An infection that’s good for the gut? How enteric bacteria can protect the GI tract

Gut infections may resolve in a day or two without treatment. There are others, however, that can cause long-term gastrointestinal (GI) diseases by destroying many of the 100 million neurons distributed along the GI tract. A new study indicates that some enteric bacteria may help mice tolerate GI infections.

Recently published in the journal Cell, the study describes how immune cells (macrophages) in the gut that responded during previous infections may then protect the neurons from new infections. That protective effect may be important in some conditions, such as irritable bowel syndrome (IBS). The condition has been linked to the death of GI neurons.

“We’re describing a sort of innate memory that persists after the primary infection is gone,” says scientist Daniel Mucida, of Rockefeller University, in a statement. “This tolerance does not exist to kill future pathogens, but to deal with the damage that infection causes—preserving the number of neurons in the intestine.” 

The GI nervous system is the site of the most neurons in the body other than the brain itself. It works without input from the brain. It controls the movement of nutrients and waste by coordinating fluid exchange and blood flow. If enough neurons die, the GI tract malfunctions. 

Researchers note that the symptoms of IBS are similar to the effects of enteric neurons dying in large numbers. It raises the question that some minor gut infections cause much more damage in some people than others, causing unexplained GI conditions. 

In previous work, the researchers wondered whether the body has some mechanism of preventing neuronal loss following infection. The lab had demonstrated that gut macrophages produce molecules that prevent neurons from dying in stressful conditions.  

Tomasz Ahrends and colleagues infected mice with a strain of Salmonella, a common source of food poisoning. Some enteric neurons were lost, but the mice cleared the infection in about a week. The same mice were then infected with another foodborne bacterium. The mice had no additional loss of enteric neurons. The finding suggested that the first infection had created tolerance preventing neuronal loss in additional infections.  

Future studies on enteric neurons

Mucida plans to determine the precise impact of neuronal loss in the GI tract. “We’ve observed that animals consume more calories without gaining more weight after neuronal loss,” he says. “This may mean that the loss of enteric neurons is also affecting the absorption of nutrients and caloric intake. There may be more consequences of neuronal loss than we expected.”

Mucida believes that this research could contribute to understanding of the underlying causes of IBS and related conditions. “One speculation is that the number of enteric neurons throughout your life is set by early childhood infections, which prevent you from losing neurons after every subsequent infection,” Mucida explains.  

People who for some reason do not develop tolerance may continue to lose enteric neurons throughout their life with subsequent infection(s). Future studies will explore alternative methods of protecting enteric neurons, hopefully paving the way for therapies.

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