Production Of Metabolites Research Articles

Agrobacterium transformation of Rhodiola sp.: current status and limitations

The study of secondary metabolites has led to the discovery of new drugs for treating human diseases. However, consistent plant supply can be challenging, leading to the use of plant tissue culture techniques such as hairy root culture. Hairy roots have stable genetics, lateral branching, and can produce secondary metabolites, including alkaloids, flavonoids, and terpenoids. Research on hairy roots as a subject began in the late 19th century, and for the last four decades, hairy roots have been utilized for producing secondary metabolites and recombinant proteins. This article focuses on Rhodiola species - genus of perennial plants that belongs to the family Crassulaceae - and its potential as a source of secondary metabolites using hairy root culture techniques. Rhodiola sp. is widely distributed throughout the Arctic regions of the Northern Hemisphere, with several species having significant medicinal properties. The article discusses the possible use of hairy root cultures for the production of Rhodiola secondary metabolites, including salidroside and rosavins, which have demonstrated significant pharmacological activity in various studies. The use of elicitation and genetic engineering techniques to boost secondary metabolite production in Rhodiola hairy roots is also explored. Overall, the article highlights the potential of Rhodiola hairy root cultures as a valuable source of secondary metabolites with medicinal properties. However, despite some studies Rhodiola hairy root induction and culturing still remains highly unexplored.

Mass Spectrometry Imaging to map metabolites in plant-microbe interactions: grapevine as a case study

Every year, viticulture faces several disease outbreaks caused by pathogens with different life cycles and modes of action, and due to climate changes, the appearance of new pathogens is a concern for viticulture. To cope with the different pathogenic microorganisms, the plant must recognise the invading agent and arm itself with an arsenal of defence reactions, including the accumulation of antimicrobial metabolites.The modulation of plant metabolites is one of the first responses to biotic factors. Their rapid synthesis can greatly contribute to strengthening plant defence allowing it to adapt, minimise pathogen colonisation and survive. Despite the scientific community's efforts to characterise the grapevine defence responses to pathogens, the molecules involved in pathogen control and their specific localisation remain to be deciphered.Mass Spectrometry Imaging (MSI) analytical techniques enable one to visualise and map the spatial distribution of numerous biological molecules within plant tissues allowing a better understanding of their biosynthesis, localisation and function.In this review, we explore the applications of MSI techniques to the study of plant/microbe interactions focusing on grapevine studies. This review opens new doors to gain a comprehensive understanding of the dynamics and variations of metabolite profiles in grapevine organs, at different developmental stages and under various stress conditions. This knowledge is crucial for elucidating the role of specific metabolites in grapevine defence mechanisms, and for identifying specific regions of high or low metabolite production, which can contribute to targeted breeding to improve disease resistance traits and have an impact on grapevine productivity and quality.

CRISPR driven Cyanobacterial Metabolic Engineering and its role in metabolite production

Recently, the advancement in sustainable methods for fabricating novel metabolites is one of the prime challenges in metabolic engineering. The current increase in fuel prices and its limited supply made the scientific community more concerned about finding an alternate source of fuel generation. Scientists are now interested in biofuel because of its low cost and ease of production. An intriguing area of research in metabolic engineering is using imaginative manipulation of microbes to manufacture chemicals or molecules of commercial importance. One such bacterium whose commercial potential is rapidly attracting the attention of the scientific fraternity is Cyanobacteria, which are either single-celled or multi-cellular filamentous photosynthetic organisms that can also fix CO2. The generation of biofuel has been transformed by the use of CRISPR (clustered regularly interspaced short palindromic repeats) technology in cyanobacteria, which allows for precise genetic alterations to improve their metabolic processes. Scientists can effectively modify the cyanobacterial genome using CRISPR to increase lipid accumulation, maximize photosynthetic efficiency, and enhance stress tolerance. Cyanobacteria have gained attention in the scientific community as a potential source for biofuel production due to several advantageous characteristics like photosynthetic capacity, genetic manipulation, lack of dependency on fertile land, high biomass yield, versatile biofuel production etc. which our present manuscript aims to catalogue. Cyanobacteria play a pivotal role in developing environmentally friendly energy solutions by converting CO2 into renewable energy sources, serving as a flexible platform for producing different types of biofuels and reducing greenhouse gas emissions.

Biosynthesis of secondary metabolites in aromatic and medicinal plants in response to abiotic stresses: A review

Climate change has massive consequences on non-living factors in the environment, resulting in irregular precipitation, fluctuating atmospheric temperature, and variations in humidity. These changes cause biotic and abiotic stresses; plants must have defense mechanisms to survive. Therefore, plants divert some synthesized energy towards producing numerous plant secondary metabolites (PSMs), viz., flavonoids, alkaloids, and essential oils. These compounds act as protections for the plants, helping them to survive under stressful conditions. Medicinal and aromatic plants (MAPs) are sessile organisms that are not immune to harmful consequences of various abiotic stresses in which the PSMs have an important role in acting against the adverse effects. In this regard, the MAPs have a coherent defense mechanism for abiotic stresses. The secondary metabolites produced by these plants are useful as medicines and aromatic products for humans. However, not all stresses produce high secondary metabolites, as their production is highly specific to certain stresses. This review provides a comprehensive understanding of secondary metabolite production under various stressful conditions, including extreme temperature, drought, water logging, salinity, harmful radiation, elevated levels of ozone and CO2, heavy metals, and agrochemicals on MAPs. Additionally, the production of these compounds can be modified by subjecting plants to various stressors. Many authors have reported on PSMs in MAPs, which need to be well documented and exploited for humankind.

Stress responses of the seagrass Cymodocea nodosa to environmentally relevant concentrations of pharmaceutical ibuprofen: Ecological implications

Pharmaceuticals like ibuprofen (IBU) entering marine environments are of great concern due to their increasing consumption and impact on wildlife. No information on IBU toxicity to seagrasses is yet available. Seagrasses form key habitats and are threatened worldwide by multiple stressors. Here, the responses of the seagrass Cymodocea nodosa to a short-term exposure (12 days) to environmentally realistic IBU concentrations (0.25–2.5-25 µg L−1), both at organism (plant growth) and sub-organism level (oxidative status, photosynthetic efficiency, and specialized metabolites production), were assessed in mesocosm. Chemical analyses to detect the presence of IBU and its metabolites in seawater and plants were also performed. IBU did not affect plant growth but caused physiological alterations which varied in severity depending on its concentration. Concentrations of 0.25 and 2.5 µg L−1 resulted in oxidative stress, but an increased antioxidant enzyme activity enabled plants to tolerate stress. A concentration of 25 µg L−1 caused greater oxidative stress, reduced antioxidant enzyme activity and specialized metabolites production, and impaired photosynthetic machinery functioning (particularly PSII). IBU was detected in seawater but not in plants suggesting no bioaccumulation. These findings indicate that C. nodosa could not withstand high IBU stress, and this could reduce its resilience to additional environmental stressors.

Onion‐pathogenic Burkholderia species: Role and regulation of characterized virulence determinants

AbstractMembers of the bacterial genus Burkholderia are a routine threat to onion production worldwide. In addition to the common onion‐pathogenic species, Burkholderia cepacia, Burkholderia orbicola and Burkholderia gladioli, other Burkholderia species have the potential to cause onion disease. Despite their impacts and long‐known association with onion disease, the virulence mechanisms of onion‐pathogenic Burkholderia are far less well understood than Burkholderia in human and murine infection models. In this review, we will focus on genetically characterized virulence factors in species that contribute to symptom production in onion and other plant hosts. Specifically, we will focus on the variable roles of specialized protein secretion systems (T2SS, T3SS and T4SS) and secreted proteins, thiosulphinate tolerance gene (TTG) clusters and the well‐characterized phytotoxin toxoflavin in virulence. The regulation and roles of LuxI/LuxS quorum‐sensing system and IclR‐type transcriptional regulator, qsmR, as master regulators of secondary metabolite production and virulence factors will also be discussed. The TTG clusters, involved in bacterial tolerance to thiosulphinate defence compounds, exhibit onion tissue‐specific contributions to virulence. This suggests that Burkholderia onion pathogens have tissue‐specific virulence strategies for causing disease.

Decoding host cell interaction– and fluconazole-induced metabolic alterations and drug resistance in Candida auris

ABSTRACT Candida auris is an emerging drug-resistant pathogen associated with high mortality rates. This study aimed to explore the metabolic alterations and associated pathogenesis and drug resistance in fluconazole-treated Candida auris–host cell interaction. Compared with controls, secreted metabolites from fluconazole-treated C. auris and fluconazole-treated C. auris–host cell co-culture demonstrated notable anti-Candida activity. Fluconazole caused significant reductions in C. auris cell numbers and aggregated phenotype. Metabolites produced by C. auris with potential fungal colonization, invasion, and host immune evasion effects were identified. Metabolites known to enhance biofilm formation produced during C. auris–host cell interaction were inhibited by fluconazole. Fluconazole enhanced the production of metabolites with biofilm inhibition activity, including behenyl alcohol and decanoic acid. Metabolites with potential Candida growth inhibition activity such as 2-palmitoyl glycerol, 1-tetradecanol, and 1-nonadecene were activated by fluconazole. Different patterns of proinflammatory cytokine expression presented due to fluconazole concentration and host cell type (fibroblasts versus macrophages). This highlights the immune response’s complexity, emphasizing the necessity for additional research to comprehend cell-type-specific responses to antifungal therapies. Both host cell interaction and fluconazole treatment increased the expression of CDR1 and ERG11 genes, both associated with drug resistance. This study provides insights into pathogenesis in C. auris due to host cell interaction and fluconazole treatment. Understanding these interactions is crucial for enhancing fluconazole sensitivity and effectively combating C. auris.

The Role of Gut Microbiome in Sleep Quality and Health: Dietary Strategies for Microbiota Support.

Dietary components, including dietary fiber, unsaturated fatty acids, and polyphenols, along with meal timing and spacing, significantly affect the microbiota's capacity to produce various metabolites essential for quality sleep and overall health. This review explores the role of gut microbiota in regulating sleep through various metabolites such as short-chain fatty acids, tryptophan, serotonin, melatonin, and gamma-aminobutyric acid. A balanced diet rich in plant-based foods enhances the production of these sleep-regulating metabolites, potentially benefiting overall health. This review aims to investigate how dietary habits affect gut microbiota composition, the metabolites it produces, and the subsequent impact on sleep quality and related health conditions.

Effects of the Thiol Methyltransferase Inhibitor (±)-2,3-Dichloro-α-Methylbenzylamine (DCMB) on the Pharmacokinetics and Metabolism of Vicagrel in Rats.

P2Y12 receptor inhibitors are commonly used in clinical antiplatelet therapy, typically alongside other medications. Vicagrel, a promising P2Y12 receptor inhibitor, has submitted a new drug marketing application to the United States Food and Drug Administration. Its primary metabolites and some metabolic pathways are identical to those of clopidogrel. The aim of this study was to investigate the effects of the thiol methyltransferase inhibitor (±)-2,3-dichloro-α-methylbenzylamine (DCMB) on the metabolism and pharmacokinetics of vicagrel. In vitro incubation with human and rat liver microsomes revealed that DCMB significantly inhibited the methylation of vicagrel's thiol metabolite M15-1. Rats were orally administered 6 mg/kg [14C]vicagrel (100 μCi/kg) 1 hour after peritoneal injection with or without DCMB (80 mg/kg). Compared with the control group, the plasma of DCMB-pretreated rats exhibited maximum plasma concentration (C max) decrease and time to reach C max (T max) delay for all vicagrel-related substances, the methylation product of the thiol metabolite (M9-2), and the derivatization product of the active thiol metabolite (MP-M15-2). However, no significant changes in area under the curve (AUC) or half-life (t 1/2) were observed. DCMB had negligible effect on the total radiological recovery of vicagrel within 72 hours, although the rate of vicagrel excretion slowed down within 48 hours. DCMB had a negligible impact on the metabolic pathway of vicagrel. Overall, the present study found that DCMB did not significantly affect the total exposure, metabolic pathways, metabolite profiles, or total excretion rates of vicagrel-related metabolites in rats, but led to C max decrease, T max delay, and slower excretion rate within 48 hours. SIGNIFICANCE STATEMENT: This study used liquid chromatography-tandem mass spectrometry combined with radiolabeling technology to investigate the effects of the thiol methyltransferase inhibitor (±)-2,3-dichloro-α-methylbenzylamine on the absorption, metabolism, and excretion of vicagrel in rats. This work helps to better understand the in vivo metabolism of active thiol metabolites of P2Y12 inhibitors such as clopidogrel, vicagrel, etc.

Small Structural Differences in Proline-Rich Decapeptides Have Specific Effects on Oxidative Stress-Induced Neurotoxicity and L-Arginine Generation by Arginosuccinate Synthase.

The proline-rich decapeptide 10c (Bj-PRO-10c; ENWPHPQIPP) from the Bothrops jararaca snake modulates argininosuccinate synthetase (AsS) activity to stimulate L-arginine metabolite production and neuroprotection in the SH-SY5Y cell line. The relationships between structure, interactions with AsS, and neuroprotection are little known. We evaluated the neuroprotective effects of Bj-PRO-10c and three other PROs (Bn-PRO-10a, <ENWPRPKIPP; Bn-PRO-10a-MK, <ENWPRPKIPPMK; and, Bn-PRO-10c, <ENWPRPKVPP) identified from Bitis nasicornis snake venom, with a high degree of similarity to Bj-PRO-10c, on oxidative stress-induced toxicity in neuronal PC12 cells and L-arginine metabolite generation via AsS activity regulation. Cell integrity, metabolic activity, reactive oxygen species (ROS) production, and arginase activity were examined after 4 h of PRO pre-treatment and 20 h of H2O2-induced damage. Only Bn-PRO-10a-MK and Bn-PRO-10c restored cell integrity and arginase function under oxidative stress settings, but they did not reduce ROS or cell metabolism. The MK dipeptide in Bn-PRO-10a-MK and valine (V8) in Bn-PRO-10c are important to these effects when compared to Bn-PRO-10a. Bj-PRO-10c is not neuroprotective in PC12 cells, perhaps because of their limited NMDA-type glutamate receptor activity. The PROs interaction analysis on AsS activation can be rated as follows: Bj-PRO-10c > Bn-PRO-10c > Bn-PRO-10a-MK > Bn-PRO-10a. The structure of PROs and their correlations with enzyme activity revealed that histidine (H5) and glutamine (Q7) in Bj-PRO-10c potentiated their affinity for AsS. Our investigation provides the first insights into the structure and molecular interactions of PROs with AsS, which could possibly further their neuropharmacological applications.

Enhancing growth and bioactive metabolites characteristics in Mentha pulegium L. via silicon nanoparticles during in vitro drought stress

The development and production of secondary metabolites from priceless medicinal plants are restricted by drought stress. Mentha pulegium L. belongs to the Lamiaceae family and is a significant plant grown in the Mediterranean region for its medicinal and aesthetic properties. This study investigated the effects of three polyethylene glycol (PEG) (0, 5, and 10%) as a drought stress inducer and four silicon nanoparticle (SiNP) (0, 25, 50, and 100 ppm) concentrations as an elicitor to overcome the adverse effect of drought stress, on the growth parameters and bioactive chemical composition of M. pulegium L. plants grown in vitro. The experiment was performed as a factorial experiment using a completely randomized design (CRD) consisting of 12 treatments with two factors (3 PEG × 4 SiNPs concentrations), 6 replicates were used for each treatment for a total of 72 experimental units.The percentage of shoot formation was inversely proportional to the PEG concentration; for the highest PEG concentration, the lowest percentage of shoot formation (70.26%) was achieved at 10% PEG. SiNPs at 50 ppm enhanced shoot formation, the number of shoots, shoot height, fresh and dry weight, rosmarinic acid, total phenols, and 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging activity. The methanol extract from M. pulegium revealed the presence of significant secondary metabolites using gas chromatography‒mass spectrometry (GC–MS). The principal constituents of the extract were limonene (2.51, 2.99%), linalool (3.84, 4.64%), geraniol (6.49, 8.77%), menthol (59.73, 65.43%), pulegone (3.76, 2.76%) and hexadecanoic acid methyl ester or methyl palmitate (3.2, 4.71%) for the 0 ppm SiNPs, PEG 0% and 50 ppm SiNPs, and PEG 10%, respectively. Most of the chemical components identified by GC‒MS in the methanol extract were greater in the 50 ppm SiNP and 10% PEG treatment groups than in the control group. SiNP improves drought tolerance by regulating biosynthesis and accumulating some osmolytes and lessens the negative effects of polyethylene glycol-induced drought stress.Based on the results, the best treatment for most of the parameters was 50 ppm SiNPs combined with 10% PEG, the morphological and chemical characteristics were inversely proportional to the PEG concentration, as the highest PEG concentration (10%) had the lowest results. Most parameters decreased at the highest SiNP concentration (100 ppm), except for the DPPH scavenging percentage, as there was no significant difference between the 50 and 100 ppm SiNPs.

Construction of a beneficial microbes-enriched rhizosphere system assists plants in phytophagous insect defense: current status, challenges and opportunities.

The construction of a plant rhizosphere system enriched with beneficial microbes (BMs) can efficiently help plants defend against phytophagous insects. However, our comprehensive understanding of this approach is still incomplete. In this review, we methodically analyzed the progress made over the last decade, identifying both challenges and opportunities. The main methods for developing a BMs-enriched rhizosphere system include inoculating exogenous BMs into plants, amending the existing soil microbiomes with amendments, and utilizing plants to shape the soil microbiomes. BMs can assist plants in suppressing phytophagous insects across many orders, including 13 Lepidoptera, seven Homoptera, five Hemiptera, five Coleoptera, four Diptera, and one Thysanoptera species by inducing plant systemic resistance, enhancing plant tolerance, augmenting plant secondary metabolite production, and directly suppressing herbivores. Context-dependent factors such as abiotic and biotic conditions, as well as the response of insect herbivores, can affect the outcomes of BM-assisted plant defense. Several challenges and opportunities have emerged, including the development of synthetic microbial communities for herbivore control, the integration of biosensors for effectiveness assessment, the confirmation of BM targets for phytophagous insect defense, and the regulation of outcomes via smart farming with artificial intelligence. This study offers valuable insights for developing a BM-enriched rhizosphere system within an integrated pest management approach. © 2024 Society of Chemical Industry.

Nutraceutical prospects of genetically engineered cyanobacteria- technological updates and significance.

Genetically engineered cyanobacterial strains that have improved growth rate, biomass productivity, and metabolite productivity could be a better option for sustainable bio-metabolite production. The global demand for biobased metabolites with nutraceuticals and health benefits has increased due to their safety and plausible therapeutic and nutritional utility. Cyanobacteria are solar-powered green cellular factories that can be genetically tuned to produce metabolites with nutraceutical and pharmaceutical benefits. The present review discusses biotechnological endeavors for producing bioprospective compounds from genetically engineered cyanobacteria and discusses the challenges and troubleshooting faced during metabolite production. This review explores the cyanobacterial versatility, the use of engineered strains, and the techno-economic challenges associated with scaling up metabolite production from cyanobacteria. Challenges to produce cyanobacterial bioactive compounds with remarkable nutraceutical values have been discussed. Additionally, this review also summarises the challenges and future prospects of metabolite production from genetically engineered cyanobacteria as a sustainable approach.

Effect of ozone treatment on phenylpropanoid metabolism in harvested cantaloupes.

Phenylpropanoid metabolism plays an important role in cantaloupe ripening and senescence, but the mechanism of ozone regulation on phenylpropanoid metabolism remains unclear. This study investigated how ozone treatment modulates the levels of secondary metabolites associated with phenylpropanoid metabolism, the related enzyme activities, and gene expression in cantaloupe. Treating cantaloupes with 15mg/m3 of ozone after precooling can help maintain postharvest hardness. This treatment also enhances the production and accumulation of secondary metabolites, such as total phenols, flavonoids, and lignin. These metabolites are essential components of the phenylpropanoid metabolic pathway, activating enzymes like phenylalanine ammonia-lyase, cinnamate 4-hydroxylase, 4CL, chalcone synthase, and chalcone isomerase. The results of the transcriptional expression patterns showed that differential gene expression related to phenylpropanoid metabolism in the peel of ozone-treated cantaloupes was primarily observed during the middle and late storage stages. In contrast, the pulp exhibited significant differential gene expression mainly during the early storage stage. Furthermore, it was observed that the level of gene expression in the peel was generally higher than that in the pulp. The correlation between the relative amount of gene changes in cantaloupe, activity of selected enzymes, and concentration of secondary metabolites could be accompanied by positive regulation of the phenylpropanoid metabolic pathway. Therefore, ozone stress induction positively enhances the biosynthesis of flavonoids in cantaloupes, leading to an increased accumulation of secondary metabolites. Additionally, it also improves the postharvest storage quality of cantaloupes.

The Effect of Salinity Stress on the Antibacterial Activity of SpirulinaPlatensis Algae

Background: The production of secondary metabolites in different strains of microalgae varies and is likely dependent on environmental conditions. Consequently, the production of bioactive substances as secondary metabolites occurs in microalgae to aid their survival in adverse environmental conditions such as salinity stress. Objectives: The purpose of this study is to investigate the antibacterial activity of the methanolic extract of S. platensis algae cultivated under different salinity stresses against Yersinia rukeri, Escherichia coli, Salmonella sp., and Vibrio cholerae. Methods: The broth microdilution method was used to evaluate the growth inhibitory activity of the extracts against Yersinia ruckeri, Salmonella sp., Escherichia coli, and Vibrio cholerae bacteria. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) were determined by this method, and the diameter of the inhibition zone was assessed through the well diffusion method. Results: In the treatment with algae extract grown under 3.5 ppt salinity stress, the concentrations of 50 and 25 mg/mL extract showed the largest inhibition zone diameter against Salmonella sp. compared to other bacteria. Under 7 ppt salinity stress, all studied concentrations of algal extract exhibited a higher inhibition zone diameter against V. cholerae compared to other bacteria. The results of comparing different concentrations of algae extract between the two salinity stresses of 3.5 and 7 ppt for each bacterium showed a significant difference (P &lt; 0.05). As salinity increased, the diameter of the inhibition zone also increased for all bacteria. Conclusions: Our results showed an increase in the antibacterial activity of the methanolic extract of Spirulina platensis with higher salinity stress levels. Therefore, cultivating Spirulina algae in salt water can be a cost-effective and suitable method to produce more secondary metabolites for use in the pharmaceutical industry.

Metabolic picture of microbial interaction: chemical crosstalk during co-cultivation between three dominant genera of bacteria and fungi in medicinal plants rhizosphere.

Microbial communities affect several aspects of the earth's ecosystem through their metabolic interaction. The dynamics of this interaction emerge from complex multilevel networks of crosstalk. Elucidation of this interaction could help us to maintain the balance for a sustainable future. To investigate the chemical language among highly abundant microbial genera in the rhizospheres of medicinal plants based on the metabolomic analysis at the interaction level. Coculturing experiments involving three microbial species: Aspergillus (A), Trichoderma (T), and Bacillus (B), representing fungi (A, T) and bacteria (B), respectively. These experiments encompassed various interaction levels, including dual cultures (AB, AT, TB) and triple cultures (ATB). Metabolic profiling by LC-QTOFMS revealed the effect of interaction level on the productivity and diversity of microbial specialized metabolites. The ATB interaction had the richest profile, while the bacterial profile in the monoculture condition had the lowest. Two native compounds of the Aspergillus genus, aspergillic acid and the dipeptide asperopiperazine B, exhibited decreased levels in the presence of the AT interaction and were undetectable in the presence of bacteria during the interaction. Trichodermarin N and Trichodermatide D isolated from Trichoderma species exclusively detected during coexistence with bacteria (TB and ATB). These findings indicate that the presence of Bacillus activates cryptic biosynthetic gene clusters in Trichoderma. The antibacterial activity of mixed culture extracts was stronger than that of the monoculture extracts. The TB extract exhibited strong antifungal activity compared to the monoculture extract and other mixed culture treatments. The elucidation of medicinal plant microbiome interaction chemistry and its effect on the environment will also be of great interest in the context of medicinal plant health Additionally, it sheds light on the content of bioactive constituents,and facilitating the discovery of novel antimicrobials.

Synbiotics containing sea buckthorn polysaccharides ameliorate DSS-induced colitis in mice via regulating Th17/Treg homeostasis through intestinal microbiota and their production of BA metabolites and SCFAs

Inflammatory Bowel Disease (IBD) is a chronic condition whose incidence has been rising globally. Synbiotic (SYN) is an effective means of preventing IBD. This study investigated the preventive effects and potential biological mechanisms of SYN (Bifidobacterium longum, Lactobacillus acidophilus, and sea buckthorn polysaccharides) on DSS-induced colitis in mice. The results indicated that dietary supplementation with SYN has a significant improvement effect on DSS mice. SYN ameliorated disease activity index (DAI), colon length, and intestinal barrier permeability in mice. In addition, RT-qPCR results indicated that after SYN intervention, the expression levels of pro-inflammatory factors (IL-6, IL-1β, TNF-α, and IL-17F) and transcription factor RORγt secreted by Th17 cells were significantly reduced, and the expression levels of anti-inflammatory factors (IL-10 and TGF-β) and transcription factor Foxp3 secreted by Treg cells were robustly increased. 16S rDNA sequencing analysis revealed that key intestinal microbiota related to Th17/Treg balance (Ligilactobacillus, Lactobacillus, Bacteroides, and Akkermansia) was significantly enriched. At the same time, a significant increase in microbial metabolites SCFAs and BAs was observed. We speculate that SYN may regulate the Th17/Treg balance by restructuring the structure and composition of the intestinal microbiota, thereby mitigating DSS-induced colitis.

Co-regulatory network analysis of the main secondary metabolite (SM) biosynthesis in Crocus sativus L.

Saffron (Crocus sativus L.) is being embraced as the most important medicinal plant and the commercial source of saffron spice. Despite the beneficial economic and medicinal properties of saffron, the regulatory mechanism of the correlation of TFs and genes related to the biosynthesis of the apocarotenoids pathway is less obvious. Realizing these regulatory hierarchies of gene expression networks related to secondary metabolites production events is the main challenge owing to the complex and extensive interactions between the genetic behaviors. Recently, high throughput expression data have been highly feasible for constructing co-regulation networks to reveal the regulated processes and identifying novel candidate hub genes in response to complex processes of the biosynthesis of secondary metabolites. Herein, we performed Weighted Gene Co-expression Network Analysis (WGCNA), a systems biology method, to identify 11 regulated modules and hub TFs related to secondary metabolites. Three specialized modules were found in the apocarotenoids pathway. Several hub TFs were identified in notable modules, including MADS, C2H2, ERF, bZIP, HD-ZIP, and zinc finger protein MYB and HB, which were potentially associated with apocarotenoid biosynthesis. Furthermore, the expression levels of six hub TFs and six co-regulated genes of apocarotenoids were validated with RT-qPCR. The results confirmed that hub TFs specially MADS, C2H2, and ERF had a high correlation (P < 0.05) and a positive effect on genes under their control in apocarotenoid biosynthesis (CCD2, GLT2, and ADH) among different C. sativus ecotypes in which the metabolite contents were assayed. Promoter analysis of the co-expressed genes of the modules involved in apocarotenoids biosynthesis pathway suggested that not only are the genes co-expressed, but also share common regulatory motifs specially related to hub TFs of each module and that they may describe their common regulation. The result can be used to engineer valuable secondary metabolites of C. sativus by manipulating the hub regulatory TFs.

The Gut and Skin Microbiome and Its Association with Aging Clocks.

Aging clocks are predictive models of biological age derived from age-related changes, such as epigenetic changes, blood biomarkers, and, more recently, the microbiome. Gut and skin microbiota regulate more than barrier and immune function. Recent studies have shown that human microbiomes may predict aging. In this narrative review, we aim to discuss how the gut and skin microbiomes influence aging clocks as well as clarify the distinction between chronological and biological age. A literature search was performed on PubMed/MEDLINE databases with the following keywords: "skin microbiome" OR "gut microbiome" AND "aging clock" OR "epigenetic". Gut and skin microbiomes may be utilized to create aging clocks based on taxonomy, biodiversity, and functionality. The top contributing microbiota or metabolic pathways in these aging clocks may influence aging clock predictions and biological age. Furthermore, gut and skin microbiota may directly and indirectly influence aging clocks through the regulation of clock genes and the production of metabolites that serve as substrates or enzymatic regulators. Microbiome-based aging clock models may have therapeutic potential. However, more research is needed to advance our understanding of the role of microbiota in aging clocks.

The Role of Nondigestible Oligosaccharides in Alleviating Human Chronic Diseases by Regulating the Gut Microbiota: A Review.

The gut has been a focus of chronic disease research. The gut microbiota produces metabolites that act as signaling molecules and substrates, closely influencing host health. Nondigestible oligosaccharides (NDOs), as a common dietary fiber, play an important role in regulating the structure and function of the gut microbiota. Their mechanism of action is mainly attributed to providing a carbon source as specific probiotics, producing related metabolites, and regulating the gut microbial community. However, due to the selective utilization of oligosaccharides, some factors, such as the type and structure of oligosaccharides, have different impacts on the composition of microbial populations and the production of metabolites in the colon ecosystem. This review systematically describes the key factors influencing the selective utilization of oligosaccharides by microorganisms and elaborates how oligosaccharides affect the host's immune system, inflammation levels, and energy metabolism by regulating microbial diversity and metabolic function, which in turn affects the onset and progress of chronic diseases, especially diabetes, obesity, depression, intestinal inflammatory diseases, and constipation. In this review, we re-examine the interaction mechanisms between the gut microbiota and its associated metabolites and diseases, and we explore new strategies for promoting human health and combating chronic diseases through dietary interventions.