Impact of fiber-containing enteral nutrition on microbial community dynamics in critically ill trauma patients: a pilot-randomized trial.

backgroundGut microbial dysbiosis is common in the intensive care unit and certain derangements, like expansion of Enterobacteriaceae and other potential pathogens (pathobionts), are associated with increased morbidity. In other populations, dysbiosis is improved by enteral nutrition supplemented with prebiotic short-chain fructooligosaccharides (scFOS-EN). The impact of scFOS-EN on the microbiota in critical illness is unknown and difficult to predict in a dysbiotic environment. Thus, we conducted a pilot randomized control trial (RCT) in critically ill trauma patients to evaluate the effects of scFOS-EN versus a fiber-free enteral formula (NF-EN) on gut microbial dynamics.

methodsIn this single-center, prospective, double-blind RCT, mechanically ventilated trauma ICU patients received scFOS-EN or a similar fiber-free formula (NF-EN). Microbial communities in longitudinally collected stool samples were characterized using 16S rRNA gene sequencing. We used linear mixed-effects models to assess microbial dynamics in the 10-day study period after scFOS-EN or NF-EN initiation, as well as a time-informed dimensionality reduction method to identify patient-specific temporal responses and clinical correlates and network approaches for microbe:microbe interactions.

resultsA total of 57 stool samples were analyzed from 17 patients (7 NF-EN, 10 scFOS-EN). All participants had profound baseline dysbiosis and received broad-spectrum antibiotics. Compared to NF-EN, scFOS-EN was associated with an accelerated loss of Bifidobacterium (- 0.6%/day p = .026) and Firmicutes (3.5%/day, p < .001) and greater increases in several Bacteroidaceae members, with expansion of pathobiont Enterobacteriaceae (0.3%/day, p = .003) unique to scFOS-EN participants. Detrimental microbial responses to scFOS-EN, including high Enterobacteriaceae burden, were dictated by pre-existing and ongoing antibiotic exposure and associated with enhanced microbial competition.

conclusionsIn the dysbiotic gut of critically ill trauma patients, the effect of scFOS-EN is context-dependent. Prior exposure to anaerobic antibiotics appears to modify the microbial response from beneficial to detrimental. These findings challenge a universal approach to prebiotic therapy and underscore the need for personalized nutritional strategies in the ICU.

trial registrationThe trial was prospectively registered at ClinicalTrials.gov (Identifier: NCT03153397; first posted May 15, 2017) prior to participant enrollment and approved by the Duke Health Institutional Review Board (IRB Pro00081414).