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

PLoS One. 2018 Oct 25;13(10):e0206214. doi: 10.1371/journal.pone.0206214. eCollection 2018.

Abstract

Background and aims: Lactulose 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). H2 is a substrate for enteropathogens including Salmonella Typhimurium (S. Typhimurium) and increased H2 production 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 intrinsic Escherichia coli (E. coli), which can be efficiently quantified by plating and which share most metabolic requirements with S. Typhimurium.

Methods: 32 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, H2 in 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 of E. coli isolates.

Results: Lactulose 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. coli was detectable in feces of all subjects (2 x 10(2)-10(9) CFU/g). However, the number of E. coli colony 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.

Conclusion: Ingestion of a single dose of 50 g lactulose does not significantly alter E. coli density 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 as S. Typhimurium (www.clinicaltrials.gov NCT02397512).

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Colon / drug effects
  • Colon / microbiology
  • Diarrhea / chemically induced
  • Diarrhea / microbiology
  • Dietary Sucrose / pharmacology
  • Dose-Response Relationship, Drug
  • Feces / microbiology
  • Female
  • Gastrointestinal Microbiome / drug effects*
  • Healthy Volunteers
  • Humans
  • Lactulose / pharmacology*
  • Male
  • Microbial Viability / drug effects*
  • Middle Aged
  • Young Adult

Substances

  • Dietary Sucrose
  • Lactulose

Associated data

  • ClinicalTrials.gov/NCT02397512

Grants and funding

This work was supported by a Seed grant from Hochschulmedizin Zurich (to GR and WDH), a grant from ETH Zurich (ETH-33 12-2; to WDH, partially covering the salary of SYW), a grant from the Novartis Foundation (#15C181; to WDH, partially covering the salary of SYW), the Swiss National Science Foundation (SNF 310030_153074, 3130030B_173338 and CRSII3_154414/1; to WDH, partially or completely covering the salary of MK, LM, BD), the Helmut Horten Foundation (to WDH and SS), the Promedica Foundation to WDH and a grant from the Swiss National Science Foundation to BM (SNF 32473B_156525). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.