The gut microbiome emerges as an integral component of precision medicine because of its signature variability among individuals and its plasticity, which enables personalized therapeutic interventions, especially when integrated with other multiomics data. This promise is further fueled by advances in next-generation sequencing and metabolomics, which allow in-depth high-precision profiling of microbiome communities, their genetic contents, and secreted chemistry. This knowledge has advanced our understanding of our microbial partners, their interaction with cellular targets, and their implication in human conditions such as inflammatory bowel disease (IBD). This explosion of microbiome data inspired the development of next-generation therapeutics for treating IBD that depend on manipulating the gut microbiome by diet modulation or using live products as therapeutics. The current landscape of artificial microbiome therapeutics is not limited to probiotics and fecal transplants but has expanded to include community consortia, engineered probiotics, and defined metabolites, bypassing several limitations that hindered rapid progress in this field such as safety and regulatory issues. More integrated research will reveal new therapeutic targets such as enzymes or receptors mediating interactions between microbiota-secreted molecules that drive or modulate diseases. With the shift toward precision medicine and the enhanced integration of host genetics and polymorphism in treatment regimes, the following key questions emerge: How can we effectively implement microbiomics to further personalize the treatment of diseases like IBD, leveraging proven and validated microbiome links? Can we modulate the microbiome to manage IBD by altering the host immune response? In this review, we discuss recent advances in understanding the mechanism underpinning the role of gut microbes in driving or preventing IBD. We highlight developed targeted approaches to reverse dysbiosis through precision editing of the microbiome. We analyze limitations and opportunities while defining the specific clinical niche for this innovative therapeutic modality for the treatment, prevention, and diagnosis of IBD and its potential implication in precision medicine.

Lung cancer remains the leading cause of cancer-related deaths worldwide, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of cases. Conventional therapies, including surgery, chemotherapy, and targeted treatments, often show limited efficacy, especially in advanced stages. Pulmonary drug delivery systems (PDDSs) have gained attention as an innovative approach for NSCLC management by enabling direct drug administration to the lungs. This method improves therapeutic outcomes while minimizing systemic side effects. Advances in nanotechnology have further enhanced the potential of inhalable chemotherapy, with nanoparticles offering notable benefits such as improved drug solubility, stability, and protection from premature degradation. Additionally, their small size and modifiable surfaces allow for targeted delivery to tumor cells, increasing treatment efficacy and reducing harm to healthy tissues. This review outlines the formulations used in PDDSs for NSCLC, evaluates suitable inhalation devices, and examines the physicochemical characteristics of nanoparticles critical for pulmonary delivery. It also discusses both passive and active targeting mechanisms and explores current challenges in inhalable nanomedicine. Emphasis is placed on recent innovations in inhalable nanomaterials, providing a comprehensive and current perspective on their application in NSCLC therapy. Graphical Abstract

The human body harbors distinct microbial communities at each body site. One microbial niche of particular interest within the human body is the tumor microenvironment. These intratumor microbes are linked to tumor initiation, progression, and metastasis through diverse mechanisms, including activation of oncogenic pathways and modulation of antitumor immunity. Recent studies have emphasized the role of intratumor microbes in influencing the response and outcome of cancer immunotherapeutics and vaccines. Further data suggest a crucial role of microbial metabolites in the metabolic rewiring of CD8+ T cells controlling antitumor immunity. This knowledge is vital to promote our understanding of the role of microbes in the tumor microenvironment and advance translational applications. In this review, we discuss factors that shape the structure of the intratumor microbiome, such as the translocation of gut microbes and the development of local microbial communities. This study highlights the remote control of gut microbes in the tumor microenvironment, disease progression, and therapy outcome. We detail interactions of intratumor microbes and their crosstalk with tumor and immune cells, such as tissue-resident and tumor-infiltrating T cells. We discuss open research questions in this field, including defining oncomicrobiotics, the subset of microbiota with biotherapeutic potential in inducing antitumor immunity. We highlight challenges and opportunities, emphasizing the future direction of developing next-generation engineered probiotics that can advance delivery, maximize the efficacy of cancer therapy, or even serve as a non-invasive technique to sense and detect tumor cells.