for their biosynthesis remain largely unknown. Here, we combined genetic mapping, protein regulatory network and bioinformatics analysis to further enhance the understanding of maize phenolamides biosynthesis. Sixteen phenolamides were identified in multiple populations, and they were all significantly correlated with one or several of 19 phenotypic traits. By linkage mapping, 58, 58, 39 and 67 QTLs, with an average of 3.9, 3.6, 3.6 and 4.2 QTLs for each trait were mapped in BBE1, BBE2, ZYE1 and ZYE2, explaining 9.47%, 10.78%, 9.51% and 11.40% phenotypic variation for each QTL on average, respectively. By GWAS, 39 and 36 significant loci were detected in two different environments, 3.3 and 2.8 loci for each trait, explaining 10.00% and 9.97% phenotypic variation for each locus on average, respectively. Totally, 58 unique candidate genes were identified, 31% of them encoding enzymes involved in amine and derivative metabolic processes. Gene Ontology term analysis of the 358 protein-protein interrelated genes revealed significant enrichment in terms relating to cellular nitrogen metabolism, amine metabolism. GRMZM2G066142, GRMZM2G066049, GRMZM2G165390 and GRMZM2G159587 were further validated involvement in phenolamides biosynthesis. Our results provide insights into the genetic basis of phenolamides biosynthesis in maize kernels, understanding phenolamides biosynthesis and its nutritional content and ability to withstand biotic and abiotic stress.

Current Advances in the Functional Diversity and Mechanisms Underlying Endophyte-Plant Interactions.

Plant phenotype is a complex entity largely controlled by the genotype and various environmental factors. Importantly, co-evolution has allowed plants to coexist with the biotic factors in their surroundings. Recently, plant endophytes as an external plant phenotype, forming part of the complex plethora of the plant microbial assemblage, have gained immense attention from plant scientists. Functionally, endophytes impact the plant in many ways, including increasing nutrient availability, enhancing the ability of plants to cope with both abiotic and biotic stress, and enhancing the accumulation of important plant secondary metabolites. The current state of research has been devoted to evaluating the phenotypic impacts of endophytes on host plants, including their direct influence on plant metabolite accumulation and stress response. However, there is a knowledge gap in how genetic factors influence the interaction of endophytes with host plants, pathogens, and other plant microbial communities, eventually controlling the extended microbial plant phenotype. This review will summarize how host genetic factors can impact the abundance and functional diversity of the endophytic microbial community, how endophytes influence host gene expression, and the host-endophyte-pathogen disease triangle. This information will provide novel insights into how breeders could specifically target the plant-endophyte extended phenotype for crop improvement.

Biosynthetic and catabolic pathways control amino acid δ2H values in aerobic heterotrophs.

The hydrogen isotope ratios (δ2HAA values) of amino acids in all organisms are substantially fractionated relative to growth water. In addition, they exhibit large variations within microbial biomass, animals, and human tissues, hinting at rich biochemical information encoded in such signals. In lipids, such δ2H variations are thought to primarily reflect NADPH metabolism. Analogous biochemical controls for amino acids remain largely unknown, but must be elucidated to inform the interpretation of these measurements. Here, we measured the δ2H values of amino acids from five aerobic, heterotrophic microbes grown on different carbon substrates, as well as five Escherichia coli mutant organisms with perturbed NADPH metabolisms. We observed similar δ2HAA patterns across all organisms and growth conditions, which-consistent with previous hypotheses-suggests a first-order control by biosynthetic pathways. Moreover, δ2HAA values varied systematically with the catabolic pathways activated for substrate degradation, with variations explainable by the isotopic compositions of important cellular metabolites, including pyruvate and NADPH, during growth on each substrate. As such, amino acid δ2H values may be useful for interrogating organismal physiology and metabolism in the environment, provided we can further elucidate the mechanisms underpinning these signals.

Oxytetracycline hyper-production through targeted genome reduction of Streptomyces rimosus.

Most biosynthetic gene clusters (BGC) encoding the synthesis of important microbial secondary metabolites, such as antibiotics, are either silent or poorly expressed; therefore, to ensure a strong pipeline of novel antibiotics, there is a need to develop rapid and efficient strain development approaches. This study uses comparative genome analysis to instruct rational strain improvement, using Streptomyces rimosus, the producer of the important antibiotic oxytetracycline (OTC) as a model system. Sequencing of the genomes of two industrial strains M4018 and R6-500, developed independently from a common ancestor, identified large DNA rearrangements located at the chromosome end. We evaluated the effect of these genome deletions on the parental S. rimosus Type Strain (ATCC 10970) genome where introduction of a 145 kb deletion close to the OTC BGC in the Type Strain resulted in massive OTC overproduction, achieving titers that were equivalent to M4018 and R6-500. Transcriptome data supported the hypothesis that the reason for such an increase in OTC biosynthesis was due to enhanced transcription of the OTC BGC and not due to enhanced substrate supply. We also observed changes in the expression of other cryptic BGCs; some metabolites, undetectable in ATCC 10970, were now produced at high titers. This study demonstrated for the first time that the main force behind BGC overexpression is genome rearrangement. This new approach demonstrates great potential to activate cryptic gene clusters of yet unexplored natural products of medical and industrial value.IMPORTANCEThere is a critical need to develop novel antibiotics to combat antimicrobial resistance. Streptomyces species are very rich source of antibiotics, typically encoding 20-60 biosynthetic gene clusters (BGCs). However, under laboratory conditions, most are either silent or poorly expressed so that their products are only detectable at nanogram quantities, which hampers drug development efforts. To address this subject, we used comparative genome analysis of industrial Streptomyces rimosus strains producing high titers of a broad spectrum antibiotic oxytetracycline (OTC), developed during decades of industrial strain improvement. Interestingly, large-scale chromosomal deletions were observed. Based on this information, we carried out targeted genome deletions in the native strain S. rimosus ATCC 10970, and we show that a targeted deletion in the vicinity of the OTC BGC significantly induced expression of the OTC BGC, as well as some other silent BGCs, thus suggesting that this approach may be a useful way to identify new natural products.

Comparative transcriptome and metabolome reveal the role of acidic electrolyzed oxidizing water in improving postharvest disease resistance of longan fruit

Acidic electrolyzed oxidizing water (AEOW) was applied to suppress disease development and maintain good quality of fresh fruit. However, the involvement of AEOW in improving disease resistance of fresh longan remains unknown. Here, transcriptomic and metabolic analyses were performed to compare non-treated and AEOW-treated longan during storage. The transcriptome analysis showed AEOW-induced genes associated with phenylpropanoid and flavonoid biosynthesis. The metabolome analysis found the contents of coumarin, phenolic acid, and tannin maintained higher levels in AEOW-treated longan than non-treated longan. Moreover, the weighted correlation network analysis (WGCNA) was performed to identify hub genes, and a gene-metabolite correlation network associated with AEOW-improved disease resistance in longan was constructed by the co-analysis of transcriptomics and metabolomics. These findings identified a series of important genes and metabolites involving in AEOW-induced disease resistance of longan fruit, expanding our knowledges on fruit disease resistance and quality maintenance at the transcript and metabolic levels.

Isoprenoid emissions from Schima superba and Cunninghamia lanceolata: Their responses to elevated temperature by two warming facilities

Isoprenoids (including isoprene (ISO) and monoterpenes (MTs)) are the majority of biogenic volatile organic compounds (BVOCs) which are important carbon-containing secondary metabolites biosynthesized by organisms, especially plant in terrestrial ecosystem. Results of the warming effects on isoprenoid emissions vary within species and warming facilities, and thus conclusions remain controversial. In this study, two typical subtropical tree species seedlings of Schima superba and Cunninghamia lanceolata were cultivated under three conditions, namely no warming (CK) and two warming facilities (with infrared radiators (IR) and heating wires (HW)) in open top chamber (OTC), and the isoprenoid emissions were measured with preconcentor-GC–MS system after warming for one, two and four months. The results showed that the isoprenoid emissions from S. superba and C. lanceolata exhibited uniformity in response to two warming facilities. IR and HW both stimulated isoprenoid emissions in two plants after one month of treatment, with increased ratios of 16.3 % and 72.5 % for S. superba, and 2.47 and 5.96 times for C. lanceolata. However, the emissions were suppressed after four months, with more pronounced effect for HW. The variation in isoprenoid emissions was primarily associated with the levels of Pn, Tr, monoterpene synthase (MTPS) activity. C. lanceolata predominantly released MTs (mainly α-pinene, α-terpene, γ-terpene, and limonene), with 39.7 % to 99.6 % of the total isoprenoid but ISO was only a very minor constituent. For S. superba, MTs constituted 24.7 % to 96.1 % of total isoprenoid. It is noteworthy that HW generated a greater disturbance to physiology activity in plants. Our study provided more comprehensive and more convincing support for integrating temperature-elevation experiments of different ecosystems and assessing response and adaptation of forest carbon cycle to global warming.

Gc-ms analysis of leaf and rhizome essential oil of zingiber purpureum roxb. From bangladesh

Essential oils (EOs) are among the most important plant secondary metabolites. Zingiber purpureum Roxb. is a tropical ginger from Bangladesh, but its chemical constituents of leaves and rhizomes, both EOs, may have pharmacological effects. The aim of this study was carried out to analyze the qualitative composition of both Essential oils (EOs) of both leaf and rhizomes of Z. purpureum. The EOs from the leaves and rhizomes were extracted by hydrodistillation. Chemical constituents of the EOs were separated and identified by gas chromatography/mass spectrometry (GC/MS), and the relative percentage of each constituent was determined by area normalization. In total, 81 compounds were identified from leaf EOs, whereas 44 were from rhizome EOs. The common compounds identified from both rhizome and leaf EOs were triquinacene, 1,4, bis (methoxy), b-phellandrene and b-sesquiphellandrene, respectively. Besides, the major constituents of leaf EOs were sabinine (14.99%), b-pinene (14.32%), caryophyllene oxide (13.85%), and caryophyllene (9.47%), whereas the rhizome EOs confirmed (Z)-ocimene (21.97%), 4-terpineol (18.45%), γ-terpinene (3.86%) and cis-sabinenehydrate (3%). These EOs could be a promising source for the development of nutraceuticals, functional foods, and pharmaceutical products due to their potent activities and exploitation. Bangladesh J. Bot. 53(1): 153-158, 2024 (March)

Targeting NAD+ Metabolism: Preclinical Insights into Potential Cancer Therapy Strategies.

NAD+ is one of the most important metabolites for cellular activities, and its biosynthesis mainly occurs through the salvage pathway using the nicotinamide phosphoribosyl transferase (NAMPT) enzyme. The main nicotinamide adenine dinucleotide (NAD) consumers, poly-ADP-ribose-polymerases and sirtuins enzymes, are heavily involved in DNA repair and chromatin remodeling. Since cancer cells shift their energy production pathway, NAD levels are significantly affected. NAD's roles in cell survival led to the use of NAD depletion in cancer therapies. NAMPT inhibition (alone or in combination with other cancer therapies, including endocrine therapy and chemotherapy) results in decreased cell viability and tumor burden for many cancer types. Many NAMPT inhibitors (NAMPTi) tested before were discontinued due to toxicity; however, a novel NAMPTi, KPT-9274, is a promising, low-toxicity option currently in clinical trials.

Potential contributions of keystone species to intestinal ecosystem in patients with Crohn's disease.

Ravelling the central but poorly understood issue that potential contributions of keystone species to intestinal ecosystem functioning of patients with certain life-altering diseases including Crohn's disease (CD). In this study, a combination of 16S rRNA gene amplicon sequencing and amplicon-oriented metagenomic profiling was applied to gain insights into the shifts in bacterial community composition at different stages of CD course, and explore the functional roles of identified keystone species in intestinal microecosystem. Our results showed significant alterations in structure and composition of gut microbiota between CD patients and healthy control (P < 0.05), but was no difference at active and remission stages. Whole-community-based comprehensive analyses were employed to identify the differential species such as Escherichia coli, Anaerostipes hadrus, and Eubacterium hallii in CD patients, with healthy populations as the control. Metagenome-wide functional analyses further revealed that the relative abundance of specialized metabolism-related genes such as cynS, frdB, serA and gltB from these bacterial species in CD group was significantly different (P < 0.05) from that in healthy control, and highlighted the potential roles of the keystone species in regulating the accumulation of important metabolites such as succinate, formate, ammonia, L-glutamate, and L-serine, which might have an effect on homeostasis of intestinal ecosystem. The findings identify several potential keystone species that may influence the intestinal microecosystem functioning of CD patients and provide some reference for future CD treatment.

Mesenchymal stem cell-derived exosomes promote tissue repair injury in rats with liver trauma by regulating gut microbiota and metabolism

ObjectiveThe effects of mesenchymal stem cells (MSCs) and MSC-derived exosomes (MSC-exos) on serum metabolites and intestinal microbiota in rats after liver trauma were discussed. MethodsAdult Wistar Albino rats were assigned into control, model (liver trauma), MSCs, and MSC-exos groups (n = 6). The study examined changes in the inflammatory environment in liver tissues were analyzed by histological examination and analysis of macrophage phenotypes. Alterations in serum metabolites were determined by untargeted metabonomics, and gut microbiota composition was characterized by 16S rDNA sequencing. Correlations between specific gut microbiota, metabolites, and inflammatory response were calculated using Spearman correlation analysis. ResultsRats with liver trauma after MSCs and MSC-exos treatment exhibited attenuated inflammatory infiltration and necrosis in liver tissues. MSCs and MSC-exos treatment reduced the proportion of M1 macrophages, accompanied by a decrease in inducible nitric oxide synthase (iNOS) and tumor necrosis factor-alpha (TNF-α) levels. Furthermore, MSCs and MSC-exos treatment expanded the proportion of M2 macrophages, accompanied by an increase in arginase-1 (Arg-1) and interleukin-10 (IL-10) levels. The beneficial effects of MSC-exo treatment on rats with liver trauma were superior to those of MSC treatment. The composition and abundance of the gut microbiota and metabolites were altered in pathological rats, whereas MSC and MSC-exo intervention partially restored specific gut microbiota and metabolite alterations. At the phylum level, alterations in Bacteroidota, Proteobacteria, and Verrucomicrobiota were observed after MSC and MSC-exo intervention. At the genus level, Intestinimonas, Alistipes, Aerococcus, Faecalibaculum, and Lachnospiraceae_ND3007_group were the main differential microbiota. 6-Methylnicotinamide, N-Methylnicotinamide, Glutathione, oxidized, ISOBUTYRATE, ASCORBATE, EICOSAPENTAENOATE, GLYCEROL 3-PHOSPHATE, and Ascorbate radical were selected as important differential metabolites. There was a clear correlation between Ascorbate, Intestinimonas/Faecalibaculum and inflammatory cytokines. ConclusionMSC-exos promoted the repair of tissue damage in rats with liver trauma by regulating serum metabolites and intestinal microbiota, providing new insights into how MSC-exos reduced inflammation in rats with liver trauma.