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

All critically ill trauma patients enrolled in the study had profound baseline gut microbial dysbiosis and received broad-spectrum antibiotics.

• Single-center, prospective, double-blind RCT in mechanically ventilated trauma ICU patients.
• 57 stool samples were analyzed from 17 patients (7 NF-EN, 10 scFOS-EN).
• Microbial communities were characterized using 16S rRNA gene sequencing.
• Baseline dysbiosis was present in all participants regardless of treatment assignment.

scFOS-EN was associated with an accelerated loss of Bifidobacterium compared to NF-EN.

• Bifidobacterium declined at a rate of -0.6%/day in scFOS-EN compared to NF-EN (p = .026).
• This finding is contrary to the expected beneficial effect of prebiotic supplementation on Bifidobacterium in non-critically ill populations.
• Linear mixed-effects models were used to assess microbial dynamics over the 10-day study period.

scFOS-EN was associated with accelerated loss of Firmicutes compared to NF-EN.

• Firmicutes declined at a rate of 3.5%/day in the scFOS-EN group (p < .001).
• This reduction was observed over the 10-day study period after formula initiation.
• Linear mixed-effects models were used to assess these dynamics longitudinally.

scFOS-EN was associated with expansion of pathobiont Enterobacteriaceae, a finding unique to scFOS-EN participants.

• Enterobacteriaceae increased at a rate of 0.3%/day in scFOS-EN participants (p = .003).
• This expansion was not observed in NF-EN participants.
• Expansion of Enterobacteriaceae is considered detrimental as these organisms are associated with increased morbidity in the ICU.

scFOS-EN was associated with greater increases in several Bacteroidaceae members compared to NF-EN.

• Multiple members of the Bacteroidaceae family showed increased relative abundance in scFOS-EN participants.
• These changes were identified using linear mixed-effects models over the 10-day observation period.
• A time-informed dimensionality reduction method was used to identify patient-specific temporal responses.

Detrimental microbial responses to scFOS-EN, including high Enterobacteriaceae burden, were associated with pre-existing and ongoing antibiotic exposure and enhanced microbial competition.

• Prior exposure to anaerobic antibiotics appeared to modify the microbial response to scFOS-EN from beneficial to detrimental.
• Network approaches were used to assess microbe:microbe interactions.
• High Enterobacteriaceae burden was associated with enhanced microbial competition in the context of scFOS-EN.
• Antibiotic exposure was identified as a key modifier of the microbial response to prebiotic supplementation.

In other (non-critically ill) populations, dysbiosis is improved by enteral nutrition supplemented with prebiotic short-chain fructooligosaccharides, but the impact in critical illness was unknown prior to this study.

• The study was designed as a pilot RCT because the impact of scFOS-EN on the microbiota in critical illness was considered unknown and difficult to predict in a dysbiotic environment.
• Expansion of Enterobacteriaceae and other pathobionts in the ICU is associated with increased morbidity.
• The trial was prospectively registered at ClinicalTrials.gov (NCT03153397; first posted May 15, 2017).

The findings challenge a universal approach to prebiotic therapy and underscore the need for personalized nutritional strategies in the ICU.

• The effect of scFOS-EN was described as context-dependent in the dysbiotic gut of critically ill trauma patients.
• Prior anaerobic antibiotic exposure was identified as a key contextual factor modifying the response to scFOS-EN.
• The authors conclude that personalized nutritional strategies are needed rather than a universal prebiotic approach in the ICU.