Altered Gut Archaea Composition and Interaction With Bacteria Are Associated With Colorectal Cancer

Abstract

BACKGROUND & AIMS: Changes in the intestinal microbiota have been associated with development and progression of colorectal cancer (CRC). Archaea are stable components of the microbiota, but little is known about their composition or contribution to colorectal carcinogenesis. We analyzed archaea in fecal microbiomes of 2 large cohorts of patients with CRC. METHODS: We performed shotgun metagenomic analyses of fecal samples from 585 participants (184 patients with CRC, 197 patients with adenomas, and 204 healthy individuals) from discovery (165 individuals) and validation (420 individuals) cohorts. Assignment of taxonomies was performed by exact k-mer alignment against an integrated microbial reference genome database. RESULTS: Principal component analysis of archaeomes showed distinct clusters in fecal samples from patients with CRC, patients with adenomas, and control individuals (P < .001), indicating an alteration in the composition of enteric archaea during tumorigenesis. Fecal samples from patients with CRC had significant enrichment of halophilic and depletion of methanogenic archaea. The halophilic Natrinema sp. J7-2 increased progressively in samples from control individuals, to patients with adenomas, to patients with CRC. Abundances of 9 archaea species that were enriched in fecal samples from patients with CRC distinguished them from control individuals with areas under the receiver operating characteristic curve of 0.82 in the discovery cohort and 0.83 in the validation cohort. An association between archaea and bacteria diversities was observed in fecal samples from control individuals but not from patients with CRC. Archaea that were enriched in fecal samples from patients with CRC had an extensive mutual association with bacteria that were enriched in the same samples and exclusivity with bacteria that were lost from these samples. CONCLUSIONS: Archaeomes of fecal samples from patients with CRC are characterized by enrichment of halophiles and depletion of methanogens. Studies are needed to determine whether associations between specific archaea and bacteria species in samples from patients with CRC contribute to or are a response to colorectal tumorigenesis.

Impaired Intestinal Sodium Transport in Inflammatory Bowel Disease: From the Passenger to the Driver's Seat

“…Recent studies have shown that high gut salinity is associated with enrichment of halophiles that have pro-obesity and cancer-promoting properties [79,80]. Future studies aimed at finding specific halophilic bacteria in the intestinal microbiota that are under Darwinian selection in the increased fecal salinity environment seen in patients with CSD may yield novel pathobionts that may be important for mediating IBD pathology and could provide actionable therapeutic approaches.…”

Metagenomic Analysis of the Fecal Archaeome in Suckling Piglets Following Perinatal Tulathromycin Metaphylaxis

“…The current advancement of metagenomic methods and optimization of next-generation sequencing protocols have leveraged our current understanding of the dynamics of gastrointestinal archaeal populations and their role in health and disease [ 13 , 14 , 15 ]. The archaeal population, or ‘archaeome’, is comprised of unicellular microorganisms with a distinct biology compared with bacteria and has been shown to be an important component of host-associated microbes [ 16 ].…”

Role of Gut Microbiota and Probiotics in Colorectal Cancer: Onset and Progression

“…In particular, fecal samples from patients with CRC demonstrated significant enrichments in halophilic archaea and depletions in methanogenic archaea. Furthermore, CRC-associated halophiles were positively associated with the oncogenic bacterium B. fragilis and were negatively correlated with butyrate-producing Clostridium species [ 87 ].…”