Abstract

Purpose: Diarrhea is common and impairs outcome in critically ill patients dependent on tube feeding (EN). We hypothesize that conventional EN deprives the microbiota of their usual nutrition, leading to dysbiosis and diarrhea: to determine whether ‘normalization' of the fiber content of tube feeds can prevent this. Methods: Thirteen patients receiving EN for predominantly necrotizing pancreatitis were studied. Management included IV antibiotics and proton pump inhibitors. The study was divided into 2 parts: First, short-term (3-9 days) clinical tolerance and fermentation to short chain fatty acids (SCFA) and breath hydrogen and methane (BHM) during progressive fiber supplementation of EN to requirement levels of 25-28g/d. Second, 4 patients with diarrhea, were followed 2-5 weeks to additionally assess changes in fecal microbiota quantitated by qPCR of 16S rRNA and HITChip microarray. Results: Fecal microbiota mass was dramatically lower in patients compared to matched healthy volunteers consuming a normal diet, as were fecal SCFA, while BHM were high suggesting small bowel bacterial overgrowth. Compositional analysis showed that the major butyrate-producers and starch-degraders (Eubacterium rectale, Roseburia, Faecalibacterium prausnitzi, and Rumminococcus) as well as Bifidobacterium spp. were particularly depleted. Fiber (wheat dextrin) supplementation resolved diarrhea in 5/8 patients, without an increase in abdominal signs or symptoms. This was associated with some evidence (increased BHM, SCFA, butyrate-producers and starch-degraders) of improvement, but not normalization, of fermentation. Conclusion: Our study suggests that the microbiota and butyrate production are dramatically suppressed in critical illness possibly explaining the high prevalence of diarrhea in tube-fed patients. Fiber supplementation was well tolerated but only partly improved fermentation and diarrhea, suggesting other factors, such as antibiotics and PPIs, contribute to dysbiosis.Figure: Changes in some of the indices of bacterial fermentation. Statistics: ** p=0.008, *** p<0.0001, unpaired Student's t test.

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