Abstract
Simple SummaryIn the past decade, the interaction between intestinal microbiota and colorectal cancer has been an active research area. Microbial metabolites, which could act locally and systematically, have a significant impact on the development of colorectal cancer, especially by inciting immune responses. In this paper, we systematically reviewed the recent insights on microbial metabolites and their immunoregulation on colorectal cancer and discussed the controversial role of some metabolites, hoping to provide a different understanding of the role of bacterial metabolites in colon carcinogenesis.A growing body of research has found close links between the human gut microbiota and colorectal cancer (CRC), associated with the direct actions of specific bacteria and the activities of microbiota-derived metabolites, which are implicated in complex immune responses, thus influencing carcinogenesis. Diet has a significant impact on the structure of the microbiota and also undergoes microbial metabolism. Some metabolites, such as short-chain fatty acids (SCFAs) and indole derivatives, act as protectors against cancer by regulating immune responses, while others may promote cancer. However, the specific influence of these metabolites on the host is conditional. We reviewed the recent insights on the relationships among diet, microbiota-derived metabolites, and CRC, focusing on their intricate immunomodulatory responses, which might influence the progression of colorectal cancer.
Highlights
The microbiome contains a metagenome 100 times larger than that of the human host [1], playing an increasingly critical role in human health, including digesting indigestible macronutrients and producing vitamins, defending against pathogens, and maintaining immune homeostasis [2]
putative cell wall binding repeat 2 (PCWBR2) directly interacts with α2/β integrin, a receptor generally overexpressed in human colorectal cancer (CRC) tumors and cell lines, which might explain why P. anaerobius preferentially colonizes the CRC tumors [156]; and second, P. anaerobius activated the α2/β1-PI3K–Akt–nuclear factor-κB (NF-κB) signaling cascade to trigger the inflammation in ApcMin/+ mice
The experimental and clinical evidence discussed above indicates that specific pathogens and microbial metabolites play a critical role in the interactions between the microbiome and immune responses regarding tumorigenesis
Summary
The microbiome contains a metagenome 100 times larger than that of the human host [1], playing an increasingly critical role in human health, including digesting indigestible macronutrients and producing vitamins, defending against pathogens, and maintaining immune homeostasis [2]. Diet can influence the composition and metabolism of the intestinal flora (Box 1), which helps to produce metabolites that link the microbiota with the host by reprogramming enterocyte metabolism [12], regulating immune responses [13], and impacting tumor formation [3]. Once the intestinal structural barrier is impaired, colonocytes are continuously exposed to microorganisms and their metabolites Such sustained stimulation of the immune responses might induce chronic mucosal inflammation, which is widely accepted to promote the neoplastic transformation of the intestinal epithelium [19]. The intricate interplay among the intestinal flora, metabolites, chronic inflammation or immune responses, host genetics, and essential environmental factors jointly contribute to the development of colon tumors [15]. Some representative metabolites associated with CRC and their related mechanisms, especially those implicated in immune regulation, are discussed in detail
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
