Editors' ChoiceMicrobiome

How to train your microbiome to eat broccoli

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Science Translational Medicine  14 Feb 2018:
Vol. 10, Issue 428, eaar7534
DOI: 10.1126/scitranslmed.aar7534

Abstract

Engineered commensal bacteria produce colorectal cancer–fighting compounds from ingested broccoli.

Ingesting live probiotic microorganisms, such as those found in yogurt, kimchi, and sauerkraut, is often touted to improve the health of the microbial communities residing in our guts. Although the compositions of our microbiomes have been associated with a wide range of disorders, including diabetes, obesity, depression, Alzheimer’s disease, and Parkinson’s disease, we have few studies establishing firm causative relationships between the abundance of an ingested microbe and measurable health benefits. Instead of searching for probiotic strains, a recent report by Ho et al. describes the engineering of commensal bacteria to fight colon cancer using a reagent rarely found in the laboratory: broccoli.

The cruciferous family of vegetables, which includes broccoli, brussels sprouts, cabbage, and kale, are unique in their near-ubiquitous prevalence of glucosinolates. These sulfur-rich organic compounds lend these vegetables their notoriously bitter taste but also happen to be useful chemical precursors. The group engineered E. coli Nissle 1917 to constitutively produce and secrete myrosinase, a type of self-defense enzyme naturally present in plants that hydrolyze glucosinolates into isothiocyanates, which have anticancer activity. To aid specificity, bacteria were also engineered to bind heparan sulfate proteoglycans enriched on colon cancer cells. Engineered bacteria successfully bound to human and murine colorectal cancer cell lines in vitro and were cytotoxic in the presence of glucosinolate. Carcinogen-exposed mice fed both bacteria and broccoli developed approximately fourfold fewer colorectal tumors versus untreated, bacteria-only, and broccoli-only controls and had significantly reduced average tumor diameters.

Though this study reports promising results for chemoprevention, more work needs to be done before such strategies should be attempted in humans. One concern is that high doses of isothiocyanates are known to be hepatotoxic and can inhibit iodine uptake. Furthermore, it is unclear to what degree nitriles and other toxic reaction products of myrosinase are generated as bacteria pass through the various pH environments of the gastrointestinal tract. Nonetheless, if rationally designed food-converting bacteria can be stably engrafted into our microbiota, we may be on the path to long-term sustainable solutions for disease prevention and the treatment of chronic ailments. Now if only we had enzymes capable of converting substrates from more palatable menu items…

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