Bariatric-induced microbiome changes alter MASLD development in association with changes in the innate immune system

Area of Science:

• Gastroenterology and Hepatology
• Immunology
• Microbiome Research

Background:

• Metabolic dysfunction-associated steatotic liver disease (MASLD) affects 25% of the population, driving liver mortality.
• Bariatric surgery is an effective treatment for MASLD and obesity, but mechanisms are under investigation.
• The gut microbiome and host immune system play roles in MASLD pathogenesis.

Purpose of the Study:

• To investigate the interplay between gut microbiota composition after bariatric surgery and the immune system in MASLD.
• To understand how surgical alterations to the microbiome impact liver inflammation and fibrosis.

Main Methods:

• Human study: 18 obese females underwent sleeve gastrectomy, with pre- and post-surgery monitoring.
• Animal model: Antibiotic-treated mice received fecal transplants from human patients (pre- or post-surgery) and were fed standard or high-fat diets.
• Data collection included body weight, food intake, metabolic parameters, and immune cell profiling.

Main Results:

• Bariatric surgery significantly reduced weight, inflammation, and improved glucose levels in humans.
• Microbiome analysis revealed increased *Bacteroides* post-surgery in patients with significant weight loss.
• Mice receiving post-surgery fecal transplants showed reduced weight gain, liver steatosis, and decreased inflammatory cytokines, with altered liver immune cell populations (increased NKT cells, decreased Kupffer cells).

Conclusions:

• Bariatric surgery-induced microbial shifts are key in reducing MASLD progression and inflammation.
• A potential causal link exists between the microbiome and host immune response in MASLD, involving liver NKT and Kupffer cells.