Clostridioides difficile, which causes life-threatening diarrheal disease, is considered an urgent threat to healthcare setting worldwide. The current standards of care solely rely on conventional antibiotic treatment, however, there is a risk of promoting recurrent C. difficile infection (rCDI) because of the emergence of antibiotic-resistant strains. Globally, the alarming spread of antibiotic-resistant strains of C. difficile has resulted in a quest for alternative therapeutics. The use of fecal microbiota transplantation (FMT), which involves direct infusion of fecal suspension from a healthy donor into a diseased recipient, has been approved as a highly efficient therapeutic option for patients with rCDI. Bacteriophages or phages are a group of viruses that can infect and destroy bacterial hosts, and are recognized as the dominant viral component of the human gut microbiome. Accumulating data has demonstrated that phages play a vital role in microbial balance of the human gut microbiome. Recently, phage therapy and fecal virome transplantation (FVT) have been introduced as promising alternatives for the treatment of C. difficile -related infections, in particular drug-resistant CDI. Herein, we review the latest updates on C. difficile- specific phages, and phage-mediated treatments, and highlight the current and future prospects of phage therapy in the management of CDI.

Colorectal cancer (CRC) ranks as the third most prevalent cancer worldwide, causing a serious threat to global health and social burden. Clostridioides difficile infection (CDI) is one of the most important nosocomial infections and has a higher incidence in cancerous population compared with non-cancerous cases. Different risk factors, including gut microbiota dysbiosis, extensive surgery, chemotherapy, prolonged hospitalization, and antimicrobial therapy, compromise host defenses against CDI and contribute to cancer patients’ susceptibility to this infection. The emergence of CDI in patients with CRC creates conditions for therapy escalation and prolonged hospitalization, highlighting the need for correct and effective CDI management in these patients. Here, common risk factors associated with CDI in patients with CRC are discussed. In addition, different available techniques for the prevention, detection, and treatment of CDI with the lowest impact on gut microbiota diversity are summarized. This review aims to improve the understanding of the interplay between CDI and CRC and provide new insights into restoring and maintaining gut microbiota balance during CDI management in patients with CRC.

Colorectal cancer (CRC) is the second deadliest cancer worldwide, posing a great threat to human health and a social burden. Various genetic and epigenetic alterations can activate tumourigenesis-related signalling pathways, leading to CRC development and progression. Over the past two decades, the understanding of the role of S100 family proteins in different types of cancer has received great attention. S100 proteins, as intracellular and extracellular, play important roles in regulating various cellular processes, such as calcium homeostasis, apoptosis, tumour cell proliferation, invasion and motility. It is well documented that alteration in expression of S100 proteins can be associated with tumourigenesis and cancer progression. These proteins play important roles in CRC carcinogenesis by activating different signalling pathways, especially the nuclear factor kappa B (NF-κB) signalling pathway, which is involved in cell proliferation, invasion and migration. In this review, we describe the functions of S100 proteins in the context of inflammation, tumourigenesis, cancer progression, metastasis, and drug resistance in CRC. We also discuss the potential of targeting different S100 proteins as prognostic factors and therapeutic agents for CRC treatment. This narrative review will increase our understanding of the role of S100 proteins in the progression of CRC and provide insights into the use of S100 proteins as new biomarkers and therapeutic targets for CRC therapy.

S100A8 plays a critical role in the pathogenesis of several inflammatory diseases and multiple types of cancer. Therefore, targeting the S100A8 function may alleviate the pathogenic process in various diseases. Here, specific single-chain variable fragment (scFv) antibodies targeting recombinant S100A8 (rS100A8) were selected by phage display technique and characterized using cDNA sequencing, immunoassay tests, and molecular docking. The neutralizing activity of scFvs was examined by a cell viability assay in rS100A8-treated macrophages. Furthermore, the modulatory effects of scFvs on the expression of inflammatory markers and apoptosis-related genes in macrophages and human colorectal carcinoma HT-29 cells treated with rS100A8 or dextran sulfate sodium (DSS) were assessed by RT-qPCR and flow cytometry. Based on our results, four scFvs were identified to be capable of detecting rS100A8 in the immunoassay tests. Among the selected scFvs, two clones (SA8-E6 and SA8-E12), alone or in combination, exhibited the highest blocking activity on rS100A8 and potently inhibited S100A8-induced cytotoxicity in macrophages. The use of a SA8-E6 and SA8-E12 (SA8-E6-12) cocktail inhibited the upregulation of TLR4 and RAGE, as well as inflammation and apoptosis-related genes in macrophages and HT-29 cells stimulated with rS100A8. Additionally, SA8-E6-12 exerted a significant inhibitory effect on inflammation and apoptosis induced by the S100A8/A9 complex in DSS-stimulated macrophages. We also demonstrated by molecular docking that the interaction of S100A8 with SA8-E6-12 was mainly restricted to the binding domain involved in the connection of S100A8 to TLR4. Further studies are required to explore the efficacy of these anti-S100A8 scFvs as potential therapeutic agents using in vivo models of S100A8-driven inflammatory diseases.