Obesity has reached epidemic levels in the United Kingdom (UK), affecting a significant portion of the adult and pediatric population. Approximately one in four adults are obese, and one in three are overweight, highlighting that carrying excess body weight is increasingly the norm. The UK has the second-highest prevalence of obesity in Europe and the sixth-highest worldwide. Obesity is associated with significant morbidity and mortality. Gastroenterologists and hepatologists often encounter the gastrointestinal and hepatic complications of obesity before cardiometabolic diseases manifest. This places them in a unique position to implement early weight loss interventions or to refer patients to specialist weight management centers.
The Intersection of Gastroenterology and Obesity
Obesity is associated with important gastrointestinal and hepatic complications. Abdominal obesity, best captured by measuring waist circumference, is implicated in oesophageal, hepatobiliary, and malignant disorders. These complications often present sooner than cardiometabolic diseases.
Understanding the Gut-Brain Axis
In the past 50 years, environmental changes encouraging increased energy intake and reduced energy expenditure have led to 20%-30% of entire populations becoming obese. The availability of large portions of highly palatable, energy-dense processed foods is a key driver for weight gain. Food intake is influenced by external variables like food palatability and availability and the internal gut-brain axis. Hunger and satiety are regulated in the brain via complex reciprocal connections between the hypothalamus, brainstem, and higher cortical areas. These areas receive peripheral neuroendocrine signals from the gastrointestinal tract, regulating meal initiation and termination.
Neuroendocrine regulation of appetite involves gastrointestinal and peripheral hormones communicating directly (via the blood-brain barrier) and indirectly (enteric nervous system) to the subconscious hypothalamus and brainstem. This communication either stimulates appetite via agouti-related peptide (AgRP) and neuropeptide Y (NYP) or suppresses appetite via pro-opiomelanocortin (POMC) and cocaine and amphetamine regulated transcript (CART).
Medical and Surgical Interventions for Weight Loss
The multifactorial nature of obesity requires a multidisciplinary and multicomponent approach that incorporates lifestyle, medical, and/or surgical intervention. Empowering patients with the skills and strategies to facilitate weight loss, maintain weight loss, and prevent weight regain is the foundation of obesity management. These approaches should be maintained alongside medical and surgical treatment.
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Pharmacotherapy can be considered an adjunct in patients struggling to lose weight (e.g., 5-10% after 3-6 months) or maintain weight loss with lifestyle interventions. Orlistat tablets and liraglutide (Saxenda) injections are currently the only medications licensed for the treatment of obesity in the UK.
Response to bariatric surgery is variable and operation-specific, but Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG) can achieve clinically significant weight loss and metabolic improvements. A retrospective UK cohort study in 2016 found that RYGB and VSG are favored over gastric banding, which is declining due to complication rates (e.g., band slippage or intolerance) and the need for eventual surgery.
Roux-en-Y Gastric Bypass (RYGB)
During RYGB, the upper part of the stomach is divided to create a small gastric pouch (15-30 mL), which is anastomosed to the mid-jejunum, creating the roux or alimentary limb. The remaining stomach, duodenum, and proximal jejunum, which form the bilopancreatic limb, are thus bypassed.
Vertical Sleeve Gastrectomy (VSG)
VSG involves excising 70-80% of the stomach along the greater curvature to create a banana-sized gastric tube.
Biliopancreatic Diversion with Duodenal Switch (BPD-DS)
Historically, partial gastrectomy was the first stage of BPD-DS, a two-stage procedure. The distal small bowel is anastomosed to the duodenum. The distal end of the excised small bowel, which contains bilopancreatic secretions, is attached approximately 100 cm before the ileocaecal valve, thus allowing a long intestinal bypass with a short common channel for nutrient absorption.
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The Role of Gut Hormones
Substantial evidence suggests that the anatomical changes specific to RYGB and VSG differentially alter gastrointestinal signaling to the brain to reduce hunger, increase satiety, and change food preferences from high-sugar and high-fat foods to healthier alternatives. These subconscious changes in eating behavior result in durable weight loss following bariatric surgery. This complex gut-endocrine-brain axis is mediated by profound changes in pathways involving gut hormones, bile acids, gut microbiota, and the enteric nervous system.
Glucagon-like peptide-1 (GLP-1) and peptide YY3-36 (PYY) are two potent gut-derived appetite suppressor peptides elevated following RYGB and VSG. They have been consistently associated with weight loss, and blocking these hormones in postoperative bariatric patients leads to increased appetite, food intake, and weight gain. Accelerated nutrient presentation to the enteroendocrine L-cells of the distal intestine is a key mechanism explaining the postoperative elevations in GLP-1 and PYY, which has been more consistently demonstrated following RYGB than VSG.
Gastroenterologists and Emerging Therapies
Incretin-modifying agents, including glucagon-like peptide-1 (GLP-1) receptor agonists, are emerging as the most promising drug treatments for obesity itself and nonalcoholic fatty liver disease (NAFLD). These agents also appear to provide an effective way to target central appetite mechanisms. They also slow gastric emptying, and this helps increase postprandial fullness and decrease appetite. Meta-analyses suggest that the GLP-1 agents SQ semaglutide and liraglutide perform well in this role. GLP-1 agonists are associated with an increased risk of biliary tract and gallbladder diseases, so it's necessary to watch for adverse effects. Researchers have demonstrated the ability of other dual incretin agonists, such as cotadutide and pemvidutide, to reduce significant hepatic fibrosis in both animal models and humans.
The Microbiome's Influence
The gut microbiome affects body weight in multiple ways, modulating metabolism, appetite, bile acid metabolism, and the hormonal and immune systems. Fecal microbiota transplantation (FMT) may impact incretin signaling, metabolism, bile acid dehydroxylation, or weight loss.
Complications and Considerations Post-Bariatric Surgery
The safety of bariatric surgery has improved in the past 20 years. Almost all operations are done laparoscopically, and increased experience and volume of procedures, along with enhanced recovery after surgery programs, have contributed to reduced operation times, length of stay, and complications. Late complications are procedure-specific. Obstructive symptoms following RYGB may be secondary to a gastro-jejunal anastomotic stricture, while after VSG may suggest narrowing at the gastro-oesophageal junction or incisura angularis, which can present as gastric outlet obstruction. Endoscopic dilatation can be used to treat upper gastrointestinal stenosis. Internal herniation can also present with obstructive symptoms and is more likely following RYGB. Early recognition is required to avoid life-threatening bowel ischaemia.
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Dumping Syndrome
Dumping syndrome can affect up to 50% of patients post-RYGB. Early dumping presents with gastrointestinal symptoms (abdominal pain, nausea, diarrhoea) and sympathetic nervous system features (tremors, sweating, dizziness, tachycardia) within 15 min of eating large amounts of refined sugars and eating too quickly. These symptoms develop because of rapid emptying of food into the small bowel followed by rapid fluid shifts due to the hyperosmolar food content. Early dumping is often self-limiting. Late dumping or hyperinsulinaemic hypoglycaemia is less common and can present 1 to 3 hours after eating a high glycaemic index carbohydrate meal with neuroglycopenic symptoms. The mainstay of management is to adhere to a low GI carbohydrate diet and to eat small frequent meals. Medications such as diazoxide, octreotide or calcium channel antagonists are available for refractory cases of dumping syndrome.
Nutritional Deficiencies
Prolonged vomiting is a risk factor for thiamine deficiency, which can manifest as Wernicke’s encephalopathy.
Endoscopic Bariatric Interventions
Although bariatric surgery is safe, effective, and cost-effective, it is not a practical strategy to treat the epidemic levels of obesity. Endoscopic bariatric interventions could be an alternative for unwilling or unsuitable surgical candidates, as well as an adjunct to medical therapy. Endoscopic placement of balloons (Orbera or Reshape) filled with 400-700mls of blue saline can be performed, with removal after 6 months.
The Gastroenterologist's Unique Opportunity
Gastrointestinal and hepatic diseases are often the first manifestations of obesity. Gastroenterologists and hepatologists are at the forefront of obesity management and have a unique opportunity to implement timely weight loss interventions or refer to specialist weight management centers. With more patients meeting the criteria for bariatric surgery, awareness of postoperative complications is essential.
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