Lactose intolerance: the role of colonic metabolism
Year: 2006
Type: dissertation
Abstract: Dairy products provide us with calcium and other valuable nutrients. However, they also contain lactose which is maldigested by a large part of the world adult population. The mechanisms by which lactose maldigestion causes symptoms of lactose intolerance are not fully understood. Studies on the pathophysiology of lactose intolerance may aid to design strategies for dietary management of lactose intolerance. Limited evidence suggests that colonic metabolism of lactose, in addition to the small-intestinal lactase activity and transit, might be involved in the development of symptoms. Data on digestion and transit of lactose in the small intestine are needed when clarifying possible involvement of the colon in lactose intolerance. The oro-cecal transit time (OCTT) and the degree of lactose digestion were determined using newly developed stable isotope-based methods. Lactose triggered faster oro-cecal transit in lactose maldigesters, but not in digesters. This could not be explained by intestinal distention resulting from the osmotic load posed by maldigested lactose, and thus suggested a direct effect of lactose on intrinsic factors regulating intestinal motility. The lactose tolerant and intolerant subjects did not differ in OCTT or the degree of lactose digestion, which indicates the involvement of other pathophysiological mechanisms in lactose intolerance. We hypothesize that colonic metabolism of lactose is one of these mechanisms. Two in vitro studies were carried out to investigate the possible role of fermentation of lactose by the colonic microbiota in lactose intolerance. During colonic fermentation, lactose is first hydrolyzed to glucose and galactose, catalyzed by ß-galactosidase. Glucose and galactose are subsequently fermented, leading to production of short-chain fatty acids (SCFA) and gases. When incubated with lactose in vitro, fecal bacteria from the lactose intolerant subjects produced more lactate, acetate, propionate and butyrate at a higher rate than the tolerant subjects. The results suggest that a faster and higher production of microbial intermediate and end metabolites during colonic fermentation of lactose, may be related to the development of lactose-induced symptoms. It is unlikely that the degree and rate of lactose hydrolysis are involved. Bacterial ß-galactosidase activity is abundant in the colon as more than 80% of the cultured fecal bacteria were found to possess this activity. The lactose tolerant and intolerant subjects did not differ in the relative amount or composition of the fecal bacteria with ß-galactosidase activity, ß-galactosidase activity in feces, or hydrolysis of lactose in vitro. We hypothesize that accumulation of SCFA and/or other metabolites resulting from fast fermentation of lactose in combination with insufficient removal plays a role in onset of symptoms. As the in vitro study indicates that colonic fermentation may be involved in lactose intolerance, we continued to: (i) investigate whether the colonic microbiota could be modulated by dietary supplementation for the purpose of alleviating symptoms; (ii) explore proteomics techniques to study metabolic pathways of lactose fermentation by the colonic microbiota; (iii) design an in vivo study to verify the observations of the in vitro study. A 2-w supplementation of probiotic bacteria (Bifidobacterium longum) and a yogurt enriched with Bifidobacterium animalis modified the amount and probably the metabolic activities of the colonic microbiota of lactose intolerance subjects. Lactose-induced symptoms decreased after the supplementation. The supplementation did not increase the endogenous lactase activity in the small intestine. Results indicate that the changes in the colonic microbiota may play a role in alleviation of intolerant symptoms. Bifidobacteria were used as a model system to explore proteomic methodology which can be used to study metabolic pathways of lactose by the colonic microbiota. Differential protein expression profiles of Bifidobacterium grown on lactose, glucose or galactose were obtained by using surface-enhanced laser desorption ionization - time of flight MS and sodium dodecyl sulfate polyacrylamide gel electrophoresis. LC-MS/MS was used for identification of proteins . An in vivo study is proposed to verify our observations in the in vitro study that fast colonic fermentation of lactose plays a role in lactose intolerance. Stable isotope-labeled lactose will be delivered to the cecum via a catheter and kinetics of 13C-acetate in the peripheral blood will be monitored. The results presented in this dissertation contribute to the understanding of the colonic metabolism of lactose in the context of lactose intolerance. Colonic fermentation of lactose may play a role in lactose intolerance. Dietary modulation of the colonic microbiota provides a promising strategy for management of lactose intolerance.
Author: Tao He
Language: English
Subfield: Gastroenterology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2123133013