Introduction/ Objective: Neutrophils are crucial for an effective innate immune response. However, overactivation is associated with chronic inflammation, as in systemic lupus erythematosus (SLE). Gingival mesenchymal stromal cells (GMSCs) are used as anti-inflammatory therapies because they possess strong immunomodulatory properties, primarily acting through paracrine mechanisms. GMSCs exhibit immunoplasticity in response to their microenvironment and adjust their secretion profile. This study aimed to investigate the effects of conditioned media derived from human gingival mesenchymal stromal cells (hGMSC-CM) or from cells pretreated with IFNγ (hGMSCγ- CM) on neutrophil antimicrobial and proinflammatory functions. METHODS:hGMSCs were isolated to meet the criteria of the International Society for Cell & Gene Therapy (ISCT). Neutrophil intracellular reactive oxygen species (ROS) production; neutrophil elastase (NE), cathepsin G (CG), and myeloperoxidase (MPO) enzymatic activities; induction of lytic and vital neutrophil extracellular traps (NETs); and bacterial uptake and engulfment were analyzed using flow cytometry, photometric methods, and fluorescence and confocal microscopy. RESULTS:Both hGMSC-derived CMs significantly reduced intracellular ROS levels, reduced the enzymatic activities of MPO, CG, and NE by decreasing degranulation, and diminished NET formation (DNA, LL37, and PAD4) through both the lytic and vital pathways, including NET production observed in an inflammatory environment using plasma from SLE patients. DISCUSSION:These inhibitory effects were more pronounced with hGMSCγ-CM. Interestingly, hGMSCγ-CM did not impair bacterial uptake, engulfment, or neutrophil microbicidal activity against Staphylococcus aureus and Escherichia coli, thereby maintaining the functional balance of neutrophils. CONCLUSION:These findings support the use of hGMSCγ-CM as a cell-free biological product for therapies targeting inflammation driven by neutrophil overactivation.
An abdominal aortic aneurysm (AAA) is a serious vascular disease characterized by progressive dilation of the abdominal aorta, resulting in an increased risk of rupture. AAA develops through multiple pathogenic mechanisms, including chronic inflammation, extracellular matrix (ECM) degradation, oxidative stress, and vascular smooth muscle cell (VSMC) apoptosis. Surgical intervention is the primary treatment for AAA; however, no effective pharmacological therapies are currently available to halt or reverse disease progression. This review evaluates the therapeutic potential of multipotent mesenchymal stromal/stem cells (MSCs) for AAA, with particular emphasis on their immunomodulatory and regenerative properties. Preclinical studies suggest that MSCs can attenuate AAA progression in animal models by modulating the inflammatory microenvironment, reducing matrix metalloproteinase activity, and promoting tissue repair. In addition, interactions between MSCs and various immune cells decrease inflammatory responses, thereby positively impacting the structure of the aortic wall. Collectively, the available evidence highlights the broad therapeutic potential of MSCs in modulating key molecular and cellular pathways involved in AAA progression. Given their ability to modulate the immune system and promote vascular regeneration, MSCs may have significant potential for developing disease-modifying therapies for AAA. By targeting key pathogenic processes involved in AAA progression, MSCs offer the potential to complement existing surgical management and address mechanisms that are not targeted by current therapies. However, additional well-designed laboratory-based and clinical studies are needed to optimize MSC-based therapeutic strategies and to establish their long-term efficacy and safety before clinical translation.
Introduction: Mesenchymal stem cells (MSCs) possess immunomodulatory and tissuereparative properties and have shown therapeutic potential in acute lung injury (ALI). However, the mechanisms underlying their protective effects remain unclear. This study aimed to evaluate the effects of MSCs on bleomycin-induced ALI and to explore the underlying molecular mechanisms. Methods: A bleomycin-induced ALI mouse model was established, followed by human umbilical cord-derived MSC administration. Lung injury, pulmonary edema, neutrophil infiltration, and apoptosis of alveolar type II epithelial cells (AT2) were assessed. RNA-seq and molecular validation were performed using sorted AT2 cells to investigate the underlying mechanism. In vitro assays were carried out to examine the role of Ntrk2 in MSC-mediated epithelial repair. Results: MSC treatment alleviated lung injury, improved alveolar structure, reduced pulmonary edema, and decreased neutrophil infiltration and AT2 cell apoptosis. RNA-seq and molecular analyses indicated that MSCs regulated Ntrk2 expression by suppressing NF-κB signaling and enhancing STAT3 signaling, thereby promoting alveolar epithelial regeneration. In vitro, inhibition of Ntrk2 impaired the promotive effects of MSCs on A549 cell migration and alveolar organoid repair. Discussion: These findings suggest that MSCs protect against ALI by attenuating inflammatory injury and promoting alveolar epithelial repair, with the NF-κB/STAT3-Ntrk2 axis contributing to this process. Conclusion: MSC treatment ameliorated bleomycin-induced ALI and promoted alveolar epithelial regeneration, at least partly through the NF-κB/STAT3-Ntrk2 axis. These results provide further mechanistic support for MSC-based therapy in ALI.
Microbial food, food and ingredients produced leveraging microorganisms, represents a promising pathway toward sustainable and nutritious food systems. Translation of microbial food to everyday life, however, has lagged behind because of economic feasibility, regulations, and public perception. Innovative solutions are awaited to address current bottlenecks of microbial food in feedstock supply, microbial diversity, infrastructure requirements, and societal acceptance. At this point, local fermented food, an indispensable part of sustainable local food systems over a long period of time, can provide clues for innovation. Here, taking Indonesian fermented foods as example cases, we discuss alternative strategies for microbial food development, including feedstock and microbial host diversification, decentralized production, and culinary transformation of microbial biomass. Integrating such lessons from the local traditional fermentation strategies can help drive the translation of microbial food to daily life and sustainable production and consumption of nutritious food for human and planetary health.
Bile acids (BAs) are emerging as key signaling metabolites at the interface of diet, the gut microbiota, and host physiology. Microbial transformation generates structurally diverse BA species that regulate host metabolism and immunity via receptor-mediated signaling pathways. Recent advances in synthetic biology enable the modular reconstruction of BA metabolic pathways in tractable microbial hosts, moving the field toward programmable control of BA composition. Integrating engineered chassis with process optimization and emerging technologies such as computational design, biosensors, and encapsulation is accelerating the development of scalable and predictable BA-remodeling platforms. These advances contribute to an emerging paradigm of precision microbiome engineering with broad implications in pharmabiotics, functional foods, and personalized microbiome therapies.
Terpenoids are key contributors to aroma in fermented foods and beverages, yet yeast has traditionally been considered a poor source of de novo monoterpenes. Increasing evidence shows that fermentative yeasts possess an intrinsic capacity to produce volatile isoprenoids through the native mevalonate pathway in the absence of plant precursors. Central to this metabolic plasticity is the prenyltransferase Erg20p, which regulates the balance between geranyl diphosphate (GPP) and farnesyl diphosphate. Variations in ERG20 structure and kinetics can enhance GPP availability, enabling monoterpene formation via metabolic ‘leakage’, as previously observed for geraniol production. In parallel, several yeast species naturally produce sesquiterpenes such as farnesol and nerolidol. These insights highlight new opportunities to exploit yeast metabolic diversity through non-GMO (Genetic Modified Organisms) strategies for terpene-driven flavor innovation in food fermentations.
Extracellular vesicles (EVs) are cell-released nanoparticles whose lipid membranes enclose molecular cargo and contribute to vesicle stability, uptake, and biological activity. EV composition encodes and transmits biological information, reflecting cellular origin, membrane remodeling, metabolism, and disease-associated stress. This makes EV lipidomics highly relevant for diagnostics, therapeutics, mechanism-informed discovery, and emerging biotechnology. Recent advances in isolation, characterization, and lipidomics approaches are making EV lipid profiles increasingly interpretable. At the same time, low sample biomass, heterogeneity, co-isolated particles, extraction bias, and variable confidence in lipid detection, annotation, and quantification remain important design considerations.In this review, we discuss how recent EV lipidomics studies are moving beyond untargeted biomarker discovery toward mechanistic questions about membrane adaptation, cellular origin, intercellular communication, and function. We then examine applications in cancer and neurodegeneration, where recent work illustrates the biological and biotechnological potential of EV lipidomes. We argue that the next phase of EV lipidomics will require stronger integration of EV characterization, quality controls, matched biofluid comparisons, and functional assays. With rigorous analytical design, EV lipidomics is evolving into a powerful platform for mechanistic discovery, diagnostic development, and therapeutic delivery.
Production of customized yeast single-cell protein (SCP) from CO2 offers a sustainable avenue to convert a major carbon emission process into a carbon-conserving production route of food and feed. Here, we highlight a specific approach for SCP production from CO2 using sequentially connected yet spatially separated tandem biological systems, which consist of a first unit for CO2 fixation followed by a second unit for precision fermentation toward customized SCPs. We discuss the design principles of the system, review current efforts to convert CO2 using natural and engineered autotrophs, and outline the potential of yeast for customized SCP production. Finally, we underscore the critical role of nitrogen sources for efficient SCP production.
BACKGROUND:This study aimed to investigate the therapeutic effect and potential mechanism of intravenous injection of human umbilical cord mesenchymal stem cells (hUCMSCs) on acute lung injury (ALI) in rats. METHODS:Wistar albino rats were used to establish an ALI animal model via intravenous oleic acid suspension injection. Rats in the low-dose and high-dose mesenchymal stem cell (MSC) groups were treated with 2.5×10^5 hUCMSCs and 5×10^5 hUCMSCs, respectively. After 24 hours of modelling, the rats were sacrificed and samples were collected. The lung coefficient was calculated, and lung tissue morphology was examined. The expression levels of TNF-α, IL-1β, IL-4, IL-6, and IL-10 in lung tissue and serum were assessed. Additionally, the expression of Claudin-5, Occludin, and ZO-1 in the lung was measured. RESULTS AND DISCUSSION:Compared with the control group, lung volume and lung coefficient significantly increased, and lung tissue exhibited pathological changes with an increased lung injury score. Levels of TNF-α, IL-1β, and IL-6 in lung tissue and serum significantly increased, while IL-4 and IL10 levels significantly decreased. The proportion of neutrophils markedly increased, and the expression of Claudin-5, Occludin, and ZO-1 in the lung significantly decreased in the model group. These results indicate that oleic acid can induce acute lung injury and activate inflammatory. Compared with the model group, both MSC-treated groups showed significant reductions in lung coefficient and lung injury score. Levels of TNF-α, IL-1β, and IL-6 in lung tissue and serum significantly decreased, while IL-4 and IL-10 levels significantly increased. Furthermore, the proportion of neutrophils decreased significantly, and the expression of Claudin-5, Occludin, and ZO-1 in the lung increased significantly in the two MSC-treated groups. The therapeutic effect can likely be ascribed to the immunomodulatory properties of hUCMSCs and capacity to mitigate barrier damage, as substantiated by the decreased levels of pro-inflammatory cytokines, along with the elevated expression of antiinflammatory factors and tight junction proteins in lung tissue. CONCLUSION:The hUCMSCs can effectively ameliorate oleic acid-induced ALI in rats by exerting anti-inflammatory effects and protecting the alveolar-capillary endothelial barrier.
INTRODUCTION:Pancreatic stellate cells (PSCs) play a central role in pancreatic physiology and disease, and the transition between their quiescent and activated states influences processes such as fibrosis and regeneration. However, the stem cell-like properties of PSCs remain unclear. This study aims to clarify the stem cell characteristics of PSCs and establish a method to maintain their quiescent state, thereby providing a new perspective on pancreatic regeneration. METHODS:PSCs from Lrat-cre; Rosa26-tdTomato mice were fate-traced, and immunofluorescence was used to assess Lrat, Oct4, and Nanog co-localization. Primary PSCs from C57BL/6 mice were cultured in mesenchymal stem cell (MSC) or DMEM/F12 medium. Lipid droplets, morphology, activation markers (α-SMA, collagen-I, fibronectin), and stemness-associated markers were analysed via qRT-PCR and immunofluorescence. RESULTS:Lrat co-localized with Oct4/Nanog in mice. MSC-cultured PSCs had more lipid droplets, a quiescent morphology, and lower levels of activation markers than DMEM/F12-cultured cells. They also expressed stemness-associated markers (Pdx1, Oct4, Nkx6.1, Ngn3, Sox2, Pax6). DISCUSSION:These results indicate that PSCs possess stemness and can be preserved under specific culture conditions. The ability of MSC medium to maintain PSCs in a quiescent and stem-like state provides a valuable model for studying their biology. CONCLUSION:PSCs exhibit stemness, and MSC medium maintains their quiescence, offering a novel experimental platform to study PSC biology and lineage plasticity.
Metabolomics data are currently generated at scale thanks to the evolution of technologies that have led to marked improvements in the number of metabolites detected, spanning all chemical classes. These data are increasingly submitted to public repositories for data reuse, integration, and interpretation. Despite the availability of public resources and associated computational tools, the field still lacks a widely adopted, consistent data and analytics infrastructure capable of transforming this wealth of information into scientific insight. Indeed, the metabolomics field is just now scratching the surface of being able to harness the power of new computational technologies. In this review, we summarize discussions from the “Dagstuhl-Seminar 24181 Computational Metabolomics: Towards Molecules, Models, and their Meaning” with a focus on public data availability, open data standards, data and knowledge integration, and education. Our goal is to raise awareness and adoption of the latest open science resources while highlighting key areas needing further development.
Microbial consortia offer significant advantages over monocultures in biotechnological applications, including access to a broader metabolic repertoire, functional redundancy and the capacity for division of labour. Adaptive laboratory evolution (ALE) has similarly proven to be a powerful tool in metabolic engineering, uncovering solutions inaccessible through rational design alone. Despite their individual potential, the intersection of ALE and synthetic microbial consortia in bioproduction contexts remains underexplored. This review examines recent advances at this intersection, with a focus on bottom-up synthetic consortia and co-cultures.Artificial selection operates at organismal and supra-organismal levels in microbial communities, and this not only shapes their productive output, but it may also compromise the evolvability of costly production functions. This effect can be limited by engineering ecological interactions that stabilise community composition. ALE and synthetic consortia mutually expand each other's applicability through a variety of implementation logics. However, current approaches predominantly rely on growth-based selection, and we argue that implementing inter-community artificial selection strategies holds considerable untapped potential.
The food microbiome, comprising microorganisms present in foods and fermentation, links diet, environment, and host physiology. This review examines its evolutionary, contemporary, and future nutritional relevance, including emerging applications of artificial intelligence (AI). In early human diets, fermentation likely improved food safety and nutrient accessibility, although its contribution to encephalization remains unproven. In modern populations, fermented foods and microbial metabolites shape the composition of the gut microbiome and modulate host metabolic, immune, and neuroactive functions. Rising atmospheric CO₂ is projected to reduce protein and micronutrient concentrations in staple crops, increasing interest in microbial fermentation as a strategy to enhance nutrient availability. Integration of AI with multi-omics enables functional characterisation of fermentation ecosystems and supports the development of targeted, personalised nutritional strategies, although translational and mechanistic challenges remain unresolved.
Fermented foods are produced from established bioprocesses where microbes convert raw materials into safe, sensory-rich products. Multi-omics can help elucidate how fermentation dynamics shape metabolites and microbial components that have the potential to influence the gut microbiota and host metabolism. The practical bottleneck is translation: many omics observations remain associative, and translating them into health-directed starter cultures requires verification of product-level markers, demonstration of process scalability, and compliance with regulatory requirements. Health-directed starter cultures are defined as single strains or designed consortia selected to control fermentation while enriching a small set of trait axes, such as indole-derivative formation and bile-acid transformation. Here, we propose a stepwise framework that connects genome-encoded functional capacity and genomic safety assessment with pathway execution in the target matrix, quantitative product chemistry, and mechanism-aligned functional assays. Lastly, we outline requirements for human trials, emphasizing individual variability and the need for study designs that connect quantified food components to measurable health benefits.
Fermented foods exemplify self-organized microbial ecosystems shaped by ecological filtering, domestication, and sustained human selection. This review explores how ecological insights from traditional fermentations guide the rational design of engineered microbial consortia in contemporary food biotechnology. Across various substrates and cultural contexts, fermented systems illustrate that functional stability, metabolic complementarity, and reproducible biochemical outputs arise from structured community interactions rather than from individual strains. Recent advances in multiomics, culturomics, and genome-scale metabolic modeling facilitate the systematic identification of core microbiota and ecosystem-level functional phenotypes that underpin fermentation performance. These developments are shifting fermentation from an empirical practice to a predictive, design-oriented discipline. Integrating ecological theory with systems-level biotechnology, traditional fermentations offer conceptual and experimental frameworks for constructing minimal yet robust microbial consortia. Such strategies enable the development of next-generation fermented foods with enhanced nutritional, functional, and sensory attributes, while preserving ecological robustness and process reproducibility.
We survey recent works on designing and implementing CO2 fixation pathways. We describe how these studies reveal a gap between a well-designed pathway and a productive strain. This gap includes phenomena that are often not accounted for in design, such as hidden enzyme energy usage and regulatory rewiring during adaptive evolution. Several systems biology tools can help overcome this gap. Kinetic models can be generated rapidly using new algorithms, and when coupled with retrobiosynthesis, can evaluate pathway dynamics and stability in the context of the native network. Quantitative and interaction proteomics reveal how the host strain adapts to novel pathways and can identify interference from native metabolites. In vivo optimization through adaptive laboratory evolution is used extensively to optimize modules or whole pathways, but requires the pathway phenotype to be linked to growth. Post-evolution characterization reveals that cells optimize pathway integration through substantial proteome reallocation.
Sustainable biomanufacturing seeks to replace fossil-fuel-based production with renewable bioeconomies, with microbial cell factories serving as key platforms for producing fuels, chemicals, and high-value products. This review highlights recent advances that have transformed pathway engineering from an empirical practice into a predictive and integrated discipline. Artificial intelligence-assisted retrosynthesis expands biosynthetic route design, while genome-scale metabolic models and host-aware simulations improve pathway evaluation under cellular constraints. Enzyme engineering is increasingly integrated with pathway design through machine learning, high-throughput screening, and cell-free platforms. Dynamic regulation, including biosensor-based feedback systems, further optimizes metabolic performance. Together with automation and design-build-test-learn workflows, these advances establish a multiscale framework that accelerates the development of robust microbial production systems.
Fermented foods are a globally important source of dietary microbes, cultural heritage, and functional diversity, yet current microbiome research captures only a narrow fraction of this richness. Public sequencing datasets are heavily skewed toward a limited set of regions and fermentation types, leaving vast areas of geographic, substrate, and process diversity underrepresented. This imbalance constrains the discovery of novel microbial species, enzymes, and biosynthetic capacities, and risks accelerating homogenization through standardized starter cultures. We argue that coordinated, ethically grounded global efforts integrating metagenomics, multi-omics, standardized metadata, and biobanking are urgently needed to document, preserve, and responsibly leverage fermented food microbial diversity for sustainable food systems and innovation.
C1 compounds are abundant, non-food and renewable feedstocks, making them attractive substrates for producing value-added chemicals via microbial bioconversion. In nature, autotrophic microorganisms assimilate C1 substrates, including CO, CO2, methane, methanol and formate, through native C1 fixation and assimilation pathways. Building on these natural routes, synthetic C1 assimilation pathways and engineered microbial cell factories have improved C1 utilization and broaden product portfolios. This review presents the recent progress and current strategies in producing high-value compounds using microbes possessing natural and non-natural C1 assimilation modules. We highlight key bottlenecks that limit efficient C1 assimilation and discuss potential strategies to address them, outlining opportunities for future C1-based biomanufacturing.
