Two-year follow-up of gut microbiota alterations in patients after COVID-19: from the perspective of gut enterotype

Abstract

Gut microbiota dysbiosis plays a role in the pathogenesis of post-acute coronavirus disease (COVID-19); however, the long-term recovery of the gut microbiota following SARS-CoV-2 infection remains insufficiently understood. In this study, 239 fecal samples were collected from 87 COVID-19 patients during the acute phase, and at 6 months, 1 year, and 2 years post-discharge. An additional 48 fecal samples from non-COVID-19 controls were also analyzed. Gut enterotypes were determined through 16S rRNA sequencing, and dynamic changes from the acute phase through recovery were assessed. Correlations between enterotypes and clinical characteristics were also examined. Two distinct enterotypes were identified: a Blautia-dominated enterotype (Enterotype-B) and a Streptococcus-dominated enterotype (Enterotype-S). Species diversity and richness were significantly higher in Enterotype-B. Enterotype-S, associated with inflammation, was more prevalent during the acute phase. Six months post-discharge, the ratio of Enterotype-B to Enterotype-S approached normal levels. Patients with Enterotype-S at admission had a higher incidence of severe cases during hospitalization and a longer duration of nasopharyngeal viral shedding compared with those with Enterotype-B. Furthermore, at 6 months post-discharge, residual pulmonary Computed Tomography (CT) abnormalities were more common in patients with Enterotype-S (55%) than in those with Enterotype-B (20%, P = 0.046). An index, B/S, representing the ratio of Blautia and Bifidobacterium to Streptococcus, was introduced and found to correlate closely with clinical characteristics. The Streptococcus-dominated enterotype is associated with inflammation and appears to influence both the severity of illness during the acute phase and cardiopulmonary recovery.

Importance: This study sheds new light on the intricate process of rehabilitating the gut microbiota following disruptions caused by COVID-19. Our approach, which examines the dynamics from the vantage point of enterotypes, reveals a more rapid recovery than previously reported, with the majority of the microbiota rebounding within a 6-month timeframe. Furthermore, our findings underscore the importance of the Blautia-dominated enterotype as a marker of gut health, which plays a pivotal role in mitigating the risk of severe progression and lingering effects post-SARS-CoV-2 infection. By scrutinizing these enterotypes, we can now foresee the potential severity and aftermath of COVID-19, offering a valuable tool for prognosis and intervention.

Keywords: COVID-19; Streptococcus; convalescence; gut microbiota; pneumonia.

Fig 1

The schematic demonstrates the enrollment of participants and follow-up schedule.

Fig 2

Two-year follow-up of gut enterotype alterations in patients after COVID-19. (A) Gut enterotype distribution of COVID-19 patients at different follow-up time points and healthy controls. (B) Comparison of microbial diversity and richness between Enterotype-B (E-B) and Enterotype-S (E-S). (C) Linear discrimination analysis (LDA) effect size (LEfSe) analysis was used to differentiate the Enterotype-B (E-B) and Enterotype-S (E-S) at the genus level. LDA scores showed significant differences in microbiota composition between Enterotype-B (blue) and Enterotype-S (orange). Only taxa with an LDA threshold >3 are shown.