Probiotics improve glycaemic response in type 1 diabetes patients – Taiwan-RCT

Fasting blood glucose levels and glycated haemoglobin (HbA1c) had significantly decreased in these patients, according to the findings. 

There were also changes in their gut microbiome and serum levels of cytokines.

Findings of the research were published in Frontiers in Endocrinology. ​

Unlike type 2 diabetes, the cause of type 1 diabetes mellitus (T1DM) remains unclear, while the former is related to factors such as weight gain.  

The study, performed at China Medical University Hospital, is a six-month randomised, double-blind, and placebo-controlled trial.

Fifty-nine patients with T1DM, age between six and 18, were randomised into two groups. Results from 56 patients were included for final analysis.  

The intervention group underwent the regular insulin injection therapy and capsules containing 10bn CFU of probiotics – which consisted of three strains, namely Lactobacillus salivarius​ subsp. salicinius​ AP-32, L. johnsonii​ MH-68, and Bifidobacterium animalis​ subsp. lactis​ CP-9.

The probiotic strains AP-32 and MH-68 were isolated from human gut and CP-9 strain from breast milk.

Provided by Taiwan-headquartered firm Bioflag Biotech, the probiotic blend is not yet commercialised.

On the other hand, the placebo group took the insulin therapy and placebo capsules that do not contain probiotics.

Post intervention, the subjects were followed up for three months, with their fasting blood glucose and HbA1c measured and analysed.

Their stool microbiota, serum levels of inflammatory cytokines and anti-inflammatory cytokine were also assessed.

Finding 1 – blood glucose level​

Fasting blood glucose levels had significantly decreased in patients who took the probiotics.

For instance, it dropped from an average of 185.4 mg/dL to 161.9 mg/dL, whereas there were not much changes in the placebo group, with fasting blood glucose recorded at 172.2 mg/dL and 171.5 mg/dL before and after intervention.

In addition, the amount of glycated haemoglobin also decreased in patients taking probiotics, with average glycated haemoglobin decreased from 9.3 per cent (78.0 mmol/mol) to 8.5 per cent (69.7 mmol/mol).

In the placebo group, it remained at 9.5 per cent (79.9 mmol/mol) before and after the trial.

Effects of the probiotics had persisted even three months after the intervention had ended, as the average fasting blood glucose and glycated haemoglobin levels were 163.9 mg/dL and 8.9 per cent respectively – lower than the baseline levels.

“At present study, it is suggested that probiotics plus regular insulin treatment would present steadier control of Glucose AC (fasting blood glucose) level and HbA1c than insulin treatment only,” ​the researchers said.

Finding 2 – gut microbiome​

Certain bacteria population had increased in the patients’ gut after probiotics supplementation – including Bifidobacterium animalis, Akkermansia muciniphila​ and Lactobacillus salivarius​.

Before the trial, the dominant gut microbiota phyla in both the groups were Actinobacteria, Bacteroidetes, Firmicutes, Proteobacteria, and Verrucomicrobia – with firmicutes accounting for the largest proportion.

“The colonised beneficial microbiota may play an important role in slowing down the levels of Glucose AC and HbA1c in patients with T1DM,”​ said the researchers.

They noted that the abundance of Akkermansia muciniphila​ has been reported to negatively correlate with glycated haemoglobin levels.  

Citing a previous study​, they said that obese children had lower levels of Akkermansia muciniphila​ in their gut microbiota and how Akkermansia muciniphila ​was present in higher amounts in semi-supercenternarians. 

“A. muciniphila can restore the gut barrier at the mucous layer, facilitate lipid metabolism, reduce fat mass accumulation, and reduce the incidence of fatty liver and hypercholesterol. ​This may account for the higher distribution of A. muciniphila among semi-supercentenarians.​

“In our study, patients with T1DM who received the novel probiotic product slowed down the declined rate of Akkermansia uncultured bacterium in their gut, compared with patients who received the placebo. ​

“The molecular mechanism underlying the modulation of glycemic levels by the colonised microbiota warrants further investigation,” ​the researchers said. 

Finding 3 – cytokines levels ​

The concentrations of pro-inflammatory cytokines, namely IL-8, IL-17, MIP-1β, RANTES, and TNF-α were significantly reduced in the group taking probiotics.

At the same time, the anti-inflammatory cytokine, TGF- β1 had significantly increased from 5624.2 pg/mL to 8034.4 pg/mL in the group taking probiotics.

For these patients, the serum levels of pro-inflammatory cytokines IL-8, TNF-α, and MIP-1β remained significantly lower than the baseline three months after they stopped receiving the intervention. 

“Previous studies ​discovered that​​ elevation in the concentrations of inflammatory cytokines such as TNF-α associated with glycemic control and cardiovascular risk factors among patients with T1DM. ​

“The results of this study suggested that probiotics may play an important role in reducing immune inflammatory cytokines and glycemic control in patients with T1DM. ​

“However, the mechanism by which the elevated inflammatory cytokines stimulate blood glucose (through which glucose transporters or insulin receptors) among patients with T1DM warrants further investigation,”​ the researchers said.

Source: Frontiers in Endocrinology ​

Adjuvant Probiotics of Lactobacillus salivarius subsp. salicinius AP-32, L. johnsonii MH-68, and Bifidobacterium animalis subsp. lactis CP-9 Attenuate Glycemic Levels and Inflammatory Cytokines in Patients With Type 1 Diabetes Mellitus​

DOI: 10.3389/fendo.2022.754401

Authors: Wang C-H et al​