Ammonia is constantly produced as a metabolic waste of the amino acid catabolism in mammals. The production of toxic ammonia is resolved in the liver where urea cycle resides to convert free ammonia to urea. The malfunctions of liver cause hyperammonemia that leads to CNS dysfunctions such as brain edema, convulsions, and coma. Current treatments for hyperammonemia, such as antibiotics or lactulose, are designed to decrease the intestinal production of ammonia and/or its absorption into the body, which are not effective but also often accompanied with side effects. In recent years, increasing evidences have shown that modification of gut microbiota could be used to treat hyperammonemia. Considering the role of gut microbiota and the physiological characteristics of the intestine, removal of ammonia in the intestine by modulating gut microbiota would be an ideal approach to treat hyperammonemia. In this work, we developed Lactobacillus reuteri JBL2-03601 and Streptococcus subneri JBS15-02101 co-culture to efficiently treat hyperammonemia that can remove ammonia from its surrounding environment. This work not only provided a new concept of very efficient treatment of hyperammonemia but also showed that modulation of intestinal microbiota could lead to develop a revolutionary therapeutic agent for various diseases.