Gut Microbiota from Patients with Long COVID Persisting for 2 Years Result in Alterations in Mice that Resemble...

Human gut microbiota (GM) has been identified as a potentially important factor influencing the development of long COVID (LCOVID). The aim of this study was to understand the GM of LCOVID, which lasted for two years, in order to improve public awareness. Human gut microbiota and its metabolites were assessed in a healthy control group (n = 11) (HC) unexposed to SARS-CoV-2 and an LCOVID group (n = 11) in Hainan, China, using Shotgun metagenomics and liquid chromatography-mass spectrometry (LC-MS) of feces. The causal role of the microbiota in LCOVID was further validated by transplanting feces from the subjects into ABx mice using Histopathology and 16 S rRNA sequencing. Fecal microbial diversity was lower in patients with LCOVID compared with that in HC. Pro-inflammatory bacteria such as Streptococcus_salivarius and Streptococcus_parasanguinis increased, whereas anti-inflammatory bacteria such as Faecalibacterium_SGB15346 and Alistipes_onderdonkii decreased. Fecal metabolites from LCOVID were impaired in carbohydrate degradation, indole production, SCFA production, and fatty acid degradation. Transplantation of feces from patients with LCOVID into mice results in lung inflammation, intestinal inflammation, and anxiety. In addition, transplanted mice showed worse outcomes during Klebsiella_pneumoniae infections. Transplanted mice and the key bacteria Streptococcus_salivarius had the same worse outcomes in the D-IBS model by limb binding. GM from patients with LCOVID was altered significantly and sufficiently to promote LCOVID symptoms in mice, suggesting that it may be a potential therapeutic target.