Changes in intestinal permeability and gut microbiota following diet-induced weight loss in patients with metabolic dysfunction-associated steatohepatitis and liver fibrosis.
Koutoukidis DA., Yen S., Gomez Castro P., Misheva M., Jebb SA., Aveyard P., Tomlinson JW., Mozes FE., Cobbold JF., Johnson JS., Marchesi JR.
Weight loss improves metabolic dysfunction-associated steatohepatitis (MASH). We investigated whether there were associated changes in intestinal permeability, short-chain fatty acids (SCFAs), and gut microbiota, which are implicated in the pathophysiology of MASH. Sixteen adults with MASH, moderate fibrosis, and obesity received a low-energy total diet replacement program for 12 weeks and stepped food re-introduction over the following 12 weeks (ISRCTN12900952). Intestinal permeability, fecal SCFAs, and fecal microbiota were assessed at 0, 12, and 24 weeks. Data were analyzed using mixed-effects linear regression and sparse partial least-squares regression. Fourteen participants completed the trial, lost 15% (95% CI: 11.2-18.6%) of their weight, and 93% had clinically relevant reductions in liver disease severity markers. Serum zonulin concentrations were reduced at both 12 and 24 weeks (152.0 ng/ml, 95% CI: 88.0-217.4, p