The osmolyte xylitol reduces the salt concentration of airway surface liquid and may enhance bacterial killing

Abstract

The thin layer of airway surface liquid (ASL) contains antimicrobial substances that kill the small numbers of bacteria that are constantly being deposited in the lungs. An increase in ASL salt concentration inhibits the activity of airway antimicrobial factors and may partially explain the pathogenesis of cystic fibrosis (CF). We tested the hypothesis that an osmolyte with a low transepithelial permeability may lower the ASL salt concentration, thereby enhancing innate immunity. We found that the five-carbon sugar xylitol has a low transepithelial permeability, is poorly metabolized by several bacteria, and can lower the ASL salt concentration in both CF and non-CF airway epithelia in vitro. Furthermore, in a double-blind, randomized, crossover study, xylitol sprayed for 4 days into each nostril of normal volunteers significantly decreased the number of nasal coagulase-negative Staphylococcus compared with saline control. Xylitol may be of value in decreasing ASL salt concentration and enhancing the innate antimicrobial defense at the airway surface.

Figures

Figure 1

Apical xylitol and volume after the addition of xylitol to the apical surface of non-CF airway epithelia. Xylitol (138 mM in 60 μl) was added to the apical surface of differentiated airway epithelia at time 0. Then, at the times indicated, the apical liquid was removed and the quantity of xylitol (A), the liquid volume (B), and the xylitol concentration (C) were determined. Data are mean ± SEM (n = 6). Some SEM bars are hidden by symbols. The asterisk indicates P < 0.01 compared with time 0.

Figure 2

Effect of apical xylitol on the rate of liquid absorption by non-CF and CF epithelia. Sixty microliters of saline solution, xylitol solution, or indicated mixtures of the two was applied to the apical solution. Four hours later the solution was removed to measure the rate of liquid absorption. A short incubation period was chosen to avoid secondary changes in the epithelium due to the large volume of apical liquid. Data are mean ± SEM (n = 15) from three different experiments. Some SEM bars are hidden by symbols.

Figure 3

Effect of apical xylitol on non-CF and CF ASL Cl− concentration and volume. Isosmotic xylitol or saline (5 μl) was applied to the apical surface. Twenty-four hours later, ASL Cl− concentration (A) and volume (B) were determined. The asterisk indicates a difference between the saline and the xylitol solutions (P < 0.05; n = 15–18) from three CF and three non-CF specimens.

Figure 4

Effect of modifying ionic strength and xylitol concentration on killing of E. coli by nasal lavage liquid. Nasal lavage liquid was diluted with increasing concentrations of NaCl (bottom x axis) or xylitol (top x axis). SEMs are smaller than the symbols.

Figure 5

Effect of xylitol on growth of several bacteria. Growth of P. aeruginosa (A), S. aureus (B), and coagulase-negative Staphylococcus (C) was measured as OD ▵, M9 medium alone. Xylitol (●) or succinate, mannitol, or sucrose (○) was added to M9 medium at 100 mM as indicated. (D) S. saprophyticus was grown in log phase in the presence (open symbols) and absence (closed symbols) of xylitol for 18 h. Starting bacterial concentrations were 108 cfu (circles), 107 cfu (triangles), and 103 cfu (squares). P. aeruginosa (E), S. aureus (F), and coagulase-negative Staphylococcus (G) were cultured in LB medium alone (▵), LB medium with 100 mM xylitol (●), and LB medium containing tobramycin or levofloxacin (○). (H) Nasal swabs were collected and cultured for 3 days in LB medium (○), in minimal M9 medium (□), or in M9 medium supplemented with 100 mM xylitol (●).

Figure 6

Effect of xylitol administration to nasal mucosa on coagulase-negative Staphylococcus. Data are the decrease in colony-forming units of coagulase-negative Staphylococcus after treatment with either saline or xylitol. Shown are median ± one quartile. The asterisk indicates P = 0.05.