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.
This extreme range of symptoms is caused by variations in individual responses to the virus. 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.,
Which patient-specific factors determine the clinical course of COVID-19? Can these factors be altered through diet and nutrition?
- 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.,,,,,,,
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.,,,
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.,,
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.,, However, scientists believe that individuals who already have a weakened microbiota are predisposed to an excessive inflammatory response and a more severe clinical course.,
Recent evidence from studies of COVID-19 patients suggests that dysbiosis weakens the intestinal barrier.,,, 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. 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. Similar changes have been seen in clinical studies from researchers around the world.,,,,
F. prausnitzii is renowned for its ability to synthesize butyrate, a short-chain fatty acid (SCFA) with anti-inflammatory effects.,, Lower fecal butyrate levels were associated with excessive inflammation in COVID-19 patients. 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.
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. 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. “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.
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., If probiotics are taken daily, they may help correct dysbiosis before the onset of an acute illness. 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.,,
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.,,, Individuals with these and other comorbidities are predisposed to a more severe clinical course of illness., 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.,
Maintaining a healthy gut microbiome may also help improve vaccine efficacy.,, 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.
Supplemental bifidobacteria may help reduce inflammation and boost the synthesis of beneficial SCFAs., 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. 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. 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. 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.”
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. 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.”Click here to see References
 Wong LY, Perlman S. Immune dysregulation and immunopathology induced by SARS-CoV-2 and related coronaviruses—are we our own worst enemy? Nat Rev Immunol. 2021 Nov 26;1-10.
 Patel P, Roper J. Gut microbiome composition is associated with COVID-19 disease severity. Gastroenterology. 2021 Aug;161(2):722-4.
 Wong RSY. Inflammation in COVID-19: from pathogenesis to treatment. Int J Clin Exp Pathol. 2021 Jul 15;14(7):831-44.
 Shcherbak SG, et al. Basic predictive risk factors for cytokine storms in COVID-19 patients. Front Immunol. 2021 Nov 10;12:745515.
 Vignesh R, et al. Could perturbation of gut microbiota possibly exacerbate the severity of COVID-19 via cytokine storm? Front Immunol. 2021 Jan 25;11:607734.
 Venzon M, et al. Gut microbiome dysbiosis during COVID-19 is associated with increased risk for bacteremia and microbial translocation. Res Sq. 2021 Jul 27 [Preprint]. doi: 10.21203/rs.3.rs-726620/v1.
 Gou W, et al. Gut microbiota may underlie the predisposition of healthy individuals to COVID-19. MedRxiv. 2020 Jan 1 [Preprint]. doi: 10.1101/2020.04.22.20076091.
 Zuo T, et al. Alterations in gut microbiota of patients with COVID-19 during time of hospitalization. Gastroenterology. 2020 Sep;159(3):944-55.
 Zuo T, et al. Gut microbiome alterations in COVID-19. Genomics Proteomics Bioinformatics. 2021 Sep 21 [Online ahead of print]. doi: 10.1016/j.gpb.2021.09.004
 Zuo T, et al. Depicting SARS-CoV-2 faecal viral activity in association with gut microbiota composition in patients with COVID-19. Gut. 2021;70:276-84.
 Li S, et al. Microbiome profiling using shotgun metagenomic sequencing identified unique microorganisms in COVID-19 patients with altered gut microbiota. Front Microbiol. 2021 Oct 11;12:712081.
 Gu S, et al. Alterations of the gut microbiota in patients with Coronavirus Disease 2019 or H1N1 influenza. Clin Infect Dis. 2020 Dec 17;71(10):2669-78.
 Hazan S, et al. The lost microbes of COVID-19: bifidobacteria depletion and decreased microbiome diversity are a predictability marker of severe COVID 19, a cross sectional study. medRxiv, 06 Sep 2021 [Preprint]. doi: 10.1101/2021.09.02.21262832.
 Reinold J, et al. A pro-inflammatory gut microbiome characterizes SARS-CoV-2 infected patients and a reduction in the connectivity of an anti-inflammatory bacterial network associates with severe COVID-19. Front Cell Infect Microbiol. 2021 Nov 17;11:747816.
 Gaibani P, et al. The gut microbiota of critically ill patients with COVID-19. Front Cell Infect Microbiol. 2021 Jun 29;11:670424.
 Yeoh YK, et al. Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19. Gut. 2021 Apr;70(4):698-706.
 Zhang F, et al. Prolonged impairment of short-chain fatty acid and L-isoleucine biosynthesis in gut microbiome in patients with COVID-19. Gastroenterology. 2021 Oct 21:S0016-5085(21)03650-7.
 Chen Y, et al. Six-month follow-up of gut microbiota richness in patients with COVID-19. Gut. 2022 Jan;71(1):222-5.
 Tang L, et al. Clinical significance of the correlation between changes in the major intestinal bacteria species and COVID-19 severity. Engineering (Beijing). 2020 Oct;6(10):1178-84.
 Lv L, et al. Gut mycobiota alterations in patients with COVID-19 and H1N1 infections and their associations with clinical features. Commun Biol. 2021 Apr 13;4(1):480.
 Devaux CA, et al. New insights into the physiopathology of COVID-19: SARS-CoV-2-associated gastrointestinal illness. Front Med (Lausanne). 2021 Feb 18;8:640073.
 Xiao F, et al. Evidence for gastrointestinal infection of SARS-CoV-2. Gastroenterology. 2020 May;158(6):1831-3.
 Wang W, et al. Detection of SARS-CoV-2 in different types of clinical specimens. JAMA. 2020 May 12;323(18):1843-4.
 Oliva A, et al. Low-grade endotoxemia and thrombosis in COVID-19. Clin Transl Gastroenterol. 2021 Jun 4;12(6):e00348.
Oliva A, et al. Persistent systemic microbial translocation and intestinal damage during Coronavirus Disease-19. Front Immunol. 2021 Jul 14;12:708149.
 Giron LB, et al. Plasma markers of disrupted gut permeability in severe COVID-19 patients. Front Immunol. 2021 Jun 9;12:686240.
 Hussain I, et al. Role of gut microbiome in COVID-19: an insight into pathogenesis and therapeutic potential. Front Immunol. 2021 Oct 14;12:765965.
 Hosseinkhani F, et al. The contribution of gut bacterial metabolites in the human immune signaling pathway of non-communicable diseases. Gut Microbes. Jan-Dec 2021;13(1):1-22.
 Geirnaert A, et al. Butyrate-producing bacteria supplemented in vitro to Crohn’s disease patient microbiota increased butyrate production and enhanced intestinal epithelial barrier integrity. Sci Rep. 2017 Sep 13;7(1):11450.
 Siddiqui MT, Cresci GAM. The immunomodulatory functions of butyrate. J Inflamm Res. 2021 Nov 18;14:6025-41.
 Sajdel-Sulkowska EM, et al. Neuropsychiatric ramifications of COVID-19: short-chain fatty acid deficiency and disturbance of microbiota-gut-brain axis signaling. Biomed Res Int. 2021 Oct 5;2021:7880448.
 Conte L, Toraldo DM. Targeting the gut-lung microbiota axis by means of a high-fibre diet and probiotics may have anti-inflammatory effects in COVID-19 infection. Ther Adv Respir Dis. Jan-Dec 2020;14:1753466620937170.
 Dhar D, Mohanty A. (2020) A gut microbiota and Covid-19 – possible link and implications. Virus Res. 2020;285:198018.
 Kim SK, et al. Role of probiotics in human gut microbiome-associated diseases. J Microbiol Biotechnol. 2019 Sep 28;29(9):1335-40.
 Toscano M, et al. Effect of Lactobacillus rhamnosus HN001 and Bifidobacterium longum BB536 on the healthy gut microbiota composition at phyla and species level: a preliminary study. World J Gastroenterol. 2017 Apr 21;23(15):2696-704.
 Darbandi A, et al. The effect of probiotics on respiratory tract infection with special emphasis on COVID-19: systemic review 2010-20. Int J Infect Dis. 2021 Apr;105:91-104.
 Walton GE, et al. Mechanisms linking the human gut microbiome to prophylactic and treatment strategies for COVID-19. Br J Nutr. 2021 Jul 28;126(2):219-27.
 Batista KS, et al. Probiotics and prebiotics: potential prevention and therapeutic target for nutritional management of COVID-19? Nutr Res Rev. 2021 Oct 20:1-8.
 Peng J, et al. Probiotics as adjunctive treatment for patients contracted COVID-19: current understanding and future needs. Front Nutr. 2021 Jun 10;8:304.
 Magalhães NS, et al. Gut microbiota dysbiosis is a crucial player for the poor outcomes for COVID-19 in elderly, diabetic and hypertensive patients. Front Med (Lausanne). 2021 Aug 11;8:644751.
 Belančić A. Gut microbiome dysbiosis and endotoxemia – additional pathophysiological explanation for increased COVID-19 severity in obesity. Obes Med. 2020 Dec;20:100302.
 Demeulemeester F, et al. Obesity as a risk factor for severe COVID-19 and complications: a review. Cells. 2021 Apr 17;10(4):933.
 Kandasamy S, et al. Lactobacilli and bifidobacteria enhance mucosal B cell responses and differentially modulate systemic antibody responses to an oral human rotavirus vaccine in a neonatal gnotobiotic pig disease model. Gut Microbes. 2014 Sep 3;5(5):639-51.
 Vlasova AN, et al. Lactobacilli and bifidobacteria promote immune homeostasis by modulating innate immune responses to human rotavirus in neonatal gnotobiotic pigs. PLoS One. 2013 Oct 2;8(10):e76962.
 Lei WT, et al. Effect of probiotics and prebiotics on immune response to influenza vaccination in adults: a systematic review and meta-analysis of randomized controlled trials. Nutrients. 2017 Nov;9(11):1175.
 Davidson LE, et al. Lactobacillus GG as an immune adjuvant for live-attenuated influenza vaccine in healthy adults: a randomized double-blind placebo-controlled trial. Eur J Clin Nutr. 2011 Apr;65(4):501-7.
 Uusitupa HM, et al. Bifidobacterium animalis subsp. lactis 420 for metabolic health: review of the research. Nutrients. 2020 Mar 25;12(4):892.
 Hiippala K, et al. The potential of gut commensals in reinforcing intestinal barrier function and alleviating inflammation. Nutrients. 2018 Jul 29;10(8):988.
 Bozkurt HS, Bilen O. Oral booster probiotic bifidobacteria in SARS-COV-2 patients. Int J Immunopathol Pharmacol. Jan-Dec 2021;35:20587384211059677.
 Wu C, et al. The volatile and heterogenous gut microbiota shifts of COVID-19 patients over the course of a probiotics-assisted therapy. Res Square. 2020 Sep 10 [Preprint]. doi: 10.21203/rs.3.rs-72753/v1.
 Rawson TM, et al. Bacterial and fungal coinfection in individuals with coronavirus: a rapid review to support COVID-19 antimicrobial prescribing. Clin Infect Dis. 2020 Dec 3;71(9):2459-68.
 Sarkar A, et al. The gut microbiome as a biomarker of differential susceptibility to SARS-CoV-2. Trends Mol Med. 2021 Dec;27(12):1115-34.
 Leal F, et al. Effect of a nutritional support system to increase survival and reduce mortality in patients with COVID-19 in Stage III and comorbidities: a blinded randomized controlled clinical trial. SSRN. 25 Oct 2021 [Preprint]. doi: 10.2139/ssrn.3949424
 Hawryłkowicz V, et al. Patient nutrition and probiotic therapy in COVID-19: what do we know in 2021? Nutrients. 2021 Sep 26;13(10):3385.
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Marina MacDonald, MS, PhD
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