Progress in Molecular Biology and Translational Science最新文献

{"title":"Artificial Intelligence (AI) in microbiome-directed biotherapeutics development.","authors":"Debarshi Roy, Soumita Banerjee, Alisha Ansari, Sourav Goswami, Nidhi P Raval, Kaustav Adhikary, Tarini Shankar Ghosh","doi":"10.1016/bs.pmbts.2026.01.005","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2026.01.005","url":null,"abstract":"<p><p>The human gut is home to trillions of microbial lineages, which collectively along with their genomic content form the human microbiome. This community of microbes is crucial to maintaining our health. Imbalance in this community, a state referred to as 'Dysbiosis', has been linked to many diseases. A large domain of research in the human microbiome thus focuses on identifying and administering microbes to restore this imbalance and potentially ameliorate diseases linked to the gut microbiome. These 'microbial medicines', known as live biotherapeutics, are basically living organisms, such as novel types of probiotics or specifically designed groups of bacteria to enhance health. A significant challenge in this context is discovering the right set of microbes. Variability in the baseline gut microbiome even across normal individuals based on demographic factors and context-dependent behavior of specific microbes and strain-specific variations are amongst the various factors that make the microbiome highly individual-specific, resulting in highly personalized responses to different therapeutics. In this, advanced artificial intelligence (AI) derived tools like, Machine Learning (ML) and Deep Learning (DL), can potentially provide major breakthroughs, by facilitating complex analysis of massive amount of microbiome and host OMICs. In this chapter, we discuss ways in which AI can be leveraged to identify patterns \"signatures\", in microbiome data can facilitate microbiome-derived diagnostics and therapeutics. Using examples, we explore how AI-based models can also look at the complex interactions between microbes and our bodies to discover new, promising bacteria that could be turned into \"Live Biotherapeutic Products\" (LBPs). This chapter will cover the primary ways of how AI is being utilized, the challenges we still face (such as the need for improved data), and the promising future of using AI to develop a new generation of microbiome-based medicines.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"220 ","pages":"87-102"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146229567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancements in technology for developing recombinant live biotherapeutics.","authors":"Jyoti Verma, Deepjyoti Paul","doi":"10.1016/bs.pmbts.2026.01.006","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2026.01.006","url":null,"abstract":"<p><p>There is a growing recognition of the critical role microbes play in human health, with increasing evidence that engineered live biotherapeutics can target disease mechanisms directly. This chapter reviews recent advances in the development of recombinant live biotherapeutics (rLBPs), which include genetically and metabolically engineered microbial species designed to restore microbial balance, modulate immunity, and treat specific diseases through local action or gut-body axis interactions. Leveraging synthetic biology, genetic engineering, multi-omics, and artificial intelligence/machine learning (AI/ML) approaches, rLBPs are being designed for greater efficacy, regulatory acceptance, and clinical translation. While early studies show promising therapeutic potential, significant challenges remain in scalability, safety, and clinical application. This chapter highlights both the opportunities and hurdles in advancing rLBPs, emphasizing the need for continued innovation, rigorous clinical evaluation, and translational strategies to establish their role as next-generation therapeutics in human health.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"220 ","pages":"139-174"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146229597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recombinant live biotherapeutics and synthetic biology: Recent advancement and perspective.","authors":"Karan Murjani, Dharmisha Solanki, Vijai Singh","doi":"10.1016/bs.pmbts.2026.01.004","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2026.01.004","url":null,"abstract":"<p><p>The human gut microbiota is complex environment of diverse microbes that constitutes a key factor in health, immune responses, balance between the microbial community, metabolism, and prevention of diseases. Live biotherapeutic products (LBPs) are engineered live microorganisms that are being used to treat different diseases. LBPs have emerged as promising therapy for the treatment of different human diseases, which include metabolic disorders, pathogenic infections, inflammatory bowel disease (IBD), and cancer overcoming the traditional use of probiotics. Current progress in synthetic biology and genetic engineering have enabled the precise modifications of microbes, which leads to the targeted modulation of interactions with host-microbiome, disease pathways, and immune responses. This chapter highlights the principle of LBPs, interaction between host and its immune response, delivery mechanism and strategy of colonization and applications of LBPs. Key role of synthetic biology in development of LBPs is also discussed. The application of LBPs into clinical use leads to the introduction of safety and regulatory considerations. The delivery of LBPs can be regulated by introducing the biocontainment strategy into the microbes. Looking forward, synergistic engineering methods, personalized microbial consortia, computational biology tools for design of genetic circuits may serve as the foundation for further improvement in the LBPs with the future potential.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"220 ","pages":"65-86"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146228982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The human reproductive tract microbiome: A novel source of live biotherapeutics.","authors":"Lekshmi Narendrakumar, Proxima Dhiman, Bhabatosh Das","doi":"10.1016/bs.pmbts.2026.01.027","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2026.01.027","url":null,"abstract":"<p><p>Live biotherapeutics which are live microorganisms with clinically validated therapeutic benefits are rapidly emerging as innovative interventions for a broad spectrum of health disorders. The human reproductive tract, particularly the female vagina is home to specific microbial community that play a vital role in maintaining mucosal immunity, preventing pathogen colonization and supporting successful pregnancy outcomes. Disruption to this microbial balance have been strongly associated with conditions such as bacterial vaginosis (BV), sexually transmitted infections (STI), infertility and pregnancy complications such as pre-term birth. Given the adverse effects of conventional pharmaceutical treatments, microbiome based therapeutic strategies are gaining increasing popularity as safer and more sustainable alternatives. Recent advancements in synthetic biology, genetic engineering and microbiome science have enabled the development of next generation live biotherapeutics that go beyond traditional probiotics which are intended for only maintaining general health. This chapter explores the human reproductive tract microbiome as a novel and promising source of live biotherapeutics candidates. We examine the composition and functional potential of microbial communities within the reproductive tract, the mechanisms by which they interact with the host, and the emerging evidence supporting the therapeutic applications of vaginally isolated microorganisms. Additionally, we highlight recent advancements in research focused on reproductive tract microbiome, strategies of mining live biotherapeutic product (LBP) candidates, and enlist few potential vaginal origin-LBPs and their associated studies. In addition, this chapter briefly introduces emerging strategies aimed at addressing reproductive health challenges such as vaginal microbiome transplantation (VMT) as innovative tool for addressing persistent challenges in reproductive health.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"220 ","pages":"267-303"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146229208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Live biotherapeutics: Emerging trends and future directions in microbial therapy.","authors":"Bharti Kandiyal, Manjari Gupta, Bhabatosh Das","doi":"10.1016/bs.pmbts.2025.12.001","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2025.12.001","url":null,"abstract":"<p><p>Live Biotherapeutic Products (LBPs) represent a promising and rapidly advancing class of therapeutics that harness live microorganisms to prevent, treat, or manage a wide spectrum of health disorders. Distinct from traditional probiotics, prebiotics, and synbiotics, LBPs are rigorously developed and regulated as medicinal products with defined compositions, mechanisms of action, and clinical indications. Looking ahead, the therapeutic potential of LBPs is expanding well beyond gastrointestinal disorders, with promising applications in areas such as metabolic, neurological, and immune-mediated diseases. Their integration into precision medicine frameworks holds significant promise for shaping the future of public health. This chapter provides an overview of currently available LBPs, their mode of actions, clinical applications, and the regulatory frameworks that distinguish them from other microbial-based therapies. It also highlights the growing diversity of LBPs from single-strain products to engineered microbial communities and natural formulations, emphasizing their unique clinical value and increasingly advanced mechanisms of action. The clinical development of LBPs faces key challenges, including strain selection, complex manufacturing, viability issue and safety concerns in vulnerable populations with comorbidities, and navigating evolving regulatory frameworks. Advances in synthetic biology, CRISPR genome editing, and multi-omics are transforming LBP design, enabling more precise and personalized therapies. The evolving LBP landscape with key industry players, clinical trials, and strategic partnerships offers critical insights into the innovation and commercialization driving this dynamic field.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"220 ","pages":"1-35"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146229609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Explainable artificial intelligence for multi-omics data.","authors":"Sudipto Bhattacharjee","doi":"10.1016/bs.pmbts.2026.01.020","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2026.01.020","url":null,"abstract":"<p><p>The integration of multiple omics, known as multi-omics, is growing rapidly for developing machine learning (ML) models for biomedical predictions due to the recent advent in next-generation sequencing, clinical investigations, and computing technologies, along with deep learning models for handling high-dimensional features. The multi-omics data allows the models to find complex patterns from the complementary aspects of the data. But, the large number of features in multi-omics data and the black-box nature of ML models induce a lack of interpretability, which can be tackled using eXplainable Artificial Intelligence (XAI) approaches. XAI provides explanations to the model predictions, which impart transparency and a sense of trustworthiness. This chapter discusses the different XAI algorithms and XAI models for multi-omics-based biomedical prediction tasks. In summary, the multi-omics XAI models are crucial for biomedical prediction tasks as multiple omics provide a holistic understanding of the biomedical processes, and XAI imparts interpretability to the ML-based predictions.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"221 ","pages":"421-452"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147693352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recombinant live biotherapeutics against chronic metabolic diseases: Challenges and opportunities.","authors":"Prajwal Swamy, Lakhwinder Singh, Priya Sehrawat, Dinesh Mahajan","doi":"10.1016/bs.pmbts.2026.01.008","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2026.01.008","url":null,"abstract":"<p><p>Chronic metabolic diseases (CMDs) such as obesity, type 2 Diabetes mellitus (T2DM), metabolic dysfunction-associated steatotic liver disease (MASLD), and cardiovascular diseases (CVDs) represent an escalating global health crisis. The etiology and pathophysiology of CMDs are linked to persistent metabolic, inflammatory, and gut microbiome dysfunctions. Recombinant Live Biotherapeutic Products (rLBPs) are engineered microbes designed to deliver targeted metabolic, anti-inflammatory, or hormonal effects in situ, offering a promising alternative to conventional therapies. The development of the rLBPs is expected to bring a paradigm shift in the clinical management of chronic diseases. This chapter provides an overview of rLBPs by highlighting seminal examples of rLBPs, which are in the early phase of development for CMDs. It also deliberates on existing scientific, technical and regulatory challenges along with potential opportunities associated with the development of rLBPs.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"220 ","pages":"209-227"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146228976","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bacteriophage based live biotherapeutics: A novel approach to tackle drug resistant infectious diseases.","authors":"Kajal Kamboj, Bhabatosh Das, Christophe Possoz","doi":"10.1016/bs.pmbts.2026.01.007","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2026.01.007","url":null,"abstract":"<p><p>The global rise of antimicrobial resistance (AMR) presents a critical threat to public health, with multidrug-resistant (MDR) bacterial infections rendering conventional antibiotic therapies increasingly ineffective. In this context, bacteriophage-based live biotherapeutics have emerged as a promising alternative or adjunct to traditional antibiotics. Bacteriophages, viruses that selectively infect and lyse bacteria, offer a unique therapeutic potential due to their specificity, self-amplification at the site of infection, and ability to disrupt biofilms. These phages offer a range of strategies to combat resistant infections, from traditional phage therapy to advanced approaches such as genetically engineered phages, phage-derived enzymes, and phage-antibiotic combinations. Understanding the mechanisms by which bacteriophages identify and destroy their bacterial hosts not only enhances our knowledge of their therapeutic potential but also supports the development of more effective treatments. Their high specificity allows targeted bacterial clearance with minimal impact on the normal microbiota. In addition, phages can adapt to bacterial mutations, making them a dynamic tool in the fight against resistance. Evidence from clinical trials further reinforces their efficacy in real-world healthcare settings, validating their role as viable biotherapeutics. Together, these advantages position bacteriophages as a powerful and adaptable tool in the global fight against AMR.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"220 ","pages":"247-265"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146229584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Introduction to artificial intelligence in multi-omics analysis.","authors":"Arpan Saha Mondal, Rajat Kumar Pal, Sudipto Saha","doi":"10.1016/bs.pmbts.2026.01.022","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2026.01.022","url":null,"abstract":"<p><p>Multi-omics refers to various high-throughput datasets, including genomics, transcriptomics (Bulk, single-cell, spatial), proteomics, and metabolomics, which are used to understand complex biological systems at multiple molecular levels. This chapter focuses on different open-source tools, corresponding databases, and standardized bioinformatics pipelines for each omics data analysis. It describes how different machine learning algorithms, such as supervised, unsupervised, and reinforcement learning approaches, are employed to extract meaningful features for predicting disease phenotype and potential biomarkers. Furthermore, this chapter discusses the challenges with omics data analysis using machine learning algorithms and examines different strategies for integrating the multi-omics dataset with machine learning methods. It also described various AI-based tools and frameworks that can be employed to analyze multi-omics datasets. The chapter concludes with current studies and future directions of analyzing omics datasets using artificial intelligence techniques.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"221 ","pages":"1-42"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147693355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Live biotherapeutics in the clinic: Regulatory pathways, market dynamics, and future trends.","authors":"Bhabatosh Das","doi":"10.1016/bs.pmbts.2026.01.029","DOIUrl":"https://doi.org/10.1016/bs.pmbts.2026.01.029","url":null,"abstract":"<p><p>Live Biotherapeutic Products (LBPs), as defined by the U.S. Food and Drug Administration, are biological products containing live microorganisms intended for the prevention, treatment, or cure of human disease. Distinct from vaccines, their therapeutic effects derive from the biological activity of the living organism itself, including intrinsic functions and, where applicable, metabolites produced in situ. LBPs may originate from human or environmental sources or be rationally designed and are developed, manufactured, and regulated as drugs or biologics for clinical use. Once confined to experimental research, LBPs are now transitioning into approved therapeutics. The approvals of Rebyota and Vowst for recurrent Clostridioides difficile infection mark a pivotal milestone, establishing LBPs as a new therapeutic class. Although the global LBP market currently remains in the tens to low hundreds of millions of U.S. dollars, it is projected to grow at compound annual rates of approximately 13-25 %, with estimates ranging from USD 400 million to 2.6 billion by 2030-2034. Emerging recombinant LBPs further expand this paradigm, enabling enzymatic and peptide drug synthesis and precision delivery platforms. In parallel, regulatory frameworks are evolving, with both the FDA and EMA defining pathways that emphasize quality control, donor sourcing, potency, biosafety, and environmental risk assessment, particularly for genetically modified organisms. Commercial opportunities are driven by unmet needs in gastrointestinal, immune, and metabolic disorders, with potential extension into oncology. Progress, however, is tempered by manufacturing complexity, regulatory burden, reimbursement challenges, public perception, and incomplete mechanistic understanding. Despite these hurdles, the future is compelling, marked by expanding indications, engineered strains, standardized consortia, scalable manufacturing, regulatory harmonization, and accelerating investment.</p>","PeriodicalId":49280,"journal":{"name":"Progress in Molecular Biology and Translational Science","volume":"220 ","pages":"405-416"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146229604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}