Implication of Obesity and Gut Microbiome Dysbiosis in the Etiology of Colorectal Cancer

Abstract

The complexity and variety of gut microbiomes within and among individuals have been extensively studied in recent years in connection to human health and diseases. Our growing understanding of the bidirectional communication between metabolic diseases and the gut microbiome has also highlighted the significance of gut microbiome dysbiosis in the genesis and development of obesity-related cancers. Therefore, it is crucial to comprehend the possible role of the gut microbiota in the crosstalk between obesity and colorectal cancer (CRC). Through the induction of gut microbial dysbiosis, gut epithelial barrier impairment, metabolomic dysregulation, chronic inflammation, or dysregulation in energy harvesting, obesity may promote the development of colorectal tumors. It is well known that strategies for cancer prevention and treatment are most effective when combined with a healthy diet, physical activity, and active lifestyle choices. Recent studies also suggest that an improved understanding of the complex linkages between the gut microbiome and various cancers as well as metabolic diseases can potentially improve cancer treatments and overall outcomes. In this context, we herein review and summarize the clinical and experimental evidence supporting the functional role of the gut microbiome in the pathogenesis and progression of CRC concerning obesity and its metabolic correlates, which may pave the way for the development of novel prognostic tools for CRC prevention. Therapeutic approaches for restoring the microbiome homeostasis in conjunction with cancer treatments are also discussed herein.

Association between Surrogate Markers of Insulin Resistance and the Incidence of Colorectal Cancer in Korea: A Nationwide Population-Based Study

“…Moreover, changes in sex hormone and adipokine levels can affect cell growth, inflammation, and other processes associated with cancer development [ 36 , 37 ]. Additionally, obesity and metabolic syndrome alter the gut microbiome and play a role in these mechanisms [ 38 , 39 ]. In addition to the aforementioned factors, IR is a key mechanism involved in this process.…”

Role of circular RNAs and gut microbiome in gastrointestinal cancers and therapeutic targets

“…The host immune system [ 20 ], food metabolism [ 21 ], and a variety of bioactive metabolites produced by the gut microbiota all interact with one another to influence the gut microenvironment and general health [ 22 ]. Dysbiosis, an imbalance in the gut's microbial population, has been connected to several gastrointestinal illnesses, including esophageal cancer [ 23 ], gastric cancer [ 24 ], hepatocellular cancer [ 25 ], pancreatic cancer [ 26 ], and colorectal cancer [ 27 ]. The gut microbiota can either directly or indirectly influence tumor development and therapeutic response in GI malignancies [ 19 ].…”

Obesity under the moonlight of c-MYC

“…A thinner mucous layer, uneven localization of tight junction proteins (TJP), an abnormal immunological response involving immunoglobulin A (IgA), and antimicrobial peptides like lipopolysaccharides (LPS) can all contribute to intestinal disbiosis in obese people. Collectively, these defects cause LPS leakage, which eventually leads to TLR4/MyD88 and NF-κB activation and inflammation ( Singh et al, 2023 ).…”