Search Results (73)

The human gut microbiome is a complex adaptive ecosystem whose functions arise from interactions among microbial populations rather than from isolated taxa. Nevertheless, many microbiome-directed interventions still rely on administering individual strains, with limited consideration of the ecological processes governing community assembly, succession, and resilience. This review integrates evidence from microbial ecology, comparative genomics, systems biology, mechanistic physiology, and clinical microbiome research to propose a testable framework for ecologically engineering the human gut microbiome. Within this framework, selected spore-forming probiotics are hypothesized to function as transient pioneer organisms that modify intestinal physicochemical and metabolic conditions, thus facilitating the establishment and activity of functionally complementary microbial populations delivered through rationally designed synbiotic consortia. The proposed process comprises five stages: pioneer activity, niche remodeling, facilitated community assembly, functional-network stabilization, and the emergence of host-associated outcomes. Available genomic, physiological, and clinical observations support the biological plausibility of individual components of this model but do not yet demonstrate directed ecological succession as a complete causal process. Accordingly, the framework distinguishes established evidence from ecological inference and generates experimentally testable predictions of temporal niche modification, metabolic cross-feeding, functional redundancy, resilience after treatment withdrawal, and host metabolic responses. This ecological perspective shifts the objective of microbiome therapeutics from transient strain supplementation toward the predictable modulation of community trajectories, providing an experimental foundation for developing more resilient, mechanism-based interventions. Full article

The emergence of antimicrobial resistance (AMR) has created a need for new, targeted alternatives to conventional antibiotics. Bacteriocins and other targeted antimicrobial peptides (AMPs) are emerging therapeutic approaches that have attracted attention for their potent antimicrobial properties and potential for more specific effects on microbial communities. The review describes the development of probiotics from lactic acid bacteria (LAB) to next-generation probiotics (NGPs), incorporating genomics, metagenomics, and synthetic biology to develop and engineer antimicrobial-producing microbial platforms. A comparative analysis of the bacteriocin profiles of conventional LAB and NGPs is presented, highlighting differences in diversity, specificity, and therapeutic potential. Additionally, recent advances in large-scale bacteriocin production systems, including recombinant expression and bioengineering methods, are discussed. Issues related to delivery systems, stability, host interactions, and targeted release are discussed. Most evidence comes from in vitro and animal studies, with limited clinical data on bacteriocin-producing probiotics and NGPs. There is also a significant gap in direct experimental proof of bacteriocin production by many proposed NGPs, hindering their development as targeted antimicrobials. Regulatory, scale-up, and manufacturing challenges remain major barriers to commercialization and broad therapeutic use. Target pathogen prioritization is a final step highlighted in the review that will help in therapeutic precision and improve the outcome of treatment for multidrug-resistant pathogens. Overall, LAB-derived bacteriocins have the most substantial evidence for production, characterization, and safety, while NGP-associated systems are promising but mostly preclinical and need further structural and functional validation. Moving towards precision antimicrobial therapy will depend on developing standardized activity assays, evaluating microbiome interactions, monitoring resistance, ensuring strain safety, establishing scalable manufacturing processes, and conducting comprehensive human clinical trials. Full article

3-Hydroxybutyric acid (3-HB) is a bioactive ketone body involved in the regulation of intestinal inflammation and metabolic homeostasis. Although engineered bacterial probiotics have been developed for localized 3-HB delivery, their susceptibility to antibacterial antibiotics may limit their use during concurrent antibiotic treatment. The probiotic yeast Saccharomyces boulardii offers an alternative host for intestinal 3-HB delivery because of its compatibility with antibacterial antibiotics and the availability of well-established genetic engineering tools. Here, we engineered S. boulardii for 3-HB production using Cas9-mediated genome editing. A heterologous 3-HB biosynthetic pathway was introduced into S. boulardii MYA-797, and endogenous acetyl-CoA and ethanol metabolism was subsequently rewired by overexpressing ACS1, deleting ADH1, and overexpressing ADH7. The optimized strain, SbDY02, produced 1.7 g/L 3-HB under microaerobic conditions. Oral administration of SbDY02 to C57BL/6J mice increased fecal 3-HB and short-chain fatty acid (SCFA) concentrations by 1.89-fold and 1.68-fold, respectively, compared with mice receiving the parental strain. Repeated administration also increased fecal acetate and circulating total SCFAs, butyrate, and propionate. In human colonic epithelial cells, purified 3-HB attenuated lipopolysaccharide-induced p38 MAPK phosphorylation, supporting its direct activity toward inflammation-associated epithelial signaling. To our knowledge, this study provides the first demonstration of a 3-HB-producing probiotic yeast and links central metabolic engineering of S. boulardii with increased 3-HB availability, altered SCFA profiles, and a host-relevant epithelial response. Full article

Gamma (γ)-aminobutyric acid (GABA) is a non-proteinogenic amino acid recognized for its primary function as the main inhibitory neurotransmitter in the mammalian central nervous system and its role as a stress-responsive metabolite in various microorganisms. This review critically examines the biosynthesis of GABA by lactic acid bacteria (LAB) via the glutamate decarboxylase (GAD) system and evaluates its potential applications in food and health sectors. The mechanistic details of the GAD pathway are analyzed, focusing on the integrated roles of gadA/gadB decarboxylases, the gadC antiporter, and pyridoxal−5′-phosphate (PLP) dependency in relation to acid resistance, metabolic flux, and strain variability. Taxonomic and strain-level diversity among GABA-producing LAB is assessed, with emphasis on the highly strain-specific nature of GABA production rather than broad species or genus generalizations. Fermentation optimization parameters (pH, temperature, substrate loading, and cofactor management) and scale-up challenges, including techno-economic feasibility and downstream recovery efficiency, are critically evaluated. Integration of LAB-derived GABA into fermented food matrices is discussed with attention to sensory compromises, stability, regulatory factors, and clean-label considerations. Evidence from clinical and preclinical studies is synthesized to assess the physiological significance of dietary GABA, distinguishing between purified GABA supplementation, GABA-enriched fermented foods, and probiotic effects of live LAB, while addressing the GABA paradox and gut–brain axis interactions. Significant research gaps are identified, including the need for standardized quantification methodologies, multi-omics-guided strain engineering, predictive bioprocess modeling, and rigorously designed human trials in realistic food matrices. This review provides a systems-oriented, critical framework to promote scalable and evidence-based advancement of GABA-enriched functional foods. Full article

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract that arises from a complex interplay of genetic susceptibility, immune dysregulation, environmental exposures, and altered host–microbiome interactions. Increasing evidence identifies the gut microbiota as a central component of IBD pathogenesis. In healthy individuals, the intestinal microbiota supports epithelial integrity, metabolic homeostasis, immune education, colonization resistance, and bidirectional gut–brain communication. In IBD, this ecosystem is disrupted by reduced microbial diversity, expansion of pathobionts, and broader functional alterations affecting community stability and metabolic output. Importantly, these changes are increasingly viewed not merely as consequences of inflammation, but as active contributors to disease development and persistence. Dysbiosis may also influence neuroimmune signaling through the gut–brain axis, linking microbial metabolites, intestinal barrier dysfunction, enteric nervous system activity, and psychological comorbidities frequently observed in patients with IBD. This review provides a comprehensive overview of the role of the gut microbiota in IBD, beginning with its physiological functions in intestinal homeostasis and the evidence linking dysbiosis to disease pathogenesis, followed by a critical evaluation of current microbiome-based therapeutic strategies, their translational challenges, and prospects for personalized microbiota-directed interventions. Approaches such as fecal microbiota transplantation (FMT), probiotics, live biotherapeutic products, and genetically engineered bacteria aim to restore microbial balance and modulate intestinal inflammation. Among these, FMT has provided the strongest proof-of-concept for microbiome restoration, whereas probiotic efficacy remains variable and strain-dependent. Emerging defined microbial consortia and engineered bacterial platforms offer improved standardization and mechanistic precision, but their clinical application remains limited by challenges related to engraftment, durability of response, safety, and treatment optimization. Collectively, current evidence supports gut microbiota as both a key determinant of IBD pathogenesis and a promising therapeutic target, underscoring the need for more precise and personalized microbiota-directed approaches in IBD management. Full article

The global poultry industry faces a major transition driven by bans on antibiotic growth promoters (AGPs) and rising antimicrobial resistance threats. This has intensified the search for effective, sustainable alternatives to maintain productivity, animal health, and food safety. This review provides a comprehensive overview of next-generation probiotics (NGPs) and their evolving role in poultry production, highlighting their mechanisms of action, technological advancements, and applications for improving performance and health. Recent studies were systematically reviewed, covering conventional and NGPs, multi-omics-driven strain identification strategies, engineered microbial systems, and advanced delivery technologies. Key functional aspects, including gut microbiota modulation, immune responses, pathogen control, and productivity metrics were thoroughly assessed. NGPs exhibit enhanced capabilities over traditional probiotics, including improved gut colonization, targeted antimicrobial activity, and precise host immune modulation. Advances in synthetic biology, microencapsulation, and synbiotic formulations enhance their efficacy and stability. Additionally, NGPs also demonstrate significant potential in improving growth performance, feed conversion ratios, intestinal integrity, and enteric pathogen resistance. However, challenges such as strain-specific variability, regulatory constraints, and limited field-level validation persist. NGPs offer a promising and sustainable strategy for modern poultry production. Future integration with precision microbiome engineering, artificial intelligence, and sustainable farming will be essential to realize their full potential and ensure widespread adoption. Full article

Scientific interest in probiotics continues to grow as accumulating evidence links microbiome modulation to improvements in host health. Probiotics are usually described as live microorganisms that, when administered in adequate amounts, confer a health benefit to the host. However, products are exposed to multiple stresses during manufacturing, storage, and gastrointestinal transit. Among these, drying, often employed to stabilize powders and extend shelf life, can impose high viability loss. This review synthesizes recent advances in drying process engineering, formulation design, and viability assessment aimed at improving survival during drying. Freeze drying remains the most widely used technology, while alternative approaches, including conventional spray drying, vacuum drying, spray freeze drying, and electrostatic spray drying, are increasingly evaluated. Protective strategies are discussed, encompassing sublethal conditioning (stress adaptation), optimization of operating parameters, incorporation of excipients, and encapsulation. Lastly, methods for viability assessment are also compared, contrasting culture-dependent assays (e.g., plate enumeration) with culture-independent techniques such as flow cytometry and PCR-based approaches. However, across studies, performance is highly strain-specific, and optimization often entails trade-offs among immediate survival, cycle time, powder stability, and downstream functionality. Full article

Salmonella pullorum (S. pullorum) remains a major enteric pathogen in young chicks, causing high mortality and severe economic losses in poultry production. This study evaluated a prophylactic strategy using engineered Bacillus subtilis (B. subtilis) expressing gallus trefoil factor 2 (gTFF2) and epidermal growth factor (gEGF) to protect chicks against S. pullorum infection. In vitro, gEGF significantly promoted UMNSAH/DF-1 (DF-1) cell proliferation, whereas both gTFF2 and gEGF enhanced epithelial cell migration. In vivo, oral administration of recombinant B. subtilis significantly reduced mortality from 75.0% and 66.7% in the PBS and pHT43 groups to 50%, 33.3%, and 25.0% in the gTFF2, gEGF, and gTFF2+gEGF groups, respectively. Cecal colonization of S. pullorum was reduced by 2–4 log₁₀ CFU/g, accompanied by improved average daily gain and immune organ indices. Treatment also significantly decreased serum IL-6 levels and increased TGF-β levels (p < 0.05), indicating attenuation of the inflammatory response. Histological analysis showed significantly increased villus height (0.94–1.58-fold) and villus height-to-crypt depth ratio (1.47–3.25-fold) compared with the infected controls, together with markedly alleviated hepatic and intestinal lesions. The combined administration of gTFF2- and gEGF-expressing strains consistently exhibited the greatest protective efficacy. Collectively, these findings demonstrate that engineered probiotic-mediated delivery of mucosal repair factors represents a promising antibiotic-alternative strategy for preventing pullorum disease and improving intestinal health in poultry production. Full article

This paper examines how technological innovation in next-generation probiotics shapes consumer trust through the lens of perceived safety. Rapid advances—spanning conventional cultures (Tier 1), postbiotics (Tier 2), and engineered microbial strains (Tier 3)—are transforming functional food architectures, yet consumer trust remains a critical determinant of their successful development, application, and adoption. Drawing on interdisciplinary evidence from food microbiology, consumer perception research, and regulatory analysis, this study examines and evaluates how these distinct technological innovation tiers alter public risk dynamics. Findings indicate that processing methodologies, media framing, and the spread of misinformation significantly influence public perceptions of microbial legitimacy, while the “Animation Gap” and “Contamination Anxiety” introduce qualitatively new cognitive friction points. Furthermore, regulatory inconsistencies across jurisdictions and variability in health claim substantiation further complicate market uptake. Streamlined case-based evidence highlights physical stability, sensory performance, and explicit value metrics that determine whether technological innovations are trusted or rejected by consumers. The paper argues that bridging the gap between scientific innovation and public acceptance requires proactive communication strategies, ethical marketing practices, and participatory engagement strategies grounded in empirical integrity. In addition, digital ecosystems, including social media and algorithm-driven content exposure, play an increasingly influential role in amplifying technology neophobia, underscoring the need for robust, targeted, evidence-based public communication in the evolving landscape of probiotic and functional food innovation. Full article

Chronic atrophic gastritis (CAG) is a pivotal precancerous condition in gastric carcinogenesis, with progression typically following the classic Correa cascade. Although Helicobacter pylori (H. pylori) infection is widely recognized as the principal etiological factor, the persistence of gastric cancer (GC) risk in a subset of patients after successful eradication suggests that gastric microbiota dysbiosis may also contribute to CAG progression. In recent years, high-throughput sequencing technologies have revealed distinct microbial restructuring in patients with CAG, characterized by decreased microbial diversity, depletion of commensal taxa, and enrichment of opportunistic pathogens. These compositional changes are accompanied by metabolic dysfunction, activation of inflammatory signaling pathways, and disruption of immune homeostasis, which may contribute to a microenvironment permissive for precancerous transformation of the gastric mucosa. Probiotics and related microbiome-based therapeutics, including prebiotics, synbiotics, and postbiotics, have emerged as promising adjunctive strategies for H. pylori eradication and disease management. Their beneficial effects are mediated through multiple mechanisms, including remodeling of the microbial community, inhibition of pathogen colonization, modulation of host immune responses, and restoration of mucosal barrier integrity. However, whether these interventions can reverse established atrophic or metaplastic lesions remains unclear. In addition, how strain specificity, dose dependency, and interindividual heterogeneity influence clinical efficacy has yet to be fully elucidated. In this review, we summarize the compositional and functional features of gastric microbiota dysbiosis in patients with CAG, as well as the mechanisms and clinical applications of microbiome-based interventions. We further highlight current limitations in the field and discuss future directions for precision microecological therapies integrating multi-omics approaches, engineered probiotics, and artificial intelligence. These advances may provide a theoretical framework and practical guidance for the diagnosis and management of CAG and the prevention of GC. Full article

Acetic acid bacteria (AAB, family Acetobacteraceae) are obligate aerobic microorganisms characterized by a highly efficient oxidative metabolism driven by membrane-bound dehydrogenases. Their ability to incompletely oxidize ethanol and various carbohydrates underlies the production of key food-related metabolites, including acetic acid, gluconic acids, and bacterial cellulose. This review summarizes current knowledge on AAB physiology, metabolic pathways, and ecological adaptations, with emphasis on their relevance to food biotechnology and value-added bioprocesses. AAB plays a central role in traditional and modern food fermentations, contributing to the production of vinegar, cocoa, coffee, kombucha, and other fermented beverages. Their metabolites influence food preservation, sensory attributes, and texture formation, supporting the development of clean-label and sustainable food products. In addition, AAB are increasingly applied in environmental biotechnology, including biodegradation and wastewater treatment, owing to their tolerance to acidic and oxidative stress conditions. Recent advances in metabolic and genetic engineering have enhanced the efficiency, robustness, and product specificity of industrial AAB strains, enabling improved production of organic acids, bacterial cellulose, and other high-value compounds. Emerging evidence also highlights the potential probiotic and postbiotic functions of selected AAB strains, including modulation of gut microbiota, production of bioactive metabolites, and support of intestinal barrier integrity, although these properties remain less explored than in lactic acid bacteria. Despite significant progress, challenges persist in strain standardization, genetic accessibility, and process optimization. Future research should focus on developing advanced engineering tools, improving large-scale fermentation strategies, and further elucidating the functional and health-related properties of AAB. Overall, AAB represents versatile microbial platforms with expanding applications in food science, biotechnology, and sustainable bioprocessing. Full article

The gut microbiota is increasingly examined as a therapeutic target because it contributes to epithelial barrier integrity, microbial metabolite production, bile acid transformation, immune regulation, and communication between the gut and distant organs. This structured narrative review synthesizes evidence on microbiota involvement in metabolic, gastrointestinal, hepatic, cancer, and neuroimmune conditions, including MASLD/MASH, inflammatory bowel disease, irritable bowel syndrome, obesity, type 2 diabetes, hypertension, colorectal cancer, Parkinson’s disease, and autism spectrum disorder. Across these conditions, microbiome findings are biologically plausible but heterogeneous. Many associations are shaped by diet, geography, medication exposure, host genetics, disease stage, sampling methods, and analytical pipelines. Microbial alterations should therefore be interpreted as context-dependent signals and candidate modifiers rather than universal causal markers. Conventional microbiota targeted strategies include diet, physical activity, prebiotics, probiotics, synbiotics, postbiotics, and fecal microbiota transplantation. These approaches are clinically familiar, but their effects are often broad, host specific, strain dependent, and difficult to assign to one mechanism. Fecal microbiota transplantation has the clearest clinical role in recurrent Clostridioides difficile infection, while evidence for most other indications remains inconsistent. Engineered microbial therapeutics offer greater experimental precision through signal sensing, payload delivery, metabolic modulation, and genetic circuit design. However, most evidence remains preclinical or early translational. Progress requires stronger human trials, standardized methods, mechanistic validation, safety monitoring, ecological containment, transparent reporting, and proportionate regulation. Full article

γ-Aminobutyric acid (GABA), a vital bioactive component, is biosynthesized via the decarboxylation of L-glutamate (L-Glu) catalyzed by glutamate decarboxylase (GAD). However, the GADs from various sources commonly suffer from low thermal stability, which hampers their industrial applications. In this work, four ancestral sequences of GAD (Anc19, Anc20, Anc28, and Anc30) were designed via an ancestral sequence reconstruction (ASR) approach. Thereafter, the genes were synthesized and heterologously expressed in the probiotic Escherichia coli strain Nissle 1917 (EcN). Among all variants tested, Anc28 exhibited the highest catalytic performance. The K_m and k_cat values were determined to be 26.80 mM and 57.41 s⁻¹, respectively, yielding a catalytic efficiency (k_cat/K_m) of 2.14 s⁻¹mM⁻¹, which was 2.71-fold higher than that of the wild-type enzyme. Meanwhile, compared with the wild-type GAD, Anc28 exhibited a 6.74 °C increase in T₅₀¹⁵ and a 4.1-fold extension in t_1/2 at 60 °C. Furthermore, the GABA synthesis system using dormant Escherichia coli Nissle (T7)/pET28a-gadB_Anc28 cells as the biocatalyst and pure water as a sole medium was also constructed. Upon completion of the 4 h reaction, the GABA titer reached 307.53 g/L with a conversion ratio of 99.36%. The resulting engineered strains were successfully employed for the efficient biosynthesis of GABA. Full article

The global probiotic market is expanding rapidly, driven by growing demand for accessible strategies to support gut health, preventive care, and microbiome-based interventions. However, this commercial growth contrasts with the limited number of clinically validated, mechanism-driven products, highlighting a persistent gap between market expansion, scientific evidence, and therapeutic translation. Most current probiotics remain dominated by conventional genera, including Lactobacillus, Bifidobacterium, Bacillus, Saccharomyces, and Streptococcus, whereas live biotherapeutic products (LBPs) remain scarce. Synthetic biology is beginning to address this gap by transforming probiotics from empirically selected strains into programmable microbial platforms that sense disease-associated signals and produce defined therapeutic outputs. Escherichia coli Nissle 1917 (EcN) offers a valuable model chassis for engineered probiotics because of its long history of human use, safety record, genetic tractability, transient gut colonization, and scalable cultivation. As a rare Gram-negative probiotic, EcN naturally produces outer membrane vesicles that support host interaction, immunomodulation, and therapeutic cargo delivery. This review links probiotic market expansion with live biotherapeutic development and uses EcN to discuss emerging engineering strategies, therapeutic opportunities, and remaining translational barriers. Full article

Escherichia coli Nissle 1917 (EcN) has transformed from a traditional probiotic into a versatile microbial cell factory through innovations in genomic tools and metabolic engineering. This review summarizes recent progress in utilizing EcN for biochemical synthesis. First, the development of genetic editing tools is systematically discussed, highlighting how these methods serve as the foundation for metabolic rewiring. Second, we examine EcN bioproduction capabilities, including its application as in situ Live Biotherapeutic Products (LBPs) for targeted disease interventions and its use in the ex vivo biosynthesis of pharmaceuticals and nutraceuticals. Third, optimization strategies for fermentation processes, focusing on diverse carbon source assimilation and industrial scale-up parameters, demonstrate the potential of this strain for commercial production. Through these advancements, EcN emerges as a practical platform for next-generation biomanufacturing and precision medicine. Full article