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.
The operation span task is a well-validated measure of the executive component of working memory. Previous scoring systems of this task focus predominantly on the span part of the task, while the distractor – math task – serves as an exclusion criterion for test assessment only. Here, we propose a new Math-Item-Sequence (MIS) system to score performance on the Ospan based on both the span and math part. This new system provides three main improvements: 1) it eliminates the need to introduce arbitrary exclusion thresholds based on performance on the distractor task; 2) it takes into account remembered letters, and their relative position in the sequence separately; 3) it considers performance on the math task in the scoring of the Ospan task as a downweighing factor. In 6 independent samples we show that MIS score correlates highly with previously recommended scoring methods, suggesting that it measures the same underlying concepts. We also show that internal consistency of MIS is very good and comparable to or higher than the previous methods. We argue that MIS could be used in all samples, but might be of particular interest for small samples, where exclusions of participants are especially costly.
Background: Bariatric surgery has been widely recognized as the most efficient long-term treatment method in severe obesity, yet therapy success shows considerable interindividual variability. Postoperative metabolic adaptations, including improved gut hormone secretion (GLP-1, PYY and ghrelin), and restored executive function may play an explanatory role in weight loss, yet causes for poor success in individual patients remain unknown. This study investigates gut-hormonal and cognitive characteristics in extreme weight loss responders to bariatric surgery. Methods: Patients (n=47) with high or low excessive weight loss (EWL) at least 2 years after Roux-en-Y-gastric bypass or sleeve gastrectomy were allocated into good responders (GR, EWL 82.4 +/- 11.6%) and poor responders (PR, EWL 24.0 +/- SD 12.8%) to study differences in postprandial secretion of GLP-1, PYY, ghrelin and in working memory (WM). Results: Mean BMI was 47.1 +/- 6.2 kg/m^2 in poor responders (n=21) and 28.9 +/- 3.1 kg/m^2 in good responders (n=26, p < 0.001). Fasted GLP-1 and PYY were comparable for GR and PR (p > 0.2) and increased strongly after a standardized test meal (300 kcal liquid meal) with a peak at 15 to 30 minutes. The increase was stronger in GR compared to PR (GLP-1, PYY: Time x Group p < 0.05). Plasma ghrelin levels already differed between groups at fasted state, showing significantly higher levels for GR (p < 0.05). Postprandially, ghrelin secretion was suppressed in both groups, but suppression was higher in GR (Time x Group p < 0.05). GR showed significantly higher WM scores than PR (p < 0.05). Postprandial ghrelin (iAUC), but not GLP-1 or PYY release, significantly mediated the relationship between EWL and a WM subscore (IS score, CI = 0.07 - 1.68), but not WM main score (MIS score, CI = -0.07 - 1.54). Conclusion: Excess weight loss success after bariatric surgical procedures is associated with distinct profiles of gut-hormones at fasted and postprandial state, and differences in working memory. Working memory performance was partly mediated by postprandial incremental drops in ghrelin. Future studies need to integrate longitudinal data, larger samples and more sensitive cognitive tests.
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