2025年至今益生菌与西药、中药煎煮液或复方联用治疗疾病模型

The escalating global burden of cancer has driven research into leveraging the gut microbiome for innovative therapies, with probiotics emerging as key adjuncts that enhance immune responses, reduce inflammation, and inhibit tumor growth via mechanisms like short-chain fatty acid (SCFA) production and carcinogen detoxification. However, their efficacy is limited by gastrointestinal (GI) degradation, often resulting in > 90% viability loss. This review synthesizes recent advances in nanocarrier-based delivery systems to address these challenges, emphasizing novel strategies that achieve > 90% survival rates in simulated gut conditions and enable precise targeting to the colon or tumor sites. Key innovations include pH-responsive liposomes, polymeric nanoparticles, nanoemulsions, biomimetic exosomes, microfluidic encapsulation, and three-dimensional (3D)-bioprinted matrices, which facilitate synbiotic co-delivery, controlled release, and personalized formulations to amplify anti-cancer effects such as apoptosis induction and immunotherapy synergy. Strain-specific optimizations—e.g., chitosan nanoparticles for Lactobacillus rhamnosus (92–97% encapsulation) or liposomes for Bifidobacterium longum—highlight compatibility-driven enhancements based on cell wall properties and metabolic needs, drawn from 2023 to 2025 studies. Major findings from recent clinical trials (2023–2025) demonstrate translational promise: chitosan-coated Poly(Lactic-co-Glycolic Acid) nanoparticles yielded 63% remission in ulcerative colitis (NCT05878821), liposomal probiotics reduced mucositis by 65% in breast cancer, and folate-targeted PEGylated Poly(Lactic-co-Glycolic Acid) (PEG-PLGA) systems boosted pathological responses by 42% in colorectal cancer. Despite these breakthroughs, challenges in good manufacturing practice (GMP) scaling, biocompatibility, regulatory classification (e.g., Food and Drug Administration (FDA) / European Medicines Agency (EMA) ambiguities), and cost (average development: US$296 million) impede commercialization. By focusing on 2017–2025 preclinical and clinical evidence, this review underscores nanocarriers’ novelty in transforming probiotics into precision tools for microbiome-informed cancer therapy, advocating for larger trials to accelerate clinical adoption.

Probiotic bacteria have emerged as versatile and biocompatible platforms for drug delivery, offering a safe and efficient means of targeting diseased tissues. Advances in nanotechnology and genetic engineering have significantly expanded the potential of probiotic bacteria in precision medicine, enabling the delivery of therapeutics, proteins, antigens, and nanoparticles (NPs). This review explores diverse strategies for utilizing probiotics as drug carriers, including bacterial ghosts, outer membrane vesicles (OMVs), surface membrane proteins, and spores, focusing on applications in cancer therapy, vaccine development, and gastrointestinal disorders. We primarily focus on the strategy of integrating probiotics into nanoparticle-based delivery systems, examining key design considerations, such as functionalization strategies, targeting efficiency, and biocompatibility. Additionally, we highlight genetic engineering approaches, including plasmid-based expression and genomic integration, that enhance the probiotic functionality for targeted therapy, immunomodulation, and nanoparticle-mediated drug delivery. Further advancements in synthetic biology, biohybrid coatings, and stimulus-responsive mechanisms that could optimize the therapeutic efficacy of these systems will be discussed briefly. This review comprehensively analyzes recent progress and the outlook for harnessing probiotics for next-generation targeted drug delivery applications.

The human gut microbiome plays a crucial role in digestion, immunity and overall health. Recent advancements in microbiome engineering have led to the development of engineered probiotics, offering new therapeutic possibilities for various health conditions. Engineered probiotics can enhance gut colonization, regulate metabolic functions and deliver targeted bioactive compounds. Additionally, advancements in CRISPR-based gene editing, synthetic biology and artificial intelligence are revolutionizing microbiome research, enabling precision medicine approaches for disease prevention and treatment. Probiotics are being tailored to combat gastrointestinal disorders, metabolic diseases and immune-related conditions while also influencing the gut-brain axis for potential neurological benefits. However, challenges related to safety, regulatory approval and public acceptance remain key barriers to widespread clinical application. Addressing these concerns through standardized protocols and rigorous clinical validation will be essential for integrating microbiome engineering into mainstream healthcare. As research progresses, next-generation probiotics hold immense potential in revolutionizing personalized medicine and microbiome-based therapeutics. This review explores current trends and future directions in probiotic-based microbiome engineering, focusing on strain selection, genetic modifications and innovative therapeutic applications. The gut microbiome is crucial for digestion, metabolism, immunity and neurological health. Probiotics support gut health by aiding digestion, boosting immunity and preventing infections. Advance techniques also used for probiotic engineering includes next-generation probiotics, genetically engineered strains and precision probiotics. Technologies like metagenomics, metabolomics, AI and machine learning enhance probiotic development. Various challenges also exist during probiotic engineering includes strain stability, colonization efficiency, regulatory concerns and the need for personalized approaches. The gut microbiome is crucial for digestion, metabolism, immunity and neurological health. Probiotics support gut health by aiding digestion, boosting immunity and preventing infections. Advance techniques also used for probiotic engineering includes next-generation probiotics, genetically engineered strains and precision probiotics. Technologies like metagenomics, metabolomics, AI and machine learning enhance probiotic development. Various challenges also exist during probiotic engineering includes strain stability, colonization efficiency, regulatory concerns and the need for personalized approaches.

Engineered probiotics represent a cutting-edge therapy in intestinal inflammatory disease (IBD). Genetically modified bacteria have provided a new strategy to release therapeutically operative molecules in the intestine and have grown into promising new therapies for IBD. Current IBD treatments, such as corticosteroids and immunosuppressants, are associated with relevant side effects and a significant proportion of patients are dependent on these therapies, thus exposing them to the risk of relevant long-term side effects. Discovering new and effective therapeutic strategies is a worldwide goal in this research field and engineered probiotics could potentially provide a viable solution. This review aims at describing the proceeding of bacterial engineering and how genetically modified probiotics may represent a promising new biotechnological approach in IBD treatment.

… have achieved substantial commercial success, with the global market reaching approximately US$86 billion in 2025 (ref. 16). Although widely used, their efficacy and safety remain …

Traditional probiotics such as Lactobacillus and Bifidobacterium have long supported gut health, but recent advances in microbiome research have introduced next‐generation probiotics (NGPs) such as Akkermansia muciniphila and Faecalibacterium prausnitzii. These strains are associated with more specific functions, including mucin degradation, butyrate production, enhanced gut barrier integrity, immune regulation, and modulation of host metabolism and inflammation. Unlike conventional probiotics, which mainly promote general digestive balance, NGPs demonstrate targeted mechanisms that link them to metabolic, inflammatory, and even neurological conditions. This review provides a critical comparison of traditional and NGPs, highlighting mechanistic distinctions and functional advancements. It also explores recent innovations in synthetic biology, including programmable gene circuits, and examines how artificial intelligence and microbiome profiling are paving the way toward personalized probiotic therapies, though widespread clinical application remains in its early stages. Key safety, regulatory, and translational challenges are also addressed, outlining barriers to clinical adoption. By integrating omics technologies and precision medicine, NGPs represent a promising frontier with the potential to advance personalized nutrition and therapeutic strategies.

… In Europe, fragmented regulations hinder market growth, while the US and Russia face challenges in evaluating probiotics as live biotherapeutics under strict safety and efficacy criteria. …

Antimicrobial resistance (AMR) has become a major One Health concern, affecting the interconnected microbial systems shared by humans, animals, and the environment. Decades of antibiotic-driven control have disturbed ecological stability and contributed to the expansion of the global resistome. This Perspective approaches AMR mitigation through an ecological restoration lens, outlining a three-part strategy that brings together probiotic therapeutics, microbiome-focused public awareness, and integrated surveillance. Probiotics are presented as biologically compatible tools that promote microbial stability through competitive niche occupation, immune support, and environmental biodegradation, thereby reducing selective pressures that favor resistance. In parallel, strengthening microbiome literacy can guide behavioral choices that support stewardship and reduce unnecessary antimicrobial use. The proposed One Health Microbiome Intelligence Framework (OH-MIF) adds a data-driven layer by linking genomic, clinical, agricultural, and environmental information through AI-enabled analytics. Together, these components form an adaptable system that shifts AMR management from reactive dependence on antibiotics toward a more resilient, coexistence-based approach. By aligning ecological interventions with education and policy intelligence, this Perspective positions microbial balance as a practical foundation for sustainable AMR control within broader planetary health goals.

Background/Objectives: Advances in molecular biology, genetics, and microbiome research have significantly expanded our understanding of probiotic microorganisms and their interactions with human health, stimulating the development of both traditional and next-generation probiotic products. Although probiotics are widely used and generally considered safe for healthy individuals, accumulating evidence indicates that their safety profile varies significantly depending on the strain, dose, host, and context, with rare but clinically significant adverse events reported in vulnerable populations. Methods: This review summarizes current knowledge on the efficacy and safety of probiotics, analyzes limitations in clinical safety reporting, and compares regulatory frameworks governing the use of probiotics as dietary supplements, medicinal products, and live biotherapeutics. Particular attention is given to new genomic and computational approaches to safety assessment. Conclusions: Overall, the review emphasizes the need for coordinated regulation, rigorous clinical evidence, and integrated, modern safety assessment strategies to support the responsible expansion of probiotic use.

A substantial body of research indicates that the gut microbiota exerts a profound influence on host health. The purpose of this work was to characterize selected, most promising, well-known next-generation probiotics (NGPs) and review the potential applications of the bacteria in food technology. The isolation of gut bacteria with significant health benefits has led to the emergence of NGPs. In contrast to traditional probiotics, these originate directly from the gut microbiota, thereby ensuring their optimal adaptation to the intestinal ecosystem. NGPs exert their effects on the host organism through a variety of mechanisms, including the synthesis of bioactive compounds, modulation of the gut microbiota, and metabolism of substances provided by the host. Several bacterial species have been identified as potential candidates for NGPs, including Akkermansia muciniphila, Faecalibacterium prausnitzii, Bacteroides thetaiotaomicron, Christensenella minuta, and many others. These bacteria have demonstrated the capacity to exert beneficial effects, including the reduction of obesity, type 2 diabetes, metabolic disorders, and even cancers. The greatest limitation to their commercialization is their lack of oxygen tolerance, which presents challenges not only for research but also for their potential application in food. The most optimal approach for their application in food appears to be microencapsulation. Further research is required to establish the safety of NGP supplementation and to protect them from environmental conditions.

… Digestive Health: Probiotics have been extensively studied for their efficacy in preventing and therapy of intestinal disorders, including irritable bowel syndrome (IBS), inflammatory …