Metaproteomics characterizes human gut microbiome function in colorectal cancer

Abstract

Pathogenesis of colorectal cancer (CRC) is associated with alterations in gut microbiome. Previous studies have focused on the changes of taxonomic abundances by metagenomics. Variations of the function of intestinal bacteria in CRC patients compared to healthy crowds remain largely unknown. Here we collected fecal samples from CRC patients and healthy volunteers and characterized their microbiome using quantitative metaproteomic method. We have identified and quantified 91,902 peptides, 30,062 gut microbial protein groups, and 195 genera of microbes. Among the proteins, 341 were found significantly different in abundance between the CRC patients and the healthy volunteers. Microbial proteins related to iron intake/transport; oxidative stress; and DNA replication, recombination, and repair were significantly alternated in abundance as a result of high local concentration of iron and high oxidative stress in the large intestine of CRC patients. Our study shows that metaproteomics can provide functional information on intestinal microflora that is of great value for pathogenesis research, and can help guide clinical diagnosis in the future.

What Is Known about Theragnostic Strategies in Colorectal Cancer

“…On the other hand, the Firmicutes phylum (particularly the Ruminococcaceae and Lachnospiraceae families) [ 82 ] as well as Bifidobacteria, Lactobacilli [ 83 , 84 ] and non-enterotoxigenic Bacteroides fragilis (NTBF) [ 84 ] are substantially underrepresented in CRC patients [ 85 ] and have shown “anti-oncogenic” activities, such as a reduction of pro-inflammatory citokines, enhancement of antitumor immunity, epithelial cell renewal, regulation of intestinal barrier integrity, and short-chain fatty acid (SCFA) production [ 82 , 83 , 84 , 85 , 86 ]. SCFAs, by modulating histone deacetylase inhibitory activity, promote the accumulation and differentiation of Treg cells controlling tumor progression [ 86 ].…”

Gut Microbiota Manipulation as a Tool for Colorectal Cancer Management: Recent Advances in Its Use for Therapeutic Purposes

“…In particular, the CRC-associated microbiota is characterized by the increased abundance of Enterobacteriaceae , Streptococcus , and typical genera belonging to the oral microbiota such as Fusobacterium , Gemella , Peptostreptococcus , Prevotella , Solobacterium , and Parvimonas [ 26 , 27 , 28 ]. On the contrary, the Firmicutes phylum (especially the Ruminococcaceae and Lachnospiraceae families) as well as Bifidobacterium, Odoribacter , and Streptococcus are substantially underrepresented in CRC patients [ 29 , 30 ]. In fact, gut microbiota transplant from CRC patients into mice is sufficient to disrupt the intestinal barrier, leading to low-grade inflammation and dysbiosis.…”

“…Similarly to colibactin and BFT, Fn mediates DNA damage and promotes tumor cell proliferation through the Wnt/β-catenin pathway [ 43 ]. Furthermore, bacterial metabolism might affect CRC progression by the production of oxidative stress molecules [ 30 , 44 , 45 ], promoting chronic inflammation and disrupting intestinal barrier integrity [ 36 , 46 ]. Moreover, choline degradation by gut bacteria contributes to colon cancer via the synthesis of trimethylamine N-oxide, a potential carcinogen [ 28 ].…”

Influence of Iron on the Gut Microbiota in Colorectal Cancer

“…Many pathogenic bacteria have heightened iron acquisition mechanisms to aid in their growth and virulence. This can alter microbial populations when there is an increase in gut luminal iron concentration [122][123][124]. Along with diet, oral iron supplementation to treat anemia can also contribute to luminal iron concentration and therefore has the potential to alter colonic bacterial populations [125].…”