The beneficial effects of Lactobacillus reuteri ADR-1 or ADR-3 consumption on type 2 diabetes mellitus: a randomized, double-blinded, placebo-controlled trial

2018-11-14
Scientific Reports 8(1)
- M. Hsieh
- W. Tsai
- Yu-Pang Jheng
- S. Su
- Shu-Yi Wang
- Chi-Chen Lin
- Yi-Hsing Chen
- Wen-Wei Chang

PubMed: 30429496
DOI: 10.1038/s41598-018-35014-1

Study Design

Type: Randomized Controlled Trial (RCT)
Sample size: n = 68
Population: T2DM patients
Methods: Randomized, double-blinded, placebo-controlled trial.

Highly Cited
Rigorous Journal

Abstract

Probiotics have been reported to ameliorate symptoms of type 2 diabetes mellitus (T2DM) in animal models and human studies. We previously demonstrated that oral administration of Lactobacillus reuteri ADR-3 reduced insulin resistance in high-fructose-fed (HFD) rats. In the present study, we first identified another L. reuteri strain, ADR-1, which displayed anti-diabetes activity that reduced the levels of serum HbA1c and cholesterol and that increased antioxidant proteins in HFD rats. We further performed a randomized, double-blinded, placebo-controlled trial with a total of 68 T2DM patients to examine the beneficial effects of oral consumption of L. reuteri strains ADR-1 and ADR-3 and to investigate the associated changes in intestinal flora using a quantitative PCR method to analyze 16 S rRNA in fecal specimens. Significant reductions in HbA1c and serum cholesterol were observed in participants in the live ADR-1 consumption group (n = 22) after 3 months of intake when compared with those in the placebo group (n = 22). Although there was no significant difference in the HbA1c serum level among participants who consumed heat-killed ADR-3 (n = 24), the systolic blood pressure and mean blood pressure were significantly decreased after 6 months of intake. There was no obvious change in serum inflammatory cytokines or antioxidant proteins in participants after intaking ADR-1 or ADR-3, except for a reduction in IL-1β in the ADR-3 consumption group after 6 months of intake. With the analysis of fecal microflora, we found that L. reuteri or Bifidobacterium spp. were significantly increased in the ADR-1 and ADR-3 consumption groups, respectively, after 6 months of intake. Interestingly, a significant reduction in HbA1c was observed in the ADR-1 and ADR-3 consumption participants who displayed at least an 8-fold increase in fecal L. reuteri. We also observed that there was a significantly positive correlation between Bifidobacterium spp. and Lactobacillus spp. in participants with increased levels of fecal L. reuteri. In the ADR-1 intake group, the fecal Lactobacillus spp. level displayed a positive correlation with Bifidobacterium spp. but was negatively correlated with Bacteroidetes. The total level of fecal L. reuteri in participants in the ADR-3 consumption group was positively correlated with Firmicutes. In conclusion, L. reuteri strains ADR-1 and ADR-3 have beneficial effects on T2DM patients, and the consumption of different strains of L. reuteri may influence changes in intestinal flora, which may lead to different outcomes after probiotic intake.

Research Insights

Lactobacillus reuteri MAK02L14R→Increased Lactobacillus Levels
With the analysis of fecal microflora, we found that L. reuteri or Bifidobacterium spp. were significantly increased in the ADR-1 and ADR-3 consumption groups, respectively, after 6 months of intake.
Effect
Beneficial
Effect size
Large
Lactobacillus reuteri MAK02L14R→Increased Probiotic Co-existence
In the ADR-1 intake group, the fecal Lactobacillus spp. level displayed a positive correlation with Bifidobacterium spp. but was negatively correlated with Bacteroidetes.
Effect
Beneficial
Effect size
Small
Lactobacillus reuteri MAK02L14R→Reduced Blood HbA1c Levels
Significant reductions in HbA1c and serum cholesterol were observed in participants in the live ADR-1 consumption group (n = 22) after 3 months of intake when compared with those in the placebo group (n = 22).
Effect
Beneficial
Effect size
Moderate
Lactobacillus reuteri MAK02L14R→Reduced Interleukin-1β Levels
There was no obvious change in serum inflammatory cytokines or antioxidant proteins in participants after intaking ADR-1 or ADR-3, except for a reduction in IL-1β in the ADR-3 consumption group after 6 months of intake.
Effect
Beneficial
Effect size
Small
Lactobacillus reuteri MAK02L14R→Reduced Serum Cholesterol Levels
Significant reductions in HbA1c and serum cholesterol were observed in participants in the live ADR-1 consumption group (n = 22) after 3 months of intake when compared with those in the placebo group (n = 22).
Effect
Beneficial
Effect size
Moderate
Lactobacillus reuteri UALre-16→Increased Bifidobacterium Levels
With the analysis of fecal microflora, we found that L. reuteri or Bifidobacterium spp. were significantly increased in the ADR-1 and ADR-3 consumption groups, respectively, after 6 months of intake.
Effect
Beneficial
Effect size
Moderate
Lactobacillus reuteri UALre-16→Increased Fecal Lactobacillus reuteri Levels
With the analysis of fecal microflora, we found that L. reuteri or Bifidobacterium spp. were significantly increased in the ADR-1 and ADR-3 consumption groups, respectively, after 6 months of intake.
Effect
Beneficial
Effect size
Moderate
Lactobacillus reuteri UALre-16→Reduced Blood HbA1c Levels
Significant reductions in HbA1c and serum cholesterol were observed in participants in the live ADR-1 consumption group (n = 22) after 3 months of intake when compared with those in the placebo group (n = 22).
Effect
Beneficial
Effect size
Moderate
Lactobacillus reuteri UALre-16→Reduced Interleukin-1β Levels
There was no obvious change in serum inflammatory cytokines or antioxidant proteins in participants after intaking ADR-1 or ADR-3, except for a reduction in IL-1β in the ADR-3 consumption group after 6 months of intake.
Effect
Beneficial
Effect size
Small
Lactobacillus reuteri UALre-16→Reduced Mean Blood Pressure
Although there was no significant difference in the HbA1c serum level among participants who consumed heat-killed ADR-3 (n = 24), the systolic blood pressure and mean blood pressure were significantly decreased after 6 months of intake.
Effect
Beneficial
Effect size
Large
Lactobacillus reuteri UALre-16→Reduced Serum Cholesterol Levels
Significant reductions in HbA1c and serum cholesterol were observed in participants in the live ADR-1 consumption group (n = 22) after 3 months of intake when compared with those in the placebo group (n = 22).
Effect
Beneficial
Effect size
Moderate
Lactobacillus reuteri UALre-16→Reduced Systolic Blood Pressure
Although there was no significant difference in the HbA1c serum level among participants who consumed heat-killed ADR-3 (n = 24), the systolic blood pressure and mean blood pressure were significantly decreased after 6 months of intake.
Effect
Beneficial
Effect size
Large