Gastroesophageal reflux is mainly the reflux of gastric contents (mainly gastric acid and pepsin) and bile salts and pancreatic enzymes from duodenal reflux into the stomach into the esophagus. These refluxes individually or together cause damage to the esophageal mucosa in the development of GERD and its complications. Among them, gastric acid and pepsin are the main attacking factors, while in an alkaline environment, bile salts and pancreatic enzymes become the main attacking factors, and gastric acid enhances the damaging effect of bile acids on the mucosa. These substances in the reflux (mainly gastric acid and pepsin, followed by bile salts and pancreatic enzymes from the duodenal reflux into the stomach) impair the barrier function of the esophageal mucosa and weaken the mucosal resistance, thus causing inflammation of the esophageal mucosa. The role of gastric acid and pepsin in the mechanism of GERD injury is better established. Gastric acid and pepsin act directly on the test tube mucosa, which has a weak acid resistance barrier, causing erosion and even ulceration. Gastric acid and pepsin act synergistically in the process of damage to the esophageal mucosa, whereas gastric acid alone does not cause significant morphological changes in the esophageal mucosa. Duodenal contents include bile, pancreatic juice, and intestinal fluid. Bile is mainly bound bile acid, unconjugated bile acid and phospholipids, and pancreatic fluid is mainly pancreatic enzymes. In the intestine, phospholipase A in pancreatic fluid can hydrolyze phospholipids in bile into lysolecithin, which is very damaging to esophageal mucosa under acidic conditions. Trypsin and lipase in the regurgitated material can cause non-specific damage to the esophageal mucosa. Bile acids in duodenal contents can be divided into conjugated bile acids and unconjugated bile acids, which act in an acidic environment and both in an alkaline environment, and bile acids can cause esophagitis, Barrett’s esophagus and esophageal cancer. Duodenal contents are also an important cause of GERD. The action of bile is mainly that of bile salts and bile acids. Bile salts, cholesterol and lecithin can act as emulsifying agents to emulsify fat into microdroplets to increase the area of action of pancreatic lipase; bile acids can also combine with fatty acids to form water-soluble complexes to promote the absorption of fatty acids; bile salts themselves are also a cholagogic agent. Bile is also important in promoting the absorption of fat-soluble vitamins, and in the duodenum, bile neutralizes part of the gastric acid. However, when the bile duct is blocked and bile cannot enter the duodenum, the digestion and absorption of fat will be impaired, which can cause steatorrhea. Bile salts can inhibit the absorption of sodium and water in the colon. If the absorption of bile salts in the small intestine is impaired and a large amount of bile salts enters the colon, it often causes watery diarrhea. Bile can stimulate the intestinal tube movement, if bile is lacking, it can cause the intestinal tube movement to be weakened and make the food accumulate in the intestine. Bile salts in bile have many public utilities, which can help the body digest and absorb fat, can make fat into very small micro-droplets, increase the contact area between fat and enzymes, and facilitate the decomposition and absorption of fat; promote the absorption of vitamin A, vitamin D, vitamin E and vitamin K together with the decomposition products of fat; stimulate the peristaltic function of the intestine and inhibit the growth of intestinal bacteria; and can promote the dissolution of cholesterol. Phospholipids in turn play a role in promoting the dissolution of cholesterol, thus keeping bile in a liquid state. Bile reflux often occurs in an acidic environment, and bile reflux plays a synergistic pathogenic role with acid reflux. The direct contact of bile alone with esophageal and gastric mucosa generally does not cause damage, but it can damage the barrier role of esophageal and gastric mucosa through its role of stimulating gastric acid secretion, causing bile salts to combine with gastric acid, enhancing the activity of acid hydrolase, breaking the lysosomal membrane, and dissolving lipoproteins; and the increased reverse diffusion of H+ into the mucosa and submucosa can stimulate mast cells and release histamine, which in turn stimulates the secretion of gastric acid and pepsin, which eventually leads to inflammation, erosion and bleeding of the esophageal and gastric mucosa. When bile is mixed with pancreatic juice, the lecithin in bile interacts with phosphodiesterase A in pancreatic juice and is converted into lysolecithin, which can also cause damage to the esophageal and gastric mucosal barriers if it flows back into the stomach and esophagus.