German study finds gut microbiome disruption associated with COVID-19 complications, mortality

The role the gut microbiome plays in COVID-19 is a subject of ongoing discussion, and it's not clear whether the microbiome influences the course of the disease or vice versa. 

A small, controlled study of patients in a German hospital has provided new data which suggest that specific microbiota are associated with disease mildness, complications, or death from COVID-19. The research was published online in Gut Microbes, Feb. 17.

The researchers investigated four groups:

• 108 hospital patients with confirmed COVID-19.

• 22 patients who had cleared the virus.

• 20 controls with symptomatic pneumonia.

• 26 asymptomatic controls, age and gender matched.

The study eliminated people who had other diseases, such as cancer or inflammatory bowel disease, to minimize confounding factors. 

All patients were from the university hospital associated with the Technical University in Munich, during the first and second COVID-19 waves in 2020.

GI involvement in COVID-19

The authors report that gastrointestinal (GI) symptoms "in patients with COVID-19 appear to be associated with increased disease severity and complications, although the underlying causes are not understood." The researchers used fecal and saliva samples to look at the changes in the gut microbiome and how these correlated with common COVID-19 complications, such as venous thromboembolism, hemodynamic instability and acute kidney injury.

"Particularly in severe cases an excessive and prolonged immune response to the virus is thought to be a catalyst of severity," the researchers note.

The patients in the study were classified into three clinical groups: those with mild disease, those with severe disease and those with a fatal disease. The researchers also looked at other variables, including artificial feeding and antibiotic treatment, to see if these had confounding effects.

In general the researchers found that the microbiome of patients with mild disease were more similar to the patients in the two control groups that did not have COVID-19, while the microbiome of patients with more severe disease were more similar to those of patients who died of COVID-19. 

Specific findings

When the researchers stratified patients into groups with no complications and those with one or more complications, they found "a shift in their bacterial profile according to the number of complications." Specifically they found that the "abundance of gut bacteria decreased with the number of complications."

In particular, the researchers found that F. prausnitzii was significantly reduced in patients with complications, and negatively associated with mortality. On the other hand, Parabacteroides increased in patients with certain complications and had a positive association with mortality.

In general, a stable gut bacterial composition is associated with a favorable disease progression and outcome. The authors state: "... taxa known for protective and immunosuppressive properties were found to be decreased with an increasing complication rate, whereas rather pathogenic taxa were more prevalent." 

Recommendations

The authors recommend, as a result of their findings, that the therapeutic management of COVID-19 should consider a "healthy and diverse intestinal microbiota."

They note, however, that the conditions of medical treatment may also play a role in the course of the disease. They repeat their initial caveat that it is still unclear "whether the changes in microbiota causally influenced the severity of COVID-19 and occurrence of complications, or vice versa."

"Taken together, our results suggest that the gut and salivary microbiota are associated with the occurrence of individual complications in COVID-19, thereby influencing disease severity," the article concludes. "A stable gut bacterial composition during hospitalization is associated with a more favorable clinical course. Further studies are needed to investigate direct causality between gut bacterial dysbiosis and COVID-19 and to integrate microbial patterns for prognostic and therapeutic purposes in clinical routine."

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David Schult et al. "Gut bacterial dysbiosis and instability is associated with the onset of complications and mortality in COVID-19." Gut Microbes, Feb. 17, 2022.

DOI: 10.1080/19490976.2022.2031840