Letter: Lubiprostone—A Novel Therapeutic Avenue for Gastrointestinal Complications in MASLD

Abstract

Metabolic dysfunction-associated steatotic disease (MASLD) is a chronic liver condition, characterised by the accumulation of fat in the liver, in association with a metabolic disorder. It is characterised by lobular inflammation and hepatocyte enlargement, both of which contribute to the development of steatosis—an accumulation of fatty acids in the liver. This condition may arise due to either impaired fatty acid breakdown or increased delivery of lipids to the liver [1]. The progression of metabolic dysfunction-associated steatotic disease (MASLD) may be attributed to the leakage of intestinal bacteria [2].

Affecting about 25% of the world's population, MASLD is a growing global concern [1]. Treatment strategies for MASLD include lifestyle modification, weight loss and several medications including PPAR agonists, SGLT2 inhibitors, GLP-1 receptor agonists, ASK1 inhibitors, modulation of certain microbial communities and lubiprostone [3, 4].

A recent study by El-Kassas et al. highlighted the beneficial role of lubiprostone in patients with MASLD. This trial demonstrates that lubiprostone reduces fat content used as a treatment for patients with leaky gut and those with elevated ALT levels [5].

Lubiprostone acts as a chloride channel-2 agonist and accelerates the recovery of epithelial barrier injury. Altered intestinal bile flow affects endotoxin translocation to the liver, and lubiprostone helps mitigate this damage [6].

Another study by Kim et al. observed the beneficial effects of lubiprostone as it prevents intestinal bacterial leakage\ and strengthens the gut barrier by promoting the development of colonic mucus. Its beneficial effects on the liver include increasing portal HDL cholesterol levels, reducing bacterial burden and mitigating hepatic steatosis. In patients with high-fat diet-induced MASLD/NAFLD, lubiprostone has demonstrated high efficacy [2].

Lubiprostone emerges as a favourable therapeutic agent for MASLD. It is exhibiting effectiveness in reducing hepatic steatosis, enhancing the profiles of the liver enzymes and enforcing barrier-oriented functions of the intestine. Its benefits appear to be not dependent on liver enzyme status and constipation, and this underscores its wide potential in MASLD management. However, large-scale, randomised controlled trials are needed to authenticate these findings, explore long-term safety and render their significant role in patients with normal ALT levels. Upcoming research should also investigate its mechanisms of action in diverse populations so that it can maximise the therapeutic strategies for MASLD.

Hassan Javed: conceptualization, investigation, writing – original draft. Muhammad Umar Ahsan: conceptualization, investigation, writing – original draft, data curation, software, formal analysis, supervision. Muhammad Saeed: writing – original draft, formal analysis, data curation. Muhammad Qintar Taqi: data curation.

IRB approval was not required because no data were collected for this article.

The authors declare no conflicts of interest.

This article is linked to El-Kassas et al papers. To view these articles, visit https://doi.org/10.1111/apt.18478 and https://doi.org/10.1111/apt.70048.