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How the Gut Microbiome Influences COVID-19

How the Gut Microbiome Influences COVID-19

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Can probiotics reduce the risk?

The COVID-19 pandemic has swept the globe, killing nearly five million people to date. The disease has a broad range of outcomes, however, with many people developing only mild to moderate symptoms like sniffles, cough, shortness of breath, and fever.[1]

This extreme range of symptoms is caused by variations in individual responses to the virus.[2] It has been found that patients who develop severe forms of the disease have an immune response that causes overwhelming inflammation, which in turn contributes to mortality.[3],[4]

Which patient-specific factors determine the clinical course of COVID-19? Can these factors be altered through diet and nutrition?

Surprisingly, the answers to these critical questions may lie in studies of the gut.[5],[6],[7] Cutting-edge research suggests that:

  • People with severe forms of COVID-19 have an overgrowth of pathogenic microbes and a deficit of friendly gut bacteria.
  • These changes can trigger a leaky gut, which exacerbates inflammation.
  • Extensive microbial changes (“dysbiosis”) correlate with severe symptoms and mortality.
  • Probiotics that support microbial health may reduce the risks associated with COVID-19.

Dysbiosis increases the risks of COVID-19

The microbiome of patients with COVID-19 is significantly altered and weakened as compared with healthy individuals.

Studies from around the world have shown that the gut microbiome of patients with COVID-19 is significantly altered and weakened as compared with healthy individuals.[8],[9],[10],[11],[12],[13],[14],[15]

The changes seen in hospitalized COVID-19 patients include an overgrowth of pathogenic microbes (“bad bugs”) and a decrease in beneficial bacteria (“good bugs”). Moreover, extensive levels of dysbiosis are correlated with more severe clinical outcomes.[16],[17],[18],[19]

Also, most COVID-19 patients who are hospitalized are prescribed antibiotic drugs, which contribute to dysbiosis as discussed in more detail below.

The pathogens found in stool samples from COVID-19 patients include Clostridium hathewayi, a bacterium associated with pneumonia; Enterococcus, a gut bacterium that causes bloodstream infections; and Candida, a yeast that is normally found in the gut but can also cause blood and lung infections.[9],[14],[20]

Individuals who already have a weakened microbiota are predisposed to a more severe clinical course.

Because the virus that causes COVID-19 is able to replicate in the gastrointestinal tract as well as in the lungs, the viral infection itself may trigger changes in the gut microbiome.[21],[22],[23] However, scientists believe that individuals who already have a weakened microbiota are predisposed to an excessive inflammatory response and a more severe clinical course.[5],[7]

Recent evidence from studies of COVID-19 patients suggests that dysbiosis weakens the intestinal barrier.[24],[25],[26],[27] This can lead to leaky gut, which allows the release of bacterial and fungal products and toxins into the bloodstream, which in turn exacerbates the inflammatory response and increases the severity of COVID-19.

Friendly bacteria are depleted in COVID-19 patients

A clinical study published in October 2021 confirmed the link between dysbiosis and COVID-19 severity.[17] The researchers studied 66 hospitalized patients with mild to severe COVID-19. The control group comprised patients hospitalized with pneumonia but who were negative for COVID-19. In this study, all subjects were free of antibiotic use for at least three months before enrollment.

The COVID-19 patients had reduced numbers of beneficial bacteria, including a keystone species known as Faecalibacterium prausnitzii, one of the main butyrate producers in the human gut.[17] Similar changes have been seen in clinical studies from researchers around the world.[8],[11],[13],[14],[19] 

F. prausnitzii is renowned for its ability to synthesize butyrate, a short-chain fatty acid (SCFA) with anti-inflammatory effects.[28],[29],[30] Lower fecal butyrate levels were associated with excessive inflammation in COVID-19 patients.[17]  These findings reveal a direct link between the impairment of the gut microbiome and the severity of COVID-19.

Low SCFA levels persisted up to 41 days after hospital discharge, at which point the virus was no longer detectable.  However, the microbiota was still impaired.[17] 

Dysbiosis may explain some aspects of “long COVID”, including brain fog and depression.

Continued dysbiosis and a decline in SCFAs may explain some aspects of “long COVID”, including brain fog and depression.[31] This hypothesis is based on the similarity between the dysbiosis seen in COVID-19 patients with that seen in individuals with psychiatric and neurological disorders. Further studies are needed to confirm these findings.

Rationale for the use of probiotics

Probiotic supplementation can help restore friendly bacteria, including Lactobacillus and Bifidobacterium species.[32] “Improving the gut microbiota profile by personalized nutrition and supplementation… can be one of the prophylactic ways by which the impact of this disease can be minimized,” according to a 2020 review.[33]

Here are some of the ways in which probiotics may help:

  • Probiotics can be used to support and maintain a healthy microbiome over the long term.
  • Probiotics, especially Bifidobacterium species, can help reduce excessive inflammation in healthy individuals and those with disease conditions.
  • Probiotics, including the probiotic yeast Saccharomyces boulardii, have been shown to ameliorate the microbial damage caused by antibiotics.
  • Probiotics may also help restore the microbiome after a bout of COVID-19.

Combinations of Lactobacillus and Bifidobacterium species are frequently used for long term microbial support.[34],[35] If probiotics are taken daily, they may help correct dysbiosis before the onset of an acute illness.[36] Studies suggest that the daily consumption of probiotics may help reduce the risks of leaky gut and excessive inflammation associated with COVID-19, and other conditions for that matter.[37],[38],[39]

Probiotic formulations that include Lactobacillus and Bifidobacterium species may be particularly helpful.

Because they may already have dysbiosis, people who are elderly, obese, diabetic, or who have other diseases are at increased risk for inflammation if they contract COVID-19.[5],[40],[41],[42] Individuals with these and other comorbidities are predisposed to a more severe clinical course of illness.[5],[7] Probiotic formulations that include Lactobacillus and Bifidobacterium species may be particularly helpful, since severe COVID-19 is associated with a decline in these friendly bacteria.[13],[14]

Maintaining a healthy gut microbiome may also help improve vaccine efficacy.[43],[44],[45] In a placebo-controlled study of influenza vaccination, 84% of healthy subjects receiving a Lactobacillus probiotic developed adequate antibody levels against the H3N2 influenza strain, compared with only 55% of those in the placebo group.[46]

Supplemental bifidobacteria may help reduce inflammation and boost the synthesis of beneficial SCFAs.[47],[48] A preliminary study of hospitalized COVID-19 patients showed that high doses of Bifidobacterium lactis, a well-known probiotic species, reduced signs of inflammation and shortened the hospital stays.[49] The mortality rate in the probiotic group was reduced fivefold compared with the non-probiotic group in this small study.

Probiotics may also help restore the microbiota after a bout of COVID-19.[50] According to a 2021 review, “The intestinal microbial richness of patients of COVID-19 does not return to normal levels even six months after recovery, but probiotic adjunctive treatment has been found to restore gut homeostasis.”39

Probiotic supplementation is particularly important for anyone who is prescribed antibiotics. The majority of hospitalized COVID-19 patients receive antibiotics.[51] Unfortunately, antibiotics disrupt the microbiome and can exacerbate the risks of secondary infections. A December 2021 review states: “If antibiotics are used to treat bacterial infections associated with COVID-19, clinicians should consider whether it may be appropriate to replenish beneficial and commensal microbes via the use of prebiotics (fiber supplements) or probiotics.”[52]

Saccharomyces boulardii, a probiotic yeast, has long been used to support the microbiome during a course of antibiotics. A randomized controlled trial evaluated the benefits of Saccharomyces boulardii along with vitamins, minerals and other nutrients, in hospitalized patients with COVID-19.[53] Survival rates were significantly improved by the combined probiotic and nutrient supplements as compared with a non-supplemented group.

 

Clinical trials of probiotics are underway to confirm these findings. Meanwhile, as one author notes: “The treatment of gut dysbiosis involving an adequate intake of prebiotic dietary fiber and probiotics could turn out to be an immensely helpful instrument for immunomodulation, both in COVID-19 patients and prophylactically in individuals with no history of infection.”[54]

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