What’s the Latest in Prebiotic Research? – August 2023 Edition

The effect of a lozenge combining prebiotic arginine and probiotics on caries increment in children during 10–12 months, a randomized clinical trial

Dental caries develops through a shift in the oral microbiota from symbiosis to dysbiosis, is considered a public health issue, and affects 60-90% of school-aged children globally. This randomized, double-blinded, placebo-controlled, parallel clinical trial investigated the effects of daily use of an arginine and probiotic containing-lozenge for 10-12 months on caries increment, gingivitis, and plaque occurrence in children aged 5-9 years old. Three hundred and forty-three children were randomly assigned to one of two study arms: an intervention group receiving the lozenge with Lacticaseibacillus rhamnosus, LGG® (DSM33156) (1 × 109 colony forming units (CFU)), Lactobacillus paracasei subsp. paracasei, L. CASEI 431® (DSM33451) (1 × 109 CFU), prebiotic (arginine 20 mg ~ 2%), and xylitol (627 mg); and a placebo group receiving identical lozenges containing xylitol (671 mg). The primary study endpoint was to measure caries increment in different dentitions (primary, permanent, and mixed) along with the secondary endpoint, which was changes in plaque and gingivitis. Two hundred and eighty-eight children completed the follow-up. The results demonstrated that in healthy children with a low risk of developing caries, daily consumption of a prebiotic + probiotic containing lozenge had a statistically significant reduction in caries increment but had no effect on mean dental plaque or gingivitis. As such, the lozenge may be useful as a supplementary tool with toothbrushing using fluoride toothpaste for caries management. 

Key takeaways:

  • Dental caries is a public health issue that mainly affects school-aged children.
  • Dental caries develops due to repeated periods of pH drops in the oral biofilm caused by carbohydrate-induced acid production, which can eventually lead to teeth dissolution. 
  • Supplementing fluoridated toothpaste with prebiotics and probiotics has gained interest for its potential to reverse oral dysbiosis and prevent dental caries.
  • A lozenge containing prebiotic arginine and two probiotic strains was safe and demonstrated a statistically significant effect in reducing caries increment in children, but no effect was observed on mean plaque or gingivitis. 

Access to the study: https://pubmed.ncbi.nlm.nih.gov/37356561/ 

Reference: Pørksen, C. J., Keller, M. K., Damholt, A., Frederiksen, A. K. S., Ekstrand, K. R., Markvart, M., Larsen, T., & Bakhshandeh, A. (2023). The effect of a lozenge combining prebiotic arginine and probiotics on caries increment in children during 10-12 months, a randomized clinical trial. Journal of dentistry, 135, 104599. https://doi.org/10.1016/j.jdent.2023.104599 

Functional response to a microbial synbiotic in the gastrointestinal system of children: a randomized clinical trial

Increasing research is pointing toward the role of the gut microbiome composition in regulating bowel movements in children. As such, oral microbial therapies are being studied for various gastrointestinal disorders, including constipation. This multicenter, randomized, double-blinded, placebo-controlled pilot study evaluated the efficacy of a synbiotic formulation on increasing weekly bowel movements (WBMs) in constipated children. Sixty-four children aged 3-17 years randomly received either the synbiotic formulation (comprised of 6.2 g mixed-chain length oligosaccharides and >1010 CFUs of nine microbial strains including Bifidobacterium breve SD-B632-IT, Bifidobacterium breve SD-BR3-IT, Bifidobacterium lactis SD-Bi07-US, Bifidobacterium lactis SD-CECT8145-SP, Bifidobacterium longum SDCECT7347-SP, Lacticaseibacillus casei SD-CECT9104-SP, Lacticaseibacillus rhamnosus SD-GG-BE, Ligilactobacillus salivarius SD-LS1-IT, and Lactobacillus acidophilus SD-NCFM-US) or the placebo (maltodextrin and fructose) for 84 days. Stool microbiota at baseline and intervention completion were analyzed, with the primary outcome being a change from the baseline of WBMs in the treatment group versus placebo. The result was a significant increase in WBM numbers in children with low baseline WBMs. Sequencing revealed that low baseline microbial richness in the treatment group may significantly anticipate constipation improvement. As such, these findings support multi-species-synbiotic intervention use to improve digestive health in pediatric populations.

Key takeaways:

  • Synbiotic interventions may have a positive effect on gastrointestinal disorders in children.
  • Using a synbiotic formulation comprised of nine microbial strains and mixed-chain-length oligosaccharides improved the number of spontaneous WBMs in children in the intervention group compared to the placebo group.
  • The synbiotic intervention increased the abundance of bifidobacteria.
  • Baseline microbiome richness may serve as a biomarker to predict the response to treatment.

Access to the study: https://pubmed.ncbi.nlm.nih.gov/36319696/ 

Reference: Tierney, B. T., Versalovic, J., Fasano, A., Petrosino, J. F., Chumpitazi, B. P., Mayer, E. A., Boetes, J., Smits, G., Parkar, S. G., Voreades, N., Kartal, E., Al-Ghalith, G. A., Pane, M., Bron, P. A., Reid, G., Dhir, R., & Mason, C. E. (2023). Functional response to a microbial synbiotic in the gastrointestinal system of children: a randomized clinical trial. Pediatric research, 93(7), 2005–2013. https://doi.org/10.1038/s41390-022-02289-0

Microbiome-modulating nutraceuticals ameliorate dyslipidemia in type 2 diabetes: A systematic review, meta-analysis, and meta-regression of clinical trials

While type 2 diabetes (T2D) and cardiovascular disease (CVD) are global health concerns increasing in prevalence, the two share a link via diabetic dyslipidemia. In addition, these metabolic diseases share a connection with gut microbiome dysbiosis, where microbiome-modulation therapies may be used to ameliorate metabolic imbalances observed in patients with these diseases. This study conducted a systemic review, meta-analysis, and meta-regression after searching five databases for clinical trials investigating the effects of probiotics (pro), prebiotics (pre), and synbiotics on lipid profiles published until April 2022. The study retrieved 42 studies involving 2692 subjects with 47 trial comparisons conducted, which revealed that the administration of pro/pre/synbiotics, compared to placebo/control, was associated with a statistically significant increase in high-density lipoprotein and statistically significant decreases in total cholesterol, low-density lipoprotein, very-low-density lipoprotein, and triglycerides. Nonetheless, intervention characteristics such as dosage, duration and patient characteristics like age and baseline BMI may have influenced these results. In conclusion, this study shows that adjunct supplementation with pro/pre/synbiotics ameliorates dyslipidemia in diabetic individuals and potentially reduces CVD risk. 

Key takeaways:

  • T2D and CVD are intrinsically linked by diabetic dyslipidemia. 
  • Pro/pre/synbiotics may be used as part of diet and complementary therapy to improve dyslipidemia as a risk factor for CVD among T2D patients. 
  • This systemic review, meta-analysis, and meta-regression revealed that pro/pre/synbiotic supplementation enhances lipid profiles in T2D patients, showing statistical and potentially clinical significance. 

Access to the study: https://pubmed.ncbi.nlm.nih.gov/37381688/ 

Reference: Kaul, R., Paul, P., Harfouche, M., Saliba, R., & Chaari, A. (2023). Microbiome-modulating nutraceuticals ameliorate dyslipidemia in type 2 diabetes: A systematic review, meta-analysis, and meta-regression of clinical trials. Diabetes/metabolism research and reviews, e3675. Advance online publication. https://doi.org/10.1002/dmrr.3675 

Effect of prebiotics, probiotics, synbiotics on depression: results from a meta-analysis

Depression is ranked by the World Health Organization (WHO) as the 3rd leading cause of global disease burden, causing more years lost to disability than any other condition. With the new knowledge on the microbiota-gut-brain axis, gut microbiota management tools such as prebiotics, probiotics, and synbiotics may be used to treat psychiatric conditions, including depression. This meta-analysis evaluated the effects of prebiotics, probiotics, and synbiotics on patients with depression. Six databases were searched for relevant RCTs published before July 2022, retrieving 13 studies involving 786 participants. Most participants were females (>50% in all studies) and ranged in age from 34.5 to 53 years. Of the included studies, nine were on probiotics, one on prebiotics, and one on synbiotics. The results showed a significant improvement in symptoms of depression with prebiotics, probiotics, and synbiotics compared to placebo. However, subgroup analysis confirmed the significant antidepressant effects of probiotic agents only, regardless of whether single or multiple strains were applied. Nonetheless, data suggested that patients with mild or moderate depression could both benefit from these interventions. Interestingly, studies with a lower female proportion (<70 %) experienced a higher reduction in depressive symptoms compared with those consisting of more that 70% females. Altogether, this systemic review revealed significant anti-depressive effects of probiotics and suggested further studies may be needed to confirm prebiotic and synbiotic effects.

Key takeaways:

  • Gut microbiota-manipulating agents may serve as novel approaches in treating mild-to-moderate depression.
  • This meta-analysis revealed significant antidepressant effects of probiotics.
  • Further research is needed to confirm the effects of prebiotics and synbiotics on depression.

Access the study: https://pubmed.ncbi.nlm.nih.gov/37386630/ 

Reference: Zhang, Q., Chen, B., Zhang, J., Dong, J., Ma, J., Zhang, Y., Jin, K., & Lu, J. (2023). Effect of prebiotics, probiotics, synbiotics on depression: results from a meta-analysis. BMC psychiatry, 23(1), 477. https://doi.org/10.1186/s12888-023-04963-x