Systematic review: The gut microbiota as a link between colorectal cancer and obesity

Abstract

Microbiome modulation is one of the novel strategies in medicine with the greatest future to improve the health of individuals and reduce the risk of different conditions, including metabolic, immune, inflammatory, and degenerative diseases, as well as cancer. Regarding the latter, many studies have reported the role of the gut microbiome in carcinogenesis, formation and progression of colorectal cancer (CRC), as well as its response to different systemic therapies. Likewise, obesity, one of the most important risk factors for CRC, is also well known for its association with gut dysbiosis. Moreover, obesity and CRC display, apart from microbial dysbiosis, chronic inflammation, which participates in their pathogenesis. Although human and murine studies demonstrate the significant impact of the microbiome in regulating energy metabolism and CRC development, little is understood about the contribution of the microbiome to the development of obesity-associated CRC. Therefore, this systematic review explores the evidence for microbiome changes associated with these conditions and hypothesizes that this may contribute to the pathogenesis of obesity-related CRC. Two databases were searched, and different studies on the relationship among obesity, intestinal microbiota and CRC in clinical and preclinical models were selected. Data extraction was carried out by two reviewers independently, and 101 studies were finally considered. Findings indicate the existence of a risk association between obesity and CRC derived from metabolic, immune, and microbial disorders.

Keywords: colitis; colorectal cancer; microbiota; obesity.

FIGURE 1

Flow diagram of the literature search process.

FIGURE 2

Metabolic, immune, and microbial alterations in obesity‐associated CRC. Obesity‐associated gut dysbiosis and the release of bacteria‐derived metabolites promote CRC progression. Additionally, imbalanced adipokines and chronic inflammation, common in obesity, enhance this process. All these events induce the activation of molecular pathways involved in cell proliferation, apoptosis evasion, angiogenesis, invasion and metastasis leading to initiation, promotion and progression of CRC. BSH: bile salt hydrolase; SCFA: short‐chain fatty acid; DCA: Deoxycholic acid; LCA: lithocholic acid; T‐βMCA: tauro‐β‐muricholic acid; LPS: lipopolysaccharide; LPC: lysophosphatidylcholine; MPS1: Metallopanstimulin‐1; TAM: tumor‐associated macrophages; TAN: tumor‐associated neutrophils.

FIGURE 3

Microbiota‐derived metabolites in obese and non‐obesity and their impact on colon tumor cell malignancy. Certain bacterial genera and species are more enriched in obesity‐associated intestinal microbiota. These bacteria release some metabolites, such as SCFAs, LPS, glycerophospholipids, and bile acids that act directly on the tumor cell and induce changes in proliferation, apoptosis, migration, and stemness. SCFAs: short‐chain fatty acids; B: butyrate; P: propionate; A: acetate; GPR: G protein‐coupled receptor; CTNNB1: β‐catenin; HDACs: histone deacetylases; LPS: lipopolysaccharide; GLPs: glycerophospholipids; LPC: lysophosphatidylcholine; LPA: lysophosphatidic acid; BAs: bile acids; DCA: deoxycholic acid; LCA: lithocholic acid; GCDCA: glycochenodeoxycholate.