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. 2021 Jan-Dec;13(1):1-15.
doi: 10.1080/19490976.2021.1926840.

The gut microbiome of COVID-19 recovered patients returns to uninfected status in a minority-dominated United States cohort

Rachel C Newsome  1 , Josee Gauthier  1 , Maria C Hernandez  1 , George E Abraham  2 , Tanya O Robinson  2 , Haley B Williams  2 , Meredith Sloan  2 , Anna Owings  2 , Hannah Laird  2 , Taylor Christian  2 , Yilianys Pride  2 , Kenneth J Wilson  2 , Mohammad Hasan  2 , Adam Parker  2 , Michal Senitko  2 , Sarah C Glover  1   2 , Raad Z Gharaibeh  1 , Christian Jobin  1   3   4
Affiliations

The gut microbiome of COVID-19 recovered patients returns to uninfected status in a minority-dominated United States cohort

Rachel C Newsome et al. Gut Microbes. 2021 Jan-Dec.

Abstract

To investigate the relationship between intestinal microbiota and SARS-CoV-2-mediated pathogenicity in a United States, majority African American cohort. We prospectively collected fecal samples from 50 SARS-CoV-2 infected patients, 9 SARS-CoV-2 recovered patients, and 34 uninfected subjects seen by the hospital with unrelated respiratory medical conditions (controls). 16S rRNA sequencing and qPCR analysis was performed on fecal DNA/RNA. The fecal microbial composition was found to be significantly different between SARS-CoV-2 patients and controls (PERMANOVA FDR-P = .004), independent of antibiotic exposure. Peptoniphilus, Corynebacterium and Campylobacter were identified as the three most significantly enriched genera in COVID-19 patients compared to controls. Actively infected patients were also found to have a different gut microbiota than recovered patients (PERMANOVA FDR-P = .003), and the most enriched genus in infected patients was Campylobacter, with Agathobacter and Faecalibacterium being enriched in the recovered patients. No difference in microbial community structure between recovered patients and uninfected controls was observed, nor a difference in alpha diversity between the three groups. 24 of the 50 COVID-19 patients (48%) tested positive via RT-qPCR for fecal SARS-CoV-2 RNA. A significant difference in gut microbial composition between SARS-CoV-2 positive and negative samples was observed, with Klebsiella and Agathobacter being enriched in the positive cohort. No significant associations between microbiome composition and disease severity was found. The intestinal microbiota is sensitive to the presence of SARS-CoV-2, with increased relative abundance of genera (Campylobacter, Klebsiella) associated with gastrointestinal (GI) disease. Further studies are needed to investigate the functional impact of SARS-CoV-2 on GI health.

Keywords: 16S rRNA sequencing; COVID-19; Human gut microbiota; SARS-CoV-2; clinical study; microbiome; microbiota.

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Figures

Figure 1.
Figure 1.
COVID patients have a different gut microbiota than non-infected controls and recovered patients. (a) Principal coordinates analysis (PCoA) showing beta diversity measured by Bray-Curtis dissimilarity between COVID (n = 50), COVID recovered (n = 9) and non-COVID (control, n = 34) subjects. (b) Alpha-diversity as measured by the Shannon index for COVID (n = 50), COVID recovered (n = 9) and non-COVID (control, n = 34) subjects
Figure 2.
Figure 2.
COVID patients have a different gut microbiota than non-infected controls. (a) Principal coordinates analysis (PCoA) showing beta diversity comparison between COVID (n = 50) and non-COVID (control, n = 34) subjects. FDR-P = .004 (b) Shannon diversity index for COVID (n = 50) and non-COVID (control, n = 34) subjects. FDR-P = .78 (c) Log fold change (logFC) plot of significantly (FDR-P < .05) enriched genera in COVID patients and controls. Bars with positive values indicate enrichment in COVID subjects and bars with negative values indicate enrichment in non-COVID subjects. Only the top 75% of significantly enriched genera are shown. See Supplemental Table 2 for full list
Figure 3.
Figure 3.
COVID patients have a different gut microbiota than COVID recovered patients. (a) Principal coordinates analysis (PCoA) comparing beta diversity between COVID (n = 50) and COVID recovered (n = 9) subjects. FDR-P = .003 (b) Shannon diversity index for COVID (n = 50) and COVID recovered (n = 9) subjects. FDR P = .62 (c) Log fold change (logFC) plot of significantly (FDR-P < .05) enriched genera in COVID and COVID recovered patients. Bars with positive values indicate enrichment in COVID subjects and bars with negative values indicate enrichment in COVID recovered subjects. Only the top 75% of significantly enriched genera are shown. See Supplemental Table 3 for full list
Figure 4.
Figure 4.
No difference in gut microbiome between recovered COVID-19 patients and non-infected controls. (a) Principal coordinates analysis (PCoA) comparing beta diversity between COVID recovered (n = 9) and control (n = 34) subjects. FDR P = .93 (b) Shannon diversity index for COVID recovered (n = 9) and control (n = 34) subjects. FDR P = .92 (c) Log fold change (logFC) plot of significantly (FDR-P < .05) enriched genera in COVID recovered patients and controls. Bars with positive values indicate enrichment in COVID recovered subjects and bars with negative values indicate enrichment in controls subjects. See Supplemental Table 4 for a list of the plotted genera
Figure 5.
Figure 5.
Presence of detectable SARS-CoV-2 virus in feces indicates differences in microbial composition among COVID-19 infected patients. (a) Principal coordinates analysis (PCoA) comparing beta diversity between SARS-CoV-2 qPCR positive (n = 24) and SARS-CoV-2 qPCR negative (n = 26) subjects. FDR-P = .03 (b) Shannon diversity index for SARS-CoV-2 qPCR positive (n = 24) and SARS-CoV-2 qPCR negative (n = 26) subjects. FDR P = .78 (c) Log fold change (logFC) plot of significantly (FDR-P < .05) enriched genera in SARS-CoV-2 qPCR positive and qPCR negative patients. Bars with positive values indicate enrichment in SARS-CoV-2 qPCR positive samples and bars with negative values indicate enrichment in controls SARS-CoV-2 qPCR negative samples. Only the top 75% of significantly enriched genera are shown. See Supplemental Table 5 for full list
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