Background: The gut-lung-kidney axis is critical during viral infection, and changes in gut microbiome and metabonomics may be linked to disease severity of Coronavirus disease 2019 (COVID-19) infection in renal transplant recipients. Here, we explored the characterization of gut microbiome and metabonomics in recipients with COVID-19, and carried out a 6-months follow-up to investigate the persistent impact of gut microbiome.
Methods: A total of 30 allograft renal transplant recipients were enrolled, including 17 subjects with novel coronavirus pneumonia (NCP), 6 with COVID-19 and 7 with non-infection of COVID-19. Fecal samples at the beginning of infection were collected and gut microbiome and metabonomics were performed by 16S rRNA sequencing and UHPLC-MS/MS methods, respectively. During the 6-months follow-up, clinical parameters were recorded, and analyzed with changes in gut microbiota by generalized estimating equations (GEE) models.
Results: Gut microbiome composition was significantly altered in renal transplant recipients with NCP compared to subjects with COVID-19 infection and non-COVID-19 infection. 15 species from two phyla (Firmicutes, Actinobacteria) were significantly enriched in recipients with NCP (P < 0.01). Correlation analysis suggested the remarkable association of gut microbiota changes with inflammatory response and renal allograft function. Changes in gut metabolic profile were also reported, and 2 lipid-related metabolites (19-Nortestosterone and Perillartine) were suggested to be significantly correlated with Mucilaginosa and Fragilis (P < 0.01). GEE models based on short-term follow-up parameters indicated that serum creatinine levels in recipients with NCP were significantly higher than individuals in COVID-19 group and Control group (P < 0.01), which was close correlated with altered gut microbiota (Peptostreptococcaceae). In addition, relationship of lipid metabolism with gut microbiota changes (Clostridium) was also found.
Conclusion: Associations between gut microbiota composition, gut metabolites, allograft function in renal transplant recipients with NCP and COVID-19 infection suggested that gut microbiome is involved in the magnitude of COVID-19 severity possibly through modulating inflammatory response and lipid metabolism. Moreover, gut microbiota dysbiosis after COVID-19 infection treatment could contribute to persistent allograft dysfunction, highlighting the emerging need of gut microbiome recovery in renal transplant recipients with COVID-19 infection.