Breakthrough weight-loss study reveals non-surgical method to reduce appetite

Researchers from the University of Nottingham, King's College London, and Amsterdam University Medical Center shed insight on the molecules driving the advantages of this type of surgery on patients' appetite and metabolism in a study that was published in Cell Reports Medicine.

Bile acid levels were measured before and a year after surgery on a group of individuals in Amsterdam who had had bariatric surgery. Also, they examined data on bile acids from the TwinsUK and PREDICT population studies, both of which were conducted by King's College London and the ZOE nutrition company.

“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," said Professor Ana Valdes from the University of Nottingham’s School of Medicine.

"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 fiber might mimic some of these effects. This could help design dietary supplementation studies aimed at increasing satiety and improving liver parameters," she added.

New strategies for bariatric surgery

Scientists may be able to create new strategies that mirror the effects of bariatric surgery without subjecting patients to the actual process by better understanding these systems. Only those who are extremely fat are candidates for bariatric surgery; therefore learning if isoUDCA may be altered by lifestyle changes may help develop more precise methods of treating obesity.

“The study's results have important implications for the development of targeted interventions for metabolic disorders focused on the gut microbiome," said Dr. Cristina Menni from King’s College London.

"By better understanding the complex interplay between genetics, the gut microbiome, and diet in regulating bile acid levels and their impact on appetite and metabolic health, we may be able to develop new strategies for preventing and treating obesity and metabolic syndrome," she explained.

Seeing the significant impact of gut microorganisms on isoUDCA levels was another important discovery. This establishes the importance of the gut microbiome in influencing the results of bariatric surgery and clarifies the mechanisms by which gut microorganisms affect a person's metabolism.

Study abstract:

Primary and secondary bile acids (BAs) influence metabolism and inflammation, and the gut microbiome modulates levels of BAs. We systematically explore the host genetic, gut microbial, and habitual dietary contribution to a panel of 19 serum and 15 stool BAs in two population-based cohorts (TwinsUK, n = 2,382; ZOE PREDICT-1, n = 327) and assess changes post-bariatric surgery and after nutritional interventions. We report that BAs have a moderately heritable genetic component, and the gut microbiome accurately predicts their levels in serum and stool. The secondary BA isoursodeoxycholate (isoUDCA) can be explained mostly by gut microbes (area under the receiver operating characteristic curve [AUC] = ∼80%) and associates with post-prandial lipemia and inflammation (GlycA). Furthermore, circulating isoUDCA decreases significantly 1 year after bariatric surgery (β = −0.72, p = 1 × 10−5) and in response to fiber supplementation (β = −0.37, p < 0.03) but not omega-3 supplementation. In healthy individuals, isoUDCA fasting levels correlate with pre-meal appetite (p < 1 × 10−4). Our findings indicate an important role for isoUDCA in lipid metabolism, appetite, and, potentially, cardiometabolic risk.