Advances in synthetic biology have enabled the development of tumor-targeted live bacterial therapeutics. In a recent study published in Nature, Redenti et al. engineered Escherichia coli Nissle 1917(EcNcΔlon/ΔompT/LLO+ nAg), which exploits the advantages of living medicines to deliver arrays of tumor-specific neoantigenic epitope in optimal environments, thereby providing a novel strategy for developing effective and durable cancer immunotherapies.
MicroRNAs (miRNAs) are short, non-coding RNAs that play gene expression regulatory roles in eukaryotes. MiRNAs are also released in body fluids, and in the intestine, they are found in the lumen and feces. Here, together with exogenous dietary-derived miRNAs, they constitute the fecal miRNome. Several miRNAs were identified in the feces of healthy adults, including, as shown here, core miRNAs hsa-miR-21-5p and hsa-miR-1246. These miRNAs are important for intestinal homeostasis. Recent evidence suggests that miRNAs may interact with gut bacteria. This represents a new avenue to understand host-bacteria crosstalk in the gut and its role in health and disease. This review provides a comprehensive overview of current knowledge on fecal miRNAs, their representation across individuals, and their effects on the gut microbiota. It also discusses existing evidence on potential mechanisms of uptake and interaction with bacterial genomes, drawing from knowledge of prokaryotic small RNAs (sRNAs) regulation of gene expression. Finally, we review in silico and experimental approaches for profiling miRNA-mRNA interactions in bacterial species, highlighting challenges in target validation. This work emphasizes the need for further research into host miRNA-bacterial interactions to better understand their regulatory roles in the gut ecosystem and support their exploitation for disease prevention and treatment.
Microbial communities inhabiting various body sites play critical roles in the initiation, progression, and treatment of cancer. The gut microbiota, a highly diverse microbial ecosystem, interacts with immune cells to modulate inflammation and immune surveillance, influencing cancer risk and therapeutic outcomes. Local tissue microbiota may impact the transition from premalignant states to malignancy. Characterization of the intratumoral microbiota increasingly reveals distinct microbiomes that may influence tumor growth, immune responses, and treatment efficacy. Various bacteria species have been reported to modulate cancer therapies through mechanisms such as altering drug metabolism and shaping the tumor microenvironment (TME). For instance, gut or intratumoral bacterial enzymatic activity can convert prodrugs into active forms, enhancing therapeutic effects or, conversely, inactivating small-molecule chemotherapeutics. Specific bacterial species have also been linked to improved responses to immunotherapy, underscoring the microbiome’s role in treatment outcomes. Furthermore, unique microbial signatures in cancer patients, compared with healthy individuals, demonstrate the diagnostic potential of microbiota. Beyond the gut, tumor-associated and local microbiomes also affect therapy by influencing inflammation, tumor progression, and drug resistance. This review explores the multifaceted relationships between microbiomes and cancer, focusing on their roles in modulating the TME, immune activation, and treatment efficacy. The diagnostic and therapeutic potential of bacterial members of microbiota represents a promising avenue for advancing precision oncology and improving patient outcomes. By leveraging microbial biomarkers and interventions, new strategies can be developed to optimize cancer diagnosis and treatment.