Recently, Streptococcus has been reported to be the etiology of several infectious diseases such as brain abscess and bacteremia in Journal of Infection.1,2 Here, we reported that Streptococcus sp. C150 and Streptococcus vestibularis, which encode lantibiotics, are potential risk factors for nonalcoholic fatty liver disease (NAFLD) and liver cirrhosis (LC), as revealed by a comparison of the gut microbiome of healthy subjects (n = 2042) and patients with diseases, including metabolic disorders, liver diseases, gastrointestinal diseases, and neurological disorders (n = 1683). We showed that the lantibiotic genes are frequently present and highly abundant in the gut microbiome of the patients with NAFLD and LC. Additionally, the deletion of these genes reduces toxicity to liver cells.

Lantibiotics are a class of bacteriocins containing rare amino acids and are produced by gram-positive bacteria.3 Lantibiotics are divided into two types based on their structure and characteristic functions. Type A lantibiotics are elongated and flexible.4 Type B lantibiotics are compact, globular, and rigid.5 Lantibiotics can inhibit food decay caused by pathogens in the food industry, however, they are also associated with various human diseases. For instance, type B lantibiotics from Enterococcus faecalis have been reported to enhance alcoholic liver disease and are associated with mortality in patients with alcoholic hepatitis.6 The latent risk of disease motivated us to investigate whether lantibiotics were associated with diseases. In this study, we first collected and classified lantibiotic sequences from the protein database. We then mapped the sequences of lantibiotics to metagenomic datasets from both healthy participants and participants with disease symptoms. We found that a cluster of lantibiotics from Streptococcus was prevalent in patients with LC and NAFLD. Furthermore, cellular experiments have shown that lantibiotics are toxic to hepatocytes (The methods were described in Supplementary Materials and Methods).