The triangle relationship between human genome, gut microbiome, and COVID-19: opening of a Pandora's box

Since the pandemic started, the coronavirus disease 2019 (COVID-19) has spread worldwide. In patients with COVID-19, the gut microbiome (GM) has been supposed to be closely related to the progress of the disease. The gut microbiota composition and human genetic variation are also connected in COVID-19 patients, assuming a triangular relationship between the genome, GM, and COVID-19. Here, we reviewed the recent developments in the study of the relationship between gut microbiota and COVID-19. The keywords "COVID-19," "microbiome," and "genome" were used to search the literature in the PubMed database. We first found that the composition of the GM in COVID-19 patients varies according to the severity of the illness. Most obviously, Candida albicans abnormally increased while the probiotic Bifidobacterium decreased in severe cases of COVID-19. Interestingly, clinical studies have consistently emphasized that the family Lachnospiraceae plays a critical role in patients with COVID-19. Additionally, we have demonstrated the impact of microbiome-related genes on COVID-19. Specially, we focused on angiotensin-converting enzyme 2's dual functions in SARS-CoV-2 infection and gut microbiota alternation. In summary, these studies showed that the diversity of GMs is closely connected to COVID-19. A triangular relationship exists between COVID-19, the human genome, and the gut flora, suggesting that human genetic variations may offer a chance for a precise diagnosis of COVID-19, and the important relationships between genetic makeup and microbiome regulation may affect the therapy of COVID-19.