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

Abstract

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.

Figure 1

Consort flow-chart of screened patients. Starting from a general group of 135 symptomatic patients, and after exclusion of 21 patients with organic diseases, a subgroup of 114 patients had functional gastrointestinal symptoms. After further exclusions of 15 patients with Rome IV criteria, 99 patients underwent lactose H2 breath test and 75 were lactose intolerant, of which 34 had persisting symptoms following a lactose-free diet for at least six months, and were enrolled. Following the refusal of 11 subjects, the final study group consisted of 23 patients.

Figure 2

Crossover design of the study and timing of clinical evaluations. During the run-in (Ri) period, subjects fitting the inclusion criteria were randomized to receive either probiotic (ZR: 3 g as packets containing Bifidobacterium longum BB536 four billion CFU, Lactobacillus rhamnosus HN001 one billion CFU with B6 vitamin 1.4 mg) or placebo (PL: similar packets containing maltodextrins, corn starch, silicon dioxide, and no probiotic). The study included a first period of one month of treatment followed by 15 days of wash-out, and a second period of one month of treatment after cross-over. LI—lactose intolerant.

Figure 3

Representation of bloating (visual analogue scale (VAS) 0–100 mm) in 23 patients at baseline (T0) and after 30 days (T30) of treatment (ZR) and placebo (PL) by spaghetti graft.

Figure 4

Relative proportions (percent) of phylum in the fecal samples of treated patients (ZR) and those of placebo (PL) patients.

Figure 5

Relative proportions (percent) of genera showing significant (p < 0.05) differences between the fecal samples of treated patients (ZR) and those of placebo (PL) patients.

Figure 6

Significant correlations found between fecal microbiome and metabolome of lactose intolerant patients.