King's College London

Weight loss surgery can profoundly reduce the levels of bile acid associated with higher appetite, as can taking fibre supplements but to a lesser degree.

Scientists have suggested that if there is a way to mimic this effect through lifestyle changes, there could be potential to treat and prevent obesity without the significant risk of surgery.

The study, published today in Cell Reports Medicine by researchers from King’s, the University of Nottingham and Amsterdam University Medical Centre, sheds light on the molecules underlying the benefits of weight loss surgery (known in medical terms as bariatric surgery) on appetite and metabolism.

Bariatric surgery can be used as a treatment for people who are very obese. There are several types of bariatric surgery, including reducing the size of the stomach or rerouting the top part of the stomach to the small intestine. It is an invasive procedure but can lead to significant improvements in weight loss, metabolic health and a reduction in appetite, but the reasons are unknown.

Bile acids are a marker of poor cardiometabolic health and can affect liver function and inflammation.

Researchers studied a cohort of patients in Amsterdam who had undergone bariatric surgery. They measured levels of bile acids in this BARIA cohort before surgery and a year later. They also studied bile acids from two population studies; TwinsUK, run by King’s College London, and PREDICT, run by King’s College London and personalised nutrition company, ZOE.

The study found that a specific bile acid called isoursodeoxycholate (isoUDCA), which is associated with higher appetite and worse metabolic levels, decreased after bariatric surgery and after taking fibre supplements. Levels of isoUDCA did not decrease after consuming omega-3 supplements.

By understanding these mechanisms, scientists may be able to develop new interventions that mimic the effects of bariatric surgery without putting patients through an invasive procedure. Bariatric surgery is also only suitable for those severely obese, and understanding whether isoUDCA can be modified by lifestyle interventions could lead to targeted treatments for obesity.

Another key finding of the study was seeing the strong influence of gut microbes on the levels of isoUDCA. This observation confirms that the gut microbiome is key to determining the outcomes of bariatric surgery and sheds light on the ways in which gut microbes modify a person's metabolism.

Joint lead author Professor Ana Valdes from the University of Nottingham said: “Bariatric surgery is not only extremely effective at helping people lose weight by reducing their appetite, but also improves their liver function and their metabolism. What our study shows is that specific microbial metabolite is involved in some of these benefits and that, although to a more modest extent, dietary fibre might mimic some of these effects. This could help design dietary supplementation studies aimed at increasing satiety and improving liver parameters.”

Co-author Professor Tim Spector, Professor of Genetic Epidemiology at King's and co-founder of ZOE, the personalised nutrition company, said: “This study highlights the key role that fibre plays in appetite regulation and metabolism, harnessed by specific gut microbes. Advanced gut microbiome testing (as used by ZOE) provide personalised insights that can support metabolic health. The gut microbiome and its chemical products such as these bile acids hold huge promise for reducing obesity without the need for invasive surgery.”