Intestinal Collinsella may mitigate infection and exacerbation of COVID-19 by producing ursodeoxycholate

PLoS One. 2021 Nov 23;16(11):e0260451. doi: 10.1371/journal.pone.0260451. eCollection 2021.

Abstract

The mortality rates of COVID-19 vary widely across countries, but the underlying mechanisms remain unelucidated. We aimed at the elucidation of relationship between gut microbiota and the mortality rates of COVID-19 across countries. Raw sequencing data of 16S rRNA V3-V5 regions of gut microbiota in 953 healthy subjects in ten countries were obtained from the public database. We made a generalized linear model (GLM) to predict the COVID-19 mortality rates using gut microbiota. GLM revealed that low genus Collinsella predicted high COVID-19 mortality rates with a markedly low p-value. Unsupervised clustering of gut microbiota in 953 subjects yielded five enterotypes. The mortality rates were increased from enterotypes 1 to 5, whereas the abundances of Collinsella were decreased from enterotypes 1 to 5 except for enterotype 2. Collinsella produces ursodeoxycholate. Ursodeoxycholate was previously reported to inhibit binding of SARS-CoV-2 to angiotensin-converting enzyme 2; suppress pro-inflammatory cytokines like TNF-α, IL-1β, IL-2, IL-4, and IL-6; have antioxidant and anti-apoptotic effects; and increase alveolar fluid clearance in acute respiratory distress syndrome. Ursodeoxycholate produced by Collinsella may prevent COVID-19 infection and ameliorate acute respiratory distress syndrome in COVID-19 by suppressing cytokine storm syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actinobacteria / physiology*
  • COVID-19 / etiology
  • COVID-19 / pathology
  • COVID-19 / prevention & control*
  • Gastrointestinal Microbiome*
  • Humans
  • Intestines / microbiology*
  • SARS-CoV-2 / physiology*
  • Ursodeoxycholic Acid / metabolism*

Substances

  • Ursodeoxycholic Acid

Supplementary concepts

  • Collinsella intestinalis

Grants and funding

Kinji Ohno received the following funding. This study was supported by Grants-in-Aid from the Japan Society for the Promotion of Science (JP18K14684 and JP21H03561, https://www.jsps.go.jp/english/); the Ministry of Health, Labour and Welfare of Japan (20FC1036, https://www.mhlw.go.jp/english/); the Japan Agency for Medical Research and Development (JP21gm1010002, JP21ek0109488, and JP21bm0804005, https://www.amed.go.jp/en/), and the National Center of Neurology and Psychiatry (2-5, https://www.ncnp.go.jp/en/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.