Gut community structure as a risk factor for infection inKlebsiella-colonized patients

Abstract

The primary risk factor for infection with members of the Klebsiella pneumoniae species complex is prior gut colonization, and infection is often caused by the colonizing strain. Despite the importance of the gut as a reservoir for infectious Klebsiella, little is known about the association between the gut microbiome and infection. To explore this relationship, we undertook a case-control study comparing the gut community structure of Klebsiella-colonized intensive care and hematology/oncology patients. Cases were Klebsiella-colonized patients infected by their colonizing strain (N = 83). Controls were Klebsiella-colonized patients that remained asymptomatic (N = 149). First, we characterized the gut community structure of Klebsiella-colonized patients agnostic to case status. Next, we determined that gut community data is useful for classifying cases and controls using machine learning models and that the gut community structure differed between cases and controls. Klebsiella relative abundance, a known risk factor for infection, had the greatest feature importance but other gut microbes were also informative. Finally, we show that integration of gut community structure with bacterial genotype or clinical variable data enhanced the ability of machine learning models to discriminate cases and controls. This study demonstrates that including gut community data with patient- and Klebsiella-derived biomarkers improves our ability to predict infection in Klebsiella-colonized patients.

Type-2 diabetes mellitus enhancesKlebsiella pneumoniaepathogenesis

“…Kp is a frequent gut colonizer, and Kp-colonized individuals are at high risk for subsequent infection, implicating the gut as the primary reservoir for infectious Kp [19-21]. Moreover, specific gut microbial community structures are strongly associated with infection in colonized patients, and Kp gut dominance is highly associated with disease [22, 23]. It is unknown if T2DM-associated changes in the gut microbiome impact Kp colonization.…”