Effects of Bifidobacterium longum and Lactobacillus rhamnosus on Gut Microbiota in Patients with Lactose Intolerance and Persisting Functional Gastrointestinal Symptoms: A Randomised, Double-Blind, Cross-Over Study

Nutrients. 2019 Apr 19;11(4):886. doi: 10.3390/nu11040886.


Functional gastrointestinal symptoms are frequent, and may be driven by several pathogenic mechanisms. Symptoms may persist in lactose intolerant (LI) patients (i.e., subjects with intestinal lactase deficiency, lactose malabsorption producing symptoms), after a lactose-free diet. Our hypothesis was that probiotic and vitamin B6 treatment may be useful to alleviate symptoms in LI patients through a positive modulation of gut microbial composition and relative metabolism. We aimed to test the efficacy of a novel formulation of Bifidobacterium longum BB536 and Lactobacillus rhamnosus HN001 plus vitamin B6 (ZR) in 23 LI subjects with persistent symptoms during a lactose-free diet. Symptoms, microbiome, and metabolome were measured at baseline and after 30 days in a crossover, randomized, double-blind study of ZR versus placebo (PL). Compared with PL, the administration of probiotics and vitamin B6 significantly decreased bloating (p = 0.028) and ameliorated constipation (p = 0.045). Fecal microbiome differed between ZR and PL. ZR drove the enrichment of several genera involved in lactose digestion including Bifidobacerium. Moreover, the relative abundance of acetic acid, 2-methyl-propanoic acid, nonenal, and indolizine 3-methyl increased, while phenol decreased. Our findings highlight the importance of selected probiotics and vitamin B6 to alleviate symptoms and gut dysbiosis in lactose intolerant patients with persistent functional gastrointestinal symptoms.

Keywords: lactose intolerance; metabolome; microbiome; probiotics; vitamin B6.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Bifidobacterium longum / growth & development*
  • Constipation / etiology
  • Constipation / prevention & control
  • Cross-Over Studies
  • Diet
  • Double-Blind Method
  • Dysbiosis / prevention & control
  • Feces / microbiology
  • Gastrointestinal Microbiome*
  • Humans
  • Intestines
  • Lactase / deficiency
  • Lacticaseibacillus rhamnosus / growth & development*
  • Lactose / metabolism*
  • Lactose Intolerance / complications
  • Lactose Intolerance / drug therapy*
  • Lactose Intolerance / metabolism
  • Lactose Intolerance / microbiology
  • Male
  • Middle Aged
  • Probiotics / therapeutic use*
  • Vitamin B 6 / pharmacology
  • Vitamin B 6 / therapeutic use
  • Vitamin B Complex / pharmacology
  • Vitamin B Complex / therapeutic use


  • Vitamin B Complex
  • Vitamin B 6
  • Lactase
  • Lactose