Robust cross-cohort gut microbiome associations with COVID-19 severity

Abstract

Although many recent studies have examined associations between the gut microbiome and COVID-19 disease severity in individual patient cohorts, questions remain on the robustness across international cohorts of the biomarkers they reported. Here, we performed a meta-analysis of eight shotgun metagenomic studies of COVID-19 patients (comprising 1,023 stool samples) and 23 > 16S rRNA gene amplicon sequencing (16S) cohorts (2,415 total stool samples). We found that disease severity (as defined by the WHO clinical progression scale) was associated with taxonomic and functional microbiome differences. This alteration in gut microbiome configuration peaks at days 7–30 post diagnosis, after which the gut microbiome returns to a configuration that becomes more similar to that of healthy controls over time. Furthermore, we identified a core set of species that were consistently associated with disease severity across shotgun metagenomic and 16S cohorts, and whose abundance can accurately predict disease severity category of SARS-CoV-2 infected subjects, with Actinomyces oris abundance predicting population-level mortality rate of COVID-19. Additionally, we used relational diet-microbiome databases constructed from cohort studies to predict microbiota-targeted diet patterns that would modulate gut microbiota composition toward that of healthy controls. Finally, we demonstrated the association of disease severity with the composition of intestinal archaeal, fungal, viral, and parasitic communities. Collectively, this study has identified robust COVID-19 microbiome biomarkers, established accurate predictive models as a basis for clinical prognostic tests for disease severity, and proposed biomarker-targeted diets for managing COVID-19 infection.

Deciphering Microbial Shifts in the Gut and Lung Microbiomes of COVID-19 Patients

“…CJ11 ( p -value: 9.02 × 10 −5 ) and Lysobacter lycopersici ( p -value: 9.68 × 10 −5 ), were among the novel bacterial species underrepresented in the COVID-19 microbiomes. Apart from them, some bacteria previously reported to be differentially abundant were also identified [ 16 ]. These belong to the genus Prevotella , including Prevotella jejuni (p -value: 0.0013) and Prevotella copri ( p -value: 0.003), the genus Roseburia , including Roseburia sp.…”

“…These meta-analyses aim to identify associations consistent across various studies, reducing the risk of attributing findings to biological confounders [ 12 ]. The majority of previous microbiome meta-analyses of COVID-19 patients have relied on 16S rRNA gene amplicon data and have revealed significant overall reductions in the microbiome diversity in COVID-19 patients, but these observations were affected by either low effect size or low resolution [ 13 , 14 , 15 , 16 ].…”

Alterations in microbiota of patients with COVID‐19: implications for therapeutic interventions

“…Moreover, the abundance of actinobacteria can predict poor prognosis after infection, suggesting the feasibility of prediction models based on gut microbiota. 98 Dysbiosis of gut microbiota is associated with increased susceptibility to the respiratory tract and immune microenvironment in the lung by regulating the gut–lung axis. Dysbiosis may also play an important role in central inflammation through the gut–brain axis to mediate central symptoms.…”

Immune Mechanisms Underpinning Long COVID: Collegium Internationale Allergologicum Update 2024

“…In contrast, a high-risk microbiome configuration may consistently generate multiple pro-inflammatory metabolites that may contribute to a higher risk of inappropriate immune reactivity. Several studies have identified taxonomic and functional microbiome differences that are associated with disease severity during acute COVID-19 [57,[128][129][130][131]. Reduced abundance of well-described immune protective microbes (such as those producing SCFAs) and increased abundance of opportunistic pathogens (such as from the Enterobacteriaceae families) were often described.…”