Emerging Evidence on the Severity of Patient Outcomes & the Microbiome

The past two months I’ve been covering the newest scientific discoveries about the human microbiome -- most specifically, (1) hidden antibiotics in food which damage our beneficial microbial communities and (2) how most Infants are missing key microbes to function normally. These two major insults to the gut microbiome are some of the biggest reasons so many people are battling severe to moderate SARS-CoV-2 infections.


New Evidence for Link Between Gut Microbiome and COVID-19 Severity


Infection by the novel coronavirus elicits a robust immune response to rid the body of the viral invader. SARS-CoV-2 is just like any other infection the body encounters, but this virus is more contagious and deadly than anything we’ve seen in the last century. There are several explanations for why this virus has been more deadly than others, and you can read about them here:


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In short, disease severity is likely due to not only viral infection but also a person’s immune response directly linked to their microbiome (Shen et al., 2020; Tay et al., 2020; Laing et al., 2020; Long et al., 2020; Ong et al., 2020).


When a person has major imbalances in their microbiome, they’ve been living in a chronic state of sending off aggressive inflammatory signals throughout their bloodstream, even before being exposed to COVID. When infected with COVID, these signals grow even more out-of-control and tip them over to suffering major health complications. For example, if a person has any type of chronic health condition, he/she is already in a constant state of inflammation driven by a major imbalance between their beneficial and pathogenic bacteria inside their digestive tract. And so, when a person with a chronic disease is exposed to COVID and recovers, it is fairly common for many to continue experiencing inflammation-related symptoms, such as multisystem inflammatory syndrome and Kawasaki-like disease in children exposed to COVID (Cheung et al., 2020; Galeotti & Bayry, 2020; Verdoni et al., 2020) and suffer from a full-blown autoimmune disease later in life (Sener & Afsar, 2012).


In fact, emerging evidence sheds light on a substantial involvement of the human gastrointestinal tract and SARS-CoV-2. As initially reported, SARS-CoV-2 primarily infects the respiratory tract—not the gastrointestinal tract. Yet, the pathophysiology of COVID-19 can be attributed to abnormal immune responses in clearing the virus from the gut and causing the virus to continue infecting other tissues in the body. Several lines of evidence point to infection and replication of SARS-CoV-2 in intestinal cells (Lamers et al., 2020) with detection of viral RNA in fecal samples a consistent finding (Wölfel et al., 2020; Xu et al., 2020). And more recently, there is the population finding of a significantly altered gut microbiota composition in patients infected with SARS-CoV-2 (Gu et al., 2020; Zuo et al., 2020). All of these observations tell us that there is heavy involvement of the GI tract with COVID-19.


To test this theory, Yeoh et al. (2021) analyzed the gut microbiota and immune response in 100 patients with SARS-CoV-2 infection during hospitalization and one month after recovery. They found that the gut microbiota composition of patients infected with the virus was correlated with plasma concentrations of several inflammatory cytokines, chemokines, and other inflammation markers, suggesting that the gut microbiota indeed plays a role in modulating host immune response, with the potential to influence disease severity and outcomes. 


Specifically, what Yeoh et al. (2021) identified was the depletion of several key bacterial species in the cohort of sick patients, including Bifidobacterium adolescentis, Eubacterium rectale, and Faecalibacterium

prausnitzii. Elevations in these inflammatory biomarkers is consistent with immunological studies of other patients infected with SARS-CoV-2 (Vabret et al., 2020), indicating that the depleted beneficial microbes were essential in preventing aggressive forms of inflammatory responses


As I wrote last month, when we see less diversity and richness in the gut’s microbial composition, there is a greater likelihood for disease to set in, especially at younger ages since children will grow up without proper training and stimulation of the immune system. Low or absent populations of commensal bacteria is a real problem. When they are gone, they can’t provide an immunomodulatory role in the human GI system, and it’s as if our front line defense system is outnumbered

The more we lose, the worse off we likely are.

If key species are missing from the gut, then there is usually an overgrowth of species that takes its place. We want to avoid this dysbiotic state because it ultimately leads to microbial-mediated immune dysregulation. And that’s exactly what Yeoh et al. (2021) found in the gut:  enrichment of Ruminococcus gnavus, Ruminococcus torques, Bacteroides dorei, and Bacteroides vulgatus in SARS-CoV-2 infected patients

Remember, one cannot restore balance back to the microbiome overnight. Based on several patients surveyed for up to 30 days after clearing SARS-CoV-2, Yeoh et al. (2021) found the gut microbiota to remain significantly altered after recovery from the initial viral infection.

In light of findings that a subset of recovered COVID-19 patients experience persistent symptoms such as chronic fatigue, difficult or labored breathing (dyspnea), and joint pain (Carfì et al., 2020; Goërtz et al., 2020; Townsend et al., 2020), a dysbiotic gut microbiome likely has clinical relevance. Some of these patients have chronic symptoms months after initial onset of symptoms, and the gut microbiome could be contributing to their immune-related dysfunction post-SARS-CoV-2 infection. Longer follow-up periods (> 1 year after clearing the virus) are needed to answer questions related to the duration of gut microbiota dysbiosis post-recovery and whether the dysbiosis or enrichment/depletion of specific gut microorganisms predisposes recovered individuals to future health problems (Yeoh et al., 2021).


Yeoh et al. (2021) found no difference in patient outcomes with or without the use of antibiotics, which supports the rationale to end unnecessary administration of antibiotics in those with COVID-19. Though, this comparison was limited to individuals with moderate disease (as patient numbers in this cohort were more comparable for study purposes). Antibiotics do not improve patient outcomes; indeed, it is still possible that a higher prevalence of antibiotic administration in severe and critical patients is actually worsening inflammation and their overall outcomes. As detailed in the Journal of Medical Virology


“In terms of antibiotic prescribing patterns, 67% (n = 162) of all patients received antibiotics with 72% of these patients not having an obvious source of a bacterial infection. The most common antibiotics used were cefepime (45%), ceftriaxone (54%), vancomycin (48%), and azithromycin (47%). There was a significantly higher rate of inpatient mortality in patients who received antibiotics compared to those who did not (30% vs 5%; P < .0001). A subgroup analysis looking at patients who received antibiotic therapy showed that all inflammatory markers were statistically significantly elevated, except for ferritin, compared to patients who did not receive antibiotics.” (Goncalves Mendes Neto et al., 2021)


Fortunately, antibiotics are not being thrown at COVID-19 patients like they were at the beginning of the pandemic. Keep in mind, though, that while patients on antibiotics did have poorer outcomes and higher inflammatory markers, this could have been the result of selection bias, given that sicker people are more likely to be started on empiric antibiotic coverage. Regardless, the microbiome hangs in a delicate balance and any perturbation could have severe consequences. More antibiotics is likely not the solution for a majority of causes.


Dr. Bhandari and the Advanced Health Team Are Here to Support Your Health


Our expert team of integrative functional medicine holistic practitioners work together to help patients suffering from chronic health concerns better understand the root cause of their illness. By knowing precisely how the body works on a cellular level, we are able to effectively reverse disease and better support the body. To learn more and book an appointment, contact Advanced Health or call 1-415-506-9393.



Alameddine, J., Godefroy, E., Papargyris, L., Sarrabayrouse, G., Tabiasco, J., Bridonneau, C., ... & Jotereau, F. (2019). Faecalibacterium prausnitzii skews human DC to prime IL10-producing T cells through TLR2/6/JNK signaling and IL-10, IL-27, CD39, and IDO-1 induction. Frontiers in immunology, 10, 143. 


Carfì, A., Bernabei, R., & Landi, F. (2020). Persistent symptoms in patients after acute COVID-19. Jama, 324(6), 603-605.


Cattaneo, A., Cattane, N., Galluzzi, S., Provasi, S., Lopizzo, N., Festari, C., ... & Group, I. F. (2017). Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly. Neurobiology of aging, 49, 60-68.


Cheung, E. W., Zachariah, P., Gorelik, M., Boneparth, A., Kernie, S. G., Orange, J. S., & Milner, J. D. (2020). Multisystem inflammatory syndrome related to COVID-19 in previously healthy children and adolescents in New York City. Jama, 324(3), 294-296.


Davis-Richardson, A. G., Ardissone, A. N., Dias, R., Simell, V., Leonard, M. T., Kemppainen, K. M., ... & Triplett, E. W. (2014). Bacteroides dorei dominates gut microbiome prior to autoimmunity in Finnish children at high risk for type 1 diabetes. Frontiers in microbiology, 5, 678.


Fasano, A. (2012). Leaky gut and autoimmune diseases. Clinical reviews in allergy & immunology, 42(1), 71-78.


Galeotti, C., & Bayry, J. (2020). Autoimmune and inflammatory diseases following COVID-19. Nature Reviews Rheumatology, 16(8), 413-414.


Goërtz, Y. M., Van Herck, M., Delbressine, J. M., Vaes, A. W., Meys, R., Machado, F. V., ... & Spruit, M. A. (2020). Persistent symptoms 3 months after a SARS-CoV-2 infection: the post-COVID-19 syndrome?. ERJ open research, 6(4).


Goncalves Mendes Neto, A., Lo, K. B., Wattoo, A., Salacup, G., Pelayo, J., DeJoy III, R., ... & Azmaiparashvili, Z. (2021). Bacterial infections and patterns of antibiotic use in patients with COVID‐19. Journal of medical virology, 93(3), 1489-1495.


Gu, S., Chen, Y., Wu, Z., Chen, Y., Gao, H., Lv, L., ... & Li, L. (2020). Alterations of the gut microbiota in patients with coronavirus disease 2019 or H1N1 influenza. Clinical Infectious Diseases, 71(10), 2669-2678.


Hall, A. B., Yassour, M., Sauk, J., Garner, A., Jiang, X., Arthur, T., ... & Huttenhower, C. (2017). A novel Ruminococcus gnavus clade enriched in inflammatory bowel disease patients. Genome medicine, 9(1), 1-12.


Lamers, M. M., Beumer, J., van der Vaart, J., Knoops, K., Puschhof, J., Breugem, T. I., ... & Clevers, H. (2020). SARS-CoV-2 productively infects human gut enterocytes. Science, 369(6499), 50-54.


Laing, A. G., Lorenc, A., Del Barrio, I. D. M., Das, A., Fish, M., Monin, L., ... & Hayday, A. C. (2020). A consensus Covid-19 immune signature combines immuno-protection with discrete sepsis-like traits associated with poor prognosis. MedRxiv.


Langford, B. J., So, M., Raybardhan, S., Leung, V., Westwood, D., MacFadden, D. R., ... & Daneman, N. (2020). Bacterial co-infection and secondary infection in patients with COVID-19: a living rapid review and meta-analysis. Clinical Microbiology and Infection.


Long, Q. X., Tang, X. J., Shi, Q. L., Li, Q., Deng, H. J., Yuan, J., ... & Huang, A. L. (2020). Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections. Nature medicine, 26(8), 1200-1204.


Matsuoka, K., & Kanai, T. (2015, January). The gut microbiota and inflammatory bowel disease. In Seminars in immunopathology (Vol. 37, No. 1, pp. 47-55). Springer Berlin Heidelberg.


Mazmanian, S. K., Liu, C. H., Tzianabos, A. O., & Kasper, D. L. (2005). An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell, 122(1), 107-118.


Ong, E. Z., Chan, Y. F. Z., Leong, W. Y., Lee, N. M. Y., Kalimuddin, S., Mohideen, S. M. H., ... & Low, J. G. H. (2020). A dynamic immune response shapes COVID-19 progression. Cell host & microbe, 27(6), 879-882.


Parada Venegas, D., De la Fuente, M. K., Landskron, G., González, M. J., Quera, R., Dijkstra, G., ... & Hermoso, M. A. (2019). Short chain fatty acids (SCFAs)-mediated gut epithelial and immune regulation and its relevance for inflammatory bowel diseases. Frontiers in immunology, 10, 277.


Riedel, C. U., Foata, F., Philippe, D., Adolfsson, O., Eikmanns, B. J., & Blum, S. (2006). Anti-inflammatory effects of bifidobacteria by inhibition of LPS-induced NF-κB activation. World journal of gastroenterology: WJG, 12(23), 3729.


Schirmer, M., Smeekens, S. P., Vlamakis, H., Jaeger, M., Oosting, M., Franzosa, E. A., ... & Xavier, R. J. (2016). Linking the human gut microbiome to inflammatory cytokine production capacity. Cell, 167(4), 1125-1136.


Sener, A. G., & Afsar, I. (2012). Infection and autoimmune disease. Rheumatology international, 32(11), 3331-3338.


Shen, B., Yi, X., Sun, Y., Bi, X., Du, J., Zhang, C., ... & Guo, T. (2020). Proteomic and metabolomic characterization of COVID-19 patient sera. Cell, 182(1), 59-72.


Sokol, H., Pigneur, B., Watterlot, L., Lakhdari, O., Bermúdez-Humarán, L. G., Gratadoux, J. J., ... & Langella, P. (2008). Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proceedings of the National Academy of Sciences, 105(43), 16731-16736.


Tay, M. Z., Poh, C. M., Rénia, L., MacAry, P. A., & Ng, L. F. (2020). The trinity of COVID-19: immunity, inflammation and intervention. Nature Reviews Immunology, 20(6), 363-374.


Townsend, L., Dyer, A. H., Jones, K., Dunne, J., Mooney, A., Gaffney, F., ... & Conlon, N. (2020). Persistent fatigue following SARS-CoV-2 infection is common and independent of severity of initial infection. Plos one, 15(11), e0240784.


Vabret, N., Britton, G. J., Gruber, C., Hegde, S., Kim, J., Kuksin, M., ... & Project, T. S. I. R. (2020). Immunology of COVID-19: current state of the science. Immunity.


van den Munckhof, I. C., Kurilshikov, A., ter Horst, R., Riksen, N. P., Joosten, L. A. B., Zhernakova, A., ... & Rutten, J. H. W. (2018). Role of gut microbiota in chronic low‐grade inflammation as potential driver for atherosclerotic cardiovascular disease: a systematic review of human studies. Obesity Reviews, 19(12), 1719-1734.


Vaughn, V. M., Gandhi, T. N., Petty, L. A., Patel, P. K., Prescott, H. C., Malani, A. N., ... & Flanders, S. A. (2021). Empiric antibacterial therapy and community-onset bacterial coinfection in patients hospitalized with coronavirus disease 2019 (COVID-19): a multi-hospital cohort study. Clinical Infectious Diseases, 72(10), e533-e541.


Verdoni, L., Mazza, A., Gervasoni, A., Martelli, L., Ruggeri, M., Ciuffreda, M., ... & D'Antiga, L. (2020). An outbreak of severe Kawasaki-like disease at the Italian epicentre of the SARS-CoV-2 epidemic: an observational cohort study. The Lancet, 395(10239), 1771-1778.


Wölfel, R., Corman, V. M., Guggemos, W., Seilmaier, M., Zange, S., Müller, M. A., ... & Wendtner, C. (2020). Virological assessment of hospitalized patients with COVID-2019. Nature, 581(7809), 465-469.


Xu, Y., Li, X., Zhu, B., Liang, H., Fang, C., Gong, Y., ... & Gong, S. (2020). Characteristics of pediatric SARS-CoV-2 infection and potential evidence for persistent fecal viral shedding. Nature medicine, 26(4), 502-505.


Yeoh, Y. K., Zuo, T., Lui, G. C. Y., Zhang, F., Liu, Q., Li, A. Y., ... & Ng, S. C. (2021). Gut microbiota composition reflects disease severity and dysfunctional immune responses in patients with COVID-19. Gut, 70(4), 698-706.


Zhou, F., Yu, T., Du, R., Fan, G., Liu, Y., Liu, Z., ... & Cao, B. (2020). Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The lancet, 395(10229), 1054-1062.


Zuo, T., Zhang, F., Lui, G. C., Yeoh, Y. K., Li, A. Y., Zhan, H., ... & Ng, S. C. (2020). Alterations in gut microbiota of patients with COVID-19 during time of hospitalization. Gastroenterology, 159(3), 944-955.

Payal Bhandari M.D. Dr. Payal Bhandari M.D. Dr. Payal Bhandari M.D. is one of U.S.'s top leading integrative functional medical physicians and the founder of San Francisco' top ranked medical center, SF Advanced Health. Her well-experienced holistic healthcare team collaborates together to deliver whole-person personalized care and combines the best in Western and Eastern medicine. By being an expert of cell function, Dr. Bhandari defines the root cause of illness and is able to subside any disease within weeks to months. She specializes in cancer prevention and reversal, digestive & autoimmune disorders. Dr. Bhandari received her Bachelor of Arts degree in biology in 1997 and Doctor of Medicine degree in 2001 from West Virginia University. She the completed her Family Medicine residency in 2004 from the University of Massachusetts and joined a family medicine practice in 2005 which was eventually nationally recognized as San Francisco’s 1st patient-centered medical home. To learn more, go to www.sfadvancedhealth.com.

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