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Neurological Disorder after Severe Pneumonia is Associated with Translocation of Bacteria from Lung to Brain

Ma, Q.; Yao, C.; Wu, Y.; Wang, H.; Fan, Q.; Yang, Q.; Xu, J.; Dai, H.; Zhang, Y.; Xu, F.; Lu, T.; Wang, C.

2022-12-31 neuroscience
10.1101/2022.12.30.522351 bioRxiv
Show abstract

The neurological disorder is a common feature in patients who recovered from severe acute pneumonia. However, the underline mechanisms remain not very clear. Here we show that these neurological syndromes after severe acute pneumonia are partly attributed to the translocation of bacteria from the lung to the brain during pneumonia. We detected an emerging and increased bacteria in the brain tissue of mice with lipopolysaccharide-induced experimental severe pneumonia. Interestingly, using 16S rDNA amplification sequencing, similarities were found between the brains flora species and those of the lungs, indicating the bacteria in the brain may originate from the lung. We also observed the impairment of the lung-blood barrier and brain-blood barrier, simultaneously, allowing lung bacteria invade the brain during pneumonia. An elevated microglia and astrocytes activation signature through bacterial infection-related pathways is observed by single-cell RNA sequencing, indicating a bacteria-induced disruption of brain homeostasis. Rapamycin delivered by platelet-derived extracellular vesicles provides an effective strategy to rescue the dysfunction of microglia and astrocytes, and relief neurological disorders. Collectively, we identify lung bacteria that play a role in altering brain homeostasis, which provides new insight into the mechanism of neurological syndromes after severe pneumonia.

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