Gastrointestinal symptoms associated with COVID-19: impact on the gut microbiome

Abstract

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the greatest worldwide pandemic since the 1918 flu. The consequences of the coronavirus disease 2019 (COVID-19) are devastating and represent the current major public health issue across the globe. At the onset, SARS-CoV-2 primarily attacks the respiratory system as it represents the main point of entry in the host, but it also can affect multiple organs. Although most of the patients do not present symptoms or are mildly symptomatic, some people infected with SARS-CoV-2 that experience more severe multiorgan dysfunction. The severity of COVID-19 is typically combined with a set of comorbidities such as hypertension, diabetes, obesity, and/or advanced age that seriously exacerbates the consequences of the infection. Also, SARS-CoV-2 can cause gastrointestinal symptoms, such as vomiting, diarrhea, or abdominal pain during the early phases of the disease. Intestinal dysfunction induces changes in intestinal microbes, and an increase in inflammatory cytokines. Thus, diagnosing gastrointestinal symptoms that precede respiratory problems during COVID-19 may be necessary for improved early detection and treatment. Uncovering the composition of the microbiota and its metabolic products in the context of COVID-19 can help determine novel biomarkers of the disease and help identify new therapeutic targets. Elucidating changes to the microbiome as reliable biomarkers in the context of COVID-19 represent an overlooked piece of the disease puzzle and requires further investigation.

Fig 1

Illustrative model of SARS-CoV-2 infection and its association with the lung-gut-brain axis and microbiome dysbiosis. Angiotensin-Converting Enzyme II (ACE2) and transmembrane serine protease 2 (TMPRSS2) are expressed multiple human host tissues, including the esophagus, lungs, liver, kidneys, brain, colon, or small intestine epithelium. SARS-CoV-2 activates intestinal ACE2 receptors, induces inflammation (enteritis), and, ultimately, diarrhea. These tissues are the targets of SARS-CoV-2, which goes through an early phase of infection where a high viral load induces intestinal problems. At the same time, the microbiome dysbiosis takes place by altering the T and B cells of the intestinal immune system, as well as the activation of the enteric system that sends inflammatory signals to the circulatory current or other organs, including the brain. In the second phase of COVID-19 or a continuous phase where acute respiratory distress syndrome (ARDS) appears, the intestinal symptoms decrease, but the inflammation from the cytokines storm increases considerably. Created with Biorender.com