MicrobiotaMi Comment 20_21  by Roberto Ferrarese

Related Journal Article:  Temporal association between human upper respiratory and gut bacterial microbiomes during the course of COVID-19 in adults

Commun Biol. 2021 Feb 18;4(1):240. doi: 10.1038/s42003-021-01796-w. PMID: 33603076 Free PMC article.

Association between respiratory and gut microbiomes in SARS-CoV-2 infected patients

As we sadly know, SARS-CoV-2 virus has led to a devastating global pandemic during the past year. It has been already observed that in COVID-19 patients was present a dysbiosis that led to an enrichment of opportunistic pathogens and a depletion of beneficial bacteria. However, alterations in the respiratory microbiome of COVID-19 patients have not been evaluated yet, neither if there is any association between respiratory and gut microbiota during the development of the disease. In this manuscript, Xu and colleagues performed a longitudinal analysis on throat and anal swabs from 35 adult COVID-19 patients, 19 healthy adult controls and 10 non-COVID-19 patients with other diseases by sequencing the V4 region of bacterial 16S rRNA gene.  First, they observed that respiratory and gut microbiota of COVID-19 patients can be characterized by four and three community types respectively, and these types possibly reflect different levels from physiological microbiota to dysbiotic microbiota. In the respiratory microbiota of COVID-19 patients, they observed a decrease in alpha diversity from community type I to type IV and a significantly lower richness and evenness in community types III and IV compared to the microbiome of healthy subjects. Community type I was characterized by Alloprevotella; type II by Porphyromonas, Neisseria, Fusobacterium and unclassified Bacteroidales; type III by Pseudomonas; type IV by Rothia, Saccharibacteria and unclassified Actinomycetales. Similar to what was observed in the respiratory tract, gut microbial communities of COVID-19 patients had a decrease in richness and evenness from type I to type III. Type I microbiota was characterized by healthy gut genera (Bacteroides and butyrate-producing bacteria) and Finegoldia, an opportunistic pathogenic bacterium; type II was characterized mainly by pathogenic or opportunistic pathogenic bacteria, like Neisseria and Actinomyces; type III was dominated by Pseudomonas, implying a severe dysbiosis.

Secondly, the authors observed that the shift of microbiome community types over time appeared to match between the throat and the gut, indicating a close association between these two anatomical sites, possibly via the “airway-gut axis”. In particular, four indicator bacteria genera in throat microbiome (Porphyromonas, Neisseria, Fusobacterium and Pseudomonas) were identified as indicators of gut microbial community types II and III in COVID-19 patients: the presence of these oropharyngeal bacteria in the gut suggested that a crosstalk between the respiratory and gut microbiomes occurred by bacterial translocation during the early stage of the disease. According to the authors, several possible mechanisms could explain the translocation: 1) inflammation induced by SARS-CoV-2 infection damaged the mucosal tissues and increased mucosal permeability of the airway, lung and gut; 2) bacteria migrated from the oropharyngeal site to the gut via swallowing and passage through the gastrointestinal tract; 3) immune responses induced by infection applied similar selective pressures on both microbiota.

In conclusion, the authors revealed an association between the upper respiratory and gut microbiota during COVID-19 disease progression and observed simultaneous changes of both microbiota from early dysbiosis to later more diversified status. Moreover, they observed that some indicator bacteria, like opportunistic or beneficial bacteria, could be potentially crucial biomarkers for clinical treatment decision and prognostic evaluation. In particular, precision intervention and modulation of the respiratory and gut microbiota may offer novel therapeutic alternatives like personalized antibiotics therapy, to inhibit opportunistic pathogenic bacteria, or the use of probiotic, prebiotic or symbiotic to modulate both microbiota in order to facilitate the recovery from COVID-19 disease.

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