Oral and Gut Microbial Diversity Offers Diagnostic, Prognostic COVID-19 Insight

Microbiota in human intestine
Researchers investigated the potential use of the microbiome as a non-invasive biomarker for COVID-19 diagnosis and prognosis.

Deviations in oral and gut microbial diversity are found in patients with coronavirus disease 2019 (COVID-19) as well as recovered patients, suggesting specific microbial markers could be used to aid diagnostic and prognostic models for patients with suspected or confirmed infection. This is according to a study published in Gut.

The gold standard for COVID-19 diagnosis is nucleic acid testing using reverse-transcription polymerase chain reactions. However, this method has been questioned given its relatively high false negative rate, which is caused by factors such as sampling and experimental error.

To gauge the value of oral and gut microbiomes and lipidomics in diagnosing COVID-19, researchers sequenced 392 tongue-coating samples, 155 serum samples, and 172 fecal samples taken from patients in central and eastern China. A total of 100 healthy controls and 48 patients with confirmed COVID-19 provided data for the tongue-coating samples, while 48 healthy controls and 24 COVID-19 confirmed patients offered fecal samples for the study.

The investigators characterized microbiome and lipid molecules and generated microbial classifiers in a discovery cohort. The diagnostic potential of these classifiers was verified in 74 patients with confirmed COVID-19 and 37 patients with suspected infection.

Patients with confirmed COVID-19 had significantly reduced oral and fecal microbial diversity compared with healthy controls (all P <.001). Additionally, patients with confirmed COVID-19 had significantly decreased genera belonging to the butyric acid-producing bacteria families and significantly increased genera belonging to lipopolysaccharide-producing bacteria in the oral cavity (all P <0.05). The investigators noted butyric acid had an anti-inflammatory role, suggesting its depletion could hold clinical insight into COVID-19 status.

A total of 47 lipid molecules were considered depleted in confirmed patients in recovery, while another 122 lipid molecules were enriched in confirmed but recovered patients.

Classifiers using 8 optimal oral microbial markers featured good diagnostic efficiency across several cohorts. The diagnostic efficacy using these markers was 87.24% in a cross-regional cohort. The 8 classifiers also successfully diagnosed suspected COVID-19 cases with Immunoglobulin G (IgG) antibody positivity as confirmed cases, with diagnostic efficacy topping 92.11%.

According to the investigators, microbiota appear to affect COVID-19 progression via secretion of lipid molecules into the blood. “With further study of the possible mechanism of the microbiome affecting diseases, the use of microbial-assisted diagnosis, treatment and prognosis is promising for COVID-19,” they wrote.


Ren Z, Wang H, Cui G, et al. Alterations in the human oral and gut microbiomes and lipidomics in COVID-19. Published online March 31, 2021. Gut. doi: 10.1136/gutjnl-2020-323826