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

• Published in: PloS one Vol. 16; no. 11; p. e0260451
• Main Authors: Hirayama, Masaaki, Nishiwaki, Hiroshi, Hamaguchi, Tomonari, Ito, Mikako, Ueyama, Jun, Maeda, Tetsuya, Kashihara, Kenichi, Tsuboi, Yoshio, Ohno, Kinji
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 23.11.2021; Public Library of Science (PLoS)
• Subjects: ACE2; Actinobacteria - physiology; Alveoli; Analysis; Angiotensin; Angiotensin-converting enzyme 2; Antioxidants; Apoptosis; Bacteria; Biology and Life Sciences; Cancer; Chronic obstructive pulmonary disease; Clustering; Complications and side effects; Coronaviruses; COVID-19; COVID-19 - etiology; COVID-19 - pathology; COVID-19 - prevention & control; Cytokine storm; Cytokines; Digestive system; Digestive tract; Dosage and administration; Gastrointestinal Microbiome; Gastrointestinal tract; Generalized linear models; Health aspects; Humans; Identification and classification; IL-1β; Infections; Inflammation; Interleukin 2; Interleukin 4; Interleukin 6; Intestinal microflora; Intestines - microbiology; Laboratories; Medicine; Medicine and Health Sciences; Microbiota; Microbiota (Symbiotic organisms); Mortality; Neurology; Peptidyl-dipeptidase A; Respiratory distress syndrome; RNA sequencing; rRNA 16S; SARS-CoV-2 - physiology; Severe acute respiratory syndrome coronavirus 2; Statistical models; Supervision; Tumor necrosis factor-α; University graduates; Ursodeoxycholic Acid - metabolism; Ursodiol; Japan; Asia; Europe
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0260451

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.