Alterations of the Gut Microbiota in Patients With Coronavirus Disease 2019 or H1N1 Influenza

Abstract

Background Coronavirus disease 2019 (COVID-19) is an emerging serious global health problem. Gastrointestinal symptoms are common in COVID-19 patients, and severe acute respiratory syndrome coronavirus 2 RNA has been detected in stool specimens. However, the relationship between the gut microbiome and disease remains to be established. Methods We conducted a cross-sectional study of 30 patients with COVID-19, 24 patients with influenza A(H1N1), and 30 matched healthy controls (HCs) to identify differences in the gut microbiota by 16S ribosomal RNA gene V3–V4 region sequencing. Results Compared with HCs, COVID-19 patients had significantly reduced bacterial diversity; a significantly higher relative abundance of opportunistic pathogens, such as Streptococcus, Rothia, Veillonella, and Actinomyces; and a lower relative abundance of beneficial symbionts. Five biomarkers showed high accuracy for distinguishing COVID-19 patients from HCs with an area under the curve (AUC) up to 0.89. Patients with H1N1 displayed lower diversity and different overall microbial composition compared with COVID-19 patients. Seven biomarkers were selected to distinguish the 2 cohorts (AUC = 0.94). Conclusions The gut microbial signature of patients with COVID-19 was different from that of H1N1 patients and HCs. Our study suggests the potential value of the gut microbiota as a diagnostic biomarker and therapeutic target for COVID-19, but further validation is needed.

<p>Dynamic Interplay Between Microbiota and Mucosal Immunity in Early Shaping of Asthma and its Implication for the COVID-19 Pandemic</p>

“…130,131 In this regard, COVID-19 patients exhibit reduced bacterial diversity in the gut and reduction of healthy symbionts, in addition to an increase in the abundance of pathogenic Streptococcus, Rothia, Veillonella, and Actinomyces. 132 Consistent with this report, the gut microbiome of COVID-19 patients was documented with an enrichment of opportunistic bacteria (Clostridium, Actinomyces, and Bacteroides) and fungi (Candida albicans, Candida auris, and Aspergillus flavus) and depletion of beneficial commensals, such as Eubacterium, Faecalibacterium prausnitzii, and Lachnospiraceae. 133 More importantly, the severity of the symptoms related to COVID-19 was linked to an expansion of pathogenic Clostridium and reduction of Alistipes and Bacteroides commensals.…”

Gut Microbiota Dysbiosis–Immune Hyperresponse–Inflammation Triad in Coronavirus Disease 2019 (COVID-19): Impact of Pharmacological and Nutraceutical Approaches

“…Even though SARS-CoV-2 fecal-oral transmission is still an open debate, accumulating evidence points to GIT as a battleground for continual viral replication as ACE-2 receptors are highly expressed in the intestinal epithelium [ 43 , 44 ]. Accordingly, high-throughput 16S rRNA gene and shotgun MGS analyses have shown significant alterations in the gut bacteriome of hospitalized COVID-19 patients, characterized by a significant decrease in GM diversity, depletion of beneficial bacterial symbionts, and enrichment of opportunistic pathogens (e.g., Streptococcus, Rothia, Actinomyces), which may correlate with the gastrointestinal complaints (e.g., abdominal pain, nausea, vomiting, diarrhoea) of the acute phase of the infection [ 22 , 23 ]. Interestingly, these symptoms often occur in the onset of the infection and may precede respiratory complaints [ 45 , 46 , 47 ].…”

“…Interestingly, these symptoms often occur in the onset of the infection and may precede respiratory complaints [ 45 , 46 , 47 ]. Taking into account that ACE2 is able to regulate nutrient absorption and intestinal inflammation, it is currently postulated that enteric SARS-COV-2 infection and ACE2 imbalance may cause the gastroenteritis-like symptoms, intestinal homeostasis disruption, and GM dysbiosis observed in COVID-19 patients [ 22 , 47 , 48 ]. Likewise, several clinical trials are ongoing aiming to deeply characterize GM composition in COVID-19 patients and evaluate the putative crosstalk between GM and the disease outcome, as summarized in Table 1 .…”

“…Apart from relevant metabolic functions for the host homeostasis, GM exerts protective actions against pathogenic colonization of bacteria and virus, which could be at least partially attributed to their role in educating and strengthening the immune system [ 21 ]. There is evidence that SARS-CoV-2-infected individuals present deregulated GM [ 22 , 23 ], which might contribute to the poor outcomes in COVID-19 patients with pre-existing diseases influenced by GM dysbiosis, namely, cardiovascular, metabolic, and renal disorders. In this sense, therapeutic and nutraceutical interventions able to promote microbiota symbiosis, reinforce the immune system, and exert anti-inflammatory actions could be potentially useful.…”

Serological Determinants of COVID-19

“…Recently, the alteration of the intestinal microbiota has been described in patients with COVID-19, as occurs in chronic non-communicable diseases (CNCDs) 25,26 . In the future, the possible understanding of the mechanisms underlying the alterations of the intestinal microbiota following SARS-CoV-2 infection could represent a new diagnostic biomarker and therapeutic target for the ght against COVID-19.…”