Editors' ChoiceSepsis

Bacteria make their way to the brain

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Science Translational Medicine  17 Jan 2018:
Vol. 10, Issue 424, eaar7515
DOI: 10.1126/scitranslmed.aar7515

Abstract

Diverse bacterial species can be detected in the brains of mice with abdominal sepsis.

Sepsis is a serious condition that necessitates immediate empiric antibiotics and supportive care. Altered mental status can occur during sepsis, but it is not clear whether this is related to the infection itself or the resulting immune response. Singer et al. investigated whether sepsis could create conditions where bacteria other than the sepsis-causing infection could enter the brain.

The authors used a cecal ligation and puncture method during laparotomy to induce sepsis in mouse models. Bacterial taxa in brains of animals surviving sepsis and the sham surgery group were compared quantitatively by sequencing the 16S ribosomal RNA–encoding gene, selected because it is conserved in different bacterial taxa. Twenty-four hours after the surgery, there were more bacterial taxa in brains from the sepsis group, with predominance of Bacteroidales by day 5. The Bacteroidales were confirmed by their presence in anaerobic culture of brain lysates. However, at the 2-week and 8-week time points, the bacterial communities were not significantly different between groups. There were no documented cases of bacteremia in the septic mice, so the authors concluded that these bacteria had disseminated to the brain without being the causative agent of sepsis.

The authors then compared bacterial populations in the brains of people who died from sepsis compared with other causes. Of note, six of the nine patients with sepsis had underlying disease of the central nervous system (CNS) recorded, compared with two of the six people without sepsis. Additionally, an important difference between the mouse model and the human patients is that the mice all had an abdominal, presumably polymicrobial, source of sepsis, whereas the human brains were from a mix of patients with pulmonary, abdominal, and urinary tract sources of infection. Furthermore, the mice examined in this study were sepsis survivors, whereas the human brains were all from people who had succumbed to sepsis. There was increased bacterial diversity in the brains of people who died from sepsis, but the taxa were different than in the mouse model. Thus, it is too early to draw firm conclusions about bacterial causes of brain dysfunction in human sepsis, but this study raises intriguing questions about the immune response during sepsis and how an activated immune response could be amplified by organisms other than the infection inciting sepsis itself.

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