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COVID-19 infection altered the gut microbiota of adult patients and caused depletion of several types of bacteria with known immunomodulatory properties, based on data from a cohort study of 100 patients with confirmed COVID-19 infections from two hospitals.
“As the GI tract is the largest immunological organ in the body and its resident microbiota are known to modulate host immune responses, we hypothesized that the gut microbiota is associated with host inflammatory immune responses in COVID19,” wrote Yun Kit Yeoh, PhD, of the Chinese University of Hong Kong, and colleagues.
In a study published in Gut, the researchers investigated patient microbiota by collecting blood, stool, and patient records between February and May 2020 from 100 confirmed SARS-CoV-2–infected patients in Hong Kong during hospitalization, as well as follow-up stool samples from 27 patients up to 30 days after they cleared the COVID-19 virus; these observations were compared with 78 non–COVID-19 controls.
Overall, 274 stool samples were sequenced. Samples collected from patients during hospitalization for COVID-19 were compared with non–COVID-19 controls. The presence of phylum Bacteroidetes was significantly higher in COVID-19 patients compared with controls (23.9% vs. 12.8%; P < .001), as were Actinobacteria (26.1% vs. 19.0%; P < .001).
After controlling for antibiotics, the investigators found that “differences between cohorts were primarily linked to enrichment of taxa such as Parabacteroides, Sutterella wadsworthensis, and Bacteroides caccae and depletion of Adlercreutzia equolifaciens, Dorea formicigenerans, and Clostridium leptum in COVID-19 relative to non-COVID-19” (P < .05). In addition, Faecalibacterium prausnitzii and Bifidobacterium bifidum were negatively correlated with COVID-19 severity after investigators controlled for patient age and antibiotic use (P < .05).
The researchers also examined bacteria in COVID-19 patients and controls in the context of cytokines and other inflammatory markers. “We hypothesized that these compositional changes play a role in exacerbating disease by contributing to dysregulation of the immune response,” they said.
In fact, species depleted in COVID-19 patients including included B. adolescentis, E. rectale, and F. prausnitzii were negatively correlated with inflammatory markers including CXCL10, IL-10, TNF-alpha, and CCL2.
In addition, 42 stool samples from 27 patients showed significantly distinct gut microbiota from controls up to 30 days (median, 6 days) after virus clearance, regardless of antibiotics use (P < .05), the researchers said.
Long-term data needed
The study findings were limited by several factors, including the potential confounding of microbial signatures associated with COVID-19 because of heterogeneous patient management in the clinical setting and the potential that gut microbiota reflects a patient’s health with no impact on disease severity, as well as lack of data on the role of antibiotics for severe and critical patients, the researchers noted. In addition, “gut microbiota composition is highly heterogeneous across human populations and changes in compositions reported here may not necessarily be reflected in patients with COVID-19 from other biogeographies,” they wrote.
The “longer follow-up of patients with COVID-19 (e.g., 3 months to 1 year after clearing the virus) is needed to address questions related to the duration of gut microbiota dysbiosis post recovery, link between microbiota dysbiosis and long-term persistent symptoms, and whether the dysbiosis or enrichment/depletion of specific gut microorganisms predisposes recovered individuals to future health problems,” they wrote.
However, the results suggest a likely role for gut microorganisms in host inflammatory responses to COVID-19 infection, and “underscore an urgent need to understand the specific roles of gut microorganisms in human immune function and systemic inflammation,” they concluded.
More than infectious
“A growing body of evidence suggests that severity of illness from COVID-19 is largely determined by the patient’s aberrant immune response to the virus,” Jatin Roper, MD, of Duke University, Durham, N.C., said in an interview. “Therefore, a critical question is: What patient factors determine this immune response? The gut microbiota closely interact with the host immune system and are altered in many immunological diseases,” he said. “Furthermore, the SARS-CoV-2 virus infects enterocytes in the intestine and causes symptomatic gastrointestinal disease in a subset of patients. Therefore, understanding a possible association between gut microbiota and COVID-19 may reveal microbial species involved in disease pathogenesis,” he emphasized.
In the current study, “I was surprised to find that COVID-19 infection is associated with depletion of immunomodulatory gut bacteria,” said Dr. Roper. “An open question is whether these changes are caused by the SARS-CoV-2 virus and then result in altered immune response. Alternatively, the changes in gut microbiota may be a result of the immune response or other changes associated with the disease,” he said.
“COVID-19 is an immunological disease, not just an infectious disease,” explained Dr. Roper. “The gut microbiota may play an important role in the pathogenesis of the disease. Thus, specific gut microbes could one day be analyzed to risk stratify patients, or even modified to treat the disease,” he noted.
Beyond COVID-19
“Given the impact of the gut microbiota on health and disease, as well as the impact of diseases on the microbiota, I am not at all surprised to find that there were significant changes in the microbiota of COVID-19 patients and that these changes are associated with inflammatory cytokines, chemokines, and blood markers of tissue damage,” said Anthony Sung, MD, also of Duke University.
According to Dr. Sung, researchers have already been investigating possible connections between gut microbiota and other conditions such as Alzheimer’s disease, and it’s been hypothesized that these connections are mediated by interactions between the gut microbiota and the immune system.
“While this is an important paper in our understanding of COVID-19, and highlights the microbiome as a potential therapeutic target, we need to conduct clinical trials of microbiota-based interventions before we can fully realize the clinical implications of these findings,” he said.
The study was supported by the Health and Medical Research Fund, the Food and Health Bureau, The Government of the Hong Kong Special Administrative Region, and donations from Hui Hoy & Chow Sin Lan Charity Fund Limited, Pine and Crane Company Limited, Mr. Hui Ming, and The D.H. Chen Foundation. The researchers had no financial conflicts to disclose. Dr. Roper and Dr. Sung had no financial conflicts to disclose.
COVID-19 infection altered the gut microbiota of adult patients and caused depletion of several types of bacteria with known immunomodulatory properties, based on data from a cohort study of 100 patients with confirmed COVID-19 infections from two hospitals.
“As the GI tract is the largest immunological organ in the body and its resident microbiota are known to modulate host immune responses, we hypothesized that the gut microbiota is associated with host inflammatory immune responses in COVID19,” wrote Yun Kit Yeoh, PhD, of the Chinese University of Hong Kong, and colleagues.
In a study published in Gut, the researchers investigated patient microbiota by collecting blood, stool, and patient records between February and May 2020 from 100 confirmed SARS-CoV-2–infected patients in Hong Kong during hospitalization, as well as follow-up stool samples from 27 patients up to 30 days after they cleared the COVID-19 virus; these observations were compared with 78 non–COVID-19 controls.
Overall, 274 stool samples were sequenced. Samples collected from patients during hospitalization for COVID-19 were compared with non–COVID-19 controls. The presence of phylum Bacteroidetes was significantly higher in COVID-19 patients compared with controls (23.9% vs. 12.8%; P < .001), as were Actinobacteria (26.1% vs. 19.0%; P < .001).
After controlling for antibiotics, the investigators found that “differences between cohorts were primarily linked to enrichment of taxa such as Parabacteroides, Sutterella wadsworthensis, and Bacteroides caccae and depletion of Adlercreutzia equolifaciens, Dorea formicigenerans, and Clostridium leptum in COVID-19 relative to non-COVID-19” (P < .05). In addition, Faecalibacterium prausnitzii and Bifidobacterium bifidum were negatively correlated with COVID-19 severity after investigators controlled for patient age and antibiotic use (P < .05).
The researchers also examined bacteria in COVID-19 patients and controls in the context of cytokines and other inflammatory markers. “We hypothesized that these compositional changes play a role in exacerbating disease by contributing to dysregulation of the immune response,” they said.
In fact, species depleted in COVID-19 patients including included B. adolescentis, E. rectale, and F. prausnitzii were negatively correlated with inflammatory markers including CXCL10, IL-10, TNF-alpha, and CCL2.
In addition, 42 stool samples from 27 patients showed significantly distinct gut microbiota from controls up to 30 days (median, 6 days) after virus clearance, regardless of antibiotics use (P < .05), the researchers said.
Long-term data needed
The study findings were limited by several factors, including the potential confounding of microbial signatures associated with COVID-19 because of heterogeneous patient management in the clinical setting and the potential that gut microbiota reflects a patient’s health with no impact on disease severity, as well as lack of data on the role of antibiotics for severe and critical patients, the researchers noted. In addition, “gut microbiota composition is highly heterogeneous across human populations and changes in compositions reported here may not necessarily be reflected in patients with COVID-19 from other biogeographies,” they wrote.
The “longer follow-up of patients with COVID-19 (e.g., 3 months to 1 year after clearing the virus) is needed to address questions related to the duration of gut microbiota dysbiosis post recovery, link between microbiota dysbiosis and long-term persistent symptoms, and whether the dysbiosis or enrichment/depletion of specific gut microorganisms predisposes recovered individuals to future health problems,” they wrote.
However, the results suggest a likely role for gut microorganisms in host inflammatory responses to COVID-19 infection, and “underscore an urgent need to understand the specific roles of gut microorganisms in human immune function and systemic inflammation,” they concluded.
More than infectious
“A growing body of evidence suggests that severity of illness from COVID-19 is largely determined by the patient’s aberrant immune response to the virus,” Jatin Roper, MD, of Duke University, Durham, N.C., said in an interview. “Therefore, a critical question is: What patient factors determine this immune response? The gut microbiota closely interact with the host immune system and are altered in many immunological diseases,” he said. “Furthermore, the SARS-CoV-2 virus infects enterocytes in the intestine and causes symptomatic gastrointestinal disease in a subset of patients. Therefore, understanding a possible association between gut microbiota and COVID-19 may reveal microbial species involved in disease pathogenesis,” he emphasized.
In the current study, “I was surprised to find that COVID-19 infection is associated with depletion of immunomodulatory gut bacteria,” said Dr. Roper. “An open question is whether these changes are caused by the SARS-CoV-2 virus and then result in altered immune response. Alternatively, the changes in gut microbiota may be a result of the immune response or other changes associated with the disease,” he said.
“COVID-19 is an immunological disease, not just an infectious disease,” explained Dr. Roper. “The gut microbiota may play an important role in the pathogenesis of the disease. Thus, specific gut microbes could one day be analyzed to risk stratify patients, or even modified to treat the disease,” he noted.
Beyond COVID-19
“Given the impact of the gut microbiota on health and disease, as well as the impact of diseases on the microbiota, I am not at all surprised to find that there were significant changes in the microbiota of COVID-19 patients and that these changes are associated with inflammatory cytokines, chemokines, and blood markers of tissue damage,” said Anthony Sung, MD, also of Duke University.
According to Dr. Sung, researchers have already been investigating possible connections between gut microbiota and other conditions such as Alzheimer’s disease, and it’s been hypothesized that these connections are mediated by interactions between the gut microbiota and the immune system.
“While this is an important paper in our understanding of COVID-19, and highlights the microbiome as a potential therapeutic target, we need to conduct clinical trials of microbiota-based interventions before we can fully realize the clinical implications of these findings,” he said.
The study was supported by the Health and Medical Research Fund, the Food and Health Bureau, The Government of the Hong Kong Special Administrative Region, and donations from Hui Hoy & Chow Sin Lan Charity Fund Limited, Pine and Crane Company Limited, Mr. Hui Ming, and The D.H. Chen Foundation. The researchers had no financial conflicts to disclose. Dr. Roper and Dr. Sung had no financial conflicts to disclose.
COVID-19 infection altered the gut microbiota of adult patients and caused depletion of several types of bacteria with known immunomodulatory properties, based on data from a cohort study of 100 patients with confirmed COVID-19 infections from two hospitals.
“As the GI tract is the largest immunological organ in the body and its resident microbiota are known to modulate host immune responses, we hypothesized that the gut microbiota is associated with host inflammatory immune responses in COVID19,” wrote Yun Kit Yeoh, PhD, of the Chinese University of Hong Kong, and colleagues.
In a study published in Gut, the researchers investigated patient microbiota by collecting blood, stool, and patient records between February and May 2020 from 100 confirmed SARS-CoV-2–infected patients in Hong Kong during hospitalization, as well as follow-up stool samples from 27 patients up to 30 days after they cleared the COVID-19 virus; these observations were compared with 78 non–COVID-19 controls.
Overall, 274 stool samples were sequenced. Samples collected from patients during hospitalization for COVID-19 were compared with non–COVID-19 controls. The presence of phylum Bacteroidetes was significantly higher in COVID-19 patients compared with controls (23.9% vs. 12.8%; P < .001), as were Actinobacteria (26.1% vs. 19.0%; P < .001).
After controlling for antibiotics, the investigators found that “differences between cohorts were primarily linked to enrichment of taxa such as Parabacteroides, Sutterella wadsworthensis, and Bacteroides caccae and depletion of Adlercreutzia equolifaciens, Dorea formicigenerans, and Clostridium leptum in COVID-19 relative to non-COVID-19” (P < .05). In addition, Faecalibacterium prausnitzii and Bifidobacterium bifidum were negatively correlated with COVID-19 severity after investigators controlled for patient age and antibiotic use (P < .05).
The researchers also examined bacteria in COVID-19 patients and controls in the context of cytokines and other inflammatory markers. “We hypothesized that these compositional changes play a role in exacerbating disease by contributing to dysregulation of the immune response,” they said.
In fact, species depleted in COVID-19 patients including included B. adolescentis, E. rectale, and F. prausnitzii were negatively correlated with inflammatory markers including CXCL10, IL-10, TNF-alpha, and CCL2.
In addition, 42 stool samples from 27 patients showed significantly distinct gut microbiota from controls up to 30 days (median, 6 days) after virus clearance, regardless of antibiotics use (P < .05), the researchers said.
Long-term data needed
The study findings were limited by several factors, including the potential confounding of microbial signatures associated with COVID-19 because of heterogeneous patient management in the clinical setting and the potential that gut microbiota reflects a patient’s health with no impact on disease severity, as well as lack of data on the role of antibiotics for severe and critical patients, the researchers noted. In addition, “gut microbiota composition is highly heterogeneous across human populations and changes in compositions reported here may not necessarily be reflected in patients with COVID-19 from other biogeographies,” they wrote.
The “longer follow-up of patients with COVID-19 (e.g., 3 months to 1 year after clearing the virus) is needed to address questions related to the duration of gut microbiota dysbiosis post recovery, link between microbiota dysbiosis and long-term persistent symptoms, and whether the dysbiosis or enrichment/depletion of specific gut microorganisms predisposes recovered individuals to future health problems,” they wrote.
However, the results suggest a likely role for gut microorganisms in host inflammatory responses to COVID-19 infection, and “underscore an urgent need to understand the specific roles of gut microorganisms in human immune function and systemic inflammation,” they concluded.
More than infectious
“A growing body of evidence suggests that severity of illness from COVID-19 is largely determined by the patient’s aberrant immune response to the virus,” Jatin Roper, MD, of Duke University, Durham, N.C., said in an interview. “Therefore, a critical question is: What patient factors determine this immune response? The gut microbiota closely interact with the host immune system and are altered in many immunological diseases,” he said. “Furthermore, the SARS-CoV-2 virus infects enterocytes in the intestine and causes symptomatic gastrointestinal disease in a subset of patients. Therefore, understanding a possible association between gut microbiota and COVID-19 may reveal microbial species involved in disease pathogenesis,” he emphasized.
In the current study, “I was surprised to find that COVID-19 infection is associated with depletion of immunomodulatory gut bacteria,” said Dr. Roper. “An open question is whether these changes are caused by the SARS-CoV-2 virus and then result in altered immune response. Alternatively, the changes in gut microbiota may be a result of the immune response or other changes associated with the disease,” he said.
“COVID-19 is an immunological disease, not just an infectious disease,” explained Dr. Roper. “The gut microbiota may play an important role in the pathogenesis of the disease. Thus, specific gut microbes could one day be analyzed to risk stratify patients, or even modified to treat the disease,” he noted.
Beyond COVID-19
“Given the impact of the gut microbiota on health and disease, as well as the impact of diseases on the microbiota, I am not at all surprised to find that there were significant changes in the microbiota of COVID-19 patients and that these changes are associated with inflammatory cytokines, chemokines, and blood markers of tissue damage,” said Anthony Sung, MD, also of Duke University.
According to Dr. Sung, researchers have already been investigating possible connections between gut microbiota and other conditions such as Alzheimer’s disease, and it’s been hypothesized that these connections are mediated by interactions between the gut microbiota and the immune system.
“While this is an important paper in our understanding of COVID-19, and highlights the microbiome as a potential therapeutic target, we need to conduct clinical trials of microbiota-based interventions before we can fully realize the clinical implications of these findings,” he said.
The study was supported by the Health and Medical Research Fund, the Food and Health Bureau, The Government of the Hong Kong Special Administrative Region, and donations from Hui Hoy & Chow Sin Lan Charity Fund Limited, Pine and Crane Company Limited, Mr. Hui Ming, and The D.H. Chen Foundation. The researchers had no financial conflicts to disclose. Dr. Roper and Dr. Sung had no financial conflicts to disclose.
FROM GUT