Potential of fecal microbiota for early‐stage detection of colorectal cancer

Abstract

Several bacterial species have been implicated in the development of colorectal carcinoma (CRC), but CRC-associated changes of fecal microbiota and their potential for cancer screening remain to be explored. Here, we used metagenomic sequencing of fecal samples to identify taxonomic markers that distinguished CRC patients from tumor-free controls in a study population of 156 participants. Accuracy of metagenomic CRC detection was similar to the standard fecal occult blood test (FOBT) and when both approaches were combined, sensitivity improved > 45% relative to the FOBT, while maintaining its specificity. Accuracy of metagenomic CRC detection did not differ significantly between early- and late-stage cancer and could be validated in independent patient and control populations (N = 335) from different countries. CRC-associated changes in the fecal microbiome at least partially reflected microbial community composition at the tumor itself, indicating that observed gene pool differences may reveal tumor-related host–microbe interactions. Indeed, we deduced a metabolic shift from fiber degradation in controls to utilization of host carbohydrates and amino acids in CRC patients, accompanied by an increase of lipopolysaccharide metabolism.

Subspecies in the global human gut microbiome

“…To this end, we assessed the microbial genetic landscape of 2,144 deeply sequenced human stool metagenomes from nine countries, spanning three continents, including published (Huttenhower et al , 2012; Qin et al , 2012; Karlsson et al , 2013; Le Chatelier et al , 2013; Zeller et al , 2014) as well as 298 newly generated ones (Table EV1). The newly sequenced samples include a Kazakh cohort as well as three individuals from Germany that have been sampled over an extended period of time (see Materials and Methods).…”

“…Specifically, we used 239 stool samples from the HMP (Huttenhower et al , 2012) collected from 139 US American individuals, as well as 676 oral samples from the same individuals; 156 samples from as many Austrian individuals (Yu et al , 2015); 368 Chinese samples (Qin et al , 2012); 387 Danish samples from the MetaHIT cohort; 156 French and 40 German samples (Zeller et al , 2014); 126 novel German samples collected from 26 individuals; 172 novel Kazakh samples from 86 individuals; 359 Spanish samples from MetaHIT; and 145 Swedish samples (Karlsson et al , 2013; Table EV1). Informed consent was obtained from the German individuals through the my.microbes project (http://my.microbes.eu).…”

“…Genomic DNA was extracted from frozen fecal samples as previously described (Zeller et al , 2014) using the GNOME ® DNA Isolation Kit (MP Biomedicals).…”

“…Reads were quality‐filtered and screened against the human genome sequence for removing contamination as previously described (Zeller et al , 2014). Species abundance was calculated using established MOCAT (Kultima et al , 2012) protocols for specI clusters (Mende et al , 2012).…”

Biomarker – vom Sein und Wesen

“…Weitere Disziplinen bieten sich hier als Kombinationspartner an, z.B. Lipidomics [8], Metagenomics [9], Interactomics [10] Was macht "Biomarker" aus?…”