In Silico Analysis of Putrefaction Pathways in Bacteria and Its Implication in Colorectal Cancer - PubMed (original) (raw)

In Silico Analysis of Putrefaction Pathways in Bacteria and Its Implication in Colorectal Cancer

Harrisham Kaur et al. Front Microbiol. 2017.

Abstract

Fermentation of undigested proteins in human gastrointestinal tract (gut) by the resident microbiota, a process called bacterial putrefaction, can sometimes disrupt the gut homeostasis. In this process, essential amino acids (e.g., histidine, tryptophan, etc.) that are required by the host may be utilized by the gut microbes. In addition, some of the products of putrefaction, like ammonia, putrescine, cresol, indole, phenol, etc., have been implicated in the disease pathogenesis of colorectal cancer (CRC). We have investigated bacterial putrefaction pathways that are known to be associated with such metabolites. Results of the comprehensive in silico analysis of the selected putrefaction pathways across bacterial genomes revealed presence of these pathways in limited bacterial groups. Majority of these bacteria are commonly found in human gut. These include Bacillus, Clostridium, Enterobacter, Escherichia, Fusobacterium, Salmonella, etc. Interestingly, while pathogens utilize almost all the analyzed pathways, commensals prefer putrescine and H2S production pathways for metabolizing the undigested proteins. Further, comparison of the putrefaction pathways in the gut microbiomes of healthy, carcinoma and adenoma datasets indicate higher abundances of putrefying bacteria in the carcinoma stage of CRC. The insights obtained from the present study indicate utilization of possible microbiome-based therapies to minimize the adverse effects of gut microbiome in enteric diseases.

Keywords: bacterial pathogenicity; colorectal cancer; genome mining; gut microbiome; protein fermentation.

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Figures

FIGURE 1

FIGURE 1

Schematic representation of putrefaction pathways. Pathways for conversions of (A) histidine to glutamate, (B) histidine to tetrahydrofolate, (C) glutamate to acetate and pyruvate, (D) arginine to putrescine, (E) tyrosine to phenol, (F) tryptophan to indole, (G) lysine to cadaverine, (H) Methionine to spermidine/spermine, (I) cysteine to H2S, and (J) tyrosine to cresol. The EC numbers and Pfam domain(s) corresponding to the enzymes involved in each reaction have been mentioned.

FIGURE 2

FIGURE 2

Putrefaction pathways across bacterial phyla. Distribution of 10 putrefaction pathways across phyla comprising of completely sequenced bacterial genomes. The pathway ‘Spermidine production’ also represents the pathway for spermine production. ‘Pfacs’ (Putrefaction score) corresponding to the putrefaction pathways in these phyla is highlighted in each cell. ‘Pfacs’ indicates the relative putrefaction capabilities of any phylum, evaluated based on the number of constituting putrefying strains and the database size of the respective phylum.

FIGURE 3

FIGURE 3

Putrefaction pathways in bacterial genera found in gut. Distribution of ten putrefaction pathways across genera comprising of completely sequenced bacterial genomes found in human gut. The pathway ‘Spermidine production’ also represents the pathway for spermine production. ‘Pfacs’ (Putrefaction score) corresponding to the putrefaction pathways in these genera is highlighted in each cell. ‘Pfacs’ indicates the relative putrefaction capabilities of any genus, evaluated based on the number of constituting putrefying strains and the database size of the respective genus.

FIGURE 4

FIGURE 4

Distribution of putrefaction pathways in pathogenic and commensal gut bacteria. Percentage of strains identified to have various putrefaction pathways in (A) pathogenic and (B) commensal gut bacteria. Pathway distribution in individual strains of the (C) pathogenic and (D) commensal gut bacteria.

FIGURE 5

FIGURE 5

Putrefaction capabilities of differentially abundant genera in gut microbiome of healthy and colorectal cancer patients. Heatmaps representing distribution of selected putrefaction pathways (associated with production of harmful compounds) in the differentially abundant genera in one of the cohorts (carcinoma/adenoma/healthy) with respect to the other(s). Each cell represents the ‘Pfacs’ (Putrefaction score) of the corresponding pathway in that particular genus. ‘Pfacs’ indicates the relative putrefaction capabilities of any genus, evaluated based on the number of constituting putrefying strains and the database size of the respective genus.

FIGURE 6

FIGURE 6

Correlation between putrefaction and oxygen requirement. Percentage of differential putrefying genera in the gut microbiome of healthy, adenoma and carcinoma datasets in different categories (based on oxygen requirement).

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