COVID-19 News: Hong Kong Study Shows That Lower Gut Abundance Of Eubacterium Rectale Is Linked To COVID-19 Mortality!

COVID-19 News: The COVID-19 pandemic has been a global health crisis of unprecedented magnitude, affecting millions of lives worldwide. As scientists and healthcare professionals continue to investigate the various factors that influence the severity of COVID-19 and its long-term consequences, emerging research has begun to shed light on the role of the gut microbiome in this context. A recent study conducted by the Microbiota I-Center (MagIC) in Hong Kong, China, in collaboration with The Chinese University of Hong Kong, has unveiled intriguing findings linking the abundance of a specific gut bacterium, Eubacterium rectale, to COVID-19 mortality. This COVID-19 News report delves into the details of this study, highlighting its methodology, results, and implications for our understanding of COVID-19.


 
The Gut Microbiome and COVID-19
Prior to the Hong Kong study, mounting evidence had already suggested a relationship between the composition and function of the gut microbiome and the severity of COVID-19, as well as its potential long-term effects. Some studies had shown alterations in gut microbial diversity in individuals infected with COVID-19, with a notable decrease in beneficial bacterial species such as Bifidobacterium adolescentis, Faecalibacterium prausnitzii, and Eubacterium rectale (E. rectale). However, the question of whether pre-existing gut microbiome status in a population could be associated with COVID-19 outcomes remained unanswered.
 
Methodology
To investigate this question, the researchers at MagIC-Hong Kong conducted an extensive analysis. They obtained gut metagenomic data from a diverse adult population consisting of 2,871 individuals from 16 different countries, sourced from ExperimentHub through the R programming language. Additionally, they gathered dynamic COVID-19 incidence and mortality data for each of these countries between January 22, 2020, and December 8, 2020, from the Johns Hopkins Coronavirus Resource Center. An adjusted stable mortality rate (SMR) was calculated for each country, serving as an indicator of the mortality rate during the specified time frame.

The researchers then correlated the mortality data with the mean relative abundance (mRA) of healthy adult gut bacterial species, aiming to uncover any potential associations between gut microbiome profiles and COVID-19 mortality.
 
Study Findings
The findings of the study revealed several key insights. While the alpha-diversity of the gut microbiota (a measure of species diversity within a sample) did not exhibit significant differences, the inverse Simpson index, which reflects diversity and evenness, showed a marginal p-value (p = 0.054). However, the beta-diversity, which measures differences in microbial composition between samples, was significantly higher in countries with high SMRs compared to those with median or low SMRs (p < 0.001).
 
Importantly, after excluding bacterial species with low prevalence rates (<0.2 in the included countries), it was observed that several of the top 20 bacteria negatively correlated with SMR were butyrate producers, which are highlighted in green.
 
To asses s the replicability of these findings, the researchers applied the same analytical approach to data from the Omicron variant pandemic. Remarkably, four species overlapped among the top 20 in both the original COVID-19 analysis and the Omicron analysis. Among these, Eubacterium rectale stood out as the only species significantly correlated with mortality across all SARS-CoV-2 variants, including Alpha, Beta, Gamma, and Omicron.
 
Validation of the results was further established through an analysis of the relative abundance of the four identified species in Hong Kong COVID-19 cohorts, conducted prior to the introduction of Hong Kong's vaccination program. The results showed significantly lower relative abundance of E. rectale and Roseburia intestinalis in patients with severe COVID-19 compared to control subjects or those with mild to moderate symptoms.
 
The study's findings have far-reaching implications for our understanding of the relationship between gut microbiome composition and COVID-19 outcomes. Specifically, the research highlights the significance of Eubacterium rectale and Roseburia intestinalis as protective factors against COVID-19 mortality. These two species, which are depleted in COVID-19 patients, have also been observed to diminish in individuals with ulcerative colitis, suggesting a potential link to the reduction of the host's inflammatory response.
 
E. rectale, in particular, is negatively correlated with markers of inflammation, such as C-X-C motif ligand 10 (CXCL10) and tumor necrosis factor-alpha (TNF-α), indicating its potential role in modulating the immune response during the early stages of COVID-19. Roseburia intestinalis has been associated with inhibiting the development of Crohn's disease by promoting the differentiation of anti-inflammatory regulatory T cells (Tregs), suggesting therapeutic avenues for conditions beyond COVID-19.
 
Furthermore, the pathway analysis conducted in the study revealed a strong association between the depletion of certain species and reduced functional pathways related to carbohydrate degradation, cofactor and vitamin biosynthesis, highlighting the potential role of these species in maintaining overall gut health and biosynthesis functions.
 
Limitations and Future Directions
Despite its valuable insights, the study does have limitations. It does not delve into the specific mechanisms by which gut microorganisms influence immune functions, which warrants further investigation for potential applications in medication or prevention. Additionally, individual and regional antibiotic usage was not considered in the analysis, which could impact metagenomic profiling and mortality rates. Future research should explore this aspect in greater detail.

The study also acknowledges the limitation of using metagenomic-based cohorts, which may not fully capture the diversity of each country and individual. Larger-scale studies with more extensive sample sizes would be needed to validate the predictive capability of the identified butyrate-producing bacteria.
 
Conclusion
In conclusion, the Hong Kong study conducted by the Microbiota I-Center (MagIC) and The Chinese University of Hong Kong offers significant insights into the relationship between gut microbiome composition and COVID-19 mortality. By highlighting the protective role of Eubacterium rectale and Roseburia intestinalis and their potential contribution to the modulation of immune responses, this research opens the door to new avenues for intervention and treatment. The findings suggest that the development of butyrate-producing probiotics, coupled with high-fiber diets, could be a promising strategy to enhance the abundance of these beneficial species and reduce COVID-19-related mortality. As the world continues to grapple with the COVID-19 pandemic and its potential future variants, further research in this area holds the promise of improving outcomes and saving lives.
 
The study findings were published in the peer reviewed journal: Frontiers in Cellular and Infection Microbiology.
https://www.frontiersin.org/articles/10.3389/fcimb.2023.1249069/full
 
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