Association of distinct microbial signatures with premalignant colorectal adenomas

Lee, Jonathan Wei Jie; Plichta, Damian R.; Asher, Shreya; Delsignore, Marisa; Jeong, Tiffany; McGoldrick, Jessica; Staller, Kyle; Khalili, Hamed; Xavier, Ramnik J.; Chung, Daniel C.

doi:10.1016/j.chom.2023.04.007

Cited by 11 publications

(3 citation statements)

References 52 publications

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“…In summary, our findings suggest typical immune responses against lesions and potential responses against the gut microbiome, known to undergo alterations with disease progression. This sheds light on the intricate interplay between the immune system, microbial communities, and disease states within the gastrointestinal tract [35][36][37][38]. Other relevant biological signatures linked to the disease include changes in the levels of digestive enzymes, regulators of tissue homeostasis, and muscle contraction, suggesting organic dysregulation.…”

Section: Discussionmentioning

confidence: 98%

Stool Glycoproteomics Signatures of Pre-Cancerous Lesions and Colorectal Cancer

Soares,

Eiras,

Ferreira

et al. 2024

IJMS

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Colorectal cancer (CRC) screening relies primarily on stool analysis to identify occult blood. However, its sensitivity for detecting precancerous lesions is limited, requiring the development of new tools to improve CRC screening. Carcinogenesis involves significant alterations in mucosal epithelium glycocalyx that decisively contribute to disease progression. Building on this knowledge, we examined patient series comprehending premalignant lesions, colorectal tumors, and healthy controls for the T-antigen—a short-chain O-glycosylation of proteins considered a surrogate marker of malignancy in multiple solid cancers. We found the T-antigen in the secretions of dysplastic lesions as well as in cancer. In CRC, T-antigen expression was associated with the presence of distant metastases. In parallel, we analyzed a broad number of stools from individuals who underwent colonoscopy, which showed high T expressions in high-grade dysplasia and carcinomas. Employing mass spectrometry-based lectin-affinity enrichment, we identified a total of 262 proteins, 67% of which potentially exhibited altered glycosylation patterns associated with cancer and advanced pre-cancerous lesions. Also, we found that the stool (glyco)proteome of pre-cancerous lesions is enriched for protein species involved in key biological processes linked to humoral and innate immune responses. This study offers a thorough analysis of the stool glycoproteome, laying the groundwork for harnessing glycosylation alterations to improve non-invasive cancer detection.

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Section: Discussionmentioning

confidence: 98%

Stool Glycoproteomics Signatures of Pre-Cancerous Lesions and Colorectal Cancer

Soares,

Eiras,

Ferreira

et al. 2024

IJMS

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“…Oscillospiraceae family is involved in damaging intestinal mucosa, 47 whereas Flavonifractor family is found higher in patients with Crohn’s disease and promotes the development of colorectal cancer. 48 , 49 The decrease in their abundance might be related to the therapeutic effect of E5555. Moreover, the treatment with E5555 per se caused a significant difference in β-diversity and in the 33 metabolic pathways ( Figure 6 ).…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Effect of Proteinase-Activated Receptor-1 Antagonist on Colitis-Associated Carcinogenesis

Li,

Kurahara,

Zhao

et al. 2024

Cellular and Molecular Gastroenterology and Hepatology

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“… 167 Lee et al have shown that there are significant differences in fecal microbial signatures between tubular adenomas and sessile serrated adenomas, and that Flavonifractor plautii and Bacteroides stercoris may influence effects of diet and medications on the development of these premalignant colon lesions. 168 Han et al have demonstrated that the gut commensal Lactobacillus reuteri can potentiate the protective effect of statins on colorectal tumorigenesis via the production of tryptophan catabolite, indole-3-lactic acid. 169 …”

Section: Microbiome and Digestive System Tumor Developmentmentioning

confidence: 99%

The microbiome and rise of early-onset cancers: knowledge gaps and research opportunities

Mima,

Hamada,

Inamura

et al. 2023

Gut Microbes

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Accumulating evidence indicates an alarming increase in the incidence of early-onset cancers, which are diagnosed among adults under 50 years of age, in the colorectum, esophagus, extrahepatic bile duct, gallbladder, liver, stomach, pancreas, as well as the bone marrow (multiple myeloma), breast, head and neck, kidney, prostate, thyroid, and uterine corpus (endometrium). While the early-onset cancer studies have encompassed research on the wide variety of organs, this article focuses on research on digestive system cancers. While a minority of early-onset cancers in the digestive system are associated with cancer-predisposing high penetrance germline genetic variants, the majority of those cancers are sporadic and multifactorial. Although potential etiological roles of diets, lifestyle, environment, and the microbiome from early life to adulthood (i.e. in one’s life course) have been hypothesized, exact contribution of each of these factors remains uncertain. Diets, lifestyle patterns, and environmental exposures have been shown to alter the oral and intestinal microbiome. To address the rising trend of early-onset cancers, transdisciplinary research approaches including lifecourse epidemiology and molecular pathological epidemiology frameworks, nutritional and environmental sciences, multi-omics technologies, etc. are needed. We review current evidence and discuss emerging research opportunities, which can improve our understanding of their etiologies and help us design better strategies for prevention and treatment to reduce the cancer burden in populations.

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Association of distinct microbial signatures with premalignant colorectal adenomas

Cited by 11 publications

References 52 publications

Stool Glycoproteomics Signatures of Pre-Cancerous Lesions and Colorectal Cancer

Stool Glycoproteomics Signatures of Pre-Cancerous Lesions and Colorectal Cancer

Therapeutic Effect of Proteinase-Activated Receptor-1 Antagonist on Colitis-Associated Carcinogenesis

The microbiome and rise of early-onset cancers: knowledge gaps and research opportunities

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