Gut Microbiota May Not Be Fully Restored in Recovered COVID-19 Patients After 3-Month Recovery

Yu Tian, Kai-Yi Sun, Tian-Qing Meng, Zhen Ye, Shi-Meng Guo, Zhi-Ming Li, Cheng-Liang Xiong, Ying Yin, Hong-Gang Li, Li-Quan Zhou, Yu Tian, Kai-Yi Sun, Tian-Qing Meng, Zhen Ye, Shi-Meng Guo, Zhi-Ming Li, Cheng-Liang Xiong, Ying Yin, Hong-Gang Li, Li-Quan Zhou

Abstract

Coronavirus disease 2019 (COVID-19) has infected over 124 million people worldwide. In addition to the development of therapeutics and vaccines, the evaluation of the sequelae in recovered patients is also important. Recent studies have indicated that COVID-19 has the ability to infect intestinal tissues and to trigger alterations of the gut microbiota. However, whether these changes in gut microbiota persist into the recovery stage remains largely unknown. Here, we recruited seven healthy Chinese men and seven recovered COVID-19 male patients with an average of 3-months after discharge and analyzed their fecal samples by 16S rRNA sequencing analysis to identify the differences in gut microbiota. Our results suggested that the gut microbiota differed in male recovered patients compared with healthy controls, in which a significant difference in Chao index, Simpson index, and β-diversity was observed. And the relative abundance of several bacterial species differed clearly between two groups, characterized by enrichment of opportunistic pathogens and insufficiency of some anti-inflammatory bacteria in producing short chain fatty acids. The above findings provide preliminary clues supporting that the imbalanced gut microbiota may not be fully restored in recovered patients, highlighting the importance of continuous monitoring of gut health in people who have recovered from COVID-19.

Keywords: 16S sequence; SARS-CoV-2; gut microbiota; recovered COVID-19 patient; short chain fatty acids.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Tian, Sun, Meng, Ye, Guo, Li, Xiong, Yin, Li and Zhou.

Figures

Figure 1
Figure 1
The relative abundance of gut microbiota at the Phylum (A) and Genus (B) levels in the healthy control group and the recovered COVID-19 patient group. The category “Other” covers all other phyla or genera with a low taxa abundance. RPs, recovered patients; HCs, healthy controls.
Figure 2
Figure 2
Differences in the diversity and richness of fecal microbiota between recovered COVID-19 patients and healthy controls. The Shannon (A), Chao (B), and Simpson index (C) were calculated at a 3% distance. (D) A Venn diagram indicates the overlapping and unique OTUs among the groups. (E) Non-metric multidimensional analysis (NMDS) was conducted at the OTU level to show the different distribution of recovered patients and controls.
Figure 3
Figure 3
The taxonomic differences of recovered COVID-19 patients and controls in the level of Class (A), Order (B), Family (C), and Genus (D).
Figure 4
Figure 4
Identifying bacterial differences by the LEfSe. (A) Taxonomic cladogram shows the taxa that were considered statistically significant between two groups from the Phylum to the Genus level. (B) the LDA score of differentially enriched taxa in healthy controls and COVID-19 group (LDA threshold value >3.5).
Figure 5
Figure 5
The levels of SCFAs in the fecal samples of recovered patients and healthy controls. Examination of fecal samples of the two groups on levels of (A) Acetic acid (AA), (B) Propionic acid (PA), (C) Isobutyric acid (IBA), (D) Butyric acid (BA), (E) Isovaleric acid (IVA), (F) Valeric acid (VA), and (G) Hexanoic acid (HA). (H) Correlation between relative abundance of bacteria genera and levels of seven SCFAs. *p < 0.05; **p < 0.01.

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Source: PubMed

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