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The COVID-19 pandemic has been the driving force behind many clinical research studies over the past two years. As the global scientific community races to better understand the virus, in order to slow its spread, every plausable angle has been examined. Amongst the research have been several studies examining a possible link between the SARS-CoV-2 virus and the gut microbiome.
One 2021 clinical study, which received worldwide press coverage, has established a link between the composition of the gut microbiome and symptom severity in COVID-19 infection1. This is not the first research article to call attention to the relationship between SARS-CoV-2, the virus strain implicated in COVID-19 and, the gut and its residing population of gut bacteria, known as the gut microbiome. (We will look at these in more detail later).
Once the link was established between the virus and the health of the gut microbiome, it logically called into question whether probiotics might have a part to play in the clinical picture. In April 2021, The British Medical Journal published the results of an observational longitudinal study6 which brings us one step closer to an understanding of this valid question.
The study considers the impact of taking various nutritional supplements on the risk of testing positive for COVID-19. In total, 1.4 million users of the ZOE COVID Symptom Study App were asked about their use of nutritional supplements. More specifically, they were asked to disclose whether they regularly took any of the following supplements: Vitamin D, probiotics, Omega-3 fatty acids, multi-vitamins, garlic, zinc and vitamin C.
Only 4 of the 7 supplement types studied showed a negative association with the likelihood of testing positive for SARS- CoV-2. A reduction in risk was found in those study participants taking: probiotics, Vitamin D, Omega-3 fatty acids and multi-vitamins. Of note, probiotics were associated with the lowest risk of testing positive for the virus. Perhaps surprisingly, the study findings showed that taking Vitamin C, zinc, or garlic supplements wasn't associated with any reduction in risk. (We will look at this study in more detail later on in this article).
Since the outbreak of the COVID-19 pandemic in early 2020, various clinical research studies have been published examining the relationship between SARS-CoV-2, gut health and the gut microbiome. Earlier in the course of the pandemic, in May 2020, researchers identified that SARS-CoV-2 can be transmitted via a faecal-oral route; infecting our gut cells2, and contributing to the gastrointestinal symptoms frequently present in acute infection3.
Several months later, further research emerged highlighting the presence of dysbiosis and a unique gut microbiome composition pattern in COVID-19 patients when compared with the microbiomes of healthy individuals4.
Several bacterial species were identified as being most commonly associated with increased disease severity including Clostridium ramosum and Clostridium hathewayi, whereas others were associated with a reduction in severity such as Alistipes oderdonkii and Faecalibacterium prausnitzi. These findings suggest that the SARS-CoV-2 virus has the ability to influence the composition of the gut microbiome and that this could ultimately have an impact on the body’s immune response to the virus.
Subsequently, a 2021 study found associations between gut microbiota composition, levels of cytokines and inflammatory markers in patients with COVID-1915. Research suggested that the gut microbiome is involved in the extent of COVID-19 severity possibly via modulating host immune responses.
A highly topical research article published in the British Medical Journal has found an association between the composition of the gut microbiome and the severity of symptoms in patients with COVID-19.
Our gut bacteria are known to influence our immune function5. This clinical study found that those with dysbiosis and low levels of known immunomodulatory commensal gut microbes have an exaggerated immune response to the SARS-CoV-2, when compared to those with a healthy gut microbiome1. This heightened immune response is recognised in the form of raised inflammatory markers and blood markers signifying tissue damage. Furthermore, this dysbiosis was suggested to be a contributing factor in the delayed resolution of symptoms after acute infection.
More recently, a 2022 Chinese study sought to investigate whether gut microbiome composition is linked to post-acute COVID-19 syndrome. The study demonstrated persistent gut dysbiosis at 6 months after recovery from COVID-19 and the link between altered gut microbiota and different symptoms19, concluding that an individual’s gut microbiota composition at admission may affect the susceptibility to long-term complications of COVID-19. Further studies are needed to investigate whether microbiota modulation can facilitate timely recovery from post-acute COVID-19 syndrome.
Can we deduce from the findings of this study that by addressing an imbalance within the gut microbiome, COVID-19 could be mitigated? Or, in other words, could probiotics help against COVID-19? Perhaps but the research is not quite there yet to confirm this claim.
In late 2020, research findings from the world’s largest ongoing study of COVID-196 were published in which probiotics were found to have ‘a small protective effect against testing positive for the virus’, as quoted by lead researcher Marica Meroni. This study (mentioned previously) was recently published by the British Medical Journal, bringing increased credibility and visibility to its findings.
After studying the data collected from 1.4 million users of the ZOE COVID Symptom Study App, a significant negative association was identified in women taking probiotic supplements, vitamin D, multi-vitamins and Omega-3 fatty acid supplements and the likelihood of testing positive for SARS-CoV-27. Of note, probiotics, of all health supplements assessed, were associated with the lowest risk of testing positive for SARS-CoV-2.
Vitamin D has been highly recognised for its role in the body’s immune response to SARS-CoV-2, with vitamin D deficiency being linked to increased COVID-19 symptoms severity8. As a result, vitamin D has garnered substantial interest in the medical community and with that, a surge in clinical research on this topic has arisen. Tens of journal articles examining the role of vitamin D in immunity related to COVID-19 have been published in 2021 already. Probiotics have not yet quite achieved this level of attention. However, there are several clinical trials in progress9 and with the release of research discussed in this article, further testing will be encouraged. We know that the properties of an individual probiotic strain are specific to that strain alone, as well documented and substantiated by clinical research10,11 . The effects of individual probiotics strains in COVID-19 infection have yet to be elucidated. High quality, well-designed clinical trials are required to ascertain which probiotic strains may be beneficial in preventing the development or reducing symptom severity of COVID-19.
This research paper is not yet peer-reviewed and several limitations of the study have already been pointed out12. These limitations include the lack of baseline nutritional status information of the population studied; the fact that self-measured data collected is subject to bias; and the lack of representation across the general population. However, as highlighted by Marica Meroni the lead researcher of this study, the findings are worth considering as only some supplements were determined to be helpful. ‘Healthy bias’, where people who use the app are more likely to engage in health-conscious behaviours, does not account for the fact that only certain supplements were found to be protective against COVID-19. It would be expected that if it was ‘healthy bias’ alone at play, the association would be the same across all supplements; when in fact, vitamin C, zinc and garlic supplements demonstrated no protective effects against COVID-19.
Although the findings of this study are promising, it demands further investigation.
As our knowledge of this field continues to expand, more evidence to support taking probiotics to help against COVID-19 is coming to light.
One major UK study, published at the end of 2021, is causing renewed interest in probiotics16. The study looked at probiotic strains influencing the duration and severity of symptoms among individuals with COVID-19. 126 participants were given a blend of probiotic Lactobacillus and prebiotic inulin for 30 days. Following this nutritional intervention, participants were found to have a significant improvement in GI and non-GI symptoms, including cough, fatigue, and subjective well-being, resulting in a meaningful improvement in overall well-being.
Another recent trial of note is a Mexican study which found that people with COVID-19 who took a specific combination of four probiotic bacterial strains had lesser symptoms two weeks after their initial infection compared to those who took a placebo18. However, more investigation is required as this trial excluded participants over the age of 60, an age group most at risk of developing severe COVID-19.
In early 2022, a study on probiotic interventions in the development of COVID-19 symptoms was published. Lactobacillus rhamnosus GG® supplementation was shown to reduce the likelihood of developing symptoms after being exposed to the COVID-19 virus17. L rhamnosus GG was also associated with a statistically significant reduction in COVID-19 diagnosis.
A 2021 study undertaken on 147 male long COVID-19 patients in England reported signification reductions in fatigue and coughs after taking a blend of Lactobacillus probiotics and prebiotics plus a capsule containing phytochemicals20.
Probiotics have also been utilised in a different manner to help against COVID-19 – to make a vaccine. Lactobacillus acidophilus has been increasingly recognised for its potential as a vaccine vector. Biomedical research carried out by a team of scientists at the Department of Microbiology, Immunology and Pathology in Colorado State University, assessed the use of genetically modified Lactobacillus acidophilus13 as a vaccine vector to target the coronavirus. Extensive clinical testing was required before it could be proven to be efficacious as a vaccine against SARS-CoV-2. In the meantime, other vaccines have been approved and disseminated.
Although it remains to be confirmed that probiotics can help against COVID-19, it can be acknowledged that maintaining a healthy gut microbiome plays an important role in normal immune function. Replenishing our gut microbiome, whether through diet or by other means, is therefore worth considering. The epidemiologist Professor Tim Spector from ZOE, the COVID symptom study app, releases a weekly video update including advice on how to support our health against COVID-19. He discusses how our gut microbiome is negatively impacted by the virus and by “keeping it in good shape, you can do something to ameliorate the disease”. He has recommended supporting the health of our gut microbiome by eating plenty of fresh fruit and vegetables, by including fermented foods in our diet, for example sauerkraut or kefir, and polyphenol-rich foods such as peanuts and berries. Along with Professor Spector’s suggestions, it is worth noting probiotic supplements are also an option for replenishing the gut microbiome with beneficial bacteria. Learn more about the microbiome over on the Probiotics Learning Lab.
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