Bacterial protein weakens the colon’s barrier

It has been previously known that the bacterium Brachyspira pilosicoli causes intestinal spirochetosis. This bacterial infection leads to diarrhea, abdominal pain, and weight loss.

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Thaher Pelaseyed's research group, in collaboration with Magnus Simrén from the Department of Molecular and Clinical Medicine, has used advanced proteomics and structural biology to study how this bacterium interacts with the surface cells of the colon. The results are published in the journal Gut Microbes.

Destabilizes the intestinal surface

The study shows that a protein, called BPP43_05035, on the surface of the bacteria attaches to N-glycans on the surface of the colon's epithelial cells and disrupts the tight junctions that normally maintain the barrier function of the intestine.

The first author of the study, Anandi Rajan, a postdoctoral researcher in the Mucin Biology Groups at the Sahlgrenska Academy, explains:

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“Our findings suggest that the bacterial protein not only helps the bacterium adhere to the intestinal tissue but also destabilizes the epithelial barrier, making it more permeable. Our discovery could have profound implications for patients suffering from intestinal spirochetosis”, says Anandi Rajan.

Barrier to infection

In patients infected with Brachyspira pilosicoli, researchers observed a clear link between the presence of the protein on the surface of the colon and decreased activity in genes crucial for the colon’s protective functions, including the integrity of both the junctions and the brush-like structures on the cell surface. This may explain why many individuals infected Brachyspira pilosicoli experience chronic symptoms and opens up possibilities for a new type of treatment.

Thaher Pelaseyed, group leader in the Mucin Biology Groups, led the research collaboration.

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“Our research reveals how the bacterium Brachyspira pilosicoli attacks and weakens the intestinal barrier. These bacterial species are common in patients suffering from intestinal disorders  such as irritable bowel syndrome (IBS), but the bacteria are very difficult to treat with antibiotics. By targeting this specific protein, we can now block one of the tools the bacterium uses to infect the human colon”, says Thaher Pelaseyed.

The discovery opens new avenues for exploring treatments that can prevent the bacteria from attaching to colon cells during infection. Since *Brachyspira* infection and intestinal permeability are linked to many health conditions, including IBS, this study represents a significant advancement in understanding and treating these conditions.

Article: BPP43_05035 is a Brachyspira pilosicoli cell surface adhesin that weakens the integrity of the epithelial barrier during infection. Gut Microbes, 16(1).