A Microbiomic Analysis in African Americans with Colonic Lesions Reveals Streptococcus sp.VT162 as a Marker of Neoplastic Transformation

Abstract

Increasing evidence suggests a role of the gut microbiota in colorectal carcinogenesis (CRC). To detect bacterial markers of colorectal cancer in African Americans a metabolomic analysis was performed on fecal water extracts. DNA from stool samples of adenoma and healthy subjects and from colon cancer and matched normal tissues was analyzed to determine the microbiota composition (using 16S rDNA) and genomic content (metagenomics). Metagenomic functions with discriminative power between healthy and neoplastic specimens were established. Quantitative Polymerase Chain Reaction (q-PCR) using primers and probes specific to Streptococcus sp. VT_162 were used to validate this bacterium association with neoplastic transformation in stool samples from two independent cohorts of African Americans and Chinese patients with colorectal lesions. The metabolomic analysis of adenomas revealed low amino acids content. The microbiota in both cancer vs. normal tissues and adenoma vs. normal stool samples were different at the 16S rRNA gene level. Cross-mapping of metagenomic data led to 9 markers with significant discriminative power between normal and diseased specimens. These markers identified with Streptococcus sp. VT_162. Q-PCR data showed a statistically significant presence of this bacterium in advanced adenoma and cancer samples in an independent cohort of CRC patients. We defined metagenomic functions from Streptococcus sp. VT_162 with discriminative power among cancers vs. matched normal and adenomas vs. healthy subjects’ stools. Streptococcus sp. VT_162 specific 16S rDNA was validated in an independent cohort. These findings might facilitate non-invasive screening for colorectal cancer.

$W_{d}^{*}$-test: robust distance-based multivariate analysis of variance

“…Several genus level bacterial taxa have been associated with CRC [7] but the role of personal characteristics in influencing the presence of CRCassociated bacteria is not well understood. A few studies have noted marked differences in the microbial environment in the gut of African-Americans (AA) versus others [7][8][9][10][11] (e.g., Caucasian (CA)) and suggested differences in microbial composition among those with and without colorectal polyps and cancer. Others found distinct differences in the microbes populating the proximal and distal colo-rectum [12,13].…”

“…Lower socioeconomic status and western diet have been associated with a lower microbial diversity, especially in the distal colon [14,15]. Microbial signature approaches have been used for development of diagnostic biomarkers [9,[16][17][18] or assessing differences in immune gene expression [13]-highlighting the increasing importance of statistical methods to analyze clusters of microbes-genes while also taking into account patient-level variables. The role of the gut microbiome in CRC disparities is likewise poorly understood [19].…”

Information Enhanced Model Selection for Gaussian Graphical Model with Application to Metabolomic Data

“…The dataset was obtained from metabolomics characterizations of stool samples collected from infants at approximately six weeks to one year of age. Sample preparation (with some modifications), 1 H NMR data acquisition, and metabolites profiling procedures have been previously described in Brim et al (2017); Sumner et al (2009Sumner et al ( , 2015; Banerjee et al (2012); Pathmasiri et al (2012). Chenomx NMR Suite 8.4 Professional software (Edmonton, Alberta, Canada) was used to determine relative concentration (Weljie et al (2006)) of selected metabolites from a curation of list of metabolites that are associated with host-microbiome metabolism, see Li et al (2008);Paul et al (2016).…”

Wd*-test: Robust Distance-Based Multivariate Analysis of Variance

“…Several genus level bacterial taxa have been associated with CRC [6] but the role of personal characteristics in influencing the presence of CRCassociated bacteria is not well understood. A few studies have noted marked di↵erences in the microbial environment in the gut of AAs versus others [6,7,8,9,10] and suggested di↵erences in microbial composition among those with and without colorectal polyps and cancer. Others found distinct di↵erences in the microbes populating the proximal and distal colo-rectum [11,12].…”

“…Lower socioeconomic status and western diet have been associated with a lower microbial diversity, especially in the distal colon [13,14]. Microbial signature approaches have been used for development of diagnostic biomarkers [8,15,16,17] or assessing di↵erences in immune gene expression [12] -highlighting the increasing importance of statistical methods to analyze clusters of microbes-genes while also taking into account patient level variables. The role of the gut microbiome in CRC disparities is likewise poorly understood [18].…”