bims-livmat 2025-10-19 papers

Acta Biomater. 2025 Oct 11. pii: S1742-7061(25)00755-X. [Epub ahead of print]

Precision Therapeutics for Inflammatory Bowel Disease Using Engineered Probiotics:Strategies and Optimization.

Yutong Xue, Mingyang Hu, Sina Cha, Chenyu Xue, Na Dong.

The incidence of inflammatory bowel disease (IBD) has been increasing annually, evolving into a global health concern. Dysbiosis of the gut microbiota plays a crucial role in the pathogenesis of IBD. Probiotics, capable of modulating the gut microbiota, enhancing intestinal barrier function, and regulating mucosal immunity, have recently emerged as potential complementary or alternative therapy for IBD. However, traditional probiotics are limited by the functional singularity of strains and non-targeted mechanisms of action, thus resulting in unstable efficacy and inter-individual variability in clinical IBD intervention. In contrast, engineered probiotics, achieved through genetic modification and synthetic biology, have enabled microenvironment responsiveness and precise therapeutic targeting of IBD, thus demonstrating significant therapeutic effects in intestinal mucosal repair and immune modulation. This review summarizes the research progress of engineered probiotics in treating IBD, covering gene editing strategies of chassis strains, the multi-dimensional roles of microorganisms in IBD treatment, bioengineering modifications, optimization of delivery systems, and artificial intelligence-driven strain screening and design. STATEMENT OF SIGNIFICANCE: Engineered probiotics represent a frontier in inflammatory bowel disease (IBD) therapy. Through genetic modification and synthetic biology, these improved strains exhibit targeted reactivity to the intestinal pathological microenvironment, demonstrating potent mucosal repair and immunomodulation. This review summarizes the recent research on engineered probiotics, including chassis strain gene editing strategies, the multi-dimensional role of the gut microbiota in IBD therapy, bioengineering modifications, delivery system optimization, and artificial intelligence-driven strain screening and design. It emphasizes their potential in enhancing therapeutic precision, safety, and personalization, thereby offering improved technological avenues for IBD treatment and providing crucial insights for researchers and clinicians to accelerate therapeutic innovation.

Keywords: Probiotics; artificial intelligence; bioengineering; inflammatory bowel disease; living biotherapy

DOI: https://doi.org/10.1016/j.actbio.2025.10.012

World J Microbiol Biotechnol. 2025 Oct 13. 41(10): 373

Engineered Lactiplantibacillus plantarum and Levilactobacillus brevis utilizing ribonucleoprotein-mediated editing for inactivation of hemolysin gene.

Hea Joon Kim, Min Young Kwon, Seongbong Song, Seong Won Cheon, Hyo Jin Kim.

Lactiplantibacillus plantarum and Levilactobacillus brevis are widely used probiotics with significant potential as chassis organisms for probiotic engineering. However, their bioengineering remains underdeveloped compared to that of other probiotic bacteria due to the limited availability of genetic tools. Although CRISPR-Cas systems have shown promise for genome editing in Lactobacillus species, strain- or site-specific targeting challenges must be overcome to enhance their broader applicability. This study aimed to develop a novel editing system with reduced dependency on plasmids and antibiotics in L. plantarum WCFS1, L. plantarum SPC 72 - 1 and L. brevis SPC-SNU 70 - 2 using a Cas9-gRNA ribonucleoprotein (RNP) complex. Although the hlyIII gene has been annotated as a hemolysin-related gene in several Lactobacillus genomes, no functional hemolytic activity has been definitively demonstrated to date. In this study, hlyIII was selected as a target to evaluate genome editing efficiency and to assess its potential relevance to strain safety. To construct ΔhlyIII strains, the RNP complex targeting hlyIII was separately transformed with recombinase RecE/T and double-stranded donor DNA. As a result, ΔhlyIII mutants were obtained under optimized electroporation conditions. Sequencing analysis revealed a 50 bp deletion and the introduction of a stop codon in hlyIII across all mutant strains. The hemolytic activity test showed a reduction in free hemoglobin levels in the ΔhlyIII strains compared to the wild type: 27.0%, 74.3%, and 5.0% in L. plantarum WCFS1, L. plantarum SPC 72 - 1, and L. brevis SPC-SNU 70 - 2, respectively. These results suggest strain-dependent differences in hemolytic activity and indicate that inactivation of hlyIII may contribute to reduced hemolysis, although further validation is needed to clarify its functional role. In conclusion, the hlyIII gene was successfully edited in L. plantarum and L. brevis using Cas9-gRNA ribonucleoprotein-mediated editing, demonstrating the feasibility of this genome editing platform for application in probiotic strains.

Keywords: CRISPR/Cas9; Genome editing; Hemolysin; Lactic acid bacteria; Ribonucleoprotein

DOI: https://doi.org/10.1007/s11274-025-04598-y

Adv Drug Deliv Rev. 2025 Oct 15. pii: S0169-409X(25)00205-4. [Epub ahead of print] 115720

Microbiome-active drug delivery systems (MADDS): Leveraging microbial stimuli for controlled drug release.

Srinivas Kamath, Amin Ariaee, Amer Abdelhafez, Zarnab Asif, Nicole S L Chan, Kate Collins, Alexander Hunter, Paul Joyce.

The human microbiome comprises diverse microbial communities that inhabit tissues and biofluids throughout the body, including the gastrointestinal tract, lungs, vagina, and skin. These sites create dynamic microenvironments rich in enzymes, metabolites, and chemical gradients that act both as biological barriers and as localised targets for drug delivery. This review provides an overview of Microbiome-Active Drug Delivery Systems (MADDS), an emerging class of platforms that exploit microbial stimuli for site-specific therapeutic release. Unlike conventional systems that simply coexist with the microbiome, MADDS harness resident microbes and their metabolites to trigger drug activation, retention, or release. This enables spatially precise delivery of small molecules, biologics, and live biotherapeutic products (LBPs). Key strategies include enzyme-, environment-, metabolite-, biofilm-, and receptor-responsive designs, each tailored to microbial niches and applied across infectious, inflammatory, and metabolic disorders. However, challenges remain, including microbiome variability between individuals, regulatory uncertainty around hybrid biologic-material systems, and the need for scalable GMP-compliant manufacturing. This review therefore outlines the current approaches for engineering MADDS and the future steps required for clinical translation. By exploiting microbial cues for controlled drug release, MADDS offer a practical route to more targeted and patient-specific therapies.

Keywords: Biofilm; Drug formulation; Live biotherapeutic products; Localised release; Microbiota; Probiotic; Stimuli-responsive

DOI: https://doi.org/10.1016/j.addr.2025.115720

Acta Biomater. 2025 Oct 15. pii: S1742-7061(25)00770-6. [Epub ahead of print]

Virus-inspired nanocages potentiate glioblastoma sonochemotherapy via structure-function mimicry.

Xiaohang Liu, Jinyuan Ma, Yuhao Zhang, Yanling Lin, Li Li, E Chen, Xinhua Tian, Feng Wei, Xiaoning Lin.

Sonochemotherapy has emerged as a promising strategy for glioma treatment through synergistic therapeutic effects and reduced systemic toxicity. Nevertheless, clinical translation remains constrained by the hypoxic tumor microenvironment, antioxidant defense mechanism, inadequate tumor accumulation, and suboptimal cellular internalization. Inspired by the rabies virus, we engineered rabies virus glycopeptide-29 (RVG29)-anchored virus-like hollow mesoporous manganese oxide (vHMMn) nanocages co-encapsulating temozolomide (TMZ) and indocyanine green (ICG) (denoted as TI@vHMMnR) for amplified sonochemotherapy through hypoxia relief and glutathione (GSH) depletion. Following tumor accumulation via the enhanced permeability and retention (EPR) effect, TI@vHMMnR nanocages achieved rapid cellular entry through structural-functional mechanisms: Structurally, TI@vHMMnR mimics the rugged and uneven topography of virus's surfaces, thereby enabling spike-facilitated adhesion to tumor cells. Functionally, the interaction of RVG29 with nicotinic acetylcholine receptors (nAChRs) induces receptor-mediated endocytosis, which allows for efficient internalization. Under ultrasound (US) triggering, the nanocages could generate reactive oxygen species (ROS) to induce mitochondrial dysfunction. Meanwhile, the nanocages could catalytically convert endogenous hydrogen peroxide (H2O2) into oxygen to relieve tumor hypoxia to improve sonodynamic efficacy. Moreover, the nanocages could be efficiently biodegraded by intracellular overexpressed GSH inside tumor cells to result in the burst release of TMZ, thus inducing effective DNA double-strand breakage. More importantly, this depletion of GSH could weaken tumor cells' antioxidant defense mechanism to amplify the sonochemotherapy. Our rabies virus-inspired nanocages with structure-function mimicry could significantly improve the therapeutic efficiency through sonochemotherapy coupled with hypoxia relief and GSH exhaustion, offering a new avenue for Glioblastoma (GBM) therapy. STATEMENT OF SIGNIFICANCE: Glioblastoma (GBM) remains a lethal brain cancer with limited treatment efficacy due to hypoxic microenvironments, glutathione (GSH)-mediated antioxidant defenses, and poor blood-brain barrier (BBB) penetration. This work overcomes these barriers by engineering rabies virus-inspired manganese oxide nanocages (TI@vHMMnR) that co-deliver temozolomide and indocyanine green. The nanocages mimic viral surface topography and receptor-targeting mechanisms (RVG29-nAChR) to enhance tumor accumulation and cellular uptake. Crucially, they simultaneously relieve hypoxia via catalytic H2O2 decomposition and exhaust GSH to amplify ultrasound-triggered reactive oxygen species (ROS) generation. This dual microenvironment remodeling synergizes sonodynamic therapy with chemotherapy, achieving 95.2% tumor growth inhibition in orthotopic GBM models. The biomimetic nanoplatform offers a transformative strategy for precision glioblastoma therapy by integrating structural mimicry, self-amplifying ROS cascades, and spatiotemporally controlled drug release.

Keywords: GSH exhaustion; oxygen supply; sonochemotherapy; tumor microenvironment; virus-inspired

DOI: https://doi.org/10.1016/j.actbio.2025.10.025

Nutrients. 2025 Sep 24. pii: 3047. [Epub ahead of print]17(19):

Lactiplantibacillus plantarum as a Psychobiotic Strategy Targeting Parkinson's Disease: A Review and Mechanistic Insights.

Wu-Lin Chen, Fu-Sheng Deng, Ying-Chieh Tsai.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the pathological aggregation of α-synuclein (α-syn), the loss of dopaminergic neurons, and the appearance of both motor and non-motor symptoms. Emerging evidence suggests a bidirectional influence of the microbiota-gut-brain axis in PD pathogenesis, where gut dysbiosis contributes to increased intestinal barrier permeability, immune activation, chronic inflammation, oxidative stress, α-syn misfolding, and neurotransmitter imbalance. These findings are increasing interest in probiotics as microbiota-targeted interventions that restore intestinal and systemic homeostasis. Lactiplantibacillus plantarum, a probiotic species with remarkable environmental adaptability and genomic plasticity, has emerged as a promising candidate for PD management. Preclinical studies demonstrate that specific Lpb. plantarum strains, such as PS128 or CCFM405, can beneficially modulate gut microbial communities, reinforce barrier integrity, regulate bile acid metabolism, attenuate neuroinflammatory responses, and improve motor deficits in PD-like mice. In addition, Lpb. plantarum DP189 or SG5 interventions can significantly reduce α-syn aggregation in the brain via suppression of oxidative stress, modulation of neuroinflammatory responses, and activation of neurotrophic factors. Recent evidence even suggests that Lpb. plantarum-derived extracellular vesicles may possess anti-PD activity by influencing host gene expression, neuronal function, and immune modulation. Although robust clinical data are still limited, preliminary clinical trials indicate that supplementation with PS128 or certain Lpb. plantarum-contained consortiums can alleviate constipation, improve gastrointestinal function, reduce systemic inflammation, and even ameliorate motor symptoms when used alongside standard dopaminergic therapies. In this review, we provide an integrated overview of preclinical, clinical, and mechanistic insights, and evaluate the translational potential of Lpb. plantarum as a safe and diet-based strategy to target the microbiota-gut-brain axis in PD.

Keywords: Lactiplantibacillus plantarum; Parkinson’s disease; microbiota-gut–brain axis (MGBA); psychobiotics

DOI: https://doi.org/10.3390/nu17193047