Gut microbiota and metabolites in patients with COVID-19 are altered by the type of SARS-CoV-2 variant

Yoshihiro Yokoyama; Tomoko Ichiki; Tsukasa Yamakawa; Yoshihisa Tsuji; Koji Kuronuma; Satoshi Takahashi; Eichi Narimatsu; Akio Katanuma; Hiroshi Nakase

doi:10.3389/fmicb.2024.1358530

Gut microbiota and metabolites in patients with COVID-19 are altered by the type of SARS-CoV-2 variant

Front Microbiol. 2024 Mar 5:15:1358530. doi: 10.3389/fmicb.2024.1358530. eCollection 2024.

Authors

Yoshihiro Yokoyama¹, Tomoko Ichiki², Tsukasa Yamakawa¹, Yoshihisa Tsuji³, Koji Kuronuma⁴, Satoshi Takahashi⁵, Eichi Narimatsu⁶, Akio Katanuma⁷, Hiroshi Nakase¹

Affiliations

¹ Department of Gastroenterology and Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan.
² Department of General Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan.
³ Department of General Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
⁴ Department of Respiratory Medicine and Allergology, Sapporo Medical University School of Medicine, Sapporo, Japan.
⁵ Department of Infection Control and Laboratory Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
⁶ Department of Intensive Care Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan.
⁷ Center for Gastroenterology, Teine-Keijinkai Hospital, Sapporo, Japan.

Abstract

Introduction: Patients with COVID-19 have dysbiosis of the intestinal microbiota with altered metabolites in the stool. However, it remains unclear whether the differences among SARS-CoV-2 variants lead to differences in intestinal microbiota and metabolites. Thus, we compared the microbiome and metabolome changes for each SARS-CoV-2 variant in patients with COVID-19.

Materials and methods: We conducted a multicenter observational study of patients with COVID-19 and performed fecal microbiome, metabolome, and calprotectin analyses and compared the results among the different SARS-CoV-2 variants.

Results: Twenty-one patients with COVID-19 were enrolled and stratified according to the SARS-CoV-2 strain: six with the Alpha, 10 with the Delta, and five with the Omicron variant. Fecal microbiome analysis showed that α-diversity was reduced in the order of the Omicron, Delta, and Alpha variants (p = 0.07). Linear discriminant analysis revealed differences in the abundance of short-chain fatty acid-producing gut microbiota for each SARS-CoV-2 variant. Fecal metabolome analysis showed that the Omicron and Delta variants had markedly reduced propionic and lactic acid levels compared to the Alpha strain (p < 0.05).

Conclusion: The intestinal microbiota of patients with COVID-19 varies depending on the SARS-CoV-2 variant. Dysbiosis of the intestinal microbiota due to differences in SARS-CoV-2 variants causes a decrease in intestinal short-chain fatty acids.

Keywords: Omicron; fecal calprotectin; metabolome; microbiome; short-chain fatty acids.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was supported by the Japan Agency for Medical Research and Development (AMED) under grant number 20ek0410057h0002, 22ek0210154h0003, 22ek0410083s0003, 22ek0410082h0003, and by MHLW Research Program on Emerging and Reemerging Infections Diseases (Grant Number JPMH23HA2011) the Japanese Society for the Promotion of Science (JSPS) KAKENHI grant number JP23K15078. The funders were not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.