Mycobacterium vaccae immunization: Inducing resilience to stress during pregnancy in the dam and protecting her offspring

• Applicants: Professor Dr. Stefan O. Reber; Professor Dr. David Slattery, Ph.D.
• Subject Area: Biological Psychiatry
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 450542225

The postpartum period represents a time with high risk for women to develop mood and anxiety disorders, such as postpartum anxiety (PPA) and postpartum depression (PPD). PPA and PPD, often comorbid, lead to impaired maternal-infant attachment during the critical stages of early brain development and increase the risk of the offspring developing long-term behavioural and emotional problems, including increased vulnerability to mental illness. Although, both the physiological and immunological adaptations that occur throughout the peripartum period and risk factors for PPA and PPD, including stress during pregnancy, are well-known, the mechanisms underlying postpartum mood and anxiety disorders remain elusive. Numerous hypotheses have been postulated to underlie these disorders, such as disruption of ongoing peripartum-associated brain plasticity. Another, less explored hypothesis is that constant immune activation and chronic low grade inflammation in the mother might underlie post-partum mood disorders as well as an increased risk for the offspring to develop somatic and affective disorders later in life, especially when facing chronic severe life stressors (=second hit). Intriguingly, chronic stress interferes with hippocampal neurogenesis and leads to chronic low-grade inflammation. Importantly, and consistent with the above detailed role of immune activation in the development of mood disorders, we have recently shown that immunoregulation induced by repeated preimmunization (s.c.) with a heat-killed preparation of Mycobacterium vaccae (National Collection of Type Cultures (NCTC) 11659), an abundant soil saprophyte with immunoregulatory properties, was able to prevent stress-induced anxiety, spontaneous colitis, and aggravation of dextran sulfate sodium (DSS)-induced colitis, a murine model of inflammatory bowel disease. Therefore, in this proposal we aim to determine whether M. vaccae given prior to mating can protect the dam from the detrimental effects of pregnancy stress on behaviour, HPA axis, inflammatory responses and hippocampal neurogenesis. Further, we will determine whether this can also protect the offspring from the effects of prenatal stress and/or subsequent exposure to chronic psychosocial stress in adulthood. Taken together, this project will determine whether immunoregulatory approaches can protect both the mother and her offspring from consequences of subsequent chronic stress during pregnancy.

• DFG Programme: Research Grants