We were able to show that dietary xylitol enhanced oxidative killing in neutrophilic leucocytes and prolonged the survival of rats suffering from sepsis caused by S. pneumoniae
type 3. These findings are in accordance with a previous report which showed that parenteral xylitol improved the survival of rats suffering from intestinal sepsis [5
]. This better survival in the presence of sepsis probably entails several contributory factors. Xylitol has effects on the growth [9
], expression of capsular polysaccharides [14
] and adhesion [13
] of S. pneumoniae
. It has also been shown to have several beneficial metabolic effects in animals suffering from trauma or sepsis [5
], and the enhanced functioning of neutrophilic leucocytes found in the present study provides an extension to this list.
The initiation of the respiratory burst in polymorphonuclear neutrophils requires NAPDH. Xylitol may affect the metabolism of neutrophils in two ways: firstly by improving the glycaemic control under the hyperglycaemic stress reaction during sepsis, or secondly by causing a marked reduction in the intracellular redox state due to the rapid production of NADH and NADPH in the polyol dehydrogenase reaction [18
]. By thus affecting the energy metabolism of the leukocytes, it may interfere with their functioning, and thus modulate the course of the invasive bacterial disease. Xylitol has also been shown to be cytoprotective during oxidative stress [19
is one of the most common bacteria causing invasive infections in otherwise healthy persons. The maximal expression of capsular polysaccharides is known to be essential for its systemic virulence, however, because of the antiphagocytic properties of the capsule [20
]. We have shown earlier that the ultrastructure of the pneumococcal capsule becomes ragged after exposure to xylitol [14
]. Interestingly, two pneumococcal isolates from xylitol-fed rats with no clinical signs of septicaemia in the present study grew rough colonies and were impossible to serotype, suggesting that the virulent type 3 pneumococci had become avirulent, not expressing the genes needed for capsular synthesis. The regM
gene, encoding catabolite control protein, has recently been identified in pneumococcus [21
]. This gene is involved in the catabolism of carbohydrates, and its mutation resulted in a significant reduction in the transcription of the locus of capsular polysaccharide biosynthesis. Further studies would be needed, however, to show, whether a xylitol diet can lead to repression of the regM gene and consequently to reduced capsular synthesis.
The serum concentrations of xylitol recorded here were low, as was to be expected, because xylitol is absorbed slowly from the gut by free diffusion, the rate of absorption being 1/5 of that of glucose [22
]. Xylitol is able to inhibit the growth of pneumococci significantly at a concentration of 65 mmol/L (1%) [9
], and concentrations of the same magnitude are expected for the morphological changes [14
]. The highest serum concentration recorded in this experiment was 1.3 mmol/L, in the 20% xylitol group, we did not measure intra-tissue or intracellular concentrations, nor do we know whether or not the serum concentrations reflect the amount of xylitol present during the critical steps in the infection process.
found that xylitol enhances survival in sepsis of intestinal origin, where the growth or virulence of the aetiological microbes is not known to be susceptible to xylitol. Parenteral xylitol has been shown to have a nitrogen-sparing effect during sepsis and after burns in rats [5
], and Ardawi [5
] suggested that this may be the mechanism for improved survival in the presence of sepsis. The nitrogen balance may nevertheless be only an indirect sign of a better state, reflecting less serious inflammation, and not the reason for the improvement in survival.
Oral xylitol is well tolerated in adults and children, the only side-effect found being osmotic diarrhoea [22
]. Parenteral xylitol can cause minimal hyperuricaemia, but without any pathophysiological consequences [3
]. Xylitol has been used as a component of parenteral nutrition, instead of or in addition to glucose, e.g. in patients with diabetes [3
]. Though tolerated well in modest doses, large doses of xylitol administered intravenously have been reported to cause renocerebral oxalosis with renal failure [23
]. These case reports of serious side-effects raise a need for caution in the use of parenteral xylitol.
The factors influencing the severity of invasive bacterial infections are quite well known, but only a few methods of treatment aimed at slowing them down are in clinical use. Xylitol, as a modulator of the functioning of leukocytes during the inflammatory process, may open up new possibilities for improving the prognosis for pneumococcal sepsis.