New Insights into Molecular Links Between Microbiota and Gastrointestinal Cancers: A Literature Review

Abstract

Despite decades of exhaustive research on cancer, questions about cancer initiation, development, recurrence, and metastasis have still not been completely answered. One of the reasons is the plethora of factors acting simultaneously in a tumour microenvironment, of which not all have garnered attention. One such factor that has long remained understudied and has only recently received due attention is the host microbiota. Our sheer-sized microbiota exists in a state of symbiosis with the body and exerts significant impact on our body’s physiology, ranging from immune-system development and regulation to neurological and cognitive development. The presence of our microbiota is integral to our development, but a change in its composition (microbiota dysbiosis) can often lead to adverse effects, increasing the propensity of serious diseases like cancers. In the present review, we discuss environmental and genetic factors that cause changes in microbiota composition, disposing of the host towards cancer, and the molecular mechanisms (such as β-catenin signalling) and biochemical pathways (like the generation of oncogenic metabolites like N-nitrosamines and hydrogen sulphide) that the microbiota uses to initiate or accelerate cancers, with emphasis on gastrointestinal cancers. Moreover, we discuss how microbiota can adversely influence the success of colorectal-cancer chemotherapy, and its role in tumour metastasis. We also attempted to resolve conflicting results obtained for the butyrate effect on tumour suppression in the colon, often referred to as the ‘butyrate paradox’. In addition, we suggest the development of microbiota-based biomarkers for early cancer diagnosis, and a few target molecules of which the inhibition can increase the overall chances of cancer cure.

Ultra-Processed Food Intake and Smoking Interact in Relation with Colorectal Adenomas

“…One potential mechanism to explain this interaction is the joint effects of smoking and diet on the gut microbiome [ 41 ], which can in turn influence CRC risk. The main proposed mechanisms linking the microbiome with colorectal neoplasia include secretion of oncogenic microbial metabolites, such as secondary bile acids, and activation and promotion of an inflammatory response in the gut mucosa, which further promote the growth of tumor cells, and inhibit apoptosis [ 42 , 43 , 44 ]…”

Entamoeba histolytica—Gut Microbiota Interaction: More Than Meets the Eye

“…In contrast, the ability of the gut microbiota to generate RNS is well discussed (for a recent review see [ 86 ]). The gut bacteria can convert nitrites into nitrosamines which have carcinogenic properties [ 87 ] and some food components present in meat and fish into trimethylamine. In the liver, trimethylamine is converted to its oxidized form (trimethylamine N -oxide) which have deleterious effects on cardiovascular and metabolic function [ 88 ].…”

The Role of Gut Microbiota in Tumor Immunotherapy

“…With the advancement of genomics and metabolomics technology, the research on the gut microbiome has gradually deepened [ 6 ]. The interaction between the intestinal microbiota and the human body was revealed, and it was also found that the intestinal microbiota is closely related to the occurrence and evolution of various diseases [ 10 – 12 ]. The intestinal microbiota plays an important role in the human body environment.…”