Dose-Dependent Prebiotic Effect of Lactulose in a Computer-Controlled In Vitro Model of the Human Large Intestine

Abstract

Lactulose, a disaccharide of galactose and fructose, used as a laxative or ammonia-lowering drug and as a functional food ingredient, enhances growth of Bifidobacterium and Lactobacillus at clinically relevant dosages. The prebiotic effect of subclinical dosages of Lactulose, however, remains to be elucidated. This study analyses changes in the microbiota and their metabolites after a 5 days Lactulose treatment using the TIM-2 system, a computer-controlled model of the proximal large intestine representing a complex, high density, metabolically active, anaerobic microbiota of human origin. Subclinical dosages of 2–5 g Lactulose were used. While 2 g Lactulose already increased the short-chain fatty acid levels of the intestinal content, 5 g Lactulose were required daily for 5 days in this study to exert the full beneficial prebiotic effect consisting of higher bacterial counts of Bifidobacterium, Lactobacillus, and Anaerostipes, a rise in acetate, butyrate and lactate, as well as a decrease in branched-chain fatty acids, pH (suggested by an increase in NaOH usage), and ammonia.

Mechanisms of Action of Prebiotics and Their Effects on Gastro-Intestinal Disorders in Adults

“…At a low dosage (2-3 g), they observed an increase in Bifidobacteria, but not in Lactobacilli, and a low production of SCFAs, while the administration of the maximal experimental dose (5 g/day) determined the correct balance among the microbial population (Bifidobacteria, Lactobacilli and Anaerostipes) and SCFAs production. By further increasing the quantities (10 g/day), the authors observed a significant reduction in the production of butyrate and an increase in acetate, probably due to the growth of the bifidobacterium population, which usually produces acetate from its metabolism [59].…”

“…At a low dosage (2-3 g/day), ↑ Bifidobacterium count [53,59], but not Lactobacilli, and determines a low production of SCFAs; 5 g/day determines the correct balance among the microbial population (Bifidobacteria, Lactobacilli and Anaerostipes) and SCFAs production, while 10 g/day ↓ butyrate production and ↑ acetate [59].…”

Lactulose Crystals Beneficially Affect Community Composition Along Entire Human Colon in Vitro, Resulting in Donor-Dependent Prebiotic Effects at Metabolic Level

“…Former studies using a computer-controlled in vitro model of the human proximal colon revealed a dosedependent increase in total short-chain fatty acid (SCFA) concentrations upon low-dose lactulose supplementation of up to 5 g/day, mainly attributed to increased acetate, butyrate and lactate production [17,18]. Butyrate production, however, was inhibited when higher lactulose amounts (i.e.…”

New Progress Regarding the Use of Lactic Acid Bacteria as Live Delivery Vectors, Treatment of Diseases and Induction of Immune Responses in Different Host Species Focusing on Lactobacillus Species

“…Daily ingested by humans playing significant roles as health-promoting probiotics which is the most important point, to improve general health and protect from different kinds of illness [3][4][5][6]. Also used as production of food and feed throughout the world [7][8][9][10][11] because widely used in the food industry for the production and the preservation of fermented products such as wholegrain sourdough bread or sourdough fermentation [12,13].…”