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Human Gut Microbiota and Its Metabolites Impact Immune Responses in COVID-19 and Its Complications.
Nagata, Naoyoshi; Takeuchi, Tadashi; Masuoka, Hiroaki; Aoki, Ryo; Ishikane, Masahiro; Iwamoto, Noriko; Sugiyama, Masaya; Suda, Wataru; Nakanishi, Yumiko; Terada-Hirashima, Junko; Kimura, Moto; Nishijima, Tomohiko; Inooka, Hiroshi; Miyoshi-Akiyama, Tohru; Kojima, Yasushi; Shimokawa, Chikako; Hisaeda, Hajime; Zhang, Fen; Yeoh, Yun Kit; Ng, Siew C; Uemura, Naomi; Itoi, Takao; Mizokami, Masashi; Kawai, Takashi; Sugiyama, Haruhito; Ohmagari, Norio; Ohno, Hiroshi.
  • Nagata N; Department of Gastroenterological Endoscopy, Tokyo Medical University, Tokyo, Japan; Department of Gastroenterology and Hepatology, National Center for Global Health and Medicine, Tokyo, Japan. Electronic address: nnagata_ncgm@yahoo.co.jp.
  • Takeuchi T; Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
  • Masuoka H; Laboratory for Microbiome Sciences, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
  • Aoki R; Mechanism-based Research Laboratory, Ezaki Glico Co, Ltd, Osaka, Japan.
  • Ishikane M; Disease Control and Prevention Center, National Center for Global Health and Medicine, Tokyo, Japan.
  • Iwamoto N; Disease Control and Prevention Center, National Center for Global Health and Medicine, Tokyo, Japan.
  • Sugiyama M; Genome Medical Sciences Project, National Center for Global Health and Medicine, Ichikawa, Japan; Department of Viral Pathogenesis and Controls, National Center for Global Health and Medicine, Ichikawa, Japan.
  • Suda W; Laboratory for Microbiome Sciences, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
  • Nakanishi Y; Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
  • Terada-Hirashima J; Division of Respiratory Medicine, National Center for Global Health and Medicine, Tokyo, Japan.
  • Kimura M; Department of Clinical Research Strategic Planning Center for Clinical Sciences, National Center for Global Health and Medicine, Tokyo, Japan.
  • Nishijima T; Mechanism-based Research Laboratory, Ezaki Glico Co, Ltd, Osaka, Japan.
  • Inooka H; Mechanism-based Research Laboratory, Ezaki Glico Co, Ltd, Osaka, Japan.
  • Miyoshi-Akiyama T; Pathogenic Microbe Laboratory, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
  • Kojima Y; Department of Gastroenterology and Hepatology, National Center for Global Health and Medicine, Tokyo, Japan.
  • Shimokawa C; Department of Parasitology, National Institute of Infectious Diseases.
  • Hisaeda H; Department of Parasitology, National Institute of Infectious Diseases.
  • Zhang F; Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, LKS Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China; Microbiota I-Center, Hong Kong, China; Center for Gut Microbiota Research, Faculty of Medicine
  • Yeoh YK; Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, LKS Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China; Microbiota I-Center, Hong Kong, China; Center for Gut Microbiota Research, Faculty of Medicine
  • Ng SC; Department of Medicine and Therapeutics, Institute of Digestive Disease, State Key Laboratory of Digestive Diseases, LKS Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China; Microbiota I-Center, Hong Kong, China; Center for Gut Microbiota Research, Faculty of Medicine
  • Uemura N; Department of Gastroenterological Endoscopy, Tokyo Medical University, Tokyo, Japan; Department of Gastroenterology and Hepatology, National Center for Global Health and Medicine, Kohnodai Hospital, Tokyo, Japan.
  • Itoi T; Department of Gastroenterology and Hepatology, Tokyo Medical University, Tokyo, Japan.
  • Mizokami M; Genome Medical Sciences Project, National Center for Global Health and Medicine, Ichikawa, Japan.
  • Kawai T; Department of Gastroenterological Endoscopy, Tokyo Medical University, Tokyo, Japan.
  • Sugiyama H; Division of Respiratory Medicine, National Center for Global Health and Medicine, Tokyo, Japan.
  • Ohmagari N; Disease Control and Prevention Center, National Center for Global Health and Medicine, Tokyo, Japan.
  • Ohno H; Laboratory for Intestinal Ecosystem, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan; Laboratory for Microbiome Sciences, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan. Electronic address: hiroshi.ohno@riken.jp.
Gastroenterology ; 2022 Sep 23.
Article in English | MEDLINE | ID: covidwho-2233634
ABSTRACT
BACKGROUND &

AIMS:

We investigate interrelationships between gut microbes, metabolites, and cytokines that characterize COVID-19 and its complications, and we validate the results with follow-up, a Japanese Disease, Drug, Diet, Daily Life microbiome cohort, and non-Japanese data sets.

METHODS:

We performed shotgun metagenomic sequencing and metabolomics on stools and cytokine measurements on plasma from 112 hospitalized patients with SARS-CoV-2 infection and 112 non-COVID-19 control individuals matched by important confounders.

RESULTS:

Multiple correlations were found between COVID-19-related microbes (eg, oral microbes and short-chain fatty acid producers) and gut metabolites (eg, branched-chain and aromatic amino acids, short-chain fatty acids, carbohydrates, neurotransmitters, and vitamin B6). Both were also linked to inflammatory cytokine dynamics (eg, interferon γ, interferon λ3, interleukin 6, CXCL-9, and CXCL-10). Such interrelationships were detected highly in severe disease and pneumonia; moderately in the high D-dimer level, kidney dysfunction, and liver dysfunction groups; but rarely in the diarrhea group. We confirmed concordances of altered metabolites (eg, branched-chain amino acids, spermidine, putrescine, and vitamin B6) in COVID-19 with their corresponding microbial functional genes. Results in microbial and metabolomic alterations with severe disease from the cross-sectional data set were partly concordant with those from the follow-up data set. Microbial signatures for COVID-19 were distinct from diabetes, inflammatory bowel disease, and proton-pump inhibitors but overlapping for rheumatoid arthritis. Random forest classifier models using microbiomes can highly predict COVID-19 and severe disease. The microbial signatures for COVID-19 showed moderate concordance between Hong Kong and Japan.

CONCLUSIONS:

Multiomics analysis revealed multiple gut microbe-metabolite-cytokine interrelationships in COVID-19 and COVID-19related complications but few in gastrointestinal complications, suggesting microbiota-mediated immune responses distinct between the organ sites. Our results underscore the existence of a gut-lung axis in COVID-19.
Keywords

Full text: Available Collection: International databases Database: MEDLINE Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study / Randomized controlled trials Language: English Year: 2022 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Cohort study / Experimental Studies / Observational study / Prognostic study / Randomized controlled trials Language: English Year: 2022 Document Type: Article