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Human Gut Microbiota and Its Metabolites Impact Immune Responses in COVID-19 and Its Complications

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, the Japanese 4D (Disease, Drug, Diet, Daily Life) microbiome cohort, and non-Japanese data sets. MET...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Author(s). Published by Elsevier Inc. on behalf of the AGA Institute. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9499989/
https://www.ncbi.nlm.nih.gov/pubmed/36155191
http://dx.doi.org/10.1053/j.gastro.2022.09.024
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author 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
author_facet 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
author_sort Nagata, Naoyoshi
collection PubMed
description 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, the Japanese 4D (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.
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spelling pubmed-94999892022-09-23 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 Gastroenterology Original Research 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, the Japanese 4D (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. The Author(s). Published by Elsevier Inc. on behalf of the AGA Institute. 2023-02 2022-09-23 /pmc/articles/PMC9499989/ /pubmed/36155191 http://dx.doi.org/10.1053/j.gastro.2022.09.024 Text en © 2023 The Authors Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Original Research
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
Human Gut Microbiota and Its Metabolites Impact Immune Responses in COVID-19 and Its Complications
title Human Gut Microbiota and Its Metabolites Impact Immune Responses in COVID-19 and Its Complications
title_full Human Gut Microbiota and Its Metabolites Impact Immune Responses in COVID-19 and Its Complications
title_fullStr Human Gut Microbiota and Its Metabolites Impact Immune Responses in COVID-19 and Its Complications
title_full_unstemmed Human Gut Microbiota and Its Metabolites Impact Immune Responses in COVID-19 and Its Complications
title_short Human Gut Microbiota and Its Metabolites Impact Immune Responses in COVID-19 and Its Complications
title_sort human gut microbiota and its metabolites impact immune responses in covid-19 and its complications
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9499989/
https://www.ncbi.nlm.nih.gov/pubmed/36155191
http://dx.doi.org/10.1053/j.gastro.2022.09.024
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