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Genetic Linkage

Battling Constipation with Synthetic Biology and DNA Manipulation

Worldwide about 15 percent of people suffer from constipation. Passing dry, compacted stools can be quite painful, but eating more fruit, drinking more water, and/or taking laxatives – common advice from friends and physicians alike – can lead to frustration rather than relief. And drugs such as linaclotide (Linzess) and plecanatide (Trulance), and even probiotics don’t work for everyone because our gut microbiomes (the bacteria in our stomachs and intestines) differ.

A few novel approaches are on the horizon, according to Clinicaltrials.com, including new laxatives, acupuncture, reflexology, Chinese herbs, and a Brazilian tea brewed from fruits of green anise and fennel and flowers of senna and elder tree. Old remedies are given new names, like "Movicol." It’s just sodium bicarb stabilized with the laxative polyethylene glycol (PEG), which is the infamous elixir taken the night before a colonoscopy. It works.

Other experimental strategies are more invasive. “Interferential therapy” zaps the abdomen with four electrodes, and is performed at home for an hour a day for two to three months. Another is a "vibrating capsule,“ presumably inserted into the anatomical area of concern. In another clinical trial, 100 people are testing “perineal self-acupressure,” massaging the anal area to break up and mobilize the stool. And fecal transplants are being tested too.

But a fecal transplant seems the opposite of precision medicine: receiving trillions of bacteria from someone else, each microbial species exuding its own smorgasbord of biochemicals. Although the approach is both ancient and effective, with such a mixed bag of ingredients, evaluation is largely empiric – it helps or it doesn’t, to treat recurrent Clostridium difficile infection and several other indications in clinical trials.

Biotech harnesses tryptamine
Purna Kashyap, M.B.B.S., associate director of the Mayo Clinic Center for Individualized Medicine and his colleagues sought to harness a specific molecule, tryptamine, to loosen stool and speed its transit from inside to outside. “Our goal with this research is to find treatments that act only in the GI tract without creating problems in other parts of the body,” he said. The work is published in the June issue of Cell Host & Microbe, including a video.

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