Diagnostic, Prognostic, and Therapeutic Roles of Gut Microbiota in COVID-19: A Comprehensive Systematic Review

Abstract

IntroductionThe Coronavirus Disease 2019 (COVID-19) pandemic caused by Severe Acute Respiratory Coronavirus 2 (SARS-CoV-2) emerged in late December 2019. Considering the important role of gut microbiota in maturation, regulation, and induction of the immune system and subsequent inflammatory processes, it seems that evaluating the composition of gut microbiota in COVID-19 patients compared with healthy individuals may have potential value as a diagnostic and/or prognostic biomarker for the disease. Also, therapeutic interventions affecting gut microbial flora may open new horizons in the treatment of COVID-19 patients and accelerating their recovery.MethodsA systematic search was conducted for relevant studies published from December 2019 to December 2021 using Pubmed/Medline, Embase, and Scopus. Articles containing the following keywords in titles or abstracts were selected: “SARS-CoV-2” or “COVID-19” or “Coronavirus Disease 19” and “gastrointestinal microbes” or “dysbiosis” or “gut microbiota” or “gut bacteria” or “gut microbes” or “gastrointestinal microbiota”.ResultsOut of 1,668 studies, 22 articles fulfilled the inclusion criteria and a total of 1,255 confirmed COVID-19 patients were examined. All included studies showed a significant association between COVID-19 and gut microbiota dysbiosis. The most alteration in bacterial composition of COVID-19 patients was depletion in genera Ruminococcus, Alistipes, Eubacterium, Bifidobacterium, Faecalibacterium, Roseburia, Fusicathenibacter, and Blautia and enrichment of Eggerthella, Bacteroides, Actinomyces, Clostridium, Streptococcus, Rothia, and Collinsella. Also, some gut microbiome alterations were associated with COVID-19 severity and poor prognosis including the increment of Bacteroides, Parabacteroides, Clostridium, Bifidobacterium, Ruminococcus, Campylobacter, Rothia, Corynebacterium, Megasphaera, Enterococcus, and Aspergillus spp. and the decrement of Roseburia, Eubacterium, Lachnospira, Faecalibacterium, and the Firmicutes/Bacteroidetes ratio.ConclusionOur study showed a significant change of gut microbiome composition in COVID-19 patients compared with healthy individuals. This great extent of impact has proposed the gut microbiota as a potential diagnostic, prognostic, and therapeutic strategy for COVID-19. There is much evidence about this issue, and it is expected to be increased in near future.

Long COVID and its Management

“…Increase in viral-induced cytokines may compromise intestinal integrity, facilitating the entry of bacteria and metabolites into circulation. Such dysbiosis triggers the innate immune responses, causing pulmonary dysfunction and secondary infections [77]. Furthermore, integrative multi-omics profiling reveals that subjects with GI complications exhibit unique T cell signature during COVID-19 recovery [20].…”

Gastrointestinal Involvement in SARS-CoV-2 Infection

“…Fecal calprotectin levels were elevated in patients infected with SARS-CoV-2, confirming that SARS-CoV-2 causes intestinal inflammation [83]. A recent comprehensive systematic review confirmed that the most common alteration in the bacterial composition of patients with COVID-19 was a depletion in the genera Ruminococcus, Alistipes, Eubacterium, Bifidobacterium, Faecalibacterium, Roseburia, Fusicathenibacter, and Blautia, as well as the enrichment of Eggerthella, Bacteroides, Actinomyces, Clostridium, Streptococcus, Rothia, and Collinsella [84]. Changes to the gut microbiome composition and function affect the respiratory tract through the common mucosal immune system, and respiratory dysbiosis also affects the digestive tract through immune regulation [85].…”

“…Viruses 2022, 14, x FOR PEER REVIEW 7 of 17 function affect the respiratory tract through the common mucosal immune system, and respiratory dysbiosis also affects the digestive tract through immune regulation [85]. Alterations in the gut microbiome are associated with severity and poor prognosis in patients with COVID-19, such as increases in Bacteroides, Parabacteria, Clostridium, Bifidobacterium, Ruminococcus, Campylobacter, Rotella, Corynebacterium Pseudomonas, Megacoccus, Enterococcus, and Aspergillus, as well as reductions in Roseburia, Eubacterium, Lachnospira, Faecalibacterium, and Firmicutes/Bacteroidetes ratios [84]. The fungal gut microbiota of patients with severe/critical COVID-19 was characterized by decreased diversity, richness, and evenness, and increased relative abundance of Ascomycota phylum compared with non-severe COVID-19 [86].…”

Gut microbiota and COVID-19: A systematic review

“…Similarly, there is evidence that altered gut microbiota composition has a crucial role in the severity and virulence of bacterial and viral infections [96]. Many studies have reported gut dysbiosis among COVID-19 patients and noted that it would be a major contributor to poor outcomes [97].…”

“…Finally, it was reported by Zuo et al that Coprobacilum spp., Clostridium Ramosum, and Clostridium hathewayi were associated with more severe diseases [20]. One similar systematic review stated that Bi dobacterium, Bacteroides, Corynebacterium, Ruminococcus, Parabacteroides, Campylobacter, Clostridium, Ruminococcus, Rothia, Enterococcus, Megasphaera, Enterococcus, and Aspergillus had high abundance among severe COVID-19 patients while, Lachnospira, Roseburia, Faecalibacterium, Eubacterium, and Firmicutes/Bacteroidetes ratio had declined among severe COVID-19 cases [97]. Other similar studies also have noted the higher abundancy of opportunistic pathogens including; Veilonella, Streptococcus, Rothia, and Actinomyces [20,88], and declining levels of bene cial commensal bacteria such asRoseburia, Agathobacter, Fusicatenibacter, and Ruminococcaceae among moderate to severe COVID-19 patients [20].…”