Critically sick patients are physiologically unstable, and recent research suggested that the intestinal microbiota might play a role in their health decrease while in the ICU. A study aimed to examine the intestinal microbiota in critically sick patients with and without sepsis and see how it affects outcomes including medical problems, ICU stays length, and mortality was conducted. A multi-center study included 250 peri-rectal swabs taken from 155 patients throughout admission and ICU stays. The V3-V4 hypervariable regions of the 16S rRNA gene were sequenced to examine the intestinal microbiota. To discover confounders and limit the effect of confounding factors, linear mixed models were employed to combine microbiota data with more than 40 clinical and demographic variables. Microbes closely related to inflammation, such as Parabacteroides, Fusobacterium, and Bilophila species, were shown to be more abundant in the microbiota of ICU patients with sepsis. Female sex and aging would be associated with a higher risk of sepsis, probably due to differences in their microbiome. During the ICU stay, the researchers also saw a significant reduction in microbial diversity. Moreover, the researchers discovered that the prevalence of pathogenic species, such as Enterococcus spp., was differently elevated in sepsis patients who died, suggesting that these species could be used as biomarkers for monitoring throughout ICU stays. The researchers concluded that certain gut microbiota profiles could predict sepsis in ICU patients. The researchers recommended potential biomarkers for use in the clinical treatment of patients in intensive care units.