Effect of fiber supplementation on the microbiota in critically ill patients

Abstract

Aim: To determine tolerance to fiber supplementation of semi-elemental tube feeds in critically ill patients and measure its effect on colonic microbiota and fermentation.

Methods: Thirteen intensive care unit patients receiving jejunal feeding with a semi-elemental diet for predominantly necrotizing pancreatitis were studied. The study was divided into 2 parts: first, short-term (3-9 d) clinical tolerance and colonic fermentation as assessed by fecal short chain fatty acid (SCFA) concentrations and breath hydrogen and methane was measured in response to progressive fiber supplementation increasing from 4 g tid up to normal requirement levels of 8 g tid; second, 4 patients with diarrhea were studied for 2-5 wk with maximal supplementation to additionally assess its influence on fecal microbiota quantitated by quantitative polymerase chain reaction (qPCR) of microbial 16S rRNA genes and Human Intestinal Tract Chip (HITChip) microarray analysis. Nearly all patients were receiving antibiotics (10/13) and acid suppressants (11/13) at some stage during the studies.

Results: In group 1, tolerance to progressive fiber supplementation was good with breath hydrogen and methane evidence (P = 0.008 and P < 0.0001, respectively) of increased fermentation with no exacerbation of abdominal symptoms and resolution of diarrhea in 2 of 4 patients. In group 2 before supplementation, fecal microbiota mass and their metabolites, SCFA, were dramatically lower in patients compared to healthy volunteers. From qPCR and HITChip analyses we calculated that there was a 97% reduction in the predominant potential butyrate producers and starch degraders. Following 2-5 wk of fiber supplementation there was a significant increase in fecal SCFA (acetate 28.4 ± 4.1 μmol/g to 42.5 ± 3.1 μmol/g dry weight, P = 0.01; propionate 1.6 ± 0.5 vs 6.22 ± 1.1, P = 0.006 and butyrate 2.5 ± 0.6 vs 5.9 ± 1.1, P = 0.04) and microbial counts of specific butyrate producers, with resolution of diarrhea in 3 of 4 patients.

Conclusion: Conventional management of critically ill patients, which includes the use of elemental diets and broad-spectrum antibiotics, was associated with gross suppression of the colonic microbiota and their production of essential colonic fuels, i.e., SCFA. Our investigations show that fiber supplementation of the feeds has the potential to improve microbiota mass and function, thereby reducing the risks of diarrhea due to dysbiosis.

Keywords: Acute pancreatitis; Critical illness; Enteral nutrition; Fiber; Microbiota.

Figure 1

Comparison of breath hydrogen responses over 360 min to a bolus of 10 g soluble fiber between group 1 and healthy subjects.

Figure 2

Summary of the changes in some of the indices of bacterial fermentation observed in the first group of 9 tube fed critically ill patients (group 1) after achievement of maximal fiber supplementation (median 22 g/d, range 12-32 g/d). ^aP = 0.008, ^bP < 0.0001, unpaired Student’s t test.

Figure 3

Comparison of total fecal bacterial copies in group 2 compared to healthy subjects consuming normal food measured by quantitative polymerase chain reaction of the 16S ribosomal RNA gene using Bacteria domain primers. qPCR: Quantitative polymerase chain reaction.

Figure 4

Fecal short chain fatty acid concentrations were significantly lower in the 4 patients in group 2 given fiber supplementation for longer periods of time (2-5 wk) compared to healthy subjects. ^aP = 0.012, ^bP = 0.007, ^cP = 0.35, unpaired Student’s t test.

Figure 5

Phylogenetic distribution at level 1 (“Phylum/Class” level) by HITChip analysis. Lentispaerea is the spike. This illustrates differences in the composition of the major phyla between 2 patients from Group 2 before and after fiber supplementation (DYS 001 and DYS 002 = patient No. 10 before and after fiber supplementation, DYS 003 and DYS 004 = patient No. 11 before and after fiber supplementation) and 2 of the healthy controls consuming normal food (DYS 005 and DYS 006). The difference in Bacteroidetes composition was striking, with this phylum making up 35% of the microbiota in healthy subjects and 60% in patients. Conversely, there was a reduction of the proportion of Firmicutes (Clostridium clusters IV and XIVa), which contain the major butyrate-producers, in patients (50%) compared to controls (30%).

Figure 6

Numbers of butyrate-producing and fiber-digesting bacteria based on HITChip phylogenetic microarray analysis of microbiota composition and 16S quantitative polymerase chain reaction of total fecal bacterial counts in two critically ill patients showing a general increase before and after 2-5 wk of fiber supplementation.