1. Human Gut Microbiota and Its Metabolites Impact Immune Responses in COVID-19 and Its Complications.
- Author
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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, and Ng, Siew C.
- Abstract
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. 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. 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. 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. [Display omitted] [ABSTRACT FROM AUTHOR]
- Published
- 2023
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