How a Gut Infection can lead to Irritable Bowel Syndrome (IBS)

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This resource was made possible through an unrestricted educational grant from IBgard®.

How a gut infection can lead to Irritable Bowel Syndrome (IBS). If you have Irritable Bowel Syndrome (IBS) you may already know that the exact cause is unknown, but several factors can contribute to its development. Some of these include:

  • imbalance of intestinal bacteria or a change in hormones,
  • change in medications,
  • change in diet,
  • gastrointestinal infection,
  • surgery,
  • food poisoning,
  • bouts of intestinal distress like traveler’s diarrhea

We’ve heard firsthand from several IBS patients who had contracted travellers’ diarrhea and developed IBS how awful this has been on them. So how does this happen?  Scientists aren’t exactly sure, but some believe a gut infection that damages the nervous system may contribute.

In a recent study from Rockefeller University, researchers conducted an experiment with mice, looking at why neurons in the gut die and how the immune system normally protects them. 1

If you are unsure what a neuron is, they are cells found in your brain and central nervous system that tell your body how to behave. There are approximately 100 billion neurons in the human brain. 2 Remarkably, there are also 500 million neurons in your gut (this is why we call it the second brain!) connected to your brain through nerves in your nervous system.

Your immune system and inflammation

Your immune system becomes activated when your body recognizes anything foreign which then triggers inflammation. Occasional spells of inflammation, directed at threatening invaders, are good as it protects you and your health!

However, sometimes inflammation persists, day in and day out, even when you are not in threat of a foreign invader. That’s when inflammation can become your enemy, and disease can occur. Daniel Mucida, an associate professor and head of the Laboratory of Mucosal Immunology, mentions that “inflammation helps the gut ward off an infection, but too much of it can cause lasting harm.”

To understand the effects of an infection on the nervous system, Mucida and his colleagues gave mice a weakened form of Salmonella, a bacterium known to cause food poisoning. Once infected, Mucida and team analyzed the neurons within the intestine and found that the Salmonella infection created a long-lasting reduction of neurons. The reduction was a result of neuron cells expressing two genes, Nlrp6 and Caspase 11, which can contribute to a specific type of inflammatory response. This response, in turn, can ultimately prompt the neuron cells to endure a form of programmed cell death. When the researchers manipulated mice to eliminate these genes in neuron cells, they saw a decrease in the number of neurons dying.

Fanny Mathesis, a graduate student in the lab at Rockefeller University, mentions that “this mechanism of cell death has been documented in other types of cells, but never before in neurons. We believe these gut neurons may be the only ones to die this way.”

So what causes neurons to die, and what can we do to stop it?

It’s not exactly clear yet why inflammation causes neurons to die, but scientists already have clues suggesting it might be possible to interfere with the process. The key may be a specialized set of gut immune cells, known as muscularis macrophages.

Mucida’s lab’s previous work showed that macrophage cellsexpress inflammation-fighting genes and collaborate with the neurons to keep food moving through the digestive tract. If these neurons die off, as happens with an infection, a possible result is constipation – just one of the not-so-nice symptoms of IBS.  

In their recent report, the team demonstrate how macrophages come to the neurons’ rescue during an infection, improving this aspect of IBS.

They revealed that macrophages possess a particular receptor molecule that receives stress signals released by another set of neurons in response to an infection. Once activated, this receptor prompts the macrophage to produce molecules called polyamines, which the scientists THINK might hinder neuron cells from dying (Rockefeller University, 2020).

Where do we go from here? Treatment for IBS

In other experiments regarding how a gut infection can lead to IBS, the researchers found that Salmonella infection alters the community of microbes within the guts of mice – and when they restored the animals’ intestinal floral back to normal, the neurons recovered.

Paul Muller, a postdoctoral fellow in the lab, says,”using what we learned about the macrophages, one could think about ways to disrupt the inflammatory process that kills the neurons.”

For example, they think it might be possible to develop better treatments for IBS that work by boosting polyamine (an organic compound responsible for cell growth and survival) production, perhaps through diet, or by restoring microbes in our gut.

Since short-term stress responses also appear to have a protective effect, Muller thinks boosting polyamine production may also help target the stress response system. 1 We will be sure to update this article as more discoveries in the treatment of IBS are made, and specifically more about how a gut infection can lead to IBS.


References:

  1. Fanny Matheis, Paul A. Muller, Christina L. Graves, Ilana Gabanyi, Zachary J. Kerner, Diego Costa-Borges, Tomasz Ahrends, Philip Rosenstiel, Daniel Mucida. Adrenergic Signaling in Muscularis Macrophages Limits Infection-Induced Neuronal LossCell, 2020; 180 (1): 64 DOI: 10.1016/j.cell.2019.12.002