Study confirms link between gut microbiota and COVID-19

Dr Kate Stephens PhD Food and Microbial Sciences; Gut Microbiology (University of Reading), BSc Medical Microbiology

The SARS-CoV-2 virus has had catastrophic effects worldwide with millions of confirmed cases and hundreds of thousands of deaths.  Since its identification the virus has been extensively researched, but many facts have yet to be established, such as the most effective preventative measures, and what the long-term effects might be.  A developing area of interest is the connection between the gut microbiome and COVID-19. Recently, Professor Tim Spector spoke about this topic on Radio 4, highlighting the importance of good gut health and what individuals can do to support your gut and microbiome.

woman wearing mask on a bus

The study: COVID-19 and the microbiome

Initially scientists believed that the virus only targeted the respiratory system, causing a cough and flu like symptoms. However recent research has suggested that COVID-19 affects gut cells and can cause gastro intestinal symptoms. One study looking at a Hong Kong cohort found that approximately 20% of individuals with the virus exhibit GI issues1. Another study analysed GI symptoms in 95 patients with COVID-192. They found that 58 of these patients (61%) suffered GI issues, particularly diarrhoea and nausea. Faecal calprotectin, a marker associated with gut inflammation, has been shown to be higher in COVID-19 individuals with diarrhoea3.

A recent pilot study has built on this research and demonstrated a fascinating microbial difference between COVID-19 sufferers and healthy individuals4. This is the first study to make the association between poor gut health and severity of COVID-19 symptoms. The study analysed the microbiome composition from stool samples in 15 hospitalised individuals with COVID-19 and compared this to healthy non infected individuals. Faecal samples were taken from patients, two-three times a week until discharge. The researchers performed shotgun metagenomic sequencing on the stool samples; this type of high-quality methodology allows for detailed analysis of the microbes present in any given sample. All patients exhibited respiratory symptoms, and one also experienced diarrhoea.

 Remarkably, the study found the following microbial patterns unique to COVID-19:

  • Higher levels of harmful bacteria; Clostridium hathewayi, Actinomyces viscosus and Bacteroides nordii
  • Lower levels of friendly bacteria; Fecalibacterium prausnitzii, Lachnospiraceae bacterium, Eubacterium rectale, Ruminococcus obeum and Dorea formicigenerans. Some of these microbes have been associated with immune modulation. 

These changes were consistent throughout hospitalisation, even when respiratory symptoms had eased. Half of the patients were prescribed antibiotics; these patients experienced more significant gut dysbiosis. At follow up, 10 out of the 15 individuals still had significantly different microbial compositions to the healthy controls.

The study also assessed the severity of COVID-19 symptoms and microbiome status. They found 23 bacterial taxa were associated with disease severity (either in a positive or negative correlation), 15 of these were from the bacterial phyla Firmicutes. Clostridium ramosum and Clostridium hathewayi were the top microbes most commonly associated with disease severity, whereas Alistipes onderdonkii and Faecalibacterium prausnitzi were the top two microbes associated with a reduction in severity. F. prausnitzi has been receiving attention recently as a potential probiotic, it’s been shown to have anti inflammatory and immune modulating abilities.

Although this is a small study, the results show consistent and compelling results. An exciting finding is that the study has seemed to have found a unique COVID-19 microbial algorithm. Plus the study also linked disease severity with specific microbes. These results suggest there is potential for microbiome manipulation and that specific targeted probiotics may have an important role. 

Probiotics for COVID-19

 Following the study by Zuo T et al., 2020, one of the authors Prof Siew Chen Ng highlighted three new studies the research group would be conducting to evaluate a unique probiotic combination in COVID-19 patients5. The new probiotic formula (strains currently unknown) is designed to replenish the microbes which were deficient in COVID-19 sufferers.The three new studies are designed as followed:

Study 1 - 200 COVID-19 sufferers will be given the probiotic for three months with a six month follow up period. Stool samples will be taken throughout and analysed.  

Study 2 - A randomised controlled trial (RCT) of 300 high and low-risk individuals, High risk individuals will include those who are likely to be more exposed to the virus or those with health conditions identified to cause more severe COVID-19 infections such as diabetes and obesity. 

Study 3 - Little detail was given on study 3. It was simply stated the study would be conducted on 500 people from the general population.

The researchers are currently recruiting for these trials so it’s not known exactly when the data will be available.

A team from Duke university in the USA are also investigating the role of probiotics in COVID- 19 infections. A new randomised, double-blind, placebo-controlled clinical trial, entitled ‘Effect of Lactobacillus on the Microbiome of Household Contacts Exposed to COVID-19’has been approved and will start later this month6. The researchers plan to use Lacticaseibacillus* (Lactobacillus) rhamnosus GG® in more than 1000 participants. The aim of the study is to explore the potential of this probiotic to improve resistance to SARS-CoV-2 virus or to ameliorate the symptoms of COVID-19 infection.

Study leaders, Dr. Paul Wishmeyer and Dr. Anthony Sung, are building on the results of a meta-analysis suggesting that supporting the gut microbiota with probiotics may be a useful part of the management protocol in those suffering from upper and lower respiratory tract infections, sepsis, and pneumonia7. Results from Dr. Wischmeyer’s team and others have suggested that probiotics may help to improve intestinal and lung barrier function and homeostasis; increase production of regulatory T cells, help to protect against viral infection, and decrease pro-inflammatory cytokines in both respiratory and systemic infections.

This is the first of several randomised clinical trials planned by Dr. Wischmeyer’s laboratories, who are very keen to find a place for probiotics in the management of COVID-19 infections.

“We hypothesise that Lactobacillus rhamnosus GG® will directly influence the microbiota which may in turn reduce COVID-19 infection risk and severity of disease and symptoms," said Dr. Wischmeyer. "This study will provide us with greater understanding of how to care for the most at-risk populations."   

To see more of the research using this probiotic, a look at this strain's entry in the Probiotics Database: Lactobacillus rhamnosus GG® 

We still have a lot to learn about the SARS-CoV-2 virus, but we’re keen to learn more about the connection between the gut microbiome and COVID-19 infection. We’ll be awaiting the results of these trials with great excitement!

*Due to taxonomic changes to the genus lactobacillus, Lactobacillus rhamnosus GG® has been reclassified as Lacticaseibacillus rhamnosus GG® 

References

1. Cheung KS et al., "Gastrointestinal Manifestations of SARS-CoV-2 Infection and Virus Load in Fecal Samples From a Hong Kong Cohort: Systematic Review and Meta-analysis," Gastroenterology, p. doi: 10.1053/j.gastro.2020.03.065, 2020.

2. Lin L et al., "Gastrointestinal symptoms of 95 cases with SARS-CoV-2 infection," GUT, vol. 69, pp. 997-1001, 2020.

3. Effenberger M et al., "Faecal calprotectin indicates intestinal inflammation in COVID-19," Gut , vol. 69, no. 8, pp. 1543-1544, 2020.

4. Zuo T et al., "Alterations in Gut Microbiota of Patients With COVID-19 During Time of Hospitalization," Gastroenterology, p. https://doi.org/10.1053/j.gastro.2020.05.048, 2020.

5. L. G, "Probiotics and COVID-19: Hong Kong researchers trialling formula in COVID-19 patients, high-risk and general population," 8 July 2020. [Online]. Available: https://www.nutraingredients-asia.com/Article/2020/07/08/Probiotics-and-COVID-19-Hong-Kong-researchers-trialling-formula-in-COVID-19-patients-high-risk-and-general-population?utm_source=newsletter_daily&utm_medium=email&utm_campaign=09-Jul-2020. [Accessed 8 July 2020].

6. Wischmeyer et al., "Effect of Lactobacillus on the Microbiome of Household Contacts Exposed to COVID-19," p. https://www.clinicaltrials.gov/ct2/show/NCT04399252.

7. Manzanares W et al., "Probiotic and synbiotic therapy in critical illness: a systematic review and meta-analysis," Crit Care, vol. 21, no. 42, pp. doi: 10.1186/s13054-017-1622-4, 2017.