The Role of Synbiotics in Modulating the Gut–Brain Axis in Attentiondeficit/Hyperactivity Disorder: A Systematic Review

Authors

  • Elfrida Noor Auliya RS Unipdu Medika Jombang
  • Margarita M. Maramis RS Dr. Soetomo, Surabaya

DOI:

https://doi.org/10.59141/-.v8i1.518

Keywords:

ADHD, gut–brain axis, probiotics, prebiotics, synbiotics

Abstract

ADHD is a neurodevelopmental disorder involving gut microbiota dysbiosis and gut–brain pathways, suggesting synbiotics as a potential adjuvant therapy. Literature searches were conducted on electronic primary databases "PubMed", "EuropePMC", and "ScienceDirect" with a range published between 2020–2025. Studies were selected based on inclusion criteria and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The methodological quality of the included studies was evaluated using the Joanna Briggs Institute (JBI) Critical Appraisal Tools for randomized clinical trials. Of the 146 articles identified, five randomized clinical trial studies met the inclusion criteria. The available evidence suggests that synbiotic interventions have varied clinical effects in ADHD patients. More obvious benefits are mainly seen in the symptomatic aspects of inattention, with secondary impacts on impulse control and adaptive function of daily behavior, as well as inflammatory biomarkers and gut microbiota. No serious side effects were reported in any of the included studies. This systematic review suggests that synbiotics have the potential to modulate the two-way gut-brain communication pathway and provide domain-specific clinical benefits in subgroups of ADHD patients with specific clinical or biological characteristics. These findings support the role of synbiotics as adjuvant therapy, but are not enough to recommend it as a single therapy for the entire ADHD patient population in general.

Downloads

Download data is not yet available.

References

Al-Beltagi, M., Mani, B. S., Hantash, E. M., Al Zahrani, A. A., & Toema, O. (2025). Challenges in diagnosing attention-deficit/hyperactivity disorder in pediatric practice: A regional and global perspective. World Journal of Clinical Pediatrics, 14(4), 111684.

Allahyari, P., Abbas Torki, S., Aminnezhad Kavkani, B., et al. (2024). A systematic review of the beneficial effects of prebiotics, probiotics, and synbiotics on ADHD. Neuropsychopharmacology Reports, 44, 300–307. https://doi.org/10.1002/npr2.12416

Arteaga-Henríquez, G., Ramos-Sayalero, C., Ibañez-Jimenez, P., et al. (2024). Efficacy of a synbiotic in the management of adults with attention-deficit and hyperactivity disorder and/or borderline personality disorder and high levels of irritability: Results from a multicenter, randomized, placebo-controlled, "basket" trial. Brain, Behavior, and Immunity, 120, 360–371. https://doi.org/10.1016/j.bbi.2024.06.015

Diale, B. M., & Eseadi, C. (2024). Perspectives on Career Transitioning of Students with Attention Deficit Hyperactivity Disorder (ADHD). IGI Global.

Gandhi, D. N., Pande, D. N., Harikrishna, A., et al. (2024). Beyond the brain: Attention deficit/hyperactivity disorder and the gut-brain axis. Cureus. https://doi.org/10.7759/cureus.76291

Levy Schwartz, M., Magzal, F., Yehuda, I., et al. (2024). Exploring the impact of probiotics on adult ADHD management through a double-blind RCT. Scientific Reports, 14, 26830. https://doi.org/10.1038/s41598-024-77564-7

Lewis, N., Villani, A., & Lagopoulos, J. (2025). Gut dysbiosis as a driver of neuroinflammation in attention-deficit/hyperactivity disorder: A review of current evidence. Neuroscience, 569, 298–321. https://doi.org/10.1016/j.neuroscience.2025.04.018

Liu, Y., Zhang, P., & Sun, H. (2025). A narrative review of research advances in gut microbiota and microecological agents in children with attention deficit hyperactivity disorder (ADHD). Frontiers in Psychiatry, 16. https://doi.org/10.3389/fpsyt.2025.1588135

Musullulu, H. (2025). Evaluating attention deficit and hyperactivity disorder (ADHD): a review of current methods and issues. Frontiers in Psychology, 16, 1466088.

Novau-Ferré, N., Papandreou, C., Rojo-Marticella, M., et al. (2025). Gut microbiome differences in children with attention deficit hyperactivity disorder and autism spectrum disorder and effects of probiotic supplementation: A randomized controlled trial. Research in Developmental Disabilities, 161. https://doi.org/10.1016/j.ridd.2025.105003

Okeke, C., Chepchirchir, D., & Dodoo, S. (2025). Impacts of societal changes in neurodevelopmental disorder in children (ADHD).

Sabir, H., Khan, M., Imran, K., Nisa, Z.-U., & Amer, S. A. (2024). The prevalence of undiagnosed attention-deficit/hyperactivity disorder among undergraduate medical students: a survey from Pakistan. BMC Psychiatry, 24(1), 845.

Sankarganesh, P., Bhunia, A., Ganesh Kumar, A., et al. (2025). Short-chain fatty acids (SCFAs) in gut health: Implications for drug metabolism and therapeutics. Medicine in Microecology, 25, 100139. https://doi.org/10.1016/j.medmic.2025.100139

Silva, Y. P., Bernardi, A., & Frozza, R. L. (2020). The role of short-chain fatty acids from gut microbiota in gut-brain communication. Frontiers in Endocrinology, 11. https://doi.org/10.3389/fendo.2020.00025

Skott, E., Yang, L. L., Stiernborg, M., et al. (2020). Effects of a synbiotic on symptoms and daily functioning in attention deficit hyperactivity disorder – A double-blind randomized controlled trial. Brain, Behavior, and Immunity, 89, 9–19. https://doi.org/10.1016/j.bbi.2020.05.056

Steckler, R., Magzal, F., Kokot, M., et al. (2024). Disrupted gut harmony in attention-deficit/hyperactivity disorder: Dysbiosis and decreased short-chain fatty acids. Brain, Behavior, & Immunity – Health, 40, 100829. https://doi.org/10.1016/j.bbih.2024.100829

Trezzi, S., Scaccabarozzi, G., Nossa, R., et al. (2025). Behavioural, cognitive, and neurophysiological effects of a synbiotic supplementation enriched with pigmented corn extract or cornstarch in drug-naïve children with attention-deficit hyperactivity disorder: A randomised, double-blind, comparison-controlled clinical trial. Clinical Nutrition ESPEN, 65, 408–417. https://doi.org/10.1016/j.clnesp.2024.11.002

Tsukuda, N., Yahagi, K., Hara, T., et al. (2021). Key bacterial taxa and metabolic pathways affecting gut short-chain fatty acid profiles in early life. ISME Journal, 15, 2574–2590. https://doi.org/10.1038/s41396-021-00937-7

Wang, X., Wang, N., Gao, T., et al. (2025). Symptom-specific gut microbial and metabolic profiles in ADHD reveal SCFA deficiency as a key pathogenic mechanism. Gut Microbes, 17. https://doi.org/10.1080/19490976.2025.2537755

Xiao, Y., Wei, L., Yu, J., et al. (2025). Fecal microbiota transplantation for attention-deficit/hyperactivity disorder: Mechanisms, evidence, and future directions. International Journal of General Medicine, 18, 6757–6767. https://doi.org/10.2147/IJGM.S527130

Yang, L. L., Stiernborg, M., Skott, E., et al. (2022). Lower plasma concentrations of short-chain fatty acids (SCFAs) in patients with ADHD. Journal of Psychiatric Research, 156, 36–43. https://doi.org/10.1016/j.jpsychires.2022.09.046

Yang, L. L., Stiernborg, M., Skott, E., et al. (2023). Effects of a synbiotic on plasma immune activity markers and short-chain fatty acids in children and adults with ADHD – A randomized controlled trial. Nutrients, 15(5), 1293. https://doi.org/10.3390/nu15051293

Downloads

Published

2026-06-17

How to Cite

Auliya, E. N., & Maramis, M. M. (2026). The Role of Synbiotics in Modulating the Gut–Brain Axis in Attentiondeficit/Hyperactivity Disorder: A Systematic Review. Jurnal Sehat Indonesia (JUSINDO), 8(1), 450–464. https://doi.org/10.59141/-.v8i1.518