Potential contribution of the gut microbiota to hypoglycemia after gastric bypass surgery

Abstract

Obesity has become a global health problem. Lifestyle modification and medical treatment only appear to yield short-term weight loss. Roux-en-Y gastric bypass (RYGB) is the most popular bariatric procedure, and it sustains weight reduction and results in the remission of obesity-associated comorbidities for obese individuals. However, patients who undergo this surgery may develop hypoglycemia. To date, the diagnosis is challenging and the prevalence of post-RYGB hypoglycemia (PRH) is unclear. RYGB alters the anatomy of the upper gastrointestinal tract and has a combined effect of caloric intake restriction and nutrient malabsorption. Nevertheless, the physiologic changes after RYGB are complex. Although hyperinsulinemia, incretin effects, dysfunction of β-cells and α-cells, and some other factors have been widely investigated and are reported to be possible mediators of PRH, the pathogenesis is still not completely understood. In light of the important role of the gut microbiome in metabolism, we hypothesized that the gut microbiome might also be a critical link between RYGB and hypoglycemia. In this review, we mainly highlight the current possible factors predisposing individuals to PRH, particularly related to the gut microbiota, which may yield significant insights into the intestinal regulation of glucose metabolic homeostasis and provide novel clues to improve the treatment of type 2 diabetes mellitus.

Effects of enteral nutrition support combined with enhanced recovery after surgery on the nutritional status, immune function, and prognosis of patients with esophageal cancer after Ivor-Lewis operation

“…Intestinal flora are an important part of the intestinal mucosal barrier, and disturbance of the intestinal flora can increase the risk of perioperative complications (28,29). Gastrointestinal surgery will destroy the intestinal mucosal barrier and increase the risk of postoperative pulmonary infection, anastomotic leakage and other complications (30). Some research has also confirmed that the cell-mediated immune response was impaired, the numbers of CD4 + and CD4 + /CD8 + T cells decreased, and the intestinal barrier function was damaged in patients with EC after laparoscopic Ivor-Lewis surgery (31).…”

<p>Hypoglycemia After Upper Gastrointestinal Surgery: Clinical Approach to Assessment, Diagnosis, and Treatment</p>

“…These include changes in bile acid composition and metabolism, which can modulate both GLP-1 and FGF-19, 20 and microbiome diversity and composition. 21,22 Interestingly, a recent study reports that individuals post-bariatric surgery who have undergone cholecystectomy (vs those without cholecystectomy) have significantly increased risk for both PBH and dumping syndrome, further supporting the potential role of changes in the kinetics or composition of circulating or enteral bile acids in the pathogenesis of PBH. 21,23 Likewise, differences in the microbiome may contribute to interindividual differences in glycemic and hormonal response to meals.…”

“…21,22 Interestingly, a recent study reports that individuals post-bariatric surgery who have undergone cholecystectomy (vs those without cholecystectomy) have significantly increased risk for both PBH and dumping syndrome, further supporting the potential role of changes in the kinetics or composition of circulating or enteral bile acids in the pathogenesis of PBH. 21,23 Likewise, differences in the microbiome may contribute to interindividual differences in glycemic and hormonal response to meals. Fermentation products of the microbiome, such as short chain fatty acids (SCFA), which are increased after RYGB, 24 can stimulate GLP1 release, 25 and may modulate insulin secretion, 6,27 potentially contributing to altered glucose metabolism.…”

Continuous glucose monitoring in patients with post‐bariatric hypoglycaemia reduces hypoglycaemia and glycaemic variability

“…17,18 Postprandial rises in glucose and exaggerated secretion of the incretin hormone glucagon-like peptide-1 (GLP-1) together trigger excessive secretion of insulin and subsequent rapid drops in glucose levels. 19,20 Additional contributors to PBH may include reduction in counterregulatory hormone response, 21,22 including blunting of hepatic glucose production during hypoglycaemia, 23 shifts in the gut microbiome 24 and alterations in the bile acid-FXR-FGF19 axis. [25][26][27] Unfortunately, PBH is a chronic condition and long-term treatment options are often incompletely effective but include dietary modification to reduce high-glycaemic-index carbohydrate intake and to ensure adequate protein and micronutrient intake, 28 acarbose or miglitol to slow carbohydrate absorption, 29 and somatostatin analogues (eg, octreotide or pasireotide) 30 and diazoxide 31,32 to reduce insulin secretion.…”

“…Postprandial rises in glucose and exaggerated secretion of the incretin hormone glucagon‐like peptide‐1 (GLP‐1) together trigger excessive secretion of insulin and subsequent rapid drops in glucose levels 19,20 . Additional contributors to PBH may include reduction in counterregulatory hormone response, 21,22 including blunting of hepatic glucose production during hypoglycaemia, 23 shifts in the gut microbiome 24 and alterations in the bile acid‐FXR‐FGF19 axis 25‐27 …”