Isolation and characterization of the viscous, high-molecular-mass microbial carbohydrate fraction from faeces of healthy subjects and patients with Crohn's disease and the consequences for a therapeutic approach.
1. An earlier study by our group revealed that the viscosity of faeces from patients with Crohn's disease is significantly lower than that of healthy subjects. This is due to low concentrations of a high-molecular-mass carbohydrate, probably of bacterial origin. The cause of this phenomenon might be the impaired barrier function of the gut mucosa. Low viscosity may allow close contact of intestinal contents (bacterial products and toxins) with the intestinal wall. This could play a role in the maintenance of the disease.2. The first aim of this study was to investigate the high-molecular-mass carbohydrate fraction, responsible for viscosity, in detail. We also tried (in a pilot study) to raise the intestinal viscosity of patients with Crohn's disease with the undegradable food additive hydroxypropylcellulose (E463), in an attempt to alleviate clinical symptoms.3. The high-molecular-mass fraction (>300 kDa) responsible for faecal viscosity was sensitive to lysozyme and contained high levels of muramic acid. It was concluded that this material consisted mainly of peptidoglycan polysaccharides and was consequently of bacterial origin. The muramic acid in material from patients with Crohn's disease was 7.5 (1.5-13.9)%, which was less than in healthy subjects [11.4 (8.5-24.1)%; P=0.0004]. Furthermore, viscosity in material from patients with Crohn's disease was found to be half [14.9 (1.0-33.6) cP] of that found in healthy subjects [35.0 (2.7-90.7) cP; P=0.004].4.A daily dose of 1 g of hydroxypropylcellulose caused an increase in faecal viscosity in patients with Crohn's disease (from 1.4 to 2.3 cP) and in healthy subjects (from 4.9 to 7.5 cP). Faecal consistency improved in patients with Crohn's disease (from watery and loose to formed) and the defecation frequency decreased from 3-4 to about 2 times a day. No changes in defecation patterns were found in healthy subjects.5. These data indicate that the high-molecular-mass fraction that is responsible for faecal viscosity is peptidoglycan. Furthermore, a daily dose of a hydroxypropylcellulose solution to increase the viscosity of the intestinal contents of patients with Crohn's disease might be beneficial. This approach merits further study.
Ruseler-van Embden
J G
JG
Department of Immunology, Erasmus University, P.O. Box 1738, 3000 DR, Rotterdam, The Netherlands.
Van Lieshout
L M
LM
Binnema
D J
DJ
Hazenberg
M P
MP
D000328:Adult; D000368:Aged; D001419:Bacteria / Q000378:metabolism; D002482:Cellulose / Q000031:analogs & derivatives / Q000627:therapeutic use; D002850:Chromatography, Gel; D003424:Crohn Disease / Q000378:metabolism* / Q000628:therapy; D005243:Feces / Q000737:chemistry*; D005503:Food Additives / Q000627:therapeutic use; D006801:Humans; D008875:Middle Aged; D008970:Molecular Weight; D010457:Peptidoglycan / Q000302:isolation & purification*; D018709:Statistics, Nonparametric; D014783:Viscosity / Q000187:drug effects
D005503:Food Additives; D010457:Peptidoglycan; D002482:Cellulose; C008079:hydroxypropylcellulose