Longitudinal alterations of the gut mycobiota and microbiota on COVID-19 severity

Abstract

Background: The impact of SARS-CoV-2 infection on the gut fungal (mycobiota) and bacterial (microbiota) communities has been elucidated individually. This study analyzed both gut mycobiota and microbiota and their correlation in the COVID-19 patients with severe and mild conditions and follow-up to monitor their alterations after recovery.

Methods: We analyzed the gut mycobiota and microbiota by bacterial 16S and fungal ITS1 metagenomic sequencing of 40 severe patients, 38 mild patients, and 30 healthy individuals and reanalyzed those of 10 patients with severe COVID-19 approximately 6 months after discharge.

Results: The mycobiota of the severe and mild groups showed lower diversity than the healthy group, and in some, characteristic patterns dominated by a single fungal species, Candida albicans, were detected. Lower microbial diversity in the severe group was observed, but no differences in its diversity or community structure were detected between the mild and healthy groups. The microbiota of the severe group was characterized by an increase in Enterococcus and Lactobacillus, and a decrease in Faecalibacterium and Bacteroides. The abundance of Candida was positively correlated with that of Enterococcus in patients with COVID-19. After the recovery of severe patients, alteration of the microbiota remained, but the mycobiota recovered its diversity comparable to that of mild and healthy groups.

Conclusion: In mild cases, the microbiota is stable during SARS-CoV-2 infection, but in severe cases, alterations persist for 6 months after recovery.

Keywords: COVID-19; Candida; Enterococcus; Gut; Microbiota; Mycobiota.

Fig. 1

Alterations in gut fungal and bacterial diversity in patients with COVID-19 compared with healthy controls. Diversity of the gut mycobiota (A–C) among patients with severe (n = 35), mild (n = 31) coronavirus disease 2019 (COVID-19) and healthy controls (n = 24). Diversity of microbiota (D–F) among patients with severe (n = 40), mild (n = 38) COVID-19 and healthy controls (n = 30). A, D Shannon index. B, E Rarefaction curves. C, F Principal coordinate analysis at amplicon sequence variants (ASV) levels. *P < 0.05, ***P < 0.001

Fig. 2

Altered composition of the gut mycobiota and microbiota in patients with COVID-19. A The log scale of viral copy number for each subject is illustrated by a red bar chart. Fungal and bacterial Shannon indices are presented as circles with three levels of colors (for fungal Shannon index: < 1, white; 1–2, light green; > 2, dark green; for the bacterial Shannon index: < 5, white; 5–6, light orange, > 6, orange) B The composition of major gut mycobiota in patients with severe or mild COVID-19 and healthy controls. C The composition of major gut microbiota in patients with severe, or mild COVID-19 and healthy controls

Fig. 3

Identifying fungal differences by linear discriminant analysis (LDA) effect size. A The LDA score of differentially enriched taxa in patients with severe coronavirus disease 2019 (COVID-19) and healthy controls (HC). B Taxonomic cladogram presents the taxa that were considered statistically significant between patients with severe COVID-19 and healthy controls (HC)

Fig. 4

Identifying bacterial differences by linear discriminant analysis (LDA) effect size. The LDA score of differentially enriched taxa in patients with severe coronavirus disease 2019 (COVID-19) patients and healthy controls (HC)

Fig. 5

Correlations of gut fungi and bacteria in patients with coronavirus disease 2019 (COVID-19). A Correlation plot for associations between two fungal genera (Candida and Aspergillus) and bacteria. B Pairwise correlation network between two fungal genera (Candida and Aspergillus) and bacteria. Bacteria that were present in 5% or more of the samples were extracted. Correlation coefficients greater than 0.2 or smaller than -0.2 are presented

Fig. 6

Longitudinal alterations of the gut mycobiota and microbiota in patients with COVID-19. Diversity of the gut mycobiota (A, B) among patients with severe COVID-19 (severe; n = 35), patients who recovered from COVID-19 (recovered; n = 10) COVID-19, and healthy controls (healthy; n = 24). Diversity of the gut microbiota (D, E) among patients with severe COVID-19 (severe; n = 40), patients who recovered from COVID-19 (recovered; n = 10) COVID-19, and healthy controls (healthy; n = 30). C Fungal composition in patients with severe COIVD-19 at baseline (pre) and after 6 months of recovery (post). F The bacterial composition of patients with severe COVID-19 at baseline (pre) and after 6 months of recovery (post)