Yang Xi

Monocytes and macrophages display elevated activity in cholesterol transport and dynamic response pathways. Five monocyte-enriched genes (CSF3R, FPR1, MNDA, MPEG1, VCAN) are implicated in cholesterol metabolism regulation. Hypercholesterolemia reshapes circulating immune cell composition and upregulates proinflammatory genes (e.g., VCAM1), mediating immunomodulatory effects.

Gut microbial single nucleotide polymorphisms (SNPs) offer stable, specific genetic markers for disease diagnosis. Escherichia coli ( E. coli ), a dominant gut bacterium, is associated with colorectal cancer (CRC), but limited enteric reference genomes hinder SNP annotation in intestinal strains. Metagenomic sequencing profiled gut microbiota in 200 CRC patients and 200 healthy controls. The E. coli strain WDP was fully sequenced via PacBio single‐molecule technology for genome assembly and functional annotation. Wilcoxon tests identified differentially abundant microbes, while Lasso regression models integrated microbial features (bacteria, viruses, virus‐host pairs) and E. coli SNPs to predict CRC risk. E. coli abundance did not differ between groups, but genomic analysis revealed 7460 CRC‐associated SNPs. The SNP‐based model achieved superior accuracy (92.86% training, 93.33% testing, 84.00% validation) and AUC (0.986, 0.983, 0.913), outperforming models based on microbial abundances (e.g., Staphylococcus capitis , Zindervirus) or virus‐host interactions. PacBio‐generated E. coli genomic maps enable precise SNP annotation, establishing E. coli SNPs as highly accurate biomarkers for CRC risk prediction. This approach leverages microbial genetic stability to advance non‐invasive early detection, offering a novel target for precision microbiome‐based diagnostics.

Abdominopelvic malignancies are lesions that occur in the abdomen and pelvis, originating from various organs and tissues in this region. According to the latest cancer statistics published in 2024, gynecological cancers, colorectal cancer, and prostate cancer rank highest in both incidence and mortality among abdominopelvic malignancies [1] . Currently, surgery, chemotherapy, radiotherapy, immunotherapy, targeted therapy, and endocrine therapy are the main treatment modalities for abdominopelvic malignancies [2] . Radiotherapy exerts its antitumor effects primarily by utilizing high-energy radiation to directly damage the DNA structure of cancer cells. Additionally, radiation interacts with intracellular water molecules to generate free radicals, inducing extensive DNA damage [3] . It is particularly indicated for patients ineligible for surgery, as postoperative adjuvant treatment, or for recurrent cases [4][5][6] , holding a significant position in the comprehensive management of abdominopelvic malignancies. Notably, radiotherapy directed at the abdominopelvic region, which includes the gastrointestinal tract, can significantly disrupt gut microbiota homeostasis, leading to dysbiosis [7] . This dysbiosis not only contributes to the development of radiotherapy-related side effects but also diminishes the radiosensitivity of tumor tissues [8,9] . Over 97% of human commensal bacteria reside within the digestive tract, predominantly in the colon, collectively forming the gut microbiota [10] . Eckburg et al. [11] demonstrated that 98% of the gut microbiota belongs to four dominant phyla: Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria. These commensal microorganisms play crucial roles in essential physiological processes, including regulating intestinal epithelial cell proliferation and differentiation, activating innate immune responses, and participating in metabolic homeostasis regulation [12] . They can also modulate the efficacy of various cancer therapies, including radiotherapy [13,14] .Gut microbiota-derived short-chain fatty acids (SCFAs) promote the production of tight junction proteins and mucins, thereby maintaining intestinal barrier integrity following radiotherapy [15] . Outer membrane vesicles (OMVs) secreted by the gut microbiota contain various bacterial-associated molecular patterns and serve as potent mediators for enhancing anti-tumor immunity [16] . Furthermore, the anaerobic or facultative anaerobic characteristics of gut microbiota enable their effective targeting of hypoxic tumor regions. Combined with bioengineering technologies, they can ameliorate hypoxia within the tumor microenvironment (TME), consequently enhancing radiosensitivity. In summary, a close interaction exists between the gut microbiota and radiotherapy. Understanding the mechanisms underlying the interplay between abdominopelvic radiotherapy and the gut microbiota will provide a theoretical foundation for developing microbiota-modulating adjuvant strategies for radiotherapy. This approach aims to achieve the dual goals of mitigating adverse effects and enhancing anti-tumor efficacy.The gut microbiota is influenced by numerous factors, among which abdominopelvic radiotherapy is one that significantly alters its diversity and abundance. A systematic review incorporating 11 studies demonstrated that exposure to radiation induces changes in intestinal bacterial composition, characterized by a reduction in beneficial bacteria and an increase in potentially harmful bacteria [17] . Due to such alterations, the gut microbiota may serve as a novel biomarker for radiation exposure [18] .In animal models, the Zhao team [19] confirmed that abdominal irradiation disrupts gut microbiota balance in mice and significantly reduces the alpha-diversity index.Following radiation exposure, the abundance of the Bacteroidetes, Firmicutes, and Actinobacteria decreased in the gut, while the abundance of Proteobacteria, which is enriched with pathogenic bacteria, significantly increased. Duan et al. [20] further revealed a pathogen-probiotic dynamic imbalance in the gut microbiota of irradiated mice: the abundance of opportunistic pathogens such as Escherichia and Shigella (Proteobacteria) increased, whereas the abundance of beneficial bacteria including Romboutsia (Firmicutes) and Bacteroides (Bacteroidetes) decreased. Lu et al. [21] also found that abdominal irradiation induces a "pathogenic remodeling" of the intestinal microenvironment, leading to Enterobacteriaceae becoming the dominant bacterial family. Collectively, these findings indicate that abdominal radiation exposure induces gut microbial dysbiosis in animal models.Clinically, alterations in the gut microbiota following abdominopelvic radiotherapy exhibit consistent trends among patients, irrespective of the presence of radiation-induced intestinal injury. He et al. [15] observed that, compared to cervical cancer patients who did not receive radiotherapy, patients undergoing radiotherapy exhibited a significant reduction in fecal microbiota alpha-diversity, increased abundance of Proteobacteria, and decreased abundance of Firmicutes and Bacteroidetes. Nam et al. [22] compared fecal microbiota changes before and after pelvic radiotherapy in nine gynecological cancer patients, reporting a 10% decrease in Firmicutes and a 3% increase in Fusobacterium. Bacteroidetes, which typically confer beneficial functions within the gut [23] , exhibit variable abundance changes across studies. While most studies observed a decrease in its abundance [15,24,25] , a minority reported an increase [26] . Furthermore, in patients developing radiation-induced intestinal injury post-radiotherapy, some studies also observed an elevated abundance of Actinobacteria [27] . Collectively, these findings reveal characteristic alterations associated with radiotherapy-induced gut microbiota dysbiosis: diminished alpha-diversity accompanied by an imbalance in the ratio of...

Radiotherapy is a crucial treatment modality for abdominopelvic malignancies, with particularly significant effects on the gut microbiota. A reciprocal relationship exists between abdominopelvic radiotherapy and the gut microbiota. The gut microbiota plays vital roles in maintaining host health, modulating immune responses, and regulating metabolic functions. Abdominopelvic radiotherapy induces significant alterations in both the diversity and abundance of the gut microbiota, which may be critically involved in the development of radiotherapy-related adverse effects and the compromised therapeutic efficacy. Concurrently, the distinct biological properties of the gut microbiota and its derivatives can also influence the host response to radiotherapy. Understanding this interplay between abdominopelvic radiotherapy and the gut microbiota is of paramount importance for improving patient quality of life and treatment outcomes. This review discusses the impact of abdominopelvic radiotherapy on gut microbiota composition and summarizes recent advances in microbiota-targeted interventions aimed at radioprotection and radiosensitization, providing a theoretical foundation for optimizing radiotherapy for abdominopelvic malignancies.

The oral surface-modified probiotic therapy, capable of maintaining activity and adhesion of probiotics under harsh gastrointestinal conditions, is effective in treating ulcerative colitis (UC). However, the currently reported surface-modified probiotics suffer from poor selective colonization at a lesion site and limited codelivery capability with other treatment modalities due to different physicochemical properties. Herein, we develop triggerable probiotic-drug conjugates that enable synchronous site-specific probiotic colonization and on-demand drug release for the treatment of UC and its complication. Specifically, the conjugates are composed of probiotic Escherichia coli Nissle 1917 encapsulated with the adhesive tannic acid-ferric inner layer and the reactive oxygen species (ROS)-responsive thioether-bridged pterostilbene-lipid outer coating. Following oral administration, the pathological high-level ROS can trigger the adaptable release of anti-inflammatory pterostilbene and adhesive probiotics from conjugates in the inflamed colon. The targeted colonization of adhesive probiotics, combined with pterostilbene at the lesion site in a synchronous manner, achieves inflammation suppression and sustained gut microbiota modulation. In both mouse models of UC and associated complications, this conjugate demonstrates significant therapeutic and prophylactic efficacy, highlighting its translational potential for clinical combined applications in gastrointestinal disorders.

Background: Gut bacteria are related to colorectal cancer (CRC) and its clinicopathologic characteristics.Objective: To develop gut bacterial subtypes and explore potential microbial targets for CRC.Methods: Stool samples from 914 volunteers (376 CRCs, 363 advanced adenomas, and 175 normal controls) were included for 16S rRNA sequencing. Unsupervised learning was used to generate gut microbial subtypes. Gut bacterial community composition and clustering effects were plotted. Differences of gut bacterial abundance were analyzed. Then, the association of CRC‐associated bacteria with subtypes and the association of gut bacteria with clinical information were assessed. The CatBoost models based on gut differential bacteria were constructed to identify the diseases including CRC and advanced adenoma (AA).Results: Four gut microbial subtypes (A, B, C, D) were finally obtained via unsupervised learning. The characteristic bacteria of each subtype were Escherichia‐Shigella in subtype A, Streptococcus in subtype B, Blautia in subtype C, and Bacteroides in subtype D. Clinical information (e.g., free fatty acids and total cholesterol) and CRC pathological information (e.g., tumor depth) varied among gut microbial subtypes. Bacilli, Lactobacillales, etc., were positively correlated with subtype B. Positive correlation of Blautia, Lachnospiraceae, etc., with subtype C and negative correlation of Coriobacteriia, Coriobacteriales, etc., with subtype D were found. Finally, the predictive ability of CatBoost models for CRC identification was improved based on gut microbial subtypes.Conclusion: Gut microbial subtypes provide characteristic gut bacteria and are expected to contribute to the diagnosis of CRC.

In recent years, bacteria have gained considerable attention as a promising drug carrier that is critical in improving the effectiveness and reducing the side effects of anti‐tumor drugs. Drug carriers can be utilised in various forms, including magnetotactic bacteria, bacterial biohybrids, minicells, bacterial ghosts and bacterial spores. Additionally, functionalised and engineered bacteria obtained through gene engineering and surface modification could provide enhanced capabilities for drug delivery. This review summarises the current studies on bacteria‐based drug delivery systems for anti‐tumor therapy and discusses the prospects and challenges of bacteria as drug carriers. Furthermore, our findings aim to provide new directions and guidance for the research on bacteria‐based drug systems.