Colorectal Cancer in Inflammatory Bowel Disease: A Review of the Role of Gut Microbiota and Bacterial Biofilms in Disease Pathogenesis.
The risk of colorectal cancer [CRC] is increased in patients with inflammatory bowel disease [IBD], particularly in extensive ulcerative colitis [UC] and Crohn's colitis. Gut microbiota have been implicated in the pathogenesis of CRC via multiple mechanisms, including the release of reactive oxygen species and genotoxins, and induction of inflammation, as well as activation of the immune response. Gut microbiota can enhance their carcinogenic and proinflammatory properties by organising into biofilms, potentially making them more resistant to the host's immune system and to antibiotics. Colonic biofilms have the capacity to invade colonic tissue and accelerate tumorigenesis in tumour-prone models of mice. In the context of IBD, the prevalence of biofilms has been estimated to be up to 95%. Although the relationship between chronic inflammation and molecular mediators that contribute to IBD-associated CRC is well established, the role of gut microbiota and biofilms in this sequence is not fully understood. Because CRC can still arise in the absence of histological inflammation, there is a growing interest in identifying chemopreventive agents against IBD-associated CRC. Commonly used in the treatment of UC, 5-aminosalicylates have antimicrobial and anticarcinogenic properties that might have a role in the chemoprevention of CRC via the inhibition or modulation of carcinogenic gut microbiota and potentially of biofilm formation. Whether biologics and other IBD-targeted therapies can decrease the progression towards dysplasia and CRC, via mechanisms independent of inflammation, is still unknown. Further research is warranted to identify potential new microbial targets in therapy for chemoprevention of dysplasia and CRC in IBD.
Muñiz Pedrogo DA
，Sears CL
，Melia JMP
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Microbiome Differences in Colorectal Cancer Patients and Healthy Individuals: Implications for Vaccine Antigen Discovery.
Colorectal cancer (CRC) is the third most prevalent cancer worldwide, with numerous risk factors contributing to its development. Recent research has illuminated the significant role of the gut microbiota in CRC pathogenesis, identifying various microbial antigens as potential targets for vaccine development.
This review aimed at exploring the potential sources of microbial antigens that could be harnessed to create effective CRC vaccines and understand the role of microbiome-CRC interactions in carcinogenesis.
A comprehensive search of original research and review articles on the pathological links between key microbial candidates, particularly those more prevalent in CRC tissues, was conducted. This involved extensive use of the PubMed and Medline databases, as well as the Google Scholar search engine, utilizing pertinent keywords. A total of one hundred and forty-three relevant articles in English, mostly published between 2018 and 2024, were selected.
Numerous microbes, particularly bacteria and viruses, are significantly overrepresented in CRC tissues and have been shown to promote tumorigenesis by inducing inflammation and modulating the immune system. This makes them promising candidates for antigens in the development of CRC vaccines.
The selection of microbial antigens focuses on their capacity to trigger a strong immune response and their link to tumor presence and progression. Identifying and validating these antigens through preclinical testing is essential in developing a CRC vaccine.
Ibeanu GC
，Rowaiye AB
，Okoli JC
，Eze DU
... -
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Gut microbiota and blood biomarkers in IBD-Related arthritis: insights from mendelian randomization.
With the ongoing rise in the incidence of inflammatory bowel disease (IBD), its extraintestinal manifestations have garnered significant attention. IBD-related arthritis is notable for its insidious onset and unpredictability, presenting considerable challenges for clinical diagnosis and management. Factors such as gut microbiota, plasma proteins, inflammatory proteins, and biomarkers found in blood and urine may be closely associated with IBD-related arthritis. However, the mechanisms by which these factors influence this condition remain poorly understood and require urgent investigation. We employed the method of linkage disequilibrium and the two-sample Mendelian randomization (MR) approach, utilizing single nucleotide polymorphisms (SNPs) identified from large-scale genome-wide association studies as instrumental variables. In this scientifically rigorous manner, we explored the potential causal relationship between gut microbiota, plasma proteins, inflammatory proteins, and blood and urine biomarkers in relation to arthritis resulting from inflammatory bowel disease (IBD). This method aids in elucidating the potential roles of these biomarkers in the development of arthritis following IBD, while minimizing the confounding factors and reverse causality commonly encountered in observational studies. To further verify and strengthen our findings, we conducted subsequent sensitivity analyses. These analyses will evaluate the strength of the association between SNPs and the studied biomarkers, as well as post-IBD arthritis, while accounting for variations in SNP distribution among populations and other potential genetic influencing factors. Through these rigorous analytical steps, our objective is to enhance the robustness and credibility of the research findings and provide more reliable scientific evidence regarding the pathogenesis of post-IBD arthritis. MR analysis provides evidence for the association between genetically predicted gut microbiota, plasma proteins, inflammatory proteins, and blood and urine biomarkers with the risk of IBD-related arthritis. This analysis investigates the characteristics of the associations between specific gut microbiota, plasma proteins, inflammatory proteins, and blood and urine biomarkers in relation to IBD-related arthritis. Among the plasma proteins, pterin-4-alpha-carbinolamine dehydratase, aldo-keto reductase family 1 member C4, cathepsin L2, angiostatin, hepatocyte growth factor-like protein, hepatitis A virus cellular receptor 2, protein O-linked mannose beta-1,4-N-acetylglucosaminyltransferase 2, epididymal-specific alpha-mannosidase, and platelet-derived growth factor receptor-like protein are associated with Crohn's disease-related arthritis. In contrast, agrin, methylenetetrahydrofolate synthetase domain-containing protein, neurotrophin-3 (NT-3) growth factor receptor, and neuropilin-1 are associated with ulcerative colitis-related arthritis. Furthermore, regarding gut bacterial pathway abundance, adenosylcobalamin, N-acetylglucosamine, N-acetylmannosamine, and N-acetylneuraminic acid degradation, as well as glycolysis metabolism and degradation pathways, are associated with Crohn's disease-related arthritis. Meanwhile, gut bacterial pathway abundance (pentose phosphate pathway) and gut microbiota abundance (Bacteroidetes, Bacteroidia, Bacteroidales, Porphyromonadaceae, Faecalibacterium, Eubacterium eligens) are linked to ulcerative colitis-related arthritis. Notably, we did not identify any connections between inflammatory protein factors, blood and urine biomarkers, and IBD-related arthritis. Lastly, in the reverse MR study, the insufficient number of SNPs available for analysis precluded the detection of a reverse causal relationship. This study employs the MR method to elucidate the potential causal relationships among gut microbiota, plasma proteins, inflammatory proteins, and blood and urine biomarkers in relation to the occurrence and progression of IBD-related arthritis. This research offers a novel perspective for a deeper understanding of the pathogenesis of IBD-related arthritis and highlights future directions for the diagnosis and treatment strategies of this condition.
Yang W
，Cui M
，Yang P
，Liu C
，Han X
，Yao W
，Li Z
... -
《Scientific Reports》
ResearchGate
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钛学术
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