Image: NTU LKCMedicine PhD student Damien Chua (left) and Assoc Prof Andrew Tan, with simulated stool samples.
An international team of scientists led by NTU Singapore has identified a potential stool biomarker that could help researchers assess gut barrier dysfunction, an early and poorly understood contributor to metabolic liver disease.
Published in Nature Communications on 22 May, the study was led by Assoc Prof Andrew Tan Nguan Soon, Vice-Dean (Innovation and Enterprise) and Provost's Chair in Metabolic Disorders at the LKCMedicine.
The study focused on angiopoietin-like 4 (Angptl4), a protein found in the gut and other parts of the body. The team found that Angptl4 in the intestines appears to link diet and gut microbes with a weakened gut barrier in metabolic dysfunction-associated steatotic liver disease (MASLD).
The findings are relevant to Singapore, where fatty liver disease is a growing health concern. The local burden of non-alcoholic fatty liver disease, the previous term for MASLD, has been projected to rise from about 1.49 million people in 2019 to 1.80 million by 2030. The condition is often under-recognised because many patients have no symptoms or abnormal liver enzyme readings.
These findings could help researchers better understand early changes along the gut-liver axis before more serious liver disease develops. Increased gut permeability has also been linked in earlier research to metabolic disorders, autoimmune diseases and allergies.
The researchers used experimental mouse models and clinical data from three patient cohorts in Thailand, China and India, which allowed them to examine the biological mechanism and assess whether the findings were also seen across different Asian populations.
The international team, which included clinicians from Tan Tock Seng Hospital and King Chulalongkorn Memorial Hospital, found that faecal Angptl4 levels increased alongside gut microbial imbalance and metabolic dysfunction.
Assoc Prof Tan adds that potential stool test could offer a simpler way to monitor people at risk of fatty liver disease, which is becoming more common in Singapore and can raise the risk of liver cancer when combined with obesity, diabetes or certain genetic factors.
They are now working to streamline the test for clinical use. As Angptl4 can already be detected using polymerase chain reaction (PCR) machines commonly found in clinical laboratories, Assoc Prof Tan says it could be incorporated into existing diagnostic workflows easily after further validation.
They are also working with partners in China and Thailand to assess how the biomarker changes before and after treatment, while collaborating with NTU engineering faculty to develop a microfluidic version of the test.
