A Probiotic Friend

Reply to Dubbert and von Bünau, “A Probiotic Friend”

“…However, the recent detection of the colibactin mutational signature in colorectal tumor banks indicates that colibactin produced by pks + E. coli is indeed produced, and genotoxic, in humans ( 14 , 15 ). We agree with Dubbert and von Bünau who stated in their letter ( 1 ) that these pks + E. coli bacteria are frequently found in young children. Previous work has shown that pks + E. coli induces DNA damage during the perinatal colonization phase in a rat model, with persistent changes to the intestinal tissue homeostasis and cell turnover ( 10 ).…”

“…We again fully agree with Dubbert and von Bünau ( 1 ) that CRC is multifactorial, diet and intestinal inflammation contributing in a major way. Indeed, we have shown that food contaminants may participate in conjunction with colibactin to the mutagenesis process ( 22 ).…”

“…The detection of the colibactin mutational signature in colorectal tumors, the understanding of the mechanism of DNA damage, mutagenesis, and transformation, as well as various epidemiological studies showing more E. coli pks + in colorectal cancer (CRC) patients and finally the experimental reproduction of colibactin-aggravated CRC in mouse models all concur to implicate colibactin in this type of cancer ( 18 ). However, we agree with Dubbert and von Bünau ( 1 ) that CRC is a multifactorial disease and that other risk factors—in particular, diet—are very important. The authors submit that the mutational signature of colibactin is found in only 5% of the analyzed tissues.…”

“…In their letter ( 1 ), the authors question our results on the in vitro and in vivo genotoxicity of Nissle 1917 ( 2 ) with respect to their previous publication in which they stated that this E. coli strain did not exert such genotoxicity in standard tests ( 3 ). These standard tests, which are recommended by the FDA and the OECD, are suitable for testing the mutagenic effect of chemicals on human health.…”

“…We read with great interest the comment letter to the editor by Dubbert and von Bünau ( 1 ) from Ardeypharm regarding our work, recently published in mSphere , on the production of the genotoxin colibactin by the Nissle 1917 probiotic ( 2 ). We fully understand and acknowledge the strong commitment made by Ardeypharm—which markets Nissle 1917 under the trade name Mutaflor—with regard to the safety of its customers and the improvement of patient health.…”