Substantial alteration in gut microbiome observed in children with with MIS-C and COVID

A team of scientists from Turkey has recently evaluated the diversity and composition of gut microbiota in children diagnosed with multisystem inflammatory syndrome (MIS-C) and acute coronavirus disease 2019 (COVID-19). They have observed significant alteration in the gut microbiota composition in children with MIS-C. These changes are associated with autoimmunity, metabolic dysfunction, and obesity. The study is currently available on the Research Square* preprint server while under consideration at the European Journal of Pediatrics.

Study: Intestinal Microbiota Composition of Children with Infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) and Multisystem Inflammatory Syndrome (MIS-C)​​​​​​​. Image Credit: Design_Cells / Shutterstock


Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative pathogen of the COVID-19 pandemic, has been found to cause severe infection in older people and those with pre-existing health conditions. However, the prevalence of severe COVID-19 remained significantly low in children throughout the pandemic.

In some children with COVID-19, the incidence of multisystem inflammatory syndrome in children (MIS-C) has been observed as post-COVID complications. There is evidence suggesting that MIS-C may develop in children as a consequence of aberrant inflammatory response and dysregulated immune response to SARS-CoV-2 infection.

Respiratory and gastrointestinal infections are known to alter the composition and diversity of the gut microbiota. Changes in gut microbiota composition have been observed in COVID-19 patients at the time of diagnosis and during the disease course. Studies have suggested that these changes may play vital roles in COVID-19 pathogenesis, disease progression, and post-COVID complications.      

In the current study, the scientists have evaluated the changes in gut microbiota composition and diversity in children diagnosed with MIS-C and COVID-19.

Study design

The study was conducted on children aged 3 to 14 years. In the study cohort, 25 children were diagnosed with MIS-C, and 20 children were diagnosed with COVID-19. Fecal samples were collected from the children to assess the composition and diversity of gut microbiota. The findings were compared with that obtained from 19 healthy children who served as study controls.

Important observations

The diagnosis of COVID-19 was conducted by polymerase chain reaction (PCR)-based method in almost all children. Rapid antigen testing was conducted in only one child. Among children with MIS-C, 24% were detected with SARS-CoV-2 infection, 52% were positive for anti-SARS-CoV-2 IgG antibodies, and 28% were positive for both IgG and IgM specific anti-SARS-CoV-2 antibodies.

Fever was the most commonly reported symptom among children with COVID-19, followed by cough, diarrhea, tachypnea, runny nose, myalgia, headache, and abdominal pain. In some children, conjunctivitis, respiratory, and neurological symptoms were also detected.

The majority of enrolled children showed involvement of multiple physiological systems. The most commonly involved systems were the hematologic and gastrointestinal systems, followed by cardiovascular, dermatological, respiratory, and neurological.

Regarding routine laboratory findings, increased serum levels of C-reactive protein, fibrinogen, and D-dimer were observed in most of the children with MIS-C. In addition, some children had reduced level of lymphocytes and increased level of ferritin, brain natriuretic peptide, interleukin 6 (IL-6), procalcitonin, lactate dehydrogenase, and neutrophils.

Alteration in gut microbiota

The Shannon Index was calculated to assess the richness and uniformity of the microbial population in the studied samples. A significantly higher Shannon Index was observed in MIS-C affected children compared to that in SARS-CoV-2-infected and healthy children.

At the phylum level, an abundance of Bacteroidetes (Gram-negative anaerobic bacteria) was observed in children with MIS-C compared to COVID-19 affected children and healthy children. In contrast, an abundance of Firmicutes (Gram-positive bacteria) was noted in healthy children.

At the genera level, a significantly higher Bacteroides, Eggerthella, and Clostridium genera was observed in children with MIS-C compared to that in SARS-CoV-2-infected and healthy children. At the species level, an abundance of Faecalibacterium prausnitzii, Gemmiger formicilis, Ruminococcus bromii, Bifidobacterium adolescentis, Lactobacillus ruminis, Butyricicoccus pullicaerocum, Collinsella aerofaciens, Ruminococcus callidledikans, and Dorea formicians was observed in healthy children compared to that in children with MIS-C. In children with MIS-C, Bacteroides uniformis, Bacteroides plebeius, Clostridium ramosum, Eubacterium dolichum, Eggerthella lenta, Bacillus thermoamylovorans, Prevotella tannerae, and Bacteroides coprophilus were the most abundant species. In children with COVID-19, Bacteroides coprophilus, Bifidobacterium adolescentis, Dorea formicigenerans, Ruminococcus albus, and Clostridium piliforme were the most abundant species.      

Study significance

The study indicates considerable changes in gut microbiota diversity and composition in children with MIS-C. A reduction in Faecalibacterium prausnitzii abundance in children with MIS-C and COVID-19 highlights the occurrence of gastrointestinal inflammation. Faecalibacterium prausnitzii, a vital member of the gut microbiota, is known to have immune-boosting and anti-inflammatory properties. In addition, an induction in Eggerthella lenta and Eubacterium dolichum abundance in MIS-C affected children indicates the possibility of autoimmune reactions and metabolic dysfunctions, respectively.   

As suggested by the scientists, the alteration in gut microbiota composition observed in children with MIS-C might affect their immune, gastrointestinal, and metabolic systems and the brain – intestinal axis during the disease course and in adulthood.

*Important notice

Research Square publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
  • Suskun C. 2022. Intestinal Microbiota Composition of Children with Infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) and Multisystem Inflammatory Syndrome (MIS-C). Research Square preprint server.