Metabolic Profile and Metabolite Analyses in Extreme Weight Responders to Gastric Bypass Surgery

Abstract

Background: Roux-en-Y gastric bypass (RYGB) surgery belongs to the most frequently performed surgical therapeutic strategies against adiposity and its comorbidities. However, outcome is limited in a substantial cohort of patients with inadequate primary weight loss or considerable weight regain. In this study, gut microbiota composition and systemically released metabolites were analyzed in a cohort of extreme weight responders after RYGB. Methods: Patients (n = 23) were categorized based on excess weight loss (EWL) at a minimum of two years after RYGB in a good responder (EWL 93 ± 4.3%) or a bad responder group (EWL 19.5 ± 13.3%) for evaluation of differences in metabolic outcome, eating behavior and gut microbiota taxonomy and metabolic activity. Results: Mean BMI was 47.2 ± 6.4 kg/m2 in the bad vs. 26.6 ± 1.2 kg/m2 in the good responder group (p = 0.0001). We found no difference in hunger and satiety sensation, in fasting or postprandial gut hormone release, or in gut microbiota composition between both groups. Differences in weight loss did not reflect in metabolic outcome after RYGB. While fecal and circulating metabolite analyses showed higher levels of propionate (p = 0.0001) in good and valerate (p = 0.04) in bad responders, respectively, conjugated primary and secondary bile acids were higher in good responders in the fasted (p = 0.03) and postprandial state (GCA, p = 0.02; GCDCA, p = 0.02; TCA, p = 0.01; TCDCA, p = 0.02; GDCA, p = 0.05; GUDCA, p = 0.04; TLCA, p = 0.04). Conclusions: Heterogenous weight loss response to RYGB surgery separates from patients’ metabolic outcome, and is linked to unique serum metabolite signatures post intervention. These findings suggest that the level of adiposity reduction alone is insufficient to assess the metabolic success of RYGB surgery, and that longitudinal metabolite profiling may eventually help us to identify markers that could predict individual adiposity response to surgery and guide patient selection and counseling.

Distinct adaptations of endocrine and cognitive functions may contribute to high variability in long-term weight loss outcome after bariatric surgery

“…For a subsample (n=23) of the herein presented data, primary and secondary serum bile acids showed distinct profiles in GR vs. PR at fasted and postprandial state, whereas gut hormones did not, possibly due to limited statistical power [100]. Also, recent studies have highlighted the role of the vagus nerve in mediating the effects of bariatric surgery [101,102].…”

“…The study design has been described previously [39]. Participants were invited for a single testing day at the Max Planck Institute for Human Cognitive and Brain Sciences (MPI CBS), Leipzig, Germany.…”

Dietary Fat Modulation of Gut Microbiota and Impact on Regulatory Pathways Controlling Food Intake

“…Also, antibiotic administration peri-operatively in mice models of VSG contributed to attenuated weight loss and metabolic improvement, indicating an intricate relationship of gut microbiota [215] in the mechanisms regulating weight loss after surgical interventions. More specifically, in humans, good responders to RYGB as measured by post-surgical estimated weight loss, increased short chain and conjugated primary and secondary bile acids, and did better compared to poorer responders [216]. Bile acids exert their effects through FXR and TGR5, with recent studies showing that hypothalamic TGR5 activation may participate in the anti-obesity effects by activating the sympathetic nervous system to protect from diet-induced obesity and promote an overall negative energy balance [217].…”