Accurate Classification of the Gut Microbiota of Patients in Intensive Care Units During the Development of Sepsis and Septic Shock

The gut microbiota of intensive care unit (ICU) patients display extreme dysbiosis, which is associated with increased susceptibility to organ failure, sepsis and septic shock. However, this dysbiosis is hard to be characterized for each patient, owing to the highly dimensional complexity of gut microbiota. We thus tested whether the concept of enterotype can be applied to the gut microbiota of ICU patients, to describe the dysbiosis. We collected 131 fecal samples from a cohort of 64 ICU patients diagnosed with sepsis or septic shock, using 16S rRNA gene sequencing to dissect their gut microbiota compositions. We find that during the development of sepsis or septic shock, as well as various medical treatments, ICU patients always contain two patterns of dysbiotic microbiota named as ICU-enterotypes, which cannot be explained by the individual host properties such as age, gender and body mass index, as well as external stressors such as infection sites and antibiotic use. ICU-enterotype I comprised predominantly Bacteroides and an unclassified genus of family Enterobacteriaceae, while ICU-enterotype II comprised predominantly Enterococcus. Among more critically ill patients with acute physiology and chronic health evaluation (APACHE) II score > 18, samples of septic shock were more likely to present with ICU-enterotype I (p = 0.041). Additionally, ICU-enterotype I was correlated with high serum lactate level (p = 0.007). Therefore, different patterns of dysbiosis are correlated with different clinical outcomes, suggesting that the diagnosis of ICU-enterotypes as an independent clinical index is crucial. For this purpose, the microbial-based human index (MHI) classifier we proposed shows high precision and effectiveness in timely monitoring of ICU-enterotypes of an individual patient. Together, our work serves as the first step toward precision medicine for septic patients based on the gut microbiota profile.