Gut and stomach


July 17, 2014

One of the most surprising revelations about human biology to emerge in recent years is that the microbes in our gut vastly outnumber our body’s own cells. Plus, it seems they play an important role in our health; when they get sick, we get sick. Now, a new study shows how a computer-assisted model can predict gut infection and inflammation before symptoms emerge by tracking changes in gut microbiota signatures over time.

Writing in the journal PLoS ONE, researchers from Brigham and Women’s Hospital (BWH), an affiliate of Harvard Medical School in Boston, MA, suggest their findings will eventually help doctors reach a better understanding of how foreign bacteria disrupt our gut microbiota, and from that find better treatments for gastrointestinal (GI) infection and inflammation.

Senior author Lyn Bry, associate professor of Pathology at Harvard Medical School, and director of the BWH Center for Clinical and Translational Metagenomics, says:

“Our gut contains 10 times more bacterial cells than there are human cells in our body. The behavior of these complex bacterial ecosystems when under attack by infection can have a big impact on our health.”

Gut bacteria show different signatures at different stages of infection

For the study, the team used new computer algorithms developed by co-first author Georg Gerber, who is also director of the BWH Center for Clinical and Translational Metagenomics, and Director of BWH’s Computational Unit.
By tracking changes in gut microbiota signatures over time, a computer-assisted model can predict gut infection and inflammation before symptoms emerge.

The team used the algorithms to analyze what happens to gut bacteria in mice during different stages of infection by the pathogen Citrobacter rodentium. The pathogen causes symptoms that are similar to food poisoning in humans.

In mice with healthy immune systems, the pathogen follows four distinct stages: early colonization, followed by symptomatic infection, which is then followed by a response from the immune system where the pathogen is cleared from the system, and finally, a “convalescence” phase, where tissue damage is repaired.

The whole process takes around 2 months.

For their study, the team produced time-series genetic signatures of the gut bacteria at various points in the mice’s gut over the 2 months of the infection process. Then, using the algorithms in a computational framework, they analyzed both local and overall changes in the bacterial colonies to identify dynamic changes that correspond to the various phases of infection and inflammation.

Families of gut microbes disrupted in different ways during course of infection

The researchers saw the normal bacteria were disrupted in several different ways, in different locations in the gut, as the infection unfolded and was resolved.

For example, they found the genetic signatures of bacterial colonies belonging to the genus Mucispirillumshowed these appeared to subside early in the infection process, before symptoms emerged. And they do not return to normal levels until the final convalescence phase, well after the pathogen has been cleared away.

Mucispirillum inhabits the mucus layer in the colon, and it is known that the pathogen actively destroys the microenvironment of that part of the gut.

“Full regeneration of the mucus layer occurs some time after the pathogen’s clearance, providing a possible explanation for the observed delay in Mucispirillum’s recolonization of distal colon,” note the authors, adding that the corresponding signature “could thus provide a marker for health of the surface mucus layer in distal colon, with potential application to other models of inflammatory colitis.”

Signatures of other bacteria types, such as those belonging to the families Clostridiales and Lactobacillalesshowed these populations increased after the pathogen disappeared.

Plus, the team thought it was interesting that some of these increases occurred in parts of the gut where the pathogen had not damaged any host cells.

Microbial signatures could help detect subtle versions or early stages of gut diseases

Prof. Bry says that from a clinical perspective, “these new microbial signatures we identified could help clinicians detect early stages of inflammation or subtle persistent disease in patients with gastrointestinal disorders, such as inflammatory bowel disease.”

She adds that several of the time-dependent signatures they identified could also be used to study other types of inflammation and infection.

Various grants and funds helped finance the study, including contributions from the National Institutes of Health, Netherlands Organization for Scientific Research, Stanley L. Robbins Memorial Research award, and organizations linked to Harvard.

Meanwhile, Medical News Today recently learned of a study that found gut bacteria diversity improves with exercise, highlighting another interesting way that our friendly gut flora affect our health.

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