It takes a village: microbiota, parainflammation, paligenosis and bystander effects in colorectal cancer initiation

Abstract

Sporadic colorectal cancer (CRC) is a leading cause of worldwide cancer mortality. It arises from a complex milieu of host and environmental factors, including genetic and epigenetic changes in colon epithelial cells that undergo mutation, selection, clonal expansion, and transformation. The gut microbiota has recently gained increasing recognition as an additional important factor contributing to CRC. Several gut bacteria are known to initiate CRC in animal models and have been associated with human CRC. In this Review, we discuss the factors that contribute to CRC and the role of the gut microbiota, focusing on a recently described mechanism for cancer initiation, the so-called microbiota-induced bystander effect (MIBE). In this cancer mechanism, microbiota-driven parainflammation is believed to act as a source of endogenous mutation, epigenetic change and induced pluripotency, leading to the cancerous transformation of colon epithelial cells. This theory links the gut microbiota to key risk factors and common histologic features of sporadic CRC. MIBE is analogous to the well-characterized radiation-induced bystander effect. Both phenomena drive DNA damage, chromosomal instability, stress response signaling, altered gene expression, epigenetic modification and cellular proliferation in bystander cells. Myeloid-derived cells are important effectors in both phenomena. A better understanding of the interactions between the gut microbiota and mucosal immune effector cells that generate bystander effects can potentially identify triggers for parainflammation, and gain new insights into CRC prevention.

Uncovering potential new biomarkers and immune infiltration characteristics in primary Sjögren’s syndrome by integrated bioinformatics analysis

“…It could mimic different immune subsets depending on the needs of the tumor. [45] In addition, the study on immune infiltrating cells found that macrophages were significantly upregulated, which was consistent with the study on immune functions. It was suggested that the study on parainflammation provided important clues for the treatment of pSS.…”

Cuproptosis-related lncRNA signatures predict prognosis and immune relevance of kidney renal papillary cell carcinoma

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Long-read sequencing revealed alterations of microbial relationship between tongue coating and gastric mucosa in patients with gastric intestinal metaplasia

“…Certainly, paligenosis is a double-edged sword: critical for repair but risky for cancer. Wang et al [25] discussed the microbiota-induced bystander effect on the development of colorectal cancer, and more studies should be done to bridge the gaps between the underlying mechanisms of cancer initiation and commensal microorganisms. In this study, oral and gastric bacteria are speculated to be the most common cause of in ammation, injury, and repair in stomach disorders.…”