Integrated microbiome and metabolome analysis reveals a novel interplay between commensal bacteria and metabolites in colorectal cancer

Abstract

Rationale : Colorectal cancer (CRC) is a malignant tumor with the third highest morbidity rate among all cancers. Driven by the host's genetic makeup and environmental exposures, the gut microbiome and its metabolites have been implicated as the causes and regulators of CRC pathogenesis. We assessed human fecal samples as noninvasive and unbiased surrogates to catalog the gut microbiota and metabolome in patients with CRC. Methods : Fecal samples collected from CRC patients (CRC group, n = 50) and healthy volunteers (H group, n = 50) were subjected to microbiome (16S rRNA gene sequencing) and metabolome (gas chromatography-mass spectrometry, GC-MS) analyses. The datasets were analyzed individually and integrated for combined analysis using various bioinformatics approaches. Results : Fecal metabolomic analysis led to the identification of 164 metabolites spread across 40 metabolic pathways in both groups. In addition, there were 42 and 17 metabolites specific to the H and CRC groups, respectively. Sequencing of microbial diversity revealed 1084 operational taxonomic units (OTUs) across the two groups, and there was less species diversity in the CRC group than in the H group. Seventy-six discriminatory OTUs were identified for the microbiota of H volunteers and CRC patients. Integrated analysis correlated CRC-associated microbes with metabolites, such as polyamines (cadaverine and putrescine). Conclusions : Our results provide substantial evidence of a novel interplay between the gut microbiome and metabolome (i.e., polyamines), which is drastically perturbed in CRC. Microbe-associated metabolites can be used as diagnostic biomarkers in therapeutic explorations.

Characteristics of fecal metabolic profiles in patients with irritable bowel syndrome with predominant diarrhea investigated using 1H‐NMR coupled with multivariate statistical analysis

“…Polyamines are synthesized from certain amino acids in the host and also produced by intestinal microorganisms. Cadaverine and putrescine levels have shown to be higher in the feces of patients with CD, UC, or colorectal cancer than HC, and the increase in the levels of these polyamines in CD was related to the decrease in intestinal microorganisms of Firmicutes phylum, and Faecalibacterium and Oscillospira species In our study, the increased levels of polyamines in IBS‐D might be caused by alterations in microbial population and metabolism. Cadaverine and putrescine might play certain roles for the development of IBS‐D.…”

Foes or Friends? Bacteria Enriched in the Tumor Microenvironment of Colorectal Cancer

“…The abundance of Porphyromonas in the intestines of CRC patients is higher than that of healthy individuals. Further, Porphyromonas is more abundant in CRC tissues compared to adjacent non-cancer tissues (Table 2) [32,33,35,42,45,47]. However, how Porphyromonas is enriched in this tumor microenvironment remains unclear.…”

“…Among them, some have been recognized as opportunistic pathogens involved not only in periodontitis, inflammatory bowel disease, pancreatic abscess, premature, and hepatic abscess but also in CRC and oral cancer [73][74][75]. Many studies show that Fusobacterium is more abundant in the intestines of CRC patients compared to the healthy individuals [32,33,36,38,42,45,46]. Comparation between CRC tissues and adjacent non-cancer tissues also reveals that Fusobacterium is more abundant in the CRC tissues (Table 2) [30,36,37,43,44].…”

“…Escherichia/Shigella show significant different abundance between CRC patients and healthy individuals. Some studies indicate that CRC patients have higher abundance of Escherichia/Shigella [33,35,36,45], whereas other studies instead reveal that those of Escherichia/Shigella are decreased in the rectal cancer patients compared to healthy individuals (Table 2) [31].…”

Microbial Biomarkers for Colorectal Cancer Identified with Random Forest Model

“…52 A Chinese study supported the identification of CRC and differentiation from the healthy group via 76 fecal potential biomarkers; the CRC group was enriched with 18 operational taxonomic units (OTUs); moreover, fecal metabolites in healthy patients and cancer groups are different. 56 Another meta-analysis of eight studies from different countries and regions identified 29 species as biomarkers of CRC. 57 Furthermore, the microbial species can predict taxonomic and functional microbiome CRC signatures as a basis for future diagnostics.…”