Supplemental probiotics may improve glycemic control Original paper

In this meta-analysis of randomized controlled trials, supplementation with probiotics improved various markers of glycemic control in adults with type 2 diabetes. This study found that the effect of probiotics may be modified by factors like the source and type of probiotics, as well as the participants’ BMI.

This Study Summary was published on September 21, 2023.

Quick Summary

In this meta-analysis of randomized controlled trials, supplementation with probiotics improved various markers of glycemic control in adults with type 2 diabetes. This study found that the effect of probiotics may be modified by factors like the source and type of probiotics, as well as the participants’ BMI.

What was studied?

The effects of supplementation with probiotics on biomarkers of glycemic control, including insulin, fasting glucose, HbA1c, and HOMA-IR.

Who was studied?

A total of 1,827 adults (average ages of 44–65) with diagnosed type 2 diabetes.

The percentages of men and women in the participant population were not reported.

How was it studied?

The researchers conducted a systematic review and meta-analysis of 30 randomized controlled trials, of which 25 were double-blinded, 1 was single-blinded, and 5 were unblinded. The study locations also varied: 24 studies were conducted in Asia, 3 in Europe, 2 in South America, and 1 each in Africa and Australia. No studies were conducted in the U.S.

The daily doses ranged from 10 million (1x107) to 600 billion (6x1011) colony-forming units. The participants ingested the probiotics as foods (bread, yogurt, and fermented milk) or as supplements (capsules, powder, and tablets). Most studies used capsules (9 studies), followed by yogurt, powder, and fermented milk (4 studies each), and also tablets, bread, and milk (2 studies each). The study duration ranged from 4 to 36 weeks (11 weeks on average).

Biomarkers of glycemic control included insulin, fasting glucose, hemoglobin A1c (HbA1c or glycated hemoglobin, a measure of average blood sugar levels over the past 2–3 months), and insulin resistance assessed by the homeostasis model assessment index for insulin resistance (HOMA-IR). The effect of probiotics on these glycemic biomarkers was evaluated compared to placebo in all studies. The researchers also determined the degree of heterogeneity to assess the variability in the effect sizes between the meta-analyzed studies.

Subgroup analyses were performed to evaluate whether the outcomes were influenced by the following factors:

  • Dose of probiotics: higher doses (>10 billion CFU) vs. lower doses (≤10 billion CFU)
  • Study duration: longer (>8 weeks) vs. shorter follow-ups (≤8 weeks)
  • BMI: participants with obesity (BMI >30) vs. those without obesity (BMI ≤30)
  • Ethnicity: participants of European origin vs. those of Asian origin
  • Type of probiotics: food-type probiotics (e.g., yogurt and fermented milk) vs. processed probiotics (e.g., powder, capsules, and tablets)
  • Genus of probiotics: Bifidobacterium (one of the major genera of beneficial bacteria found in the human gut)[1] vs. Lactobacillus (another major genera of beneficial bacteria found in the gut, mouth, and genital tract)[1] vs. a combination of both

The researchers also evaluated the quality of the studies to identify potential selection bias, detection bias, attrition bias, reporting bias, and performance bias.

What were the results?

Probiotic supplementation had a small favorable effect on biomarkers of glycemic control and reduced insulin, fasting glucose, HbA1c, and HOMA-IR. The degree of heterogeneity (i.e., variations in outcomes across studies) was low for insulin, substantial for HbA1c, and moderate for fasting glucose and HOMA-IR.

Subgroup analysis revealed the following findings:

  • Probiotics produced larger reductions in HbA1c and fasting glucose in participants with obesity compared to participants without obesity.
  • Probiotics produced larger reductions in fasting glucose and HbA1c in participants who were Caucasian (the term used by the study authors) compared to participants who were Asian.
  • Food-sourced probiotics (e.g., yogurt and fermented milk) were more effective at improving insulin and HbA1c than processed probiotics such as powders, capsules, and tablets.
  • Probiotics of the genus Bifidobacterium had more pronounced effects on HbA1c and fasting glucose than Lactobacillus or a combination of both.

Probiotics supplementation improves glycemic control in adults with type 2 diabetes.

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Four studies were classified as high quality (low risk of bias), 19 as moderate quality (low risk of bias except for one or more criteria with an unclear risk of bias), and 7 as low quality.

The big picture

Probiotics like Bifidobacterium and Lactobacillus can play a useful role in glycemic control. They can ferment dietary fiber to produce short-chain fatty acids (SCFAs) like acetate and propionate (although this capacity varies considerably between probiotic types), thereby enhancing glucose metabolism and boosting insulin sensitivity.[2] Probiotics may also foster a healthier gut by altering the microbiota composition and improving intestinal barrier function, thus preventing harmful bacterial components like LPS from entering the bloodstream.[3] On the hormonal front, animal studies suggest that probiotics might influence the secretion of incretin hormones such as glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), both of which are useful for blood glucose control.[3] Some strains of probiotics also seem to have anti-inflammatory properties, which can be beneficial because inflammation can lead to insulin resistance.[4] Additionally, probiotics can influence lipid metabolism,[5] bile acid metabolism,[6] and the gut-brain axis[7] — all pathways that can affect glucose metabolism.

This compelling mechanistic evidence has motivated extensive research on the effects of probiotics on humans. In addition to the summarized study, numerous prior meta-analyses[8][9][10][11] also concluded that probiotic supplementation could optimize several glycemic control markers. The consensus is clear: there’s burgeoning evidence that probiotics can benefit adults with type 2 diabetes. In contrast to previous research, the summarized study stands out by delving deeper into variables that could influence probiotics’ effects on glycemic control, including dose, ethnicity, study duration, and probiotic type and genus. Hence, these findings can offer more nuanced guidance for probiotic supplementation.

Dose and duration: Although these results were not statistically significant, there was a trend for better outcomes when ingesting larger doses (>10 billion CFU) and when supplementing for longer durations (>8 weeks). A lack of statistical power might explain the nonsignificant findings because some subgroup analyses only had a few studies and participants. Further studies are essential to provide definitive recommendations on the optimal dose and duration of supplemental probiotics.

BMI: People with obesity may derive greater benefits from probiotics. This may be because obesity often correlates with an altered microbiota, which might adversely affect glucose metabolism. Additionally, people with both obesity and type 2 diabetes typically have more compromised glycemic control, offering a greater scope for improvement.

Ethnicity: The study hints that Caucasians (a term used by the authors) might gain more benefit from probiotics than Asians. This discrepancy could stem from differences in gut microbiota compositions and diversity inherent to each population, which variations in dietary habits and nutrient intakes might contribute to. Furthermore, differential absorption and metabolic responses to similar microbial strains may arise due to the historically distinct evolutionary pressures that shaped the gut-brain-metabolism axis in these populations.

Type of probiotics: The popular advice to favor whole foods over processed ones seems appropriate even for probiotics. The data showed that food-based probiotics like yogurt and fermented milk outperformed processed probiotics consumed as pills, capsules, and powders. Although speculative, this superiority could be attributed to the protective qualities of fermented foods that shield probiotics from the harsh acidic conditions within the stomach. If this is true, more microbes would reach and colonize the gut in a viable state.

Genus of probiotics: Bifidobacterium was notably more effective in enhancing glycemic control than Lactobacillus alone or both combined. A possible reason is that Bifidobacterium has a greater capacity to synthesize SCFAs, which, as previously mentioned, may have a variety of biological effects that improve glucose metabolism.[12]

In conclusion, the intricate relationship between probiotics and glycemic control demonstrates how our gut microbiota can influence overall health. With strains like Bifidobacterium showing promise in managing glycemic levels, the potential benefits for people with type 2 diabetes are encouraging. However, as with any emerging evidence, it’s crucial to approach the topic with nuance, considering factors like dose, duration, and probiotic type. The existing body of evidence underscores the importance of ongoing research to harness the full potential of probiotics in diabetes management.

Anything else I need to know?

Although this study has many strengths, it’s essential to acknowledge its limitations. First, most of the included studies were conducted in Iran, which could curtail its relevance to wider global populations. Second, some subgroup analyses were performed with few studies, which could weaken the statistical conclusions for some factors. Third, the persistent heterogeneity within subgroup analyses suggests the presence of unknown factors that weren’t accounted for in the study. Finally, because most of the RCTs ranged from 4 to 24 weeks in duration, the findings about the potential long-term effects of probiotics should be interpreted with caution.

This Study Summary was published on September 21, 2023.

References

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  2. ^Portincasa P, Bonfrate L, Vacca M, De Angelis M, Farella I, Lanza E, Khalil M, Wang DQ, Sperandio M, Di Ciaula AGut Microbiota and Short Chain Fatty Acids: Implications in Glucose Homeostasis.Int J Mol Sci.(2022-Jan-20)
  3. ^Zheng Y, Zhang Z, Tang P, Wu Y, Zhang A, Li D, Wang CZ, Wan JY, Yao H, Yuan CSProbiotics fortify intestinal barrier function: a systematic review and meta-analysis of randomized trials.Front Immunol.(2023)
  4. ^de Luca C, Olefsky JMInflammation and insulin resistance.FEBS Lett.(2008-Jan-09)
  5. ^Wu T, Wang G, Xiong Z, Xia Y, Song X, Zhang H, Wu Y, Ai LProbiotics Interact With Lipids Metabolism and Affect Gut Health.Front Nutr.(2022)
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  8. ^Tao YW, Gu YL, Mao XQ, Zhang L, Pei YFEffects of probiotics on type II diabetes mellitus: a meta-analysis.J Transl Med.(2020-Jan-17)
  9. ^Li G, Feng H, Mao XL, Deng YJ, Wang XB, Zhang Q, Guo Y, Xiao SMThe effects of probiotics supplementation on glycaemic control among adults with type 2 diabetes mellitus: a systematic review and meta-analysis of randomised clinical trials.J Transl Med.(2023-Jul-06)
  10. ^Rittiphairoj T, Pongpirul K, Janchot K, Mueller NT, Li TProbiotics Contribute to Glycemic Control in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis.Adv Nutr.(2021-Jun-01)
  11. ^Liang T, Wu L, Xi Y, Li Y, Xie X, Fan C, Yang L, Yang S, Chen X, Zhang J, Wu QProbiotics supplementation improves hyperglycemia, hypercholesterolemia, and hypertension in type 2 diabetes mellitus: An update of meta-analysis.Crit Rev Food Sci Nutr.(2021)
  12. ^Vlasova AN, Kandasamy S, Chattha KS, Rajashekara G, Saif LJComparison of probiotic lactobacilli and bifidobacteria effects, immune responses and rotavirus vaccines and infection in different host species.Vet Immunol Immunopathol.(2016-Apr)