AccScience Publishing / GTM / Online First / DOI: 10.36922/GTM025460086
Submit to GTM
Cite this article
8
Download
171
Views
Journal Browser
Volume | Year
Issue
Search
Forthcoming Issue
Current Issue
View All
News and Announcements
View All
ORIGINAL RESEARCH ARTICLE

Effects of targeted colonic symbiotic supplementation with Bacillus subtilis DSM 32315 and L-alanyl-L-glutamine on mental wellbeing: An open-label pilot study

Heike tom Dieck1 ,  Diego Tomassi2 ,  Elisa Postrach3 ,  Ellen Ehring1*
Show Less
1 Research, Development, and Innovation, Creavis, Evonik Operations GmbH, Hanau, Hesse, Germany
2 Biofortis SAS, Saint-Herblain, Pays de la Loire, France
3 Analyze & Realize GmbH, Berlin, Germany
Global Translational Medicine, 025460086 https://doi.org/10.36922/GTM025460086
Received: 13 November 2025 | Revised: 3 February 2026 | Accepted: 6 February 2026 | Published online: 6 March 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Download PDF
XML
Cite
Abstract

The gut–brain axis plays a pivotal role in mental health, with synbiotic supplements emerging as promising interventions for stress and anxiety management. This observational open-label pilot study aims to evaluate the effects of a symbiotic supplement containing Bacillus subtilis DSM 32315 and L-alanyl-L-glutamine, delivered via a targeted colonic-release capsule, on stress, anxiety, and mental wellbeing. Conducted as a non-placebo-controlled real-world case study, the study recruited 100 adults with elevated perceived stress and followed them for over eight weeks. Validated self-reporting tools, including the Depression Anxiety Stress Scales-21 items (DASS-21), Perceived Stress Scale-10 items (PSS-10), Athens Insomnia Scale (AIS), Short Form Health Survey-12 items, and Gastrointestinal Symptom Rating Scale questionnaires, were used to assess outcomes. Statistical analyses, primarily using linear mixed models, indicated reductions in DASS-21, PSS-10, and AIS scores, along with self-reported improvements in gastrointestinal symptoms and mental well-being. These findings should be interpreted cautiously due to the exploratory, uncontrolled study design. Notably, DASS-21 total scores declined within one week, with reported benefits sustained at four and eight weeks. However, these rapid changes may partly reflect expectancy effects or regression to the mean. These observations provide valuable insights for further hypothesis generation, notably that the synbiotic supplement could support stress management and mental health by modulating the gut–brain axis. However, further placebo-controlled trials including measurement of relevant biomarkers are warranted to confirm these observations and explore underlying mechanisms.

Keywords
Synbiotic
Bacillus subtilis
L-alanyl-L-glutamine
Colonic delivery
Gut–brain axis
Mental well-being
Short-chain fatty acids
Real-world study
Funding
This study was sponsored by Evonik Operations GmbH.
Conflict of interest
Heike tom Dieck and Ellen Ehring declare competing interests as employees of Evonik Operations GmbH. All other authors declare no conflict of interest.
References
  1. World Health Organization. Mental health. Published 2025. Available from: https://www.who.int/news-room/factsheets/detail/mental-health-strengthening-ourresponse [Last accessed on 2026 Feb 15].

 

  1. World Health Organization. Depression and other common mental disorders: global health estimates. Published 2017. Available from: https://iris.who.int/bitstream/handle/10665/254610/WHO-MSD-MER-2017.2-eng.pdf [Last accessed on 2026 Sep 11].

 

  1. Person, H, Keefer, L. Psychological comorbidity in gastrointestinal diseases: Update on the brain–gut–microbiome axis. Prog Neuropsychopharmacol Biol Psychiatry. 2021;107:110209. doi: 10.1016/j.pnpbp.2020.110209

 

  1. Leigh, SJ, Uhlig, F, Wilmes, L, et al. The impact of acute and chronic stress on gastrointestinal physiology and function: a microbiota-gut-brain axis perspective. J Physiol. 2023;601(20):4491-4538. doi: 10.1113/JP281951

 

  1. Nazir, MM, Ghaffar, W, Mustafa, G, Saeed, S, Ijaz, MU, Ashraf, A. Modulating depression through the gut–brain axis: the role of gut microbiota in therapeutic interventions. Naunyn

Schmiedebergs Arch Pharmacol. 2025;398(12):16893-16911. doi: 10.1007/s00210-025-04464-6

 

  1. Zhou, X, Wang, S, Wang, X, et al. Mechanisms of the effect of gut microbes on depression through the microbiota–gut–brain axis. Front Nutr. 2025;12:1634548. doi: 10.3389/fnut.2025.1634548

 

  1. Cheng, J, Hu, H, Ju, Y, et al. Gut microbiota–derived short–chain fatty acids and depression: deep insight into biological mechanisms and potential applications. Gen Psychiatr. 2024;37(1):e101374. doi: 10.1136/gpsych-2023-101374

 

  1. Veronese, N, Gianfredi, V, Solmi, M, et al. The impact of dietary fiber consumption on human health: An umbrella review of evidence from 17,155,277 individuals. Clin Nutr. 2025;51:325-333. doi: 10.1016/j.clnu.2025.06.021

 

  1. Breuling, M, Tomeva, E, Ivanovic, N, Haslberger, A. Butyrate– and Beta–Hydroxybutyrate–Mediated Effects of Interventions with Pro- and Prebiotics, Fasting, and Caloric Restrictions on Depression: A Systematic Review and Meta-Analysis. Life (Basel). 2024;14(7):787. doi: 10.3390/life14070787

 

  1. Silva, YP, Bernardi, A, Frozza, RL. The Role of Short–Chain Fatty Acids From Gut Microbiota in Gut–Brain Communication. Front Endocrinol (Lausanne). 2020;11:25. doi: 10.3389/fendo.2020.00025

 

  1. van de Wouw, M, Boehme, M, Lyte, JM, et al. Short–chain fatty acids: microbial metabolites that alleviate stress-induced brain–gut axis alterations. J Physiol. 2018;596(20):4923-4944. doi: 10.1113/JP276431

 

  1. Tian, P, Zhu H, Qian X, et al. Consumption of Butylated Starch Alleviates the Chronic Restraint Stress–Induced Neurobehavioral and Gut Barrier Deficits Through Reshaping the Gut Microbiota. Front Immunol. 2021;12:755481. doi: 10.3389/fimmu.2021.755481

 

  1. Kelly, JR, Borre, Y, O’ Brien, C, et al. Transferring the blues: Depression–associated gut microbiota induces neurobehavioural changes in the rat. J Psychiatr Res. 2016;82:109-118. doi: 10.1016/j.jpsychires.2016.07.019

 

  1. Zheng, P, Zeng, B, Zhou, C, et al. Gut microbiome remodeling induces depressive–like behaviors through a pathway mediated by the host’s metabolism. Mol Psychiatry. 2016;21(6):786-796. doi: 10.1038/mp.2016.44

 

  1. Freijy, TM, Cribb, L, Oliver, G, et al. Effects of a high–prebiotic diet versus probiotic supplements versus synbiotics on adult mental health: The “Gut Feelings” randomised controlled trial. Front Neurosci. 2023;16:1097278. doi: 10.3389/fnins.2022.1097278

 

  1. tom Dieck, H, Schön, C, Wagner, T, Pankoke, HC, Fluegel, M, Speckmann, B. A Synbiotic Formulation Comprising Bacillus subtilis DSM 32315 and L–Alanyl–L–Glutamine Improves Intestinal Butyrate Levels and Lipid Metabolism in Healthy Humans. Nutrients. 2021;14(1):143. doi: 10.3390/nu14010143

 

  1. Lovibond, PF, Lovibond, SH. Manual for the Depression Anxiety Stress Scales. 2nd ed. Sydney: Psychology Foundation of Australia; 1995.

 

  1. Cohen, S, Kamarck, T, Mermelstein, R. A global measure of perceived stress. J Health Soc Behav. 1983;24(4):385-396. doi: 10.2307/2136404

 

  1. Soldatos, CR, Dikeos, DG, Paparrigopoulos, TJ. Athens Insomnia Scale: validation of an instrument based on ICD–10 criteria. J Psychosom Res. 2000;48(6):555-560. doi: 10.1016/s0022-3999(00)00095-7

 

  1. Ware, J Jr, Kosinski, M, Keller, SD. A 12–Item Short–Form Health Survey: construction of scales and preliminary tests of reliability and validity. Med Care. 1996;34(3):220-233. doi: 10.1097/00005650-199603000-00003

 

  1. Svedlund, J, Sjödin, I, Dotevall, G. GSRS? A clinical rating scale for gastrointestinal symptoms in patients with irritable bowel syndrome and peptic ulcer disease. Digest Dis Sci. 1988;33(2):129-134. doi: 10.1007/bf01535722

 

  1. Ronk, FR, Korman, JR, Hooke, GR, Page, AC. Assessing clinical significance of treatment outcomes using the DASS–21. Psychol Assess. 2013;25(4):1103-1110. doi: 10.1037/a0033100

 

  1. Cao, T, Zhou, X, Zheng, X, et al. Histone Deacetylase Inhibitor Alleviates the Neurodegenerative Phenotypes and Histone Dysregulation in Presenilins–Deficient Mice. Front Aging Neurosci. 2018;10:137. doi: 10.3389/fnagi.2018.00137

 

  1. Damiani, F, Cornuti, S, Tognini, P. The gut–brain connection: Exploring the influence of the gut microbiota on neuroplasticity and neurodevelopmental disorders. Neuropharmacology. 2023;231:109491. doi: 10.1016/j.neuropharm.2023.109491

 

  1. Fang, Y, Li, Y, Liao, X, et al. Corydalis yanhusuo Polysaccharides Ameliorate Chronic Stress–Induced Depression in Mice through Gut Microbiota–Derived Short–Chain Fatty Acid Activation of 5–Hydroxytryptamine Signaling. J Med Food. 2023;26(12):890-901. doi: 10.1089/jmf.2023.K.0050

 

  1. Duan, C, Huang, L, Zhang, C, et al. Gut commensal–derived butyrate reverses obesity–induced social deficits and anxiety–like behaviors via regulation of microglial homeostasis. Eur J Pharmacol. 2021;908:174338. doi: 10.1016/j.ejphar.2021.174338

 

  1. Cavaliere, G, Catapano, A, Trinchese, G, et al. Butyrate Improves Neuroinflammation and Mitochondrial Impairment in Cerebral Cortex and Synaptic Fraction in an Animal Model of Diet–Induced Obesity. Antioxidants (Basel). 2022;12(1):4. doi: 10.3390/antiox12010004

 

  1. Ma, X, Shi, W, Wang, Z, et al. Butyric acid and valeric acid attenuate stress–induced ferroptosis and depressive–like behaviors by suppressing hippocampal neuroinflammation. J Transl Med. 2025;23(1):974. doi: 10.1186/s12967-025-06950-0

 

  1. Blaak, EE, Canfora, EE, Theis, S, et al. Short–chain fatty acids in human gut and metabolic health. Benef Microbes. 2020;11(5):411-455. doi: 10.3920/BM2020.0057

 

  1. Napier, BA, Allegretti, JR, Feuerstadt, P, et al. Multi–Species Synbiotic Supplementation Enhances Gut Microbial Diversity, Increases Urolithin A and Butyrate Production, and Reduces Inflammation in Healthy Adults: A Randomized, Placebo–Controlled Trial. Nutrients. 2025;17(17):2734. doi: 10.3390/nu17172734

 

  1. Guan, Y, Zhu, R, Zhao, W, et al. Effects of Lacticaseibacillus paracasei K56 on perceived stress among pregraduate students: a double-blind, randomized, placebo-controlled trial. Front Nutr. 2025;12:1544713. doi: 10.3389/fnut.2025.1544713
Next article in this issue
Share
Back to top
Global Translational Medicine, Electronic ISSN: 2811-0021 Print ISSN: 3060-8600, Published by AccScience Publishing
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here
Accept