key: cord-0809994-q0ujnerj
authors: Zhang, Fen; Ng, Siew C.
title: Reply: Gut microbiome metabolism drives the resolution of patients with COVID-19?
date: 2022-03-31
journal: Gastroenterology
DOI: 10.1053/j.gastro.2022.03.033
sha: 610d103e317a2441e33b85aac03e709db37a2e3c
doc_id: 809994
cord_uid: q0ujnerj

nan

functional properties of native microbiota and its molecules mediating virus 23 colonization. 24 25 We found that impaired short chain fatty-acids (SCFAs) and L-isoleucine 26 biosynthesis in the gut microbiome correlated with COVID-19 severity as well 27 as increased plasma concentrations of CXCL-10, NT-proBNP and C-reactive 28 protein (CRP) 2 . Amongst other cytokines assessed including IL-10, IL-12, IL-29 1b, IL-6, and TNF-α and chemokines such as CXCL-8 and CCL-2, we found 30 that only increased plasma levels of IL-10 significantly associated with more 31 severe symptoms in patients with COVID-19. It is likely that elevated 32 endogenous systemic IL-10 stimulates inflammatory cytokine production and 33 directly activates and promotes effector CD8+ T cell proliferation, which may 34 play a pathological role in COVID-19 severity 3 . Intriguingly, fecal butyrate level 35 in patients with COVID-19 showed a significantly negative correlation with 36 plasma IL-10, suggesting that microbiota-derived butyrate may be involved in 37 preventing over-expression of IL-10 in COVID-19. To this end, emerging 38 studies have provided new insights into the relationship between gut 39 microbiome, host immunity and disease severity in COVID-19. In a separate 40 cohort of 100 hospitalized patient with COVID-19, we found that disrupted gut 41 microbiota were associated with higher levels of TNF-α, IL-10, and CXCL10 4 . 42

Others have reported that Enterococcus faecalis was negatively correlated with 43 CD8+T cells and IL-4, and Eubacterium ramulus was negatively correlated with 44 IL-6 in patients with COVID-19 5 . These cytokines and chemokines are involved 45 in IFN-driven Th1 response 6 , implying that the gut microbiota may regulate Th1 46 response in SARS-COV-2 infection, while more cytokines and proteins associated with immune cell activation should be determined to support this We agree with the authors that relationships between plasma markers, clinical 51 measures, and disease severity deserve in-depth exploration. In our study, we 52 In summary, current evidence support the notion that the gut microbiota may 74 contribute to disease severity in COVID-19 via regulation of Th1 response, and desperately needed to provide more mechanistic insights and this wiil be of 78 benefit to exploiting microbial-based therapy. 79 80 References: 81

Gut microbiome metabolism drives the resolution of 82 patients with COVID-19

Prolonged impairment of short-chain fatty acid 84

L-isoleucine biosynthesis in gut microbiome in patients with COVID-19

A potential role of interleukin 10 in 87 COVID-19 pathogenesis

Gut microbiota composition reflects 89 disease severity and dysfunctional immune responses in patients with COVID-90 19

Gut microbiota dysbiosis correlates with abnormal 92 immune response in moderate COVID-19 patients with fever

Immune determinants of COVID-19 disease presentation and 95 severity

Biochemical Test Results in Patients with COVID-19 Infection

Proteomic and metabolomic characterization of 100 COVID-19 patient sera