Scientists Map Complete Human Stool Proteome in Groundbreaking Weizmann Institute Research

(l-r) Dr. Avner Leshem, Dr. Alon Savidor and Prof. Eran Elinav

In a groundbreaking discovery, scientists at the Weizmann Institute have unveiled the full protein landscape within a single stool sample—deciphering not only the intricate interplay of the gut microbiome but also the silent messages of the human body and remnants of consumed food. This revelation exposes the hidden depths of intestinal health, shedding new light on its profound influence on human disease.

Our intestines hold a wealth of information about our health and lifestyle. Imagine if they could talk! Weizmann Institute of Science researchers have developed a new method that essentially gives them a “voice.” Their study, published in Cell, describes a technique that analyzes stool samples to identify all proteins present in the intestine – those from food, the body, and the gut microbiome. This breakthrough allows scientists to decode the complex interactions between these proteins with unprecedented accuracy, potentially providing crucial insights for biomedical and clinical research.

The microbiome was the starting point for the research, co-led by Drs. Rafael Valdés-Mas, Avner Leshem and Danping Zheng from Prof. Eran Elinav’s lab, in collaboration with Dr. Alon Savidor of the Nancy and Stephen Grand Israel National Center for Personalized Medicine. “We wanted to go beyond DNA sequencing, the usual method of studying the microbiome,” says Elinav, of Weizmann’s Systems Immunology Department. “DNA can tell us which bacteria are present in the gut and point to their potential activity. Bacterial proteins, in contrast, can directly reveal whether these bacteria are active, which activity they perform and how their function affects the human body in health and disease.”

“Our method could be used to tell whether someone keeps kosher or whether a person is as strictly vegetarian as they proclaim themselves to be,” Elinav says. “But on a more serious note, the traditional diet-tracking method, self-reporting, is notoriously inexact. Knowing in greater precision and detail what people eat, even when their meal is complex and made up of multiple ingredients, can help establish which of the many components of a meal are beneficial to health and which are problematic.”

To explore the use of their new method in the diagnosis and treatment of disease, the scientists applied it to stool samples of patients with inflammatory bowel disease, which is characterized by severe intestinal inflammation that is affected by diet and the microbiome. The analysis of samples from Israeli, German and American study participants enabled decoding, in great molecular detail, the altered interactions between the human gut and intestinal microbiome that drive the origins of this disease. The study led to the discovery of dozens of new proteins that could serve as potential future targets for drugs to treat this currently incurable disease. The researchers also identified human and bacterial proteins that, used together, could be developed into new biomarkers for diagnosing the type of the disease, assessing its severity and tracking its progress. These new probes promise to outperform calprotectin, the only clinically approved biomarker for inflammatory bowel disease.

In addition, using an IPHOMED analysis of the patient’s diet, the researchers were able to quantify the patients’ compliance with nutritional therapies for intestinal bowel disease and link the level of their adherence to such diets to improved control of inflammation. Moreover, they managed to apply their noninvasive method to detecting disease in the small intestine, the long, thin tube that in healthy people absorbs most of the proteins from food. Because the small intestine is notoriously difficult to visualize and access, this disease could not have been picked up by conventional means.

“Taken together, the proteins in the intestines are the ‘words’ that will one day allow us to hear exactly what our intestines are telling us and thus learn to give them exactly the help they need,” Elinav says. “This ability will help researchers devise personalized nutritional and medical interventions for a wide variety of disorders, particularly those affected by the microbiome, including inflammatory, metabolic, malignant and neurodegenerative diseases.”