This research was funded by the National Key R&D Program of China, China Dairy Industry Association Dairy Science and Technology Innovation Fund – Mengniu Special Research Support Project, and Major cooperation projects between Chinese Academy of Engineering and local authorities.
It aimed to evaluate the effects of the probiotic Bifidobacterium animalis subsp. lactis MN-Gup (MN-Gup) and a synbiotic mixture of MN-Gup and galactooligosaccharide (MN-Gup-GOS) on glycaemic control in type 2 diabetes patients.
Researchers found that the MN-Gup-GOS synbiotics were more effective in improving type 2 diabetes than MN-Gup alone, likely due to their stronger impact on gut bacteria.
This led to beneficial changes in bile acids, which help regulate blood sugar by improving insulin sensitivity. These changes also triggered a rise in glucagon-like peptide-1 (GLP-1), a hormone that supports insulin release, reduces excess sugar production, and slows digestion. These help to lower fasting blood sugar levels more effectively.
“The auxiliary effect of synbiotics MN-Gup-GOS on reducing FBG levels surpassed that of MN-Gup probiotics alone in type 2 diabetes patients, potentially attributed to the enhanced modulation of gut microbiota, bile acids, and GLP-1 secretion,” wrote researchers in Clinical Nutrition.
The concept of combining probiotics with selected prebiotics to enhance the health benefits of individual probiotics and prebiotic components is theoretically favourable. However, its practical demonstration within the same studies and populations remains limited.
Furthermore, findings from latest studies may not have accurately compared the effects of synbiotics versus probiotics.
According to researchers, MN-Gup is a promising probiotic with the potential to enhance glucose metabolism and exhibit a synergistic effect when co-cultured with GOS in vitro.
They therefore wanted to explore whether a synbiotic-probiotic combination with MN-Gup can enhance ecological properties, such as colonisation, or enhance health benefits compared to probiotics alone. They also wanted to explore the underlying mechanisms from the perspective of gut microbiota and metabolites.
The study
For this 12-week RCT, researchers studied the effects of Bifidobacterium animalis subsp. lactis MN-Gup (MN-Gup) and a synbiotic mixture of MN-Gup and galactooligosaccharide (MN-Gup-GOS) on glycemic control in type 2 diabetes patients.
This randomised, double-blind, placebo-controlled clinical trial recruited 120 type 2 diabetes patients.
The primary objective was to study the effects of synbiotics and probiotics on fasting blood glucose (FBG).
Secondary outcomes including haemoglobin A1C (HbA1C), insulin, homeostatic model assessment of insulin resistance (HOMA-IR), inflammatory indicators, oxidative stress indicators, gastrointestinal hormones, gut microbiota, and bile acids (BAs) were also analysed.
Prior to the intervention, each participant underwent a one-week washout period. During this time, the participants were instructed to abstain from consuming foods containing probiotics.
Each participant was directed to consume a prescribed daily dose of the intervention product and advised not to make any changes to their regular diet, exercise routine, or diabetes medication regimen. Participants were monitored every four weeks and provided with a four-week supply of intervention products at each visit.
The placebo, probiotics, and synbiotics were all provided as solid beverage powders, packaged in identical individual sachets. These were provided by Sanhe Fucheng Biotechnology Co., Ltd.
Participants were randomised into three equal groups.
The probiotics group received MN-Gup, with each sachet containing 0.1g of MN-Gup powder, delivering five 1010 colony-forming units (CFU) of viable bacteria, along with 3.4g of maltodextrin.
The synbiotics group received MN-Gup-GOS, with each sachet consisting of 0.1g of MN-Gup powder with five 1010 CFU of viable bacteria, 0.9g of GOS, and 2.5g of maltodextrin.
The control group received a placebo, with each sachet containing 3.5g of maltodextrin.
Participants were instructed to take the products twice daily, one sachet at a time, 30 minutes after lunch and dinner. The powders were poured into warm water, stir until fully dissolved, then consumed.
Effects on glucose metabolism
The synbiotic group saw a significantly greater reduction in fasting blood sugar, dropping by 0.69mmol/L compared to the placebo group, and by 0.59mmol/L compared to probiotic group.
“In clinical practice, a reduction in FBG of 0.5mmol/L is considered impactful. In this study, the MN-Gup-GOS synbiotic intervention led to a significant reduction in FBG levels, with a decrease of 0.69mmol/L compared to the placebo group and 0.59mmol/L compared to the MN-Gup probiotic group,” said researchers.
There was also a rise in GLP-1 levels from around 17pmol/L pre-intervention to 19pmol/L in the MN-Gup group and 20pmol/L in the MN-Gup-GOS group. The placebo group remained unchanged at approximately 17pmol/L.
“These findings are clinically significant, which suggest that MN-Gup-GOS synbiotics offer a superior approach to managing FBG levels in patients with type 2 diabetes,” said researchers.
There were also reductions in on inflammatory markers and oxidative stress levels.
After the intervention, Tumor necrosis factor alpha (TNF-α) levels decreased from approximately 450pg/mL pre-intervention to around 380pg/mL in the MN-Gup-GOS group. The placebo group showed little change, remaining close to 460pg/mL.
Similarly, gluthatione (GSH) levels increased from about 3.5mg/L pre-intervention to approximately 4.5mg/L in the MN-Gup group and nearly 5.0mg/L in the MN-Gup-GOS group. The placebo group remained around 3.5mg/L.
Reactive oxygen species (ROS) levels, which were initially about 82mg/mL, showed a slight reduction to 78mg/mL in the MN-Gup-GOS group, while the MN-Gup and placebo groups remained largely unchanged at around 82mg/mL.
The results suggest a potential synergistic effect of MN-Gup-GOS in addressing the intricate interplay of inflammation and oxidative stress in type 2 diabetes, said researchers.
However, there were no notable differences in other markers of blood sugar control – HOMA-IR decreased by 0.64 in synbiotic group, 0.38 in the probiotic group, and 0.20 in the placebo group. Additionally, insulin levels for the synbiotic, probiotic, and placebo groups changed by -0.81µIU/mL, -0.19µIU/mL, and -0.30 µIU/mL, respectively. HbA1c reduced by 0.31% in the synbiotic group, 0.12% in the probiotic group, and 0.13% in the placebo group. None of these differences reached statistical significance.
Nonetheless, researchers concluded that MN-Gup-GOS demonstrated superior efficacy in reducing FBG levels compared to MN-Gup alone.
“This improvement may be attributed to enhanced modulation of gut microbiota, bile acid profiles, and serum GLP-1 levels,” said researchers.
“These findings highlight that synbiotics offer greater effectiveness in enhancing glycaemic control compared to probiotics alone. Further well-designed studies are needed to elucidate the exact mechanisms underlying these effects,” they concluded.
Source: Clinical Nutrition
DOI: https://doi.org/10.1016/j.clnu.2024.11.042
“Effects of synbiotics surpass probiotics alone in improving type 2 diabetes mellitus: A randomized, double-blind, placebo-controlled trial”
Authors: Chao Zhang, Qi Zhang et al.
