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. 2021 Aug 30;71(7):1315–1325. doi: 10.1136/gutjnl-2020-323476

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© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

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Investigating the gut microbiome-associated serum metabolites significantly altered in abnormal colorectal patients by integrating faecal metagenome and serum metabolome analyses. (A) Diagram showing the procedure of integrated analysis of the faecal metagenome and serum metabolome in the serum and faeces matched cohort (11 normal individuals, 33 patients with adenoma and CRC). Untargeted metabolic detection of the serum samples and metagenome sequencing of the faecal samples were carried out in this cohort. Significantly altered microbiome species between the normal and colorectal abnormal populations were calculated based on their relative abundances. Pearson correlation coefficient analysis was carried out in the 33 abnormal colorectal patients, and the gut microbiome-associated serum metabolites profile was established. Additionally, we used MSI and the correlation results of the bile acids to further support our correlation analysis’s reliability. (B) Relative abundances of several CRC-associated gut microbiome species in the normal individuals and abnormal colorectal patients of the matched cohort (red indicates tumour-promoting species, blue indicates probiotics). (C) Distribution of the Pearson correlation coefficients between each serum metabolite and gut microbe species (cut-off: p<1E-3, FDR ≤18%). (D) Sankey diagram showing covariations between CRC-associated gut microbes and their correlated serum metabolites. Associations between metabolites and species that have been previously reported to be tumour-promoting in colorectal cancer are highlighted in red, while associations between metabolites and antitumoural species are highlighted in blue. Grey lines represent the associations of these metabolites with other bacterial species, which have no clear roles in CRC. The meaning of colour codes for these metabolites was as following: metabolites associated with CRC-promoting species (purple), with antitumoural species (green), with both antitumoural and tumour-promoting species (dark blue), which is consistent with the colour codes in figure 2E. (E) A heatmap showing the relative abundances of metabolites associated with CRC-promoting species (purple), with antitumoural species (green), or with both antitumoural and tumour-promoting species (dark blue) in the discovery cohort. Metabolites associated with tumour-promoting species were significantly enriched in the patients with adenoma and colorectal cancer, while metabolites associated with antitumoural species were higher in the normal individuals. All the individuals were ranked by an association index (column on the right of the heatmap) of their metabolites with the tumour-promoting species. Based on this value, the normal individuals (light blue) could be clearly distinguished from the abnormal colorectal patients (red). CRC, ryonic anti; FDR, false discovery rate; GMSM, gut microbiome-associated serum metabolites; MSI, mass spectrometry imaging.