The gut microbiome has been speculated to modulate feeding behavior through multiple factors, including short-chain fatty acids (SCFA). Evidence on this relationship in humans is however lacking. We aimed to explore if specific bacterial genera relate to eating behavior, diet, and SCFA in adults. Moreover, we tested whether eating-related microbiota relate to treatment success in patients after Roux-en-Y gastric bypass (RYGB). Anthropometrics, dietary fiber intake, eating behavior, 16S-rRNA-derived microbiota, and fecal and serum SCFA were correlated in young overweight adults (n = 27 (9 F), 21–36 years, BMI 25–31 kg/m2). Correlated genera were compared in RYGB (n = 23 (16 F), 41–70 years, BMI 25–62 kg/m2) and control patients (n = 17 (11 F), 26–69 years, BMI 25–48 kg/m2). In young adults, 7 bacteria genera, i.e., Alistipes, Blautia, Clostridiales cluster XVIII, Gemmiger, Roseburia, Ruminococcus, and Streptococcus, correlated with healthier eating behavior, while 5 genera, i.e., Clostridiales cluster IV and XIVb, Collinsella, Fusicatenibacter, and Parabacteroides, correlated with unhealthier eating (all | r | > 0.4, FDR-corrected p < 0.05). Some of these genera including Parabacteroides related to fiber intake and SCFA, and to weight status and treatment response in overweight/obese patients. In this exploratory analysis, specific bacterial genera, particularly Parabacteroides, were associated with weight status and eating behavior in two small, independent and well-characterized cross-sectional samples. These preliminary findings suggest two groups of presumably beneficial and unfavorable genera that relate to eating behavior and weight status, and indicate that dietary fiber and SCFA metabolism may modify these relationships. Larger interventional studies are needed to distinguish correlation from causation.
While the syndrome of inadequate antidiuresis (SIAD) is still the most common cause of hyponatremia in cancer patients, the rise in endocrine immune-related adverse events (irAEs) owing to immune checkpoint inhibitors (ICI) considerably shaped the differential diagnosis of electrolyte disorders in cancer patients. We here report three cases of different endocrine irAEs, first manifesting with new-onset hyponatremia under ICI therapy for malignant melanoma: one with primary adrenal insufficiency, one with hypophysitis and one with autoimmune type 1 diabetes. Early diagnosis of endocrine toxicities can save lives, but may be challenged and essentially delayed by subtle or nonspecific clinical presentation and lacking availability of readily available endocrinological laboratory evaluation in primary care setting. This exemplary case series demonstrates the broad spectrum of endocrinopathies that physicians should be aware of under ICI therapy and emphasizes new-onset hyponatremia as a possibly early, simple and low-cost biomarker of irAEs, which may be considered as a red flag in patients receiving checkpoint blockade. As ICI-induced endocrinopathies are still under-represented in clinical practice guidelines, we here propose an updated algorithm for diagnosis of cancer-related hyponatremia, highlighting the important diagnostic steps to be considered before making the diagnosis of SIAD.
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.
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