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Therapeutic implications of SARS-CoV-2 dysregulation of the gutbrain-lung axis

World Journal of Gastroenterology 2021年第29期27卷 4763-4783页

作者： Samuel D Johnson Omalla A Olwenyi Namita Bhyravbhatla Michellie Thurman Kabita Pandey Elizabeth A Klug Morgan Johnston Shetty Ravi Dyavar arpan acharya Anthony T Podany Courtney V Fletcher Mahesh Mohan Kamal Singh Siddappa N Byrareddy Department of Pathology and Microbiology University of Nebraska Medical CenterOmahaNE 68198United States Department of Pharmacology and Experimental Neuroscience University of Nebraska Medical CenterOmahaNE 68198United States Antiviral Pharmacology Laboratory University of Nebraska Medical Center(UNMC)Center for Drug DiscoveryOmahaNE 68198United States Southwest National Primate Research Center Texas Biomedical Research InstituteSan AntonioTX 78227United States Department of Molecular Microbiology and Immunology and Bond Life Sciences Center University of MissouriColumbiaMO 65212United States Department of Genetics Cell Biology and AnatomyUniversity of Nebraska Medical CenterOmahaNE 68198United States Department of Biochemistry and Molecular Biology University of Nebraska Medical CenterOmahaNE 68198United States

The emergence and rapid spread of novel severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has caused over 180 million confirmed cases resulting in over 4 million deaths worldwide with no clear end in sight for the coronavirus disease 19(COVID-19)*** SARS-CoV-2 exposed individuals experience mild to moderate symptoms,including fever,cough,fatigue,and loss of smell and ***,many individuals develop pneumonia,acute respiratory distress syndrome,septic shock,and multiorgan *** addition to these primarily respiratory symptoms,SARS-CoV-2 can also infiltrate the central nervous system,which may damage the blood-brain barrier and the neuron's *** inflammation and neurodegeneration in the brain stem can further prevent efferent signaling to cranial nerves,leading to the loss of anti-inflammatory signaling and normal respiratory and gastrointestinal ***,SARS-CoV-2 can infect enterocytes resulting in gut damage followed by microbial dysbiosis and translocation of bacteria and their byproducts across the damaged epithelial *** a result,this exacerbates pro-inflammatory responses both locally and systemically,resulting in impaired clinical *** evidence has highlighted the complex interactions that mutually modulate respiratory,neurological,and gastrointestinal *** this review,we discuss the ways SARS-CoV-2 potentially disrupts the gut-brain-lung *** further highlight targeting specific responses to SARS-CoV-2 for the development of novel,urgently needed therapeutic ***,we propose a prospective related to the individuals from Low-and Middle-Income ***,the underlying propensity for heightened gut damage/microbial translocation is likely to result in worse clinical outcomes during this COVID-19 pandemic.

关键词： SARS-CoV-2 Gut Microbiome Lungs Brain Therapeutics

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