Swell, a Pain Lesson: Gut microbes needed for immune development

Bacteria in your belly can be a pain in the neck, knee, or tuchus. Beneficial microbes that live in the colon are responsible for developing immune system responses that lead to inflammation and pain, a new study in mice shows.

People and animals host hundreds of different bacteria and microbes in their large intestines. Generally, the microbes are friends, helping to digest food and even ensuring that our intestines develop correctly.

Now, a group of researchers in Brazil has shown that our bacterial buddies help our immune systems acquire the ability to cause swelling and pain.

The news may sound like a classic case of “With friends like these … ,” but the results actually show that bacteria and other microbes that normally live in our intestines are helping protect us, says Arthur Ouwehand, a microbiologist at the University of Turku in Finland.

“When you read this paper, you might get the idea that microbes are bad, because you get more inflammation and pain,” he says.

But pain and swelling are the correct responses to a wound or infection, he points out. Inflammation and tenderness signal that something is wrong and that the immune system is on the job to correct the problem. The discomfort encourages a person or animal to treat the injured area more carefully.

“We have to see this all as a defense mechanism,” says Ouwehand, who was not involved in the new study. “Not reacting is actually potentially dangerous.” The study was published in the Feb. 12 Proceedings of the National Academy of Sciences.

Researchers led by Mauro Teixeira, an immunologist at the Federal University of Minas Gerais in Belo Horizonte, Brazil, raised mice in a sterile environment so that the mice had no bacteria in their intestines. They injected the footpads of the so-called germfree mice and of conventionally raised mice with carrageenan, a gelatin-like substance extracted from red seaweed.

Mice with normal bacteria in their guts developed tender paws when injected with the irritant. The sore feet are the result of the way the immune system normally reacts to injury. White blood cells invade the injured area and a flood of inflammatory proteins, called cytokines, cause swelling and eventually pain.

The germfree mice had 52 percent less swelling when injected with carrageenan. The mice also delayed production or made lower levels of certain cytokines at the wound area, and white blood cells in the germfree mice were sluggish in responding to the injury. Introducing intestinal bacteria in the mice later improved the reaction.

Newborn human babies don’t have any intestinal microbes. The bacteria that infants acquire help their immune systems mature and adapt to the environment, and prepare to fight infections, Teixeira says.

The result implies that changing the mix of intestinal microbes might relieve pain in people with inflammatory diseases such as Crohn’s disease and eczema. Such therapies are far away, Teixeira says.

“We don’t know how long or how much you need to change your microbiota in order to change your pain,” he says.

The new research “shows how profound an effect microbes have on your immune system and your entire health,” Ouwehand says.

Tina Hesman Saey is the senior staff writer and reports on molecular biology. She has a Ph.D. in molecular genetics from Washington University in St. Louis and a master’s degree in science journalism from Boston University.

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