Microbiota stability in healthy individuals after single-dose lactulose challenge – a randomized controlled study

Abstract

AbstractBackground and aimsLactulose is a common food ingredient and widely used as a treatment for constipation or hepatic encephalopathy and a substrate for hydrogen breath tests. Lactulose is fermented by the colon microbiota resulting in the production of hydrogen (H2). H2is a substrate for enteropathogens includingSalmonellaTyphimurium (S. Typhimurium) and increased H2production upon lactulose ingestion might favor the growth of H2-consuming enteropathogens. We aimed to analyze effects of single-dose lactulose ingestion on the growth of intrinsicEscherichia coli(E. coli), which can be efficiently quantified by plating and which share most metabolic requirements withS. Typhimurium.Methods32 healthy volunteers (18 females, 14 males) were recruited. Participants were randomized for single-dose ingestion of 50 g lactulose or 50 g sucrose (controls). After ingestion, H2in expiratory air and symptoms were recorded. Stool samples were acquired at days −1, 1 and 14. We analyzed 16S microbiota composition and abundance and characteristics ofE.coliisolates.ResultsLactulose ingestion resulted in diarrhea in 14/17 individuals. In 14/17 individuals, H2-levels in expiratory air increased by ≥20 ppm within 3 hours after lactulose challenge. H2-levels correlated with the number of defecations within 6 hours.E. coliwas detectable in feces of all subjects (2 x 102- 109CFU/g). However, the number ofE.colicolony forming units (CFU) on selective media did not differ between any time point before or after challenge with sucrose or lactulose. The microbiota composition also remained stable upon lactulose exposure.ConclusionIngestion of a single dose of 50 g lactulose does not significantly alterE.colidensity in stool samples of healthy volunteers. 50 g lactulose therefore seems unlikely to sufficiently alter growth conditions in the intestine for a significant predisposition to infection with H2-consuming enteropathogens such asS. Typhimurium (www.clinicaltrials.govNCT02397512).