Is a disrupted gut linked to how sick COVID-19 patients get?
COVID-19 patients had a different mix of gut bacteria from healthy controls, and certain bacteria and signs of a leaky gut tracked with more severe illness and stronger inflammation.
Source
Gut microbiome alterations and gut barrier dysfunction are associated with host immune homeostasis in COVID-19 patients
Study at a glance
- Design
- Case-control — Hospital-based case-control comparison of COVID-19 patients (mild vs severe) and uninfected staff controls, with serial stool shotgun metagenomics, stool metaproteomics and blood biomarker, proteomic and transcriptomic data analysed by mixed linear regression.
- N
- N=71 · 63 COVID-19 patients (39 mild, 24 severe) and 8 uninfected controls provided 106 stool samples; metaproteomics used samples from 16 people; plasma LBP was measured in 148 patients from the wider cohort.
- Population
- Adults and adolescents hospitalised with COVID-19 at the Shanghai Public Health Clinical Center, January-April 2020, plus uninfected hospital-staff volunteers.
- Outcome
- Gut microbial composition, pathways and virulence genes by COVID-19 status and severity, and their associations with blood immune and inflammation markers and gut-barrier markers.
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What they did
The researchers studied 63 patients hospitalised with COVID-19 in Shanghai early in 2020 (39 mild, 24 severe) and 8 uninfected hospital staff. They sequenced all the microbial DNA in 106 stool samples, including weekly samples from severe patients, and related bacterial species, metabolic pathways and virulence genes to blood markers of immunity and inflammation. In smaller subsets they measured human and bacterial proteins in stool and blood and a blood marker of gut leakiness, lipopolysaccharide-binding protein (LBP).
What they found
Overall bacterial diversity did not differ, but community composition did: patients lost 19 species, including beneficial ones such as Faecalibacterium prausnitzii, and gained 8, including opportunistic pathogens. Four species were more abundant in severe than mild disease; two of them, Burkholderia contaminans and Bacteroides nordii, were linked to lower lymphocyte and T-cell counts or higher white-cell counts and inflammation markers such as IL-6. Severe patients' stool had more bacterial virulence genes and more human proteins and DNA, suggesting damage to the gut lining, and blood LBP was higher in severe disease and correlated with inflammation.
The limits
What it doesn't show
The design compares groups at one time and cannot show whether gut changes cause severe COVID-19 or result from it, its treatments or hospital stay. There were only 8 controls, the metaproteomic subset was very small, and many microbe-biomarker associations were tested with a lenient false-discovery threshold, so some findings may be chance. Diet, physical activity, BMI and comorbidities were not fully controlled, and bacterial proteins in blood were too rarely detected for statistical testing, so the leaky-gut pathway remains a plausible hypothesis rather than a demonstrated mechanism.
Key terms
- Gut microbiome
- The community of bacteria and other microbes living in the intestines, along with their genes.
- Dysbiosis
- An unhealthy shift in the balance of the microbial community, such as loss of beneficial species and growth of opportunistic ones.
- Shotgun metagenomics
- Sequencing all the DNA in a sample so that species and their functional genes can be identified, rather than a single marker gene.
- Gut barrier dysfunction (leaky gut)
- Damage to the intestinal lining that lets microbes or their products pass into the bloodstream and trigger inflammation.
- Lipopolysaccharide-binding protein (LBP)
- A blood protein that rises when bacterial endotoxin enters the circulation, used as a marker of gut barrier damage.
- Opportunistic pathogen
- A microbe that usually does little harm but can cause disease when the host's defences or normal flora are disrupted.
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Quiz yourself
How many uninfected controls were included?
Common questions
Could antibiotics given in hospital explain the gut differences?
The authors checked this: among severe patients, those given oral antibiotics did not differ in overall composition, and the key disease-related species did not differ by antibiotic use. After excluding antibiotic users, most disease-related species remained different from controls. This lowers but does not remove the concern.
Does this mean probiotics could treat COVID-19?
No. The study only shows associations in a small group. It suggests the gut might be a therapeutic target, but intervention studies would be needed to test whether changing the microbiome changes outcomes.
Why measure human proteins in stool?
More human proteins and DNA in stool suggest that cells from the gut lining are being shed or damaged, which is indirect evidence of injury to the intestinal barrier.
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