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

Nutrients. 2017 Jul 18;9(7):767. doi: 10.3390/nu9070767.

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.

Keywords: Anaerostipes; Bifidobacteria; Lactulose; ammonia; butyrate; lactobacilli; microbial fermentation.

MeSH terms

  • Acetates / metabolism
  • Adult
  • Ammonia / metabolism
  • Bifidobacterium / drug effects
  • Bifidobacterium / metabolism
  • Body Mass Index
  • Butyrates / metabolism
  • Computer Simulation
  • DNA, Bacterial / isolation & purification
  • Dose-Response Relationship, Drug
  • Fatty Acids, Volatile / metabolism
  • Female
  • Gastrointestinal Microbiome / drug effects
  • Humans
  • Hydrogen-Ion Concentration
  • Intestine, Large / drug effects*
  • Intestine, Large / metabolism
  • Intestine, Large / microbiology
  • Lactic Acid / metabolism
  • Lactobacillus / drug effects
  • Lactobacillus / metabolism
  • Lactulose / administration & dosage*
  • Male
  • Models, Biological*
  • Prebiotics / administration & dosage*
  • RNA, Ribosomal, 16S / isolation & purification
  • Sequence Analysis, DNA

Substances

  • Acetates
  • Butyrates
  • DNA, Bacterial
  • Fatty Acids, Volatile
  • Prebiotics
  • RNA, Ribosomal, 16S
  • Lactic Acid
  • Lactulose
  • Ammonia