Carcinogenesis as a Result of Multiple Inflammatory and Oxidative Hits: a Comprehensive Review from Tumor Microenvironment to Gut Microbiota.
Morgillo F, Dallio M, Della Corte CM, Gravina AG, Viscardi G, Loguercio C, Ciardiello F, Federico A
Neoplasia. Jul 2018
COMMENT: In this review, Morgillo and coworkers analyze, from a particular perspective, the different ways to induce inflammation and oxidative stress in order to explain the mechanisms underlying the development of several cancers. Moreover, because of the strong scientific evidence in literature, they focused their attention to the analysis of the role that gut microbiota plays in gastrointestinal cancer development/promotion.
Gut microbiota is a complex ecological system consisting of at least 500 different bacterial species. Its qualitative and quantitative composition is deeply different depending on the considered gastroenteric tract. In the stomach, a small number of bacteria have been found, mainly consisting of lactobacilli, streptococci, staphylococci, enterobacteriaceae and yeasts. In the subsequent gastrointestinal tracts, there is a quantitative increase from 0 to 105 colony-forming unit/g (CFU/g) in the duodenum, to 108 CFU/g in the ileum, and to 1010 CFU/g in the colon. In the colon more than 99% of the microorganisms are strictly anaerobic, such as bifidobacteria, Bacteroides spp., Clostridium spp., Eubacterium spp., Fusobacterium spp., and peptostreptococci. It varies from one person to another and is modified by age, diet, type of birth, breastfeeding, ileocecal valve efficiency, use of active drugs in both heartburn and gastrointestinal mobility.
In order to understand the connection between gut microbiota and cancer, one has to bear in mind that some of the functions carried out by a eubiotic gut are resistance to intestinal colonization by pathogen bacteria able to cause dysbiosis, induction in IgA production and antimicrobial secretions, regulation of structural entirety of tight junctions and, above all, regulation of innate and adaptive immunity.
Despite the growing interest regarding this field, nowadays, a standardized protocol to study the relationship between gut microbiota and cancer, especially in the interpretation of study results, does not exist. For this reason, the authors focused their attention on the pathogenetic mechanisms sustained by gut-derived inflammation in the development of gastrointestinal cancer.
According to their conclusions:
A common mediator of carcinogenesis in inflamed tissues is the imbalance of oxidative stress induced by inflammation in a normal tissue and sustained by microenviromental inflammation in a context of malignant tumor. Another factor involved in the generation of chronic inflammation that sustains cancer is represented by endotoxemia.