by Bianca Garilli, ND and Ashley Jordan Ferira, PhD, RDN
Type 2 diabetes (T2D) is no longer a Western world phenomena, but rather a global epidemic, with research revealing an association between higher T2D rates and a country’s wealth or economic growth.1 As a clear example, in a publication titled “Prevalence of type 2 diabetes in the Arab world: impact of GDP and energy consumption”, it was observed that the higher a country’s gross domestic product (GDP), the higher the T2D prevalence.1 T2D rates in these regions include Kingdom of Saudi Arabia- 31.6%, Oman- 29%, Kuwait- 25.4%, Bahrain- 25%, and United Arab Emirates- 25%.1
Recognizing the worldwide impact of T2D, it is critical to identify underlying causes and practical, implementable tools for prevention and treatment. It is well documented that T2D is a chronic, inflammatory condition. Higher levels of lipopolysaccharides (LPS) have been observed in diabetic vs. non-diabetic individuals.2 LPS are Gram-negative bacterial fragments that are considered endotoxins, and can, if left untreated, overgrow in the gastrointestinal tract leading to increased gut permeability.3 A “leaky gut” environment increases the opportunity for these endotoxins to migrate out of the gut and into the circulation, ultimately contributing to systemic inflammation.3
Probiotics have been studied in various models to determine their effects on LPS growth and proliferation and whether targeted probiotic administration aimed at mitigating LPS effects can reduce systemic inflammation, in particular in the T2D population.4-5 The limitations of previous research included short-term duration (≤3 months) and the utilization of mono-strain supplementation.3
To augment the current literature on this topic, a longer study (6 months) was conducted in a randomized, double-blind, placebo-controlled fashion to examine the impact of probiotics on endotoxemia, inflammation, and cardiometabolic disease risk in Arab patients with T2D.3 In this study, 61 Saudi adults (35 females) aged 30-60 years completed the 6-month trial: 30 in the placebo group and 31 in the probiotic group.3 The placebo and probiotic groups were randomly allocated to powder sachets, to be dissolved in a glass of water twice daily, before breakfast and bedtime. The probiotic intervention provided 2.5 billion CFU/g BID and included the following strains: Bifidobacterium bifidum W23, Bifidobacterium lactis W52, Lactobacillus acidophilus W37, Lactobacillus brevis W63, Lactobacillus casei W56, Lactobacillus salivarius W24, Lactococcus lactis W19, and L. lactis W58.3 No additional therapeutics such as exercise or dietary recommendations were included during the course of the study in either group.3
In the probiotic group, significant changes in glycemic indices, lipid profile, inflammatory markers, endotoxin levels, and adipocytokine profile were observed at 6 months vs. baseline:3
- ↓ Circulating levels of endotoxin by ~70%
- ↓ Glucose by 38%
- ↓ Insulin by 38%
- ↓ HOMA-IR (surrogate marker of insulin resistance) by 64%
- ↓ TG by 48%
- ↓ Total cholesterol by 19%
- ↓ Total/HDL cholesterol ratio by 19%
- ↓ TNF-α by 67%
- ↓ IL-6 by 77%
- ↓ CRP by 53%
- ↓ Resistin by 53%
- ↑ Adiponectin by 72%
The improvements in endotoxin load, inflammation, and cardiometabolic profile over time in the probiotics group are noteworthy, but they were not clinically significant when compared to the placebo group.3 Comparing the probiotic intervention to the placebo group: There was a significant and clinically relevant decrease in HOMA-IR (↓64.2%) in the probiotic group.3 HOMA-IR is correlated with most other cardiometabolic indices measured, so one could posit a potentially broader cardiometabolic benefit from the probiotic intervention, but this and other hypotheses should be explored in a future study with an adequately powered sample size.
Why is this Clinically Relevant?
- T2D is a global epidemic, and efficacious anti-diabetes therapies are needed
- Probiotics that impact gut integrity, inflammation, and cardiometabolic pathophysiology represent a possible diabetes management approach
- In a clinical study, a multi-strain probiotic intervention in patients with T2D resulted in a clinically significant reduction in a surrogate marker of insulin resistance3
- Utilization of targeted probiotics as part of a personalized therapeutic plan in patients with T2D may help reduce inflammation and cardiovascular risk factors associated with this disease process, but further research is warranted
- Meo SA, Usmani AM, Qalbani E. Prevalence of type 2 diabetes in the Arab world: impact of GDP and energy consumption. Eur Rev Med Pharmacol Sci. 2017;21(6):1303-1312.
- Gomes JMG, Costa JA, Alfenas RCG. Metabolic endotoxemia and diabetes mellitus: a systematic review. Metabolism. 2017;68:133-144.
- Sabico S, Al-Mashharawi A, Al-Daghri NM, Wani K, Amer OE, Hussain DS, et al. Effects of a 6-month multi-strain probiotics supplementation in endotoxemic, inflammatory and cardiometabolic status of T2DM patients: a randomized, double-blind, placebo-controlled trial. Clin Nutr. 2018:pii:S0261-5614(18)31351-7.
- Rodes L, Khan A, Paul A, Coussa-Charley M, Marinescu D, Tomaro-Duchesneau C, et al. Effect of probiotics Lactobacillus and Bifidobacterium on gut-derived lipopolysaccharides and inflammatory cytokines: an in vitro study using a human colonic microbiota model. J Microbiol Biotechnol. 2013;23(4):518-526.
- Han C, Ding Z, Shi H, Qian W, Hou X, Lin R. The role of probiotics in lipopolysaccharide-induced autophagy in intestinal epithelial cells. Cell Physiol Biochem. 2016;38(6):2464-2478.