About this Research Topic
The microbial community in the digestive tract represents a dynamic array of diverse and complex organisms including bacteria, parasites, protists, fungi and viruses. It is assembled following birth to establish a niche that maintains a dialogue with the host. This dialogue can impact the development and functions of the digestive tract such as digestion, host metabolism, protection from enteric pathogens, immune reactivity, and local as well as systemic health. The intestinal microbiota has also been widely recognized for its role in maintaining the integrity of the intestinal mucosa, and the dysregulation of the host-microbiome interactions can directly contribute to diseases such as colorectal cancer (CRC), inflammatory bowel disease (IBD), cardiovascular disease, diabetes mellitus, and mental illness.
CRC is the result of accumulated mutations in the epithelial cells and dysregulation of the immune response. Whereas genetic background can explain the development of CRC, greater than 90% of the disease risk is attributed to environmental factors such as age and diet, where changes in microbiota can occur. In the past decade, the role of intestinal microbes in the development and progression of CRC has been established. For instance, disruption of the intestinal epithelium barrier where the host-microbiome interactions are compromised, enables commensal or pathogenic bacteria to translocate into the mucosa, and promote inflammation and cytotoxicity leading to carcinogenic mutations. This has been particularly established for E. coli, B. fragilis and, E. faecalis while other species of commensal or pathogenic bacteria could have antitumoral properties through production of antioxidant or anti-inflammatory metabolites. This exciting, emerging research field may also provide an additional etiological insight into the gene mutation spectrum during the IBD-associated carcinogenesis versus conventional (non-IBD related) CRC.
Our understanding of how the microbiome's dynamics mechanistically affects the homeostasis of host responses in health and disease remains incomplete. Thus, we aim to highlight recent findings on the cellular and molecular mechanisms of diverse microbial actors associated with the pathogenesis of CRC, including IBD-associated CRC. In addition, these insights can lead to new hypotheses regarding novel therapeutic strategies based on the short or long-term manipulation of the microbiome, in order to prevent or attenuate the impact of disease.
In this Research Topic, we therefore welcome Original Research Articles, and Brief Research Reports (both on human and animal studies relevant to human diseases), Reviews, and Mini-Reviews that cover, but are not limited to, the following subtopics related to the role of intestinal host-microbial interactions in CRC development:
• Transient or chronic changes in gut microbial communities.
• Identification of oncogenic CRC-associated microbiota.
• Microbial cytotoxicity/genotoxicity (i.e. mechanism of DNA damage/mutation/repair induced by ROS or bacterial toxins).
• Characteristics of microbial specific PAMP/DAMP cellular signalling.
• Impact of gut microbial communities on immune homeostasis (i.e. inflammation, antitumoral immunity).
• Impact of the local metabolites (from diet or microbiome itself) on host-microbial interactions.
• Novel hypotheses and strategies to enhance protective host responses by microbiome editing.
Keywords: Gut Microbiota, Microbial Toxicity, Microbiome-Based Therapy, Microbiome-Shaped Immunity, CRC, Colorectal Cancer
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