The Gut Microbiome in Colorectal Cancer

Dear Colleagues,

The trillions of microbes collectively referred to as the human microbiota inhabit the human body and have a beneficial relationship with the host. It is clear, however, that dysbiosis impacting microbial diversity in the gut may lead to the development of inflammatory and malignant gastrointestinal diseases including colorectal cancer (CRC). A growing body of evidence implicates altered gut microbiota in the development of CRC. The profiles of CRC associated microbiota have been shown to differ from those in healthy subjects, and bacterial phylotypes vary depending on the primary tumor location. The compositional variation in the microbial profile is not restricted to cancerous tissue, however, and is different between cancers of the proximal and distal colons, respectively. More recently, studies have shed light on the "driver–passenger" model for CRC, wherein driver bacteria cause inflammation, increased cell proliferation, and the production of genotoxic substances to contribute to mutational acquisition associated with the adenoma–carcinoma sequence. These changes facilitate the gradual replacement of driver bacteria by passengers that either promote or suppress tumor progression. However, the mechanisms through which the bacterial constituents of the microbiome contribute to CRC are complex and yet to be fully understood. Thus, more exhaustive and mechanistic studies are needed to identify key interactions between the diet, microbial community, and metabolites that help to facilitate the adenoma–carcinoma sequence evolution in CRC.

Significant advances have been made in associating individual bacterial species to consensus molecular subtypes (CMS) of CRC, and this remarkable development is expected to galvanize the scientific community to advance therapeutic strategies for CRC. It is expected that the development of therapeutics based on the microbial association with CMS will likely facilitate the translation of molecular subtypes into the clinic for CRCs and potentially other malignancies.

The microbiota niche in colorectal cancer can also modify the efficacy and toxicity profile of different oncotherapeutic treatment modalities from chemoradiotherapy to immunotherapy. Conversely, each of these treatment modalities has numerous effects on the gastrointestinal flora, causing changes in the gut microbial community that affect host morbidity and mortality. A closer look at the cross-talks between the commensals, epithelial cells, immune regulators, and so on needs to be established with more substantiated studies. The recurrence of chemoresistant disease following therapy undoubtedly provides the impetus for morbidity and mortality; however, the role of the gut microbiome in drug resistance remains to be fully investigated.

Prof. Dr. Shahid Umar
Prof. Dr. Mazin F. Al-Kasspooles
Guest Editors

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• gut microbiome
• colon cancer
• chemoradiation
• chemotherapy
• drug resistance
• immunotherapy