Gut microbiome composition impacts severity of COVID-19
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Correlation between gut microbiota composition, cytokine levels and inflammatory markers among COVID-19 patients demonstrated the gut microbiome is linked with the severity of COVID-19, according to a study in Gut.
“[This] survey of gut microbiota alterations in association with immune dysregulation revealed that gut microorganisms are likely involved in the modulation of host inflammatory responses in COVID-19,” Yun Kit Yeoh, MD, from the department of microbiology, The Chinese University of Hong Kong, Shatin, Hong Kong and colleagues wrote. “With mounting evidence that gut microorganisms are linked with inflammatory diseases within and beyond the gut, these findings underscore an urgent need to understand the specific roles of gut microorganisms in human immune function and systemic inflammation.”
In a two-cohort study, Yeoh and colleagues obtained blood, stool and patient records from 100 patients with laboratory-confirmed SARS-CoV-2 infection. Up to 30 days after clearance of SARS-CoV-2, investigators collected serial stool samples from 27 out of the 100 patients. Shotgun sequencing total DNA extracted from stools was used to characterize gut microbiome compositions. Plasma was used to measure concentrations of inflammatory cytokines and blood markers.
Results showed gut microbiome changed among patients with COVID-19 vs. individuals without COVID-19 regardless of whether patients received medication (P < .01).
“Several gut commensals with known immunomodulatory potential such as Faecalibacterium prausnitzii, Eubacterium rectale and bifidobacteria were underrepresented in patients and remained low in samples collected up to 30 days after disease resolution,” Yeoh and colleagues wrote.
According to researchers, this demonstrated stratification with disease severity consistent with elevated concentrations of inflammatory cytokines and blood markers including C reactive protein, lactate dehydrogenase, aspartate aminotransferase and gamma-glutamyl transferase.
“The dysbiotic gut microbiota that persists after disease resolution could be a factor in developing persistent symptoms and/or multisystem inflammation syndromes that occur in some patients after clearing the virus,” the authors wrote.
Perspective
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Brian B. Baggott, MD, FACG
Increasing evidence shows the importance and impact of the gut microbiota on health and disease. There are clear associations of the gut microbial environment with intestinal infections, C. difficile, irritable bowel syndrome, inflammatory bowel disease, obesity, allergic diseases and neuropsychiatric disorders.
The article by Yeoh et al is an interesting and compelling discussion of how the gut microbiota may have an impact on this disease state. The authors aim to correlate changes in the microbiota composition with inflammatory markers and disease severity. The authors do show that selected gut commensals are depressed in the COVID-19 state compared with non-COVID controls. They also correlate this with the elevated concentrations of selected inflammatory markers.
Although interesting, these observations do not endorse cause and effect. The authors “suggest that the gut microbiota is involved in the magnitude of COVID-19 severity” is an important observation that needs further investigation and validation. The authors note some significant limitations with the study. The largest limitation is the heterogeneity of how the study patients were managed at presentation. There is wide variability in how patients are treated in the first few days of infection, which can have a profound impact on the immune response and the gut microbiota. This was not controlled for. They note that it is not known whether the gut microbiota is a primary etiologic driver in COVID-19 infection or if the gut microbiota is altered because of the COVID-19 infection. It is noted that up to three-quarters of the patients with COVID-19 had received antibiotics; however, the authors show no difference in outcome. This comparison was only done on patients with moderate disease. It is not known how antibiotic exposure affects patients with more severe disease. Lastly, it is noted that there is great biodiversity in the gut microbiota across populations and geography further complicating the generalizability of these observations globally.
Even with these limitations, this paper adds to our appreciation of the importance of the gut microbiota in health and disease. This impact may be in initial disease severity, disease progression and resolution.
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