Gut Microbiota-Mediated Inflammation and Gut Permeability in Patients with Obesity and Colorectal Cancer

Abstract

Obesity is considered an important factor that increases the risk of colorectal cancer (CRC). So far, the association of gut microbiota with both obesity and cancer has been described independently. Nevertheless, a specific obesity-related microbial profile linked to CRC development has not been identified. The aim of this study was to determine the gut microbiota composition in fecal samples from CRC patients with (OB-CRC) and without obesity (L-CRC) compared to the microbiota profile present in non-obese healthy controls (L-HC), in order to unravel the possible relationship between gut microbiota and microbial-derived metabolite trimethylamine N-oxide (TMAO), the inflammatory status, and the intestinal permeability in the context of obesity-associated CRC. The presence of obesity does not induce significant changes in the diversity and richness of intestinal bacteria of CRC patients. Nevertheless, OB-CRC patients display a specific gut microbiota profile characterized by a reduction in butyrate-producing bacteria and an overabundance of opportunistic pathogens, which in turn could be responsible, at least in part, for the higher levels of proinflammatory cytokine IL-1β, the deleterious bacterial metabolite TMAO, and gut permeability found in these patients. These results suggest a possible role of obesity-related gut microbiota in the development of CRC, which could give new clues for the design of new diagnostic tools for CRC prevention.

Connection between the Gut Microbiome, Systemic Inflammation, Gut Permeability and FOXP3 Expression in Patients with Primary Sjögren’s Syndrome

“…To compare the alpha diversity, the Chao1, ACE, Shannon and Simpson indices were calculated after rarefying the OTU table to 1731 sequences, the size of the smallest sample to obtain equal sequencing depth. These analyses revealed a significant decrease in richness (Chao1 and ACE) and diversity (Shannon and Simpson) in pSS patients compared to healthy controls (Chao1 q < 0.001, ACE p < 0.001, Shannon p = 0.0017 and Simpson p = 0.05) (Figure 1A,B 53 species using the Quantitative Insights into Microbial Ecology (QIIME2) pipeline, with Greengenes v13.8 as the reference database for sequence classification and alignment.…”

“…Quantitative Insights into Microbial Ecology (QIIME2, version 2019.4) software [ 52 ] was used to analyze sequence quality and for diversity and taxonomic analysis as previously described [ 53 ]. Alpha (Shannon and Chao1) and beta (Bray-Curtis dissimilarity) diversity metrics were estimated with the Kruskal—Wallis test and the permutational multivariate analysis of variance (PERMANOVA) with 999 permutations respectively.…”

Growth Factors, PI3K/AKT/mTOR and MAPK Signaling Pathways in Colorectal Cancer Pathogenesis: Where Are We Now?

“…In addition, the consumption of red meat and other animal products is conducive to trimethylamine N-oxide (TMAO) synthesis, a gut microbiota-derived metabolite of choline and L-carnitine, associated with an increased risk of CRC, cardiovascular disease, and diabetes. The correlation between TMAO and cancer is performed via inflammation, OS, DNA damage, and protein folding disruption [ 33 ].…”

The Effect of Bacterial Infections, Probiotics and Zonulin on Intestinal Barrier Integrity

“…Correspondingly, we have found that plasma zonulin levels were significantly higher in obese patients compared to control groups of non-obese intestinal cancer patients, as well as healthy patients. Elevated zonulin levels were attributed to the abundance of Prevotella in the gut microbiota of obese patients [ 140 ]. Prevotella contains enzymes important in mucin degradation that can disrupt the colonic mucosal barrier and impair intestinal barrier function [ 141 ].…”