bims-livmat 2025-08-10 papers

Adv Drug Deliv Rev. 2025 Aug 05. pii: S0169-409X(25)00148-6. [Epub ahead of print] 115663

Bioinspired approaches to encapsulate and deliver bacterial live biotherapeutic products.

Bacteria-based therapies such as live biotherapeutic products (LBPs) allow for the in situ production of bioactive and therapeutic compounds, offering immense potential in the treatment of numerous diseases, including colitis, cancer, and metabolic diseases. While promising, LBPs face numerous delivery barriers that limit their translational potential. Many of these challenges stem from the specific requirements of delivering living bacteria, necessitating delivery systems with distinctive features beyond traditional drug delivery approaches. By taking inspiration from natural biological systems such as bacterial membranes, capsules, and biofilms, researchers can build upon fundamental biological insights combined with advances in materials science, chemical biology, and bioengineering to develop next-generation LBP delivery systems. In this review, we will cover the current progress in bacterial LBPs and major barriers to their delivery. We will then discuss in depth the different bioinspired LBP delivery systems that have been developed and highlight challenges that must be addressed for this nascent field to advance and achieve widespread clinical translation.

Keywords: Bacteria; Biofilms; Bioinspired materials; Coatings; Drug delivery; Dysbiosis; Inflammatory bowel diseases; Live biotherapeutic products; Microbiome; Nanomedicine; Nanotechnology; Probiotics; Synthetic biology

DOI: https://doi.org/10.1016/j.addr.2025.115663

Arch Microbiol. 2025 Aug 06. 207(9): 213

Therapeutic engineering of the gut microbiome using synthetic biology and metabolic tools: a comprehensive review with E. coli Nissle 1917 as a model case study.

Soumok Sadhu, Tania Paul, Nishant Yadav.

The human gut microbiome significantly influences host physiology, metabolism, and immune function. The engineering of microbial communities represents a significant advancement in contemporary biotechnology. Conventional methods, including Fecal Microbiota Transplantation (FMT) and probiotic administration, exhibit limitations in efficacy and raise safety and reproducibility concerns; however, they have shown potential therapeutic benefits. Recent progress in biocatalysis and metabolic engineering has led to the development of genetically tractable gut bacteria for targeted therapeutic purposes, particularly in the last five years. This chapter offers an overview of the development of microbiota-based interventions, from early recombinant probiotics to advanced synthetic biology platforms that can detect and respond to host and environmental signals. This analysis examines the mechanistic aspects of enzyme engineering, including improvements in metabolic pathways for the production of short-chain fatty acids, the breakdown of harmful metabolites, and the biosynthesis of immunomodulatory compounds. This review also examines conditions including inflammatory bowel disease, metabolic dysfunction, and colorectal cancer, highlighting microbial production systems pertinent to gut health. The engineering of Escherichia coli Nissle 1917 to produce phenylalanine ammonia-lyase (PAL) and L-amino acid deaminase (LAAD) represents a significant advancement in gut-based metabolic intervention for patients with phenylketonuria (PKU) by degrading excess phenylalanine. Recent studies offer peer-reviewed evidence supporting the translational potential of these inventions, as demonstrated through figures and tables highlighting engineered metabolic circuits, therapeutic outputs, and strain performance metrics. This combination of developments demonstrates the potential of synthetic microbiome engineering to provide precision biotherapeutics for various gut-related conditions.

Keywords: Escherichia coli Nissle 1917; Fecal microbiota transplantation; Gut microbiome; Metabolic engineering; Short-chain fatty acids

DOI: https://doi.org/10.1007/s00203-025-04417-w

Adv Mater. 2025 Aug 05. e08754

A Microalgae-Probiotic-Nanozyme Robot for Alleviating Intestinal Inflammation and Microbiota Dysbiosis.

Jinjie Hou, Mengliu Zhao, Anlai Zou, Xiaoxue Zhu, Ruijie Fu, Yunlei Xianyu.

Inflammatory bowel disease is chronic gastrointestinal disorder characterized by persistent intestinal inflammation, which can lead to severe complications such as impaired intestinal barrier function and dysbiosis. Conventional therapies have challenges such as oxidative stress and insufficient intestinal colonization that hinder the treatment efficacy. Therapeutic strategies based on micro-nano robotic delivery are promising to address the limitations of current treatments by enabling precise targeting, enhancing bioavailability, and improving therapeutic outcomes. Herein, an orally administered micro-nano robot is developed utilizing Spirulina platensis as a carrier for nanozyme-armed probiotic Lactobacillus plantarum (SP@LP@AuCe) to enhance the efficacy of oral probiotics and nanomedicine in treating intestinal diseases. SP@LP@AuCe exhibits strong fluorescence imaging capability due to its chlorophyll-rich content, allowing for non-invasive and real-time monitoring following oral administration. The helical structure of Spirulina platensis facilitates entrapment in intestinal villi that enhances intestinal retention. Importantly, SP@LP@AuCe scavenges reactive oxygen species and modulates inflammatory responses, thereby alleviating intestinal inflammation, improving bacterial viability, and restoring the balance of intestinal microbiota. This strategy integrates microalgae, probiotics, and nanozymes within a micro-nano robotic framework, presenting a promising approach to enhancing drug bioavailability and exerting potent anti-inflammatory effects in the treatment of intestinal diseases.

Keywords: inflammatory bowel disease; microalgae; micro‐nano robot; nanozyme; probiotic

DOI: https://doi.org/10.1002/adma.202508754

Microbiome. 2025 Aug 04. 13(1): 180

Lactiplantibacillus plantarum attenuate gossypol-induced hepatic lipotoxicity by altering intestinal microbiota for enriching microbial tryptophan metabolites in Nile tilapia (Oreochromis niloticus).

Fei-Fei Ding, Nan-Nan Zhou, Yue-Jian Mao, Jing Yang, Samwel M Limbu, Jorge Galindo-Villegas, Zhen-Yu Du, Mei-Ling Zhang.

BACKGROUND: Free fatty acids (FFAs) are the main cause of fatty liver disease, which can be alleviated by modulation of intestinal microbiota. Lactiplantibacillus plantarum plays a key role in maintaining liver health, but the underlying mechanism remains unclear.
RESULTS: Here, a strain affiliated to Lactiplantibacillus plantarum was isolated from the intestine of Nile tilapia (Oreochromis niloticus). We used a gossypol-induced fatty liver disease model, which only increased the FFAs level in liver, to investigate the effectiveness of L. plantarum (YC17) in alleviating FFAs-induced lipotoxicity liver injury. We found that dietary gossypol (GOS) induced a significant increase of FFAs in liver, resulting in lipotoxicity in Nile tilapia compared to control. L. plantarum YC17 supplementation reduced FFAs content by restoring esterification process, and then relieved liver injury. Addition of L. plantarum YC17 effectively increased the abundances of Lactobacillus, Clostridium and Cetobacterium in fish intestine, as well as serum levels of the microbial tryptophan metabolites, notably indole-3-propionic acid (IPA) and indole-3-acetic acid (IAA). The addition of L. plantarum YC17 significantly inhibited P53 signaling pathway and up-regulated the expression of FFAs esterification genes. In vitro experiments demonstrated that IPA inhibited P53 through ubiquitination and enhanced FFAs esterification in an aryl hydrocarbon receptor (Ahr) dependent manner.
CONCLUSION: The gut microbiota-derived tryptophan metabolites (IPA and IAA) alleviated FFAs induced lipotoxic liver injury by activating Ahr, which promoted P53 ubiquitination, leading to the enhanced FFAs esterification. Our findings demonstrated that gut microbial metabolites alleviated lipotoxicity by promoting the esterification of FFAs in the liver, offering new insights into the study of probiotics and microbial tryptophan metabolites in fatty liver disease. Video Abstract.

Keywords: Lactiplantibacillus plantarum ; Free fatty acids; Gut microbiota; Lipotoxicity; Microbial tryptophan metabolites

DOI: https://doi.org/10.1186/s40168-025-02172-0

Arch Microbiol. 2025 Aug 06. 207(9): 216

Paraprobiotics from Lactiplantibacillus plantarum and fungal β-glucan from Lignosus rhinocerus synergistically enhance macrophage activation in vitro.

Waraporn Chamnankit, Wankuson Chanasit, Monthon Lertworapreecha.

This study evaluated the immunomodulatory effects of paraprobiotics from Lactiplantibacillus plantarum TSUB-17 and β-glucan extracted from Lignosus rhinocerus mycelium using RAW 264.7 macrophages. β-glucan was produced under optimized conditions (31.5 °C, 13.5% potato powder, 13% glucose), yielding 44.7 g/L biomass with 33.60% β-glucan. NMR and FESEM confirmed its structural similarity to commercial β-glucan. β-glucan significantly reduced nitric oxide (NO) levels and proinflammatory cytokines (TNF-α, IL-6) while increasing anti-inflammatory markers IL-10 and TGF-β. Paraprobiotics strongly induced TNF-α and IL-6 but had limited anti-inflammatory effects. Co-treatment resulted in moderated proinflammatory and enhanced anti-inflammatory responses, with a synergistic increase in TGF-β. This is the first report of the synergistic immunomodulatory interaction between sonicated paraprobiotics and L. rhinocerus β-glucan. The results suggest potential applications in functional foods or therapeutic formulations to modulate inflammation and promote immune balance.

Keywords: Anti-Inflammatory cytokines; Cytokines production; Immunomodulatory; Proinflammatory cytokines; Tiger milk mushroom

DOI: https://doi.org/10.1007/s00203-025-04416-x