Effects of Lactobacillus reuteri DSM 17938 on the acute psychological, endocrine and immunological stress response in healthy city dwellers

• Applicant: Professor Dr. Stefan O. Reber
• Subject Area: Biological Psychiatry
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 570661259

Both preclinical and clinical data support the hypothesis that an excessive and inadequately regulated inflammatory stress response is causally involved in the development of many stress-associated disorders. This is consistent with studies showing that stress-associated disorders are more prevalent in urban than in rural areas and that healthy male subjects who grew up in an urban environment (=URBANs) without contact with household pets show a more pronounced inflammatory response to a standardized laboratory stressor (=“Trier Social Stress Test”; TSST) than subjects who grew up on a farm with regular contact with livestock. An innovative research approach is therefore to increase an individual's immunoregulatory capacity in order to promote stress resilience. In own preclinical studies, we have already shown that the induction of regulatory T cells (Tregs) through repeated administration of various heat-inactivated non-tuberculous mycobacteria significantly increases stress resilience in mice. In the here proposed study these promising preclinical results will now be translated to the human situation and the stress-protective effects of the probiotic Lactobacillus reuteri DSM 17938 will be investigated in healthy URBANs. The central hypothesis of this project is that daily oral administration of the probiotic L. reuteri DSM 17938 to healthy male (N = 32) and female (N = 32) URBANs over a period of 8 +/-2 weeks will reduce their inflammatory response to the TSST compared to placebo-administered male (N = 32) and female (N = 32) URBANs. L. reuteri DSM 17938 has been shown to be a potent inducer of Tregs and was abundantly present in the commensal gut microbiome (=“old friends”) of our hunter-gatherer ancestors. Nowadays, L. reuteri DSM 17938 is becoming increasingly rare in both the gut flora and breast milk, which is at least in part due to the urban lifestyle (i.e., low-fiber diet, antibiotics, drinking water treatment, increase in the rate of cesarean births, etc.) of the Western, industrialized world. Thus, in modern industrialized cities, contact with immunoregulatory “old friends” is significantly reduced, which could explain the overactivity of the immune system towards harmless environmental allergens (i.e., allergies), the body's own antigens (i.e., autoimmune diseases), but also social stressors (i.e., psychosomatic illnesses), observed primarily in urban areas. If our hypothesis is confirmed, this could lead to an innovative, unconventional, and promising therapeutic and prophylactic approach to more effectively combat stress-related illnesses in the near future.

• DFG Programme: Research Grants