New Tool Maps Gut Proteins, Opens New Possibilities for Treating Inflammatory Bowel Diseases

Jerusalem, 6 February, 2025 (TPS-IL) -- A new tool developed by Israeli scientists is making it possible to map all the proteins excreted from the body in feces, providing a deeper understanding of gut bacteria and their impact on a range of diseases. This breakthrough method opens up new possibilities for targeted therapies for diseases influenced by the microbiome, such as inflammatory bowel disease, metabolic disorders, and neurodegenerative conditions.

Recently published in the peer-reviewed Cell, the Weizmann Institute research details a method that could change how scientists study and understand human digestion and health.

“The currently accepted method for this is DNA sequencing of bacteria in stool samples, but the information obtained with this method is very limited,” said Prof. Eran Elinav, in whose lab the researchers worked. “We knew that if we could map the proteins produced by gut bacteria, we would be able to know much more – not only which bacteria are in the gut, but also what activities they perform, and how these activities affect the human body in health and disease.”

Mapping proteins in feces is a complicated task, due to the vast number of proteins present and the challenge of distinguishing those that originate from the bacteria, the human body, or the food consumed. Human cells alone produce around 20,000 different proteins, and those proteins can vary widely. To tackle this, the researchers combined DNA sequencing with mass spectrometry, creating customized databases for each individual, allowing them to pinpoint which proteins came from which sources.

The new method, called IPHOMED, represents a significant advancement in analyzing stool samples.

Not only does it allow for the detection of bacterial proteins, but it also identifies proteins secreted by the human intestines in response to the microbiome. This breakthrough enables researchers to trace the interaction between gut bacteria and the human body in various scenarios, such as when exposed to pathogens or antibiotics. The study also identified dozens of bactericidal peptides, which are small proteins that act like natural antibiotics, helping shape the microbiome and potentially explaining why each person has a unique microbial composition and health risks.

Through their analysis, the researchers found that their method could also be used to reveal a person’s diet with incredible precision. The IPHOMED method has already demonstrated its ability to identify up to 15,268 proteins secreted by gut bacteria, 528 human proteins, and 1,041 food-derived proteins in a single stool sample, the researchers said.

“The intestines speak to us, among other things, through proteins secreted from the body,” Elinav said. “The ‘words’ emitted can allow us to compose sentences from them and reconstruct what the intestines wanted to say – and perhaps also give them the response they need. The ability to tune into the intestines will help researchers develop personalized treatments, through food or drugs, for a wide range of diseases, especially those affected by the microbiome, including inflammatory and metabolic diseases, malignant diseases and neurodegenerative diseases.”

By creating a database of proteins from hundreds of different food products, they were able to track the proteins in stool samples and identify specific foods, including rare ones like a single peanut. When testing the method on volunteers from Germany and Israel, they discovered that pork protein was prevalent in the German samples, while chicken protein was more common in the Israeli samples.

The researchers also turned their attention to inflammatory bowel diseases (IBD), which are known to be influenced by diet and the microbiome. Using IPHOMED, they mapped stool samples from IBD patients in multiple countries, revealing changes in how the gut and microbiome interact in these diseases. This analysis uncovered dozens of new proteins that could serve as targets for future drugs. Additionally, the method has the potential to improve diagnostic tests for these diseases, providing more accurate assessments of inflammation severity and types.

Beyond diagnosing and treating diseases, the new tool can also track a patient’s adherence to prescribed diets. For example, in celiac patients, the method could reveal if a child is unintentionally consuming gluten, helping doctors tailor treatment plans. Prof. Elinav explained that understanding the proteins secreted by the intestines could open the door to developing personalized treatments for a range of diseases, including those related to the microbiome, such as metabolic disorders, neurodegenerative diseases, and even cancer.

“Traditional methods of monitoring nutrition are not accurate because they are based on self-reporting. If we know what people eat in more detail and with more precision – even when it comes to a complex meal – we can know which ingredients are good for each of us and which are harmful,” Elinav said.