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White feces syndrome (WFS) is a multifactorial shrimp disease that can cause severe financial losses in Litopenaeus vannamei aquaculture industry. The balance of the intestinal microbiota substantially maintains the health of the host, and dysbiosis is closely associated with diverse diseases. In the present study, intestinal samples were collected from the healthy and WFS-infected shrimp in the same cultured pond to compare the differences in intestinal histology and physiological indices as well as composition and function of intestinal microbiota. The result of intestinal histology revealed that the normal intestinal structure suffered severe damage in WFS-infected shrimp. The expression of antioxidant and immune-related genes like autophagy proteins, antimicrobial peptides were significantly decreased in WFS-infected shrimp. Through the sequencing analysis of the 16S rRNA genes, it was observed that the composition and function of intestinal microbiota had undergone an enormous alteration in WFS-infected shrimp. At phylum level, the abundance of major phylum including Cyanobacteria, Chloroflexi, Patescibacteria and Desulfobacterota were significantly increased, whereas phyla Bacteroidota and Verrucomicrobiota were decreased in WFS-infected shrimp. At the genus level, Cyanobium PCC-6307 and PeM15 were overrepresented in WFS-infected shrimp, and Cyanobium PCC-6307 was a potentially toxic cyanobacteria that could produce cyanotoxins. Functional prediction of intestinal microbiota also revealed that nutrition-related pathways were generally decreased, but disease-related pathways were increased in WFS-infected shrimp. These results illustrated that WFS of Litopenaeus vannamei was closely associated with the composition disorders of intestinal microbiota and hypoimmunity. Additionally, the identified bacterial genus Cyanobium PCC-6307 can be a signature to evaluate the occurrence probability of WFS in shrimp ponds and provide theorical basis for optimal treatments and control methods.