Comparison of the Colonic Metabolism in Patients With Lactose Intolerance and Healthy Controls
Comparison of the Colonic Metabolism in Patients With Lactose Intolerance and Healthy Controls
Most people are born with the ability to digest lactose, a dissacharide consisting of
 β-D-glucose and β-D-galactose, because of the presence of lactase at the brush border of the
 small intestine. In about 75% of the world population the activity of this enzyme decreases
 after weaning (primary hypolactasia or lactase-nonpersistence), resulting in incomplete
 digestion of lactose and lactose malabsorption in adulthood (1). Secondary forms of lactose
 malabsorption may be due to inflammation or functional loss of the intestinal mucosa such as
 celiac disease, infectious enteritis or Crohn's disease. Very rarely, lactase deficiency is
 congenital due to an autosomal recessive genetic disorder, preventing lactase expression from
 birth (2). Whereas some people with lactose malabsorption are asymptomatic, most
 lactose-nonpersisters experience symptoms like abdominal pain, bloating, excess flatulence or
 diarrhea. Lactose intolerance refers to the syndrome of having one or more symptoms after
 consumption of lactose-containing food (3). At present, the origin of the symptoms of
 lactose-intolerance is not well understood.

 Several studies have indicated a poor correlation between lactose maldigestion and symptoms
 of lactose intolerance (4). In a study by Vonk et al. (2003), lactose intolerant subjects
 with severe symptoms (diarrhea) and intolerant subjects with only mild symptoms (without
 diarrhea) did not differ in degree of lactose digestion in the small intestine indicating a
 similar lactase activity and leading them to the hypothesis of a "colon resistence factor"
 (5). It was suggested that the colonic processing of maldigested lactose may play a role in
 the symptoms experienced by lactose intolerant patients. When lactose is malabsorbed and
 enters the colon, it is rapidly fermented by the resident microbiota into a variety of
 metabolites including lactate, formate, succinate and short chain fatty acids (SCFA, acetate,
 propionate, butyrate) as well as gases (H2, CO2 and CH4). When incubating fecal samples from
 lactose-tolerant and intolerant subjects with lactose, the samples from the
 lactose-intolerant subjects showed faster production rates of D- and L-lactate, acetate,
 propionate and butyrate, as compared to tolerant subjects (6). Although the colon is thought
 to possess a high capacity to absorb SCFA, it was hypothesized that a temporary accumulation
 of these metabolites due to rapid fermentation of maldigested lactose could be responsible
 for abdominal pain, excess flatulence and bloating (7;8). Possible mechanisms proposed to
 explain how SCFA might induce symptoms included an increase in the osmotic load that draws
 fluid to the colonic lumen, changes in colonic motility and an increased colonic sensitivity
 (9-11). However, the calculated amount of fluid drawn in the colon is unlikely to cause
 symptoms considering the high water absorbing capacity of the colon and the effect of SCFA on
 colonic motility and colonic sensitivity have only been observed in rats and not in humans.

 More recently, Campbell et al. introduced the bacterial metabolic toxin hypothesis, stating
 that also other bacterial metabolites, such as alcohols, aldehydes, acids and ketones,
 resulting from carbohydrate fermentation play a role in the pathogenesis of
 lactose-intolerance. These metabolites might inhibit bacterial growth and affect eukaryotic
 cells (12). In our own previous studies in which we related colonic fermentation patterns to
 parameters of cytotoxicity, we identified compounds like propionic acid, medium chain fatty
 acids, 1-octanol and heptanal as more prevalent in the most cytotoxic samples (13),
 supporting the hypothesis of Campbell et al. Therefore, it seems necessary to include not
 only SCFA, but also other metabolites, in the investigation of the pathogenesis of lactose
 intolerance.

 Differences in fermentation patterns might be associated with differences in the composition
 and/or activity of the intestinal microbiota. Evidence on the potential role of the colonic
 microbiota in lactose intolerance is very limited. Total bacterial numbers were not
 significantly different between 16 intolerant and 11 tolerant lactose maldigesters although a
 negative correlation between total bacteria and symptom score was found (14). Similarly, the
 composition of fecal microbiota was not different between 5 intolerant and 7 tolerant
 subjects (6).
In this study we will compare colonic fermentation and parameters of gut health (fecal water
 cytotoxicity) between patients who are lactose intolerant, patients who have lactose
 malabsorption and healthy subjects.
Inclusion Criteria:

 -  healthy or positive lactose breath test

 -  > 18 Year

 -  18 kg/m²<BMI<27.5 kg/m²

 -  regular dietary pattern

 Exclusion Criteria:

 -  intake of antibiotics 1 month prior to sample collection

 -  abdominal chirurgical intervention except appendectomy

 -  intake of medication 14 days prior to sample collection

 -  vegetarian

 -  intake of pre- or probiotics