Prospective case-cohort study of intestinal colonization with enterococci that produce extracellular superoxide and the risk for colorectal adenomas or cancer

Abstract

Significant associations were found for those with large adenomas or cancer (but not small adenomas), with age, and with foods enriched for vitamin A, vitamin E, and beta-carotene. An association between colonization with O2*--producing enterococci and colorectal adenomas or cancer, however, could not be ascertained, possibly because intestinal enterococcal flora changes over time, leaving a potentially cohesive hypothesis of colon cancer and risk factors as yet unanswered.

Extracellular superoxide production by Enterococcus faecalis requires demethylmenaquinone and is attenuated by functional terminal quinol oxidases

“…Enterococci are the only intestinal bacteria known to produce extracellular superoxide (Huycke et al ., 1996; Winters et al ., 1998). Although the majority of aerotolerant prokaryotic organisms ordinarily produce small amounts of superoxide, this free radical production is located in the cytoplasm or periplasm.…”

“…Electroporation of E. faecalis with purified plasmid DNA was performed as described previously (Shepard and Gilmore, 1995). Oligonucleotides were synthesized and polymerase chain reaction (PCR) amplification performed as reported previously (Winters et al ., 1998). Chromosomal DNA flanking Tn 917 sequences was amplified by inverse PCR (Triglia et al ., 1988).…”

“…Recently, we observed that Enterococcus faecalis , an intestinal commensal of humans and animals, produces large amounts of extracellular superoxide (Huycke et al ., 1996). Whereas nearly all E. faecalis strains produce extracellular superoxide, surveys of Gram‐positive and Gram‐negative bacteria have identified only a few other strains of enterococci among a limited number of species, and Lactococcus lactis , as expressing this unusual phenotype (Huycke et al ., 1996; Winters et al ., 1998). The mechanism of superoxide generation, however, was unknown.…”

On the origin of reactive oxygen species and antioxidative mechanisms inEnterococcus faecalis

“…24 A large clinical study showed no association between colonization of the gut with E. faecalis and colorectal adenomas or cancer. 25 Interestingly, in a carefully designed study analyzing the bacterial flora in feces, patients suffering from colorectal cancer had higher populations of E. faecalis. 26 Whether this finding points to a potential cause or to a consequence of the disease is currently not clear.…”

Intestinal Host-Microbiome Interactions

“…This notion is further underscored by the finding that E. faecalis fecal carriage was increased in CRC patients, whereas the number of butyrate producing bacteria was decreased (Balamurugan et al, 2008). However, no clinical evidence has been presented that associates superoxide producing enterococci with adenomas or CRC (Winters et al, 1998). This clearly indicates that, although the in vitro data and animal studies strongly suggest that oxygen radicals from bacterial origin could play an important role in CRC initiation or progression, the clinical impact of these findings remains to be properly examined in well-designed clinical studies (Huycke & Gaskins, 2004).…”