5 P52290 Turn over U.S. Navy Recruits Gut Microbes to Fight Obesity and Disease 25. In his lab at Rice University synthetic biologist Jeff Tabor is creating a kind of Lilliputian naval academy. The midshipmen are so small they can’t be seen with the naked eye. But they’re part of a vital mission to protect U.S. naval forces from internal enemies, ranging from metabolic disorders to anxiety and depression. 26. In 2014 Tabor received a three-year grant from the U.S. Office of Naval Research (ONR) to genetically modify a harmless species of Escherichia coli bacteria normally found in the human gut. The goal is to create an edible probiotic organism that can hone in on developing disease and stave it off, even before symptoms take hold. He has recently succeeded in engineering E. coli with sensors that can detect the presence of chemicals signaling disease – at least in the mouse gut. 27. His ultimate aim is to design “a precision gut bacterium that manipulates the intestinal environment in humans to keep it healthy,” he says. This involves rewiring the genes of E. coli to transform the cells into predictable and reliable microbial medics loaded with engineered genetic circuits that can sense specific chemical disturbances and fire off a battery of molecules to neutralize them. The cells would live only a short time in the gut, perhaps six hours or so, “just long enough to do their job,” Tabor says. Then they would die naturally or self-destruct. 28. Tabor’s initial target: obesity and related metabolic issues. “We want to use a genetically engineered E. coli cell to sense the chemicals that signal gut disturbances linked with obesity,” Tabor says, “and then deliver beneficial molecules to prevent weight gain.” 29. Tabor’s work represents the fruitful collision of two hot fields: synthetic biology, the engineering of microorganisms to make useful products; and microbiomics, the study of the microbes living on and inside humans and other animals, collectively known as the microbiome. “There’s great potential in this area because there are so many widespread chronic diseases associated with the gut,” says Pamela Silver of the Wyss Institute for Biologically Inspired Engineering at Harvard University, which published a report of the first synthetic engineered gut microbe in 2014. 30. The 100 trillion bacterial cells that reside in our guts play a major role in nearly every aspect of human biology – digesting food, guiding the immune system, even dictating mental health by sending signals to the brain that affect mood, cognition and behavior. It’s not surprising, then, that disruption of these gut microbial communities can lead to disease, including obesity and related problems. 31. Tabor’s project is part of a larger program on the microbiome funded by the ONR to help U.S. naval forces be more robust in the face of stressors – changes in diet or environment, fearful situations, sleep loss or disrupted circadian rhythms from shifting time zones or living in a submarine. “We’re interested in how gut microbiota respond to these stresses,” says Linda Chrisey, program officer in the ONR’s Warfighter Protection and Application Division. “Are they contributing to the host’s response? If so, can we tweak the microbiota to insulate the host from the stress?”