Neuropsychiatric Ramifications of COVID-19: Short-Chain Fatty Acid Deficiency and Disturbance of Microbiota-Gut-Brain Axis Signaling

Figure 1

Brain impact of lung vs. gut ACE-2 deficiency. Lung ACE-2 deficiency increases local inflammation by upregulating ACE-2/DABK/BKB1R and downregulating ACE-2/Ang2/Ang-(1-7)/Mas axis; increased lung inflammation results in lung injury and exerts a hypoxic effect on the brain. Gut ACE-2 deficiency upregulates ACE-2/DABK/BKB1R and downregulates ACE-2/Ang2/Ang-(1-7)/Mas axis but also downregulates the formation of ACE-2/B⁰AT1 complexes and intestinal uptake of neutral amino acids such as glutamine and tryptophan, critical to T-cell functions. ACE-2 deficiency in the gut contributes to gut dysbiosis, inflammation, increased permeability of the gut-blood barrier, and systemic inflammation that impacts the brain.