Hot Topic: Gut Microbiota Composition May Reflect Disease Severity & Dysfunctional Immune Response in Patients With COVID-19

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Original publish date February 20, 2021

As part of the functional medicine year in review, COVID-19 was a prominent topic in the literature and in the news. This is the Hot Topic article from February 2021. Please note that new data may have been collected since this article’s publication date. Hot topics highlight recent medical research findings and appear in IFM’s monthly Connections newsletter, exclusively for IFM members. Learn more about becoming an IFM member.

Since December 2019, when COVID-19 first emerged on the world map, medical researchers have been working to understand the mechanisms of the novel virus and develop effective treatments. Now new evidence suggests that the gastrointestinal (GI) tract may influence the severity and outcome of the disease, particularly the gut microbiome.1 Writing in BMJ Gut, researchers report that in a two-hospital cohort study of 100 patients with confirmed SARS-CoV-2 infection, gut microbiome composition was significantly altered in patients with COVID-19 compared with non-COVID-19 individuals and varied with disease severity, irrespective of whether patients had received medication, including antibiotics.1

This is hopeful news, as interventions to restore and optimize the gut microbiota might help mitigate severe COVID-19.1 It also underscores the importance of managing patients’ gut microbiota before, during, and after infection, as research suggests that the gut microbiota is likely to remain significantly altered, even after recovery from COVID-19. Disease severity of the patients was varied, ranging from mild to moderate, critical, and acute. Comorbidities in the COVID-19 cohort included hypertension, hyperlipidemia, diabetes, and heart conditions.1

Specifically, researchers found that:

  • Composition of the gut microbiota in patients with COVID-19 was concordant with disease severity and magnitude of plasma concentrations of several inflammatory cytokines, chemokines, and blood markers of tissue damage.1 Other studies have reported increased concentrations of cytokines in the blood of hospitalized COVID-19 patients.2,3
  • Without controlling for use of antibiotics, patients with COVID-19 were depleted in gut bacteria with known immunomodulatory potential, such as Faecalibacterium prausnitziiEubacterium rectale, and several bifidobacterial species.1
  • The dysbiotic gut microbiota composition in patients with COVID-19 persisted for some time after clearance of the virus. To assess gut microbiota composition following recovery, 42 stool samples were collected from 27 patients up to 30 days after testing negative for SARS-CoV-2. Compared with non-COVID-19 subjects, gut microbiota composition of the 27 recovered patients remained significantly distinct, irrespective of whether they had received antibiotics.1 (The study’s short follow-up period did not permit extrapolation of data for long-term persistent symptoms).

Because the new findings show that gut microbiota composition of patients with COVID-19 may be correlated with plasma concentrations of several cytokines, chemokines, and inflammatory markers, this suggests that the gut microbiota could play a role in modulating host immune response and potentially influence disease severity and outcomes.1 For example, the potential role played by gut microorganisms in COVID-19 could allow the use of a “microbiome-based risk profile” to identify individuals at risk of severe disease.1 Similarly, a 2020 pilot study on 15 patients with COVID-19 also found persistent alterations in fecal microbiota compared with controls; these alterations were associated with levels of COVID-19 severity.4

Reformulating the gut microbiota may emerge as a new therapeutic target in the disease management of COVID-19 patients, perhaps including nutritional therapy or probiotics.5 Supporting a healthy gut microbiome may also be considered as preventative. In functional medicine, general measures that support the immune system in the pre-exposure phase include optimizing diet, gut health, and the microbiome, as well as the management of chronic diseases associated with impaired immunity. Other general considerations that are essential for immune surveillance include optimizing the modifiable lifestyle factors of sleep, exercise, and stress.

For more information on COVID-19, please read the following IFM-authored articles:

The Functional Medicine Approach to COVID-19: Virus-Specific Nutraceutical and Botanical Agents

The Functional Medicine Approach to COVID-19: Lifestyle Practices for Strengthening Host Defense 

COVID-10: Functional Medicine Resources


  1. Yeoh YK, Zuo T, Lui GC, et al. Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19. Gut. Published online January 11, 2021. doi:10.1136/gutjnl-2020-323020
  2. Wadman M, Couzin-Frankel J, Kaiser J, Matacic C. A rampage through the body. Science. 2020;368(6489):356-360. doi:10.1126/science.368.6489.356
  3. Lin L, Jiang X, Zhang Z, et al. Gastrointestinal symptoms of 95 cases with SARS-CoV-2 infection. Gut. 2020;69(6):997-1001. doi:10.1136/gutjnl-2020-321013
  4. Zuo T, Zhang F, Lui GCY, et al. Alterations in gut microbiota of patients with COVID-19 during time of hospitalization. Gastroenterology. 2020;159(3):944-955. doi:10.1053/j.gastro.2020.05.048
  5. Ahlawat S, Asha SE, Sharma KK. Immunological co-ordination between gut and lungs in SARS-CoV-2 infection. Virus Res. 2020;286:198103. doi:10.1016/j.virusres.2020.198103