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.
[1]Fudan Univ, Shanghai Canc Ctr, Dept Colorectal Surg, 270 Dongan Rd, Shanghai 200032, Peoples R China;
[2]Fudan Univ, Shanghai Med Coll, Dept Oncol, 270 Dongan Rd, Shanghai 200032, Peoples R China;
[3]Tongji Univ, Shanghai Tenth Peoples Hosp, Dept GI Surg, Shanghai 200072, Peoples R China;
[4]Ctr Precis Med, Dept Internal Med, Sect Mol Med, Med Ctr Blvd, Winston Salem, NC 27157 USA;
[5]Tongji Univ, Shanghai Peoples Hosp 10, Dept Pathol, Shanghai 200072, Peoples R China;
[6]Tongji Univ, Sch Med, Yangpu Hosp, Dept Clin Lab, Shanghai, Peoples R China;
[7]Tongji Univ, Sch Med, Yangpu Hosp, Ctr Translat Med, Shanghai, Peoples R China;
[8]Baylor Scott & White Res Inst, Ctr Epigenet Canc Prevent & Canc Gen, Ctr Gastrointestinal Res, Dallas, TX USA;
[9]Charles A Sammons Canc Ctr, Dallas, TX USA
(8.0+极速模式)