Background Minipigs are considered as ideal animal for studying atherosclerosis (AS) due to its similarities to human in terms of the anatomy and hemodynamics of the coronary artery. However, there is a lack of research on the alterations in intestinal flora in minipigs with AS.

Objective To explore the effect of high cholesterol and high fat diet (HCFD) on the intestinal flora of minipig AS model.

Methods In this study, eight 6-month-old male minipigs were randomly divided into model group (AS group, n=4) and control group (n=4). The minipigs in the AS group were fed with high-cholesterol and high-fat diet for 9 months to establish the AS model, and the minipigs in the control group were fed with normal feed diet for 9 months. The minipigs in both groups were weighed monthly to calculate the weight growth rate. After 9 months of modeling, their whole blood was collected at 16 h fasting, and serum was isolated for detection of blood lipids; minipigs were anesthetized and sacrificed, and abdominal aortic plaques were collected for pathological examination. The colon contents were collected and sequenced for the V3-V4 region of the 16S rRNA gene to analyze the characteristics of the intestinal flora of AS minipigs.

Results The weight growth rate of minipigs in the AS group from 1 to 9 months was significantly higher compared to the control group (all P<0.05). Blood lipids showed a significant increase at 9 months (P<0.05), and typical atherosclerotic plaques were observed in the intima of the abdominal aorta. The observed species results (P=0.228), Chao1 results (P=0.214), Simpson results (P=0.356), and Shannon results (P=0.089) of the intestinal flora of minipigs in the control group were higher than those in the AS group, but the differences were not significant. PCoA results (P=0.027) and NMDS results (P=0.027, Stress=0.03) showed significant differences in the intestinal flora of the two groups. The predominant intestinal flora of the AS group included Escherichia-Shigella, Ruminococcaceae-UCG-005, Lachnospiraceae-unclassified, Muribaculaceae-unclassified, and Bacteroides; while the control group had Ruminococcaceae-UCG-005, Clostridium, Lachnospiraceae-unclassified, Muribaculaceae-unclassified, and Rikenellaceae-RC9-gut-group as predominant flora. The proportion of Firmicutes/Bacteroidetes were significantly reduced in the AS group (P=0.018). The functional pathways of the intestinal flora in both groups were mainly focused on metabolic pathways involving amino acids, sugar, vitamins, Cytochrome C, and tricarboxylic acid metabolism.

Conclusion The Bama minipigs AS model, established on a high-cholesterol and high-fat diet, exhibits characteristics of obesity and the development of typical atheromatous plaque lesions in the abdominal aorta intima. The presence of these lesions can be linked to the structural imbalance of the intestinal flora.