Search Results (10)

For centuries, plant-derived natural products (NPs) have been fundamental to traditional medicine, providing essential therapeutic compounds. Ethnobotanical knowledge has historically guided NP discovery, leading to the identification of key pharmaceuticals such as aspirin, morphine, and artemisinin. However, conventional bioactivity-guided fractionation methods for NP isolation are labour-intensive and can result in the loss of bioactive properties due to the focus on a single compound. Advances in omics sciences—genomics, transcriptomics, proteomics, metabolomics, and phenomics—coupled with computational tools have altogether revolutionised NP research by enabling high-throughput screening and more precise compound identification. This review explores how integrating traditional medicinal knowledge with multi-omics strategies enhances NP discovery. We highlight emerging bioinformatics tools, mass spectrometry techniques, and metabologenomics approaches that accelerate the identification, annotation, and functional characterisation of plant-derived metabolites. Additionally, we discuss challenges in omics data integration and propose strategies to harness ethnobotanical knowledge for targeted NP discovery and drug development. By combining traditional wisdom with modern scientific advancements, this integrated approach paves the way for novel therapeutic discoveries and the sustainable utilisation of medicinal plants. Full article

Marine microorganisms have emerged as prolific sources of bioactive natural products, offering a large chemical diversity and a broad spectrum of biological activities. Over the past decade, significant progress has been made in discovering and characterizing these compounds, pushed by technological innovations in genomics, metabolomics, and bioinformatics. Furthermore, innovative isolation and cultivation approaches have improved the isolation of rare and difficult-to-culture marine microbes, leading to the identification of novel secondary metabolites. Advances in synthetic biology and metabolic engineering have further optimized natural product yields and the generation of novel compounds with improved bioactive properties. This review highlights key developments in the exploitation of marine bacteria, fungi, and microalgae for the discovery of novel natural products with potential applications in diverse fields, underscoring the immense potential of marine microorganisms in the growing Blue Economy sector. Full article

Natural product (NP)-based pesticides have emerged as a compelling alternative to traditional chemical fungicides, attracting substantial attention within the agrochemical industry as the world is pushing toward sustainable and environmentally friendly approaches to safeguard crops. Microbes, both bacteria and fungi, are a huge source of diverse secondary metabolites with versatile applications across pharmaceuticals, agriculture, and the food industry. Microbial genome mining has been accelerated for pesticide/drug discovery and development in recent years, driven by advancements in genome sequencing, bioinformatics, metabolomics/metabologenomics, and synthetic biology. Here, we isolated and identified Pseudomonas vancouverensis that had shown antifungal activities against crop fungal pathogens Colletotrichum fragariae, Botrytis cinerea, and Phomopsis obscurans in a dual-plate culture and bioautography assay. Further, we sequenced the whole bacterial genome and mined the genome of this bacterium to identify secondary metabolite biosynthetic gene clusters (BGCs) using antiSMASH 7.0, PRISM 4, and BAGEL 4. An in-silico analysis suggests that P. vancouverensis possesses a rich repertoire of BGCs with the potential to produce diverse and novel NPs, including non-ribosomal peptides (NRPs), polyketides (PKs), acyl homoserine lactone, cyclodipeptide, bacteriocins, and ribosomally synthesized and post-transcriptionally modified peptides (RiPPs). Bovienimide-A, an NRP, and putidacin L1, a lectin-like bacteriocin, were among the previously known predicted metabolites produced by this bacterium, suggesting that the NPs produced by this bacterium could have biological activities and be novel as well. Future studies on the antifungal activity of these compounds will elucidate the full biotechnological potential of P. vancouverensis. Full article

Royal jelly (RJ) is a naturally occurring substance synthesized by honeybees and has various health benefits. Herein, we focused on the medium-chain fatty acids (MCFAs) unique to RJ and evaluated their therapeutic efficacy in treating non-alcoholic fatty liver disease (NAFLD). We examined db/m mice that were exclusively fed a normal diet, db/db mice exclusively fed a normal diet, and db/db mice fed varying RJ quantities (0.2, 1, and 5%). RJ improved NAFLD activity scores and decreased gene expression related to fatty acid metabolism, fibrosis, and inflammation in the liver. RJ regulated innate immunity-related inflammatory responses in the small intestine and decreased the expression of genes associated with inflammation and nutrient absorption transporters. RJ increased the number of operational taxonomic units, the abundance of Bacteroides, and seven taxa, including bacteria that produce short-chain fatty acids. RJ increased the concentrations of RJ-related MCFAs (10-hidroxy-2-decenoic acid, 10-hydroxydecanoic acid, 2-decenedioic acid, and sebacic acid) in the serum and liver. These RJ-related MCFAs decreased saturated fatty acid deposition in HepG2 cells and decreased the gene expression associated with fibrosis and fatty acid metabolism. RJ and RJ-related MCFAs improved dysbiosis and regulated the expression of inflammation-, fibrosis-, and nutrient absorption transporter-related genes, thereby preventing NAFLD. Full article

(1) Background: Consumption of barley has been known to exert beneficial effects on glucose tolerance; however, it has also been reported that there are inter-individual differences in these responses. Recent evidence has suggested that these individual differences are mediated by the gut microbiota. (2) Methods: In the present study, we aimed to understand the relationship between the intestinal environment, including intestinal microbiome and their metabolome, and glucose tolerance. A randomized controlled trial with a 4-week consumption of barley or control food was conducted. We conducted an integrated analysis of the intestinal microbiome and metabolome and analyzed the relationship with improvement of glucose tolerance. (3) Results: We found that metabolites such as azelate were significantly increased after barley consumption. Furthermore, the subjects whose glucose tolerance was slightly impaired showed improvement in their glucose tolerance index following the barley consumption. Additionally, the analysis showed that the increase in the abundance of the Anaerostipes was correlated with the improvement in the glucose tolerance index. (4) Conclusions: Our findings indicate that the effects of barley consumption for glucose tolerance are partly defined by the intestinal environment of consumers, providing a quantitative measurement of the dietary effect based on the intestinal environment. Full article

Two novel natural products, the polyketide cuniculene and the peptide antibiotic aquimarin, were recently discovered from the marine bacterial genus Aquimarina. However, the diversity of the secondary metabolite biosynthetic gene clusters (SM-BGCs) in Aquimarina genomes indicates a far greater biosynthetic potential. In this study, nine representative Aquimarina strains were tested for antimicrobial activity against diverse human-pathogenic and marine microorganisms and subjected to metabolomic and genomic profiling. We found an inhibitory activity of most Aquimarina strains against Candida glabrata and marine Vibrio and Alphaproteobacteria species. Aquimarina sp. Aq135 and Aquimarina muelleri crude extracts showed particularly promising antimicrobial activities, amongst others against methicillin-resistant Staphylococcus aureus. The metabolomic and functional genomic profiles of Aquimarina spp. followed similar patterns and were shaped by phylogeny. SM-BGC and metabolomics networks suggest the presence of novel polyketides and peptides, including cyclic depsipeptide-related compounds. Moreover, exploration of the ‘Sponge Microbiome Project’ dataset revealed that Aquimarina spp. possess low-abundance distributions worldwide across multiple marine biotopes. Our study emphasizes the relevance of this member of the microbial rare biosphere as a promising source of novel natural products. We predict that future metabologenomics studies of Aquimarina species will expand the spectrum of known secondary metabolites and bioactivities from marine ecosystems. Full article

Enteral nutrition (EN) is a rational approach to providing nutritional intake via the intestines in patients who are unable to tolerate parenteral nutrition. We conducted a preliminary study to investigate the effects of EN on the intestinal environment in 10 patients in a persistent vegetative state (PVS) (n = 5 each in the EN and EN with probiotics; Clostridium butyricum MIYAIRI 588) groups compared with 10 healthy controls. The results of 16S amplicon sequencing of the intestinal microbiota showed that EN led to dysbiosis with a decrease in α-diversity and an obvious change in β-diversity. A particularly significant decrease was seen in useful intestinal bacteria such as Bifidobacterium and butyrate-producing bacteria. Analysis of intestinal metabolites also supported these results, showing significant decreases in butyric and pyruvic acid after EN. Although C. butyricumMIYAIRI 588 improved some intestinal metabolites that were decreased after EN, it did not improve the dysbiosis of the intestinal microbiota. These findings indicate that EN causes dysbiosis of the intestinal microbiota and an imbalance in some intestinal metabolites in patients in a PVS. Moreover, although C. butyricumMIYAIRI 588 improved the imbalance of some intestinal metabolites after EN, it did not prevent dysbiosis of the intestinal microbiota. Full article

Insulin resistance leads to the onset of medical conditions such as type 2 diabetes, and its development is associated with the alteration in the gut microbiota. Although it has been demonstrated that supplementation with prebiotics modulates the gut microbiota, limited evidence is available for effects of prebiotics on insulin resistance, especially for humans. We investigated the prebiotic effect of 1-kestose supplementation on fasting insulin concentration in obesity-prone humans and rats. In the preliminary study using rats, the hyperinsulinemia induced by high-fat diet was suppressed by intake of water with 2% (w/v) 1-kestose. In the clinical study using obese-prone volunteers, the fasting serum insulin level was significantly reduced from 6.5 µU/mL (95% CI, 5.5–7.6) to 5.3 (4.6–6.0) by the 12-week intervention with supplementation of 10 g 1-kestose/day, whereas it was not changed by the intervention with placebo (6.2 µU/mL (5.4–7.1) and 6.5 (5.5–7.6) before and after intervention, respectively). The relative abundance of fecal Bifidobacterium was significantly increased to 0.3244 (SD, 0.1526) in 1-kestose-supplemented participants compared to that in control participants (0.1971 (0.1158)). These results suggest that prebiotic intervention using 1–kestose may potentially ameliorate insulin resistance in overweight humans via the modulation of the gut microbiota. UMIN 000028824. Full article

Biosynthetic and chemical datasets are the two major pillars for microbial drug discovery in the omics era. Despite the advancement of analysis tools and platforms for multi-strain metabolomics and genomics, linking these information sources remains a considerable bottleneck in strain prioritisation and natural product discovery. In this study, molecular networking of the 100 metabolite extracts derived from applying the OSMAC approach to 25 Polar bacterial strains, showed growth media specificity and potential chemical novelty was suggested. Moreover, the metabolite extracts were screened for antibacterial activity and promising selective bioactivity against drug-persistent pathogens such as Klebsiella pneumoniae and Acinetobacter baumannii was observed. Genome sequencing data were combined with metabolomics experiments in the recently developed computational approach, NPLinker, which was used to link BGC and molecular features to prioritise strains for further investigation based on biosynthetic and chemical information. Herein, we putatively identified the known metabolites ectoine and chrloramphenicol which, through NPLinker, were linked to their associated BGCs. The metabologenomics approach followed in this study can potentially be applied to any large microbial datasets for accelerating the discovery of new (bioactive) specialised metabolites. Full article

Intestinal microbiota and their metabolites are strongly associated with host physiology. Developments in DNA sequencing and mass spectrometry technologies have allowed us to obtain additional data that enhance our understanding of the interactions among microbiota, metabolites, and the host. However, the strategies used to analyze these datasets are not yet well developed. Here, we describe an original analytical strategy, metabologenomics, consisting of an integrated analysis of mass spectrometry-based metabolome data and high-throughput-sequencing-based microbiome data. Using this approach, we compared data obtained from C57BL/6J mice fed an American diet (AD), which contained higher amounts of fat and fiber, to those from mice fed control rodent diet. The feces of the AD mice contained higher amounts of butyrate and propionate, and higher relative abundances of Oscillospira and Ruminococcus. The amount of butyrate positively correlated with the abundance of these bacterial genera. Furthermore, integrated analysis of the metabolome data and the predicted metagenomic data from Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) indicated that the abundance of genes associated with butyrate metabolism positively correlated with butyrate amounts. Thus, our metabologenomic approach is expected to provide new insights and understanding of intestinal metabolic dynamics in complex microbial ecosystems. Full article