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Simple Summary: Research increasingly shows that bacteria, the largest part of the gut microbiome, may play a significant role in cancer. These microorganisms produce metabolites that can travel through the body and interact with host cells via microbial metabolite receptors, potentially affecting cancer development. This study investigates the involvement of these receptors in human cells across twenty-three types of cancer. By analyzing data from both cancer cell lines and human tumor samples, we examined how these interactions may impact key cancer-related processes, such as immune response, tumor growth, and spread. Notably, we identified several receptors that are consistently altered in cancer, which might serve as helpful biomarkers for diagnosis or treatment. This research highlights the potential of targeting the gut microbiome in cancer therapy and provides valuable insights for developing new cancer treatments based on microbiome interactions. Background/Objectives: The role of the gut microbiome in cancer biology has become an increasingly prominent area of research, particularly regarding the role of microbial metabolites and their receptors (MMRs). These metabolites, through the various gut–organ axes, have been proven to influence several pathogenetic mechanisms. This study conducted a comprehensive pan-cancer analysis of MMR transcriptomic profiles across twenty-three cancer types, exploring the mechanisms through which they can influence cancer development and progression. Methods: Utilizing both cancer cell lines from CCLE (Cancer Cell Line Encyclopedia) and human tumor samples from TCGA (The Cancer Gene Atlas), we analyzed 107 MMRs interacting with microbial metabolites such as short-chain fatty acids, bile acids, indole derivatives, and others while studying their interactions with key known cancer genes. Results: Our results revealed that certain MMRs, such as GPR84 and serotonin receptors, are consistently upregulated in various malignancies, while others, like ADRA1A, are frequently downregulated, suggesting diverse roles in cancer pathophysiology. Furthermore, we identified significant correlations between MMR expression and cancer hallmark genes and pathways, including immune evasion, proliferation, and metastasis. Conclusions: These findings suggest that the interactions between microbial metabolites and MMRs may serve as potential biomarkers for cancer diagnosis, prognosis, and therapy, highlighting their therapeutic potential. This study underscores the significance of the microbiota–cancer axis and provides novel insights into microbiome-based strategies for cancer treatment. [ABSTRACT FROM AUTHOR]

Background and aims: Monocyte recruitment in the lamina propria and inflammatory phenotype driven by the mucosal microenvironment is critical for the pathogenesis of inflammatory bowel disease. However, the stimuli responsible remain largely unknown. Recent works have focused on stromal cells, the main steady-state cellular component in tissue, as they produce pro-inflammatory chemokines that contribute to the treatment-resistant nature of IBD. Methods: We studied the regulation of these processes by examining the communication patterns between stromal and myeloid cells in ileal Crohn's disease (CD) using a complete single-cell whole tissue sequencing analysis pipeline and in vitro experimentation in mesenchymal cells. Results: We report expansion of S4 stromal cells and monocyte-like inflammatory macrophages in the inflamed mucosa and describe interactions that may establish sustained local inflammation. These include expression of CCL2 by S1 fibroblasts to recruit and retain monocytes and macrophages in the mucosa, where they receive signals for proliferation, survival, and differentiation to inflammatory macrophages from S4 stromal cells through molecules such as MIF, IFNγ, and FN1. The overexpression of CCL2 in ileal CD and its stromal origin was further demonstrated in vitro by cultured mesenchymal cells and intestinal organoids in the context of an inflammatory milieu. Conclusions: Our findings outline an extensive cross-talk between stromal and myeloid cells, which may contribute to the onset and progression of inflammation in ileal Crohn's disease. Understanding the mechanisms underlying monocyte recruitment and polarization, as well as the role of stromal cells in sustaining inflammation, can provide new avenues for developing targeted therapies to treat IBD. [ABSTRACT FROM AUTHOR]

Crohn's disease is a relapsing chronic inflammatory condition of the intestine with increasing prevalence around the world. Biologic therapies are currently widely used and have proved safe and effective in treating moderate to severe Crohn's disease. However, contemporary bibliography contains little information about the use of these drugs in patients with end‐stage renal disease undergoing hemodialysis. Here we present a case of a 47‐year‐old female patient with treatment‐refractory Crohn's disease on hemodialysis. In this patient, treatment with the anti‐IL‐12/23 receptor antibody ustekinumab was effective in inducing and maintaining remission while being safe in administering throughout hemodialysis. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to examine the role of growth factors associated with angiogenesis and oxidative stress in the pathogenesis of spontaneous miscarriage. Methods: We performed a comparative mRNA expression analysis of VEGF, PlGF, Flt-1, Angiogenin and Endoglin using Real-Time PCR, in the placenta and decidua collected from 12 patients presenting with spontaneous abortion and from 14 women undergoing induced abortion, during the first and second trimester of pregnancy. Results: The mRNA expression of Flt-1 was significantly upregulated in the placenta of spontaneous abortions (5.17-fold, IQR: 2.72–9.11, p < 0.01). The placental expression of the soluble isoforms of Flt-1, sFlt-1 e15a and sFlt-1 i13, was also significantly upregulated in spontaneous abortions (sFlt-1 e15a: 2.35-fold, IQR: 0.98–2.83, p < 0.01; sFlt-1 i13: 3.47-fold, IQR: 2.37–5.08, p < 0,05). Placental tmFlt-1, PlGF and Endoglin showed a tendency of higher expression levels in spontaneous abortions, although they did not reach statistical significance (tmFlt-1: 7.42-fold, IQR: 3.58–14.32; PlGF: 2.36-fold, IQR: 0.90–4.12; Endoglin: 1.97-fold, IQR: 1.18–2.43). VEGF and Angiogenin mRNA expression in induced, as well as in spontaneous abortions, did not convey any statistically significant difference. In the decidua, the expression levels of Flt-1 and its splice variants sFlt-1 e15a, sFlt-1 i13 and tmFlt-1 did not show any statistically significant differences, as was the case for the rest of the herein examined growth factors. Conclusions: In this study, we observed higher levels of sFlt-1 mRNA expression in the placenta of spontaneous abortions, while expression of other growth factors in placenta and decidua remained constant. This suggests that an imbalance of sFlt-1 expression in the placenta might contribute to the pathogenesis of spontaneous abortion, probably via oxidative stress, providing a possible biomarker for prompt identification of this condition. [ABSTRACT FROM AUTHOR]

Bifidobacterium lactis, Lactobacillus acidophilus, Lactiplantibacillus plantarum and Saccharomyces boulardii are common probiotic supplements. Colonic subepithelial myofibroblasts (cSEMFs) are actively involved in mucosal wound healing and inflammation. cSEMFs, isolated from healthy individuals, were stimulated with 102 or 104 cfu/mL of these probiotic strains alone and in combination, and their effect on chemokine and wound healing factor expression was assessed by qRT-PCR, ELISA and Sircol Assay, and on cSEMFs migration, by Wound Healing Assay. These strains remained viable and altered cSEMFs' inflammatory and wound healing behavior, depending on the strain and concentration. cSEMFs treated with a combination of the four probiotics had a moderate, but statistically significant, increase in the mRNA and/or protein expression of chemokines CXCL1, CXCL2, CXCL4, CXCL8, CXCL10, CCL2 and CCL5, and healing factors, collagen type I and III, fibronectin and tissue factor. In contrast, when each strain was administered alone, different effects were observed, with greater increase or decrease in chemokine and healing factor expression, which was balanced by the mixture. Overall, this study highlights that the use of multiple probiotic strains can potentially alert the gut mucosal immune system and promote wound healing, having a better effect on mucosal immunity than the use of single probiotics. [ABSTRACT FROM AUTHOR]