High animal-fat intake changes the bile-acid composition of bile juice and enhances the development of Barrett's esophagus and esophageal adenocarcinoma in a rat duodenal-contents reflux model

Abstract

The dietary components responsible for the development of Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) remain unclear. Wistar rats were divided into four groups based on their diet: a low soybean-oil diet, a low cow-fat diet, a high soybean-oil diet, and a high cow-fat diet. First, we evaluated the bile acid composition of the bile juice in each group without operation, using high-performance liquid chromatography. Because only high cow-fat intake induced changes in the composition of bile acids in bile juice, we then selected animals fed with a low soybean-oil diet and those with a high cow-fat diet to carry out esophago-jejunostomy for reflux of the duodenal contents, and compared sequential morphological changes between these groups up to 30 weeks after surgery. At 30 weeks after surgery, the reflux animals in the high cow-fat group showed a significantly higher incidence of BE and Barrett's dysplasia than those in the low soybean-oil group, and the incidence of EAC in the high cow-fat group was also slightly higher than that in the low soybean-oil group. High dietary animal fat changed the bile-acid composition and increased the concentration of taurine conjugates in the bile juice. These increased bile acids promoted the development of BE and Barrett's dysplasia leading to EAC.

Figure 1

Animal model. We established a duodenal‐contents reflux model using esophago‐jejunostomy without gastrectomy. To reduce the volume of duodenal‐contents reflux compared with the previously reported models, a serosal suture between the esophagus and the jejunum was added after esophago‐jejunostomy as indicated. T, treitz ligament.

Figure 2

Histological findings of Barrett's esophagus (BE) and BE dysplasia. (a) BE developed in the high cow‐fat group at 10 weeks after surgery and (b) Barrett's dysplasia developed in the high cow‐fat group at 20 weeks after surgery (hematoxylin–eosin, ×200).

Figure 3

Histological finding of early esophageal adenocarcinoma in the high cow‐fat group at 30 weeks after surgery (hematoxylin–eosin, ×200).

Figure 4

Macroscopic finding in the esophagus of a rat from the high cow‐fat group with a tumor penetrating into the liver, at 30 weeks after surgery. In the mucosal side, there was a large esophageal ulcer, measuring approximately 3 cm, and a protruding tumor with ulcer, measuring approximately 1.5 cm (arrow) in the lower portion of the esophagus. An unevenly eroded surface was also detected in the oral side of the esophageal ulcer.

Figure 5

Histological findings of the tumor shown in Fig. 4. (a) At lower magnification, there were intestinal‐type cells (Barrett's esophagus) in the surface mucosal layer, and intestinal‐type atypical glands with mucin production in the deeper layer. The tumor showed invasive growth with desmoplastic reaction (hematoxylin–eosin, ×100). (b) Higher magnification of Fig. 5a. The atypical glands invaded to the adventitia and penetrated into the liver (hematoxylin–eosin, ×200).