Intestinal microbiota is crucial for the regulation of the immune system and feeding habits in aquatic animals, as well as preventing the invasion of pathogenic microorganisms. However, disorders of the intestinal microbiota can lead to numerous, possibly life-threatening diseases. In the present study, we reported a disease occurring in cultured hybrid sturgeons (Acipenser schrenckii♂×Acipenser baeri♀) in the Sichuan province, Southwest China. The diseased fish did not exhibit obvious skin lesions, with observed symptoms including intestine dilatation with large amounts of gas and a transparent intestinal wall. Pathological examinations, microbiological tests, and the high-throughput sequencing of intestinal microbiota were performed to investigate the cause of death of diseased sturgeons. Results demonstrated that no bacteria were isolated from the liver, spleen and kidney, and no obvious changes were observed in tissues, with the exception of the intestine. The intestines demonstrated marked necrotic enteritis with lumen dilatation and a large number of bacteria attached to the base of the intestinal villus. Furthermore, observations from an electron microscope revealed the invasion by bacteria of the striated border. Results from the 16 s rRNA high-throughput sequencing of intestinal microbiota indicate variations in the relative abundance and distribution uniformity of the intestinal microbiota in the diseased group. More specifically, the intestinal microbiota abundance in the diseased group was higher in Clostridium, Cetobacterium, and Lactococcus, and lower in Mycoplasma at the genus level compared to the healthy group. Our observations suggest that the death of the hybrid sturgeons was caused by intestinal enteritis, which itself was a result of the intestinal microbiota disorder. To our knowledge, this is the first study to reveal hybrid sturgeon death via enteritis caused by an intestinal microbiota disorder.