Valeur N, 2004
Denmark

Colonisation and effect on im mune cells of the gut epithelium in healthy adults.

Open 28 days + 28d follow-up

L. reuteri: 19 (4×108 CFU)

Colonisation verified after 4 weeks by biopsies from the gastric mucosa and the small intestine (duodenum and ileum) and by faecal analyses

Björkman P, 1999 Finland

Colonisation of the large intestine in healthy adults.

Open 12 days

L. reuteri: 10 (>109 CFU)

Colonisation verified after 12 days by biopsies from the large intestine and by faecal analyses

Egervärn M, 2010
Sweden

To evaluate the risk of transfer of plasmid borne antibiotic resistance in L. reuteri ATCC 55730 to other gut microbes.

R, DB 14 days + 14d follow-up

L. reuteri ATCC 55730: 7 (5×108 CFU) L. reuteri DSM 17938: 7 (5×108 CFU)

L. reuteri DSM 17938 colonized to the same extent as L. reuteri ATCC 55730

Roos S, 2013
(Substudy of Savino 2010) Italy

To analyze the global faecal micro bial composition, using large-scale DNA sequencing of 16 S rRNA genes, in a subsample of a popula tion of colicky, breastfed infants gi ven L. reuteri DSM 17938 or placebo.

R, DB, PC Faecal samples were col lected on days 1 and 21 (last day of intervention)

L. reuteri: 15 (1×108 CFU) Placebo: 14

• The infants’ faecal microbiota were composed of Proteobacte ria, Firmicutes, Actinobacteria and Bacteroidetes as the four main phyla. Infants with colic had very high inter-individual variability with Firmicutes/Bacteroidetes ratios varying from 4000 to 0.025. On an individual basis, the microbiota was, however, relatively stable over time.
• L. reuteri did not change the global composition of the micro biota, but responders to treatment had an increased relative abundance of the phyla Bacteroidetes and genus Bacteroi des at day 21 compared with day 0 vs. non-responders.
• The phyla composition of the infants at day 21 could be divided into three enterotype groups, dominated by Firmicutes, Bac teroidetes, and Actinobacteria, respectively.

Smith TJ, 2011
USA

To study colonisation and persistence of L. reuteri DSM 17938 in healthy adults after daily or alternate-day probiotic dosing in a vanilla pud ding. Colonisation was measured as faecal counts of L. reuteri All subjects were non-colonized by L. reuteri on day 0.

Open 7 days

Daily L. reuteri: 9 (1×109 CFU) Alternate day L. reuteri: 9 (1×109 CFU)

Alternate-day compared to daily probiotic intake achieved equivalent colonisation. Faecal levels on days 2-4 were of the same magnitude as on days 5-7 in both groups. Colonisation declined rapidly once dosing stopped. Whether alternate day dosing had any effect on clinical outcome measures was not studied.

Handschur M, 2007
South Africa

To test identification methods for detection and persistence of L. reuteri in the feces of 4-12 months old infants hospitalized for diarrhoea.

Open, PC 3 days

L. reuteri: 4, whereof 2 HIV-pos. (1×1010 CFU) Placebo: 3, whereof 1 HIV-pos.

L. reuteri was detected in feces after 3 days of supplementa tion to infants with diarrhoea and treated with antibiotics

Garcia Rode nas CL, 2016
(substudy of Papagaroufa lis 2014) Greece

To assess the response of newborn infants’ microbiota depending on C-section- (C) or vaginally-deli vered (V) and ingesting a formula containing
L. reuteri DSM 17938, in comparison to a similar formula without the probiotic.

R, DB, + control formula (Ct) Stool samples were collec ted at 2 weeks and 4 months of age. Micro bial DNA was extracted, amplified and pyrosequen ced

L. reuteri (V-Lr): 9 L. reuteri (C-Lr): 11 (1×109 CFU/L of formula)

Control (V-Ct): 10 Control (C-Ct): 10

At two weeks, feeding of the L. reuteri formula induced chan ges in the microbiota of C-section-delivered infants to a com position more like the one in vaginally born infants, whether given L. reuteri or not. This C-section group had significantly increased abundance and occurrence of Bifidobacterium compared to the C-Ct group. Enterobacteriaceae abundance was largely decreased. By contrast, the levels of clostridia and Enterococcus were similarly high in both C-Ct and C-Lr when compared to the vaginally born groups. Enterobac ter in C-Lr was not significantly different from C-Ct or from the vaginal delivery groups. At four months the differences between groups were gone, except for Lactobacillus, which was increased at both study ages in the Lr groups, regardless of mode of delivery.

del Campo R, 2014
Spain

To assess the effects of L. reuteri DSM 17938 in subjects with cystic fibrosis, aged 8-44y (mean age 18y), on GI and overall health (measured by validated questionnaires), the effect on gut inflammation and the composition of the gut microbiota.

R, DB, PC, crossover 2 parallel groups 6 mo probiotic 6 mo placebo

30 in total L. reuteri: 30 (1×108 CFU) Placebo: 30

Compared to the placebo test period:
• GI health score was significantly improved after 6 mo with L. reuteri, measured by the GIQLI questionnaire
• Gut inflammation, measured as faecal calprotectin levels, was significantly reduced by L. reuteri
After 6 months with L. reuteri the composition of the gut microbiota was modulated to a less dense and a more diverse one, with 31% reduction of high numbers of Proteobacteria. There was a considerable increase of Firmicutes and Bacte roidetes. The microbiota thereby became more similar to the one of healthy persons.

Rattanaprasert M, 2014
USA

To test substrate-directed synbiotic strategies to enhance the persis tence and metabolic activity of L. reuteri DSM 17938 in the human gut, in a human crossover trial. The prebiotics were galactooligosac charide (GOS) and/or rhamnose, with maltodextrin as the control. Faecal samples were analysed for numbers of L. reuteri and its meta bolic activity.

R, SB, PC, cross-over. 4 study periods of 28d each: 11d run-in/ washout pe riod + 7d with ingestion of study product + 10d test-of persistence period with ingestion of each prebiotic only.

L. reuteri (Lr): 15 (5×108 CFU) 4 study periods: 1. Lr + GOS (2 g) 2. Lr + rhamnose (2 g) 3. Lr + (GOS+rhamnose, 1+1g) 4. Lr + maltodextrin

After 7 days of ingestion of the synbiotic preparations and of L. reuteri + maltodextrin, the faecal numbers were 108 cfu/g but declined rapidly thereafter. As a single substrate, rhamnose had no effect on metabolic activity. When it was combined with GOS, this synbiotic preparation contributed to the stimulation of metabolic activity of L. reuteri n most subjects. The synbiotic preparations, as well as the prebiotics on their own, were well tolerated.