Mediating pre-diabetes with synbiotics: study

Results from the digital nutrition study on 192 subjects (sponsored by Evonik Operations and published in Nutrition)​ indicate the formula “is an effective and convenient approach to counteract hyperglycaemia​”, according to the authors.

Four weeks of daily intake had a “relevant impact on improving risk factors for metabolic disorders”​, especially in pre-diabetics, reducing their fasting blood glucose, glycated haemoglobin (HbA1c) levels, body weight, and improving glucose tolerance.

“The significant changes in these parameters referred to this subgroup (34.4% of the total cohort), while the healthy participants remained within their initial normoglycemic range,”​ they write.

“To our knowledge, the study presented here is the first to show a positive effect of a probiotic (or synbiotic)-based supplement in this population.”​

Promoting butyrate​

Hyperglycaemia, or prediabetes, manifests from impaired glucose tolerance and elevated fasting plasma glucose and is a risk factor for type 2 diabetes (T2D). However, disease onset can be prevented with treatment to optimise blood glucose homeostasis.

“The clinically asymptomatic nature of this risk factor and the difficulty of adhering to lifestyle-based intervention strategies - primarily targeting diet and physical activity -explain the continuing rise of T2D and cardiovascular disease (CVD) prevalence worldwide​,” the authors explain.

Prebiotics have been explored to promote favourable microbiota conditions, such as butyrate that regulates metabolic responses to food and can help regulate blood glucose, but effective outcomes require high consumption which can cause adverse effects.

An alternative approach is the direct application of butyrate-producing bacteria, like Bacillus subtilis​, the authors write.

A recent study on the synbiotic formula used in the present study demonstrated its ability to change the composition and activity of gut microbiome to encourage butyrate production that helps modulate glucose, cholesterol, and satiety hormone levels in young male subjects.

“The butyrogenic activity of Ala-Gln can be attributed to glutamine which is hydrolysed to glutamic acid and then catabolized to butyric acid. The alanine residue increases the stability of the dipeptide, serves as a spore germination trigger, and supports ​Bacillus subtilis metabolism.”​

The cohort in the current study is more representative of the general population, in terms of age, gender, weight and glucose control, compared to previous trials, enabling a better overview of global benefits, they add.

Non-clinical protocol​

The single-arm six-week study was performed in a non-clinical, real-life setting with participants recruited through social media channels. In the initial 14-day test phase, subjects were required to record meals and physical activity using Perfood’s MillionFriends App and consumed standardised test meals. Pre-diabetic participants were 53% female (33) and 46% male (29).

The intervention involved consumption of two capsules daily containing the synbiotic formula Samana Force (developed by Evonik Operations) for three weeks. Participants were requested to maintain their normal diet during this period.

Capsules comprised 2 × 109 CFU (colony forming unit) Bacillus subtilis​ DSM 32315, 290 mg L-alanyl-L-glutamine, 90 mg Curcuma extract, 90 mg green tea extract, 5 mg zinc, 0.56 mg vitamin B6, 20 µg D-biotin, 0.75 µg vitamin B12, 4 µg vitamin D, and 2.4 mg pantothenic acid.

Baseline and subsequent results (after 14 days) were collected using a sensor for continuous glucose monitoring (CGM) to evaluate glycaemic responses and blood glucose levels. Weekly questionnaires were completed to record intake behaviour and adherence to study protocol, and digestion and general well-being were monitored throughout.

Postprandial improvements​

Supplementation improved postprandial glucose response, fasting glucose level, calculated HbA1c, and body weight, particularly among participants at risk of developing diabetes or metabolic syndrome.

“The effects observed were robust even in such a very heterogeneous population and not overruled by the habitual diet and usual lifestyle,”​ the authors’ comment.

However, improved glucose control could not be attributed to microbiome composition and was more likely due to greater “interindividual variability in gut microbiota and host responsiveness​”, they say.

“The only microbiome effect in the current investigation was a shallow change in the ​Firmicutes/Bacteroidetes ratio when comparing the start and the end of the observation in prediabetic participants.”​

This presents a challenge when predicting microbiota modulation in response to dietary intervention, they maintain.

Furthermore, while Hb1Ac decreased by 0.20%, it was difficult to draw any conclusion regarding the extent of the change over the study period, since HbA1c measures an approximate three-month average of blood glucose concentration.

Source: Nutrition​

Published online, December 8, 2022: http://doi.org/10.3389?fnut.2022.2002419​

‘A nutritional supplement based on a synbiotic combination of Bacillus subtilis DSM 32315 and L-alanyl-L-glutamine improves glucose metabolism in healthy prediabetic subjects – A real-life post-marketing study’​

Authors:  Anna Kordowski, Vivian Valeska Tetzlaff-Lelleck, Bodo Speckmann, Gunnar Loh, Axel Künstner, Franziska Schulz, Torsten Schröder, Martin Smollich, Christian Sina and Heike tom Dieck