A body weight loss- and health-promoting gut microbiota is established after bariatric surgery in individuals with severe obesity.

Abstract Obesity has reached an epidemic level worldwide, and bariatric surgery (BS) has been proven to be the most efficient therapy to reduce severe obesity-related comorbidities. Given that the gut microbiota plays a causal role in obesity development and that surgery may alter the gut environment, investigating the impact of BS on the microbiota in the context of severe obesity is important. Although, alterations at the level of total gut bacteria, total gene content and total metabolite content have started to be disentangled, a clear deficit exists regarding the analysis of the active fraction of the microbiota, which is the fraction that is most reactive to the BS. Here, active gut microbiota and associated metabolic functions were evaluated using shotgun proteomics and metabolomics in 40 severely obese volunteers. Samples from each volunteer were obtained under basal conditions, after a short high protein and calorie-restricted diet, and 1 and 3 months after BS, including laparoscopic surgery through Roux-en-Y Gastric Bypass or Sleeve Gastrectomy. The results revealed for the first time the most active microbes and metabolic flux distribution pre- and post-surgery and deciphered main differences in the way sugars and short-fatty acids are metabolized, demonstrating that less energy-generating and anaerobic metabolism and detoxification mechanisms promoted post-surgery. A comparison with non-obese proteome data further signified different ways to metabolize sugars and produce short chain fatty acids and deficiencies in proteins involved in iron transport and metabolism in severely obese individuals compared to lean individuals.