The intestines of mammals allow nutrients to pass through to the rest of the body while stopping most harmful bacteria from doing the same. New research in mice now reveals how this is possible, suggesting implications for drug design and delivery.

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Researchers have studied the guts of mice to learn more about the intestines’ ability to both nourish and protect against harmful bacteria.

Mammals, including humans, possess two intestines — the small and the large — as part of their digestive system. These intestines together make up the lower gastrointestinal tract, and they play a crucial role in digestion and excretion.

In the lower gastrointestinal tract, partially digested food from the stomach is broken down further into its constituent nutrients, which then pass into the bloodstream through the intestinal wall, so that they can reach different organs and parts of the body.

At the same time, however, the intestinal wall prevents most harmful agents from passing through and infecting the blood. But how does it happen? This is the question that researchers from the Rockefeller University in New York, NY, have tried to answer by conducting a preliminary study in mice.

The research — the findings of which appear in the journal Nature — reveals an essential distinction in the structure and organization of the intestinal immune system, which makes certain parts of the intestines more likely to mount an immune response against pathogens (harmful agents) than other parts.

“At first glance, the intestine appears uniform throughout,” explains study author Daniel Mucida.

But we’ve found a sophisticated functional system lurking beneath the surface, organized in segments to allow different immune system functions in different locations.”

Daniel Mucida

To better understand how the intestines “screen” for harmful bacteria and keep them at bay, the researchers looked at gut-draining lymph nodes in mice. These structures help mount an immune response against pathogens, ensuring that they do not pass through the intestinal wall.

The investigators made two important findings: Firstly, that different gut lymph nodes have distinct cell compositions, and, secondly, that these depend on where in the lower gastrointestinal tract they are situated.

In order to find out how different lymph nodes responded to pathogens, the researchers introduced Salmonella enterica into the mice’s guts. In doing this, they saw that some lymph nodes were more likely to mount an immune response against the bacterium than others.

Specifically, it was the lymph nodes in the large intestine (colon) that reacted against the Salmonella, ensuring it did not infect the rest of the system.

By contrast, the lymph nodes in the small intestine played more of a role in absorbing nutrients and delivering them into the bloodstream.

The researchers explain that this separation makes sense: Once the small intestine has absorbed the nutrients, the lymph nodes in the large intestine can target and eliminate any pathogens.

Mucida and colleagues also point out that knowing which part of the intestines is able to mount the strongest immune response can help researchers devise better therapeutic strategies for gastrointestinal conditions.

Furthermore, the current revelations could pave the way to enhance the effectiveness of oral vaccines, which, so far, have been unable to generate strong enough immune responses.

After considering the findings of the present study, its authors believe that oral vaccines may be ineffective because their active ingredients engage with immune system elements in the small intestine, which are unable to mount a robust immune response.

“In theory, targeting the distant end of the intestine could be more efficient in inducing the immune response required,” notes Mucida, adding that, “[i]f we harness the right region of the gut, we might see some vaccines work that have previously failed.”