Chemical messengers could make poo transplants obsolete
Gut microbes are essential for health, but they also have a reputation for controlling our moods, and making us sick. It turns out we have more control over them than we thought. Viviane Richter reports.
Who’s in charge – you or your gut microbes? With recent research showing gut bacteria release neurotransmitters that manipulate mood, you might think the microbes have the upper hand.
Turns out your gut cells have a say too.
Howard Weiner and his colleagues at the Brigham and Women’s Hospital at Harvard Medical School have identified a messenger that gut cells use to direct microbes, and have shown its potential as a treatment for the gut disease colitis. They reported their findings in Cell Host & Microbe.
“It’s a major alteration in [our] thinking,” says David Topping, gut health researcher at Australia’s national science agency, the CSIRO, in Adelaide.
Trillions of microbes live in the gut where they are essential for breaking down food, manufacturing vitamins, and — by means not yet entirely clear — keeping the immune system on its toes. But not all gut microbes are beneficial, and the wrong mix is implicated in a variety of disorders, including obesity, irritable bowel disease, diabetes, cancer, and even anaphylactic reactions.
The research has tended to focus on how gut microbes influence the body. But there were inklings that it was not a one-way street. For instance, mice inoculated with microbes from another species quickly reverted to their own gut microbe populations, suggesting that the gut has a say in which microbes are allowed to set up shop.
The Weiner team set out to find out how the gut might do this. The lab was already studying short snippets of nucleic acids called “microRNA”. MicroRNAs are produced in the cell’s nucleus, regulate gene activity and, critically, can pass from cell to cell. That makes them candidates for gut cell-to-microbe communication, reasoned Weiner.
When the Weiner team looked in mouse and human faeces, they found that it was loaded with microRNAs produced by gut cells. Their studies in lab dishes confirmed that these microRNAs could slip inside gut bacteria and meddle with their genes to slow population growth.
Next, the team investigated whether microRNA supplements protected against the inflammatory bowel disease colitis, which affects up to 1 in 400 people in the US.
Mice genetically modified not to produce microRNAs in their gut cells were highly susceptible to colitis, the team found. But they were protected against colitis when fed microRNAs collected from normal mice.
Fecal transplants from healthy donors are currently the recommended treatment for people suffering recurring colitis caused by Clostridium difficile. A capsule of microRNA, synthesised in a lab, may be easier (and more pleasant) to handle than a suppository of someone else’s faeces.
“Now we know the pathway is there, we have to see whether indeed it can be utilised,” Weiner says.