Abstract
Background
Gut microbial dysbiosis in the intensive care unit (ICU) is common, and certain changes, such as expansion of Enterobacteriaceae and other microbes with high pathogenic potential (pathobionts), are associated with increased risk of infection and death. Enteral nutrition (EN) with prebiotic short-chain fructooligosaccharides (scFOS-EN) promotes growth of commensal microbes like Bifidobacterium and certain Firmicutes in non-critically ill patients, and thus may potentially mitigate pathobiont expansion in the ICU. Though widely available, the impact of scFOS-EN on the microbial landscape when initiated in the setting of ICU-associated dysbiosis is still unknown. To address this gap, we conducted a pilot randomized controlled trial (RCT) in critically ill trauma patients to assess effects of scFOS-EN versus a fiber-free formula (NF-EN) on microbial dynamics and ecological interactions.
Methods
In this double-blinded RCT at a level one trauma center, mechanically-ventilated ICU patients with severe trauma (excluding gastrointestinal involvement) were randomized to receive scFOS-EN or NF-EN for 10 days. Stool and oral samples were collected sequentially, and microbial communities were analyzed using 16S ribosomal RNA amplicon sequencing. Linear mixed models were used to assess longitudinal microbiota responses, and network approaches were applied to evaluate gut microbial interactions.
Results
A total of 57 stool and 88 oral samples were included from 7 NF-EN patients and 10 scFOS-EN patients. All patients received broad-spectrum antibiotics and derangements in gut microbiota were present at time of formula initiation. Compared to NF-EN, scFOS-EN was associated with an accelerated loss of Bifidobacterium (-0.6% relative abundance/day, p = .026), and Firmicutes (3.5% /day, p < .001), and expansion of numerous Bacteroidaceae. Further, only scFOS-EN patients demonstrated an expansion in pathobiont Enterobacteriaceae (0.3%/day, p = .003). Network analyses revealed that a unique alliance between co-occurring Enterobacteriaceae and Bacteroidaceae and increased competition may underly changes in the microbiota to scFOS-EN.
Conclusion
Our study suggests administration of scFOS-EN in severe dysbiosis may further deplete beneficial microbes (e.g., Bifidobacterium and Ruminococcaceae) while supporting more resilient colonizers such as Bacteroidaceae, potentially providing a context-dependent advantage to Enterobacteriaceae – pathobionts associated with harm in the ICU. Our findings underscore the importance of investigating ecological interactions in critically ill patients to inform the use of microbiota-targeted therapies.
Trial registration:
The trial was registered (ClinicalTrials.gov, NCT03153397) and approved by Duke Health Institutional Review Board (IRB Pro00081414).