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Prolonged Impairment of Short-Chain Fatty Acid and L-Isoleucine Biosynthesis in Gut Microbiome in Patients With COVID-19.
Zhang, Fen; Wan, Yating; Zuo, Tao; Yeoh, Yun Kit; Liu, Qin; Zhang, Lin; Zhan, Hui; Lu, Wenqi; Xu, Wenye; Lui, Grace C Y; Li, Amy Y L; Cheung, Chun Pan; Wong, Chun Kwok; Chan, Paul K S; Chan, Francis K L; Ng, Siew C.
  • Zhang F; Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, China; State Key Laboratory for Digestive Disease, Institute of Digestive Disease,
  • Wan Y; Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, China; State Key Laboratory for Digestive Disease, Institute of Digestive Disease,
  • Zuo T; Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, China; State Key Laboratory for Digestive Disease, Institute of Digestive Disease,
  • Yeoh YK; Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China; Department of Microbiology, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
  • Liu Q; Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, China; State Key Laboratory for Digestive Disease, Institute of Digestive Disease,
  • Zhang L; Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, China; State Key Laboratory for Digestive Disease, Institute of Digestive Disease,
  • Zhan H; Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, China; State Key Laboratory for Digestive Disease, Institute of Digestive Disease,
  • Lu W; Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, China; State Key Laboratory for Digestive Disease, Institute of Digestive Disease,
  • Xu W; Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, China; State Key Laboratory for Digestive Disease, Institute of Digestive Disease,
  • Lui GCY; Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China; Department of Chemical Pathology, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
  • Li AYL; Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
  • Cheung CP; Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, China; State Key Laboratory for Digestive Disease, Institute of Digestive Disease,
  • Wong CK; Department of Chemical Pathology, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
  • Chan PKS; Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, China; Department of Microbiology, The Chinese University of Hong Kong, Shatin, Ho
  • Chan FKL; Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China; State Key Laboratory for Digestive Disease, Institute of Digestive Disease, The Chinese University of Hong Kong, Shatin, Hong Kong, China; Department of Medicine and Therapeutics,
  • Ng SC; Center for Gut Microbiota Research, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong, China; State Key Laboratory for Digestive Disease, Institute of Digestive Disease,
Gastroenterology ; 162(2): 548-561.e4, 2022 02.
Article in English | MEDLINE | ID: covidwho-1475507
ABSTRACT
BACKGROUND AND

AIMS:

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with altered gut microbiota composition. Phylogenetic groups of gut bacteria involved in the metabolism of short chain fatty acids (SCFAs) were depleted in SARS-CoV-2-infected patients. We aimed to characterize a functional profile of the gut microbiome in patients with COVID-19 before and after disease resolution.

METHODS:

We performed shotgun metagenomic sequencing on fecal samples from 66 antibiotics-naïve patients with COVID-19 and 70 non-COVID-19 controls. Serial fecal samples were collected (at up to 6 times points) during hospitalization and beyond 1 month after discharge. We assessed gut microbial pathways in association with disease severity and blood inflammatory markers. We also determined changes of microbial functions in fecal samples before and after disease resolution and validated these functions using targeted analysis of fecal metabolites.

RESULTS:

Compared with non-COVID-19 controls, patients with COVID-19 with severe/critical illness showed significant alterations in gut microbiome functionality (P < .001), characterized by impaired capacity of gut microbiome for SCFA and L-isoleucine biosynthesis and enhanced capacity for urea production. Impaired SCFA and L-isoleucine biosynthesis in gut microbiome persisted beyond 30 days after recovery in patients with COVID-19. Targeted analysis of fecal metabolites showed significantly lower fecal concentrations of SCFAs and L-isoleucine in patients with COVID-19 before and after disease resolution. Lack of SCFA and L-isoleucine biosynthesis significantly correlated with disease severity and increased plasma concentrations of CXCL-10, NT- proB-type natriuretic peptide, and C-reactive protein (all P < .05).

CONCLUSIONS:

Gut microbiome of patients with COVID-19 displayed impaired capacity for SCFA and L-isoleucine biosynthesis that persisted even after disease resolution. These 2 microbial functions correlated with host immune response underscoring the importance of gut microbial functions in SARS-CoV-2 infection pathogenesis and outcome.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Fatty Acids, Volatile / Gastrointestinal Microbiome / COVID-19 / Immunity / Isoleucine Type of study: Observational study / Randomized controlled trials / Risk factors Limits: Adult / Female / Humans / Male / Middle aged Language: English Journal: Gastroenterology Year: 2022 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Fatty Acids, Volatile / Gastrointestinal Microbiome / COVID-19 / Immunity / Isoleucine Type of study: Observational study / Randomized controlled trials / Risk factors Limits: Adult / Female / Humans / Male / Middle aged Language: English Journal: Gastroenterology Year: 2022 Document Type: Article