It is well established that a microbe-hormone connection begins before birth. In eutherian mammals, microbes stimulate immune tolerance via sex steroid hormones, oxytocin, and Interleukin (IL)-10 to sustain a prolonged placental pregnancy [40
]. Upon birth oxytocin simultaneously up-regulates IFN-γ and CD25 expression establishing self vs. non-self [30
]. Later in life, this same oxytocin interchange sustains immune and integumentary homeostasis, biasing the immune system toward IL-10 and IFN-γ, and subsequently minimizing the deleterious systemic effects of IL-6 and IL-17 that hasten morbidity and premature death [6
]. Oxytocin also regulates neurotransmitter Gamma-Aminobutyric Acid (GABA) signaling in the central nervous system [41
] providing a favorable mood reward [16
] for social and gluttary gratification. Emerging data connect oxytocin with obesity, fat metabolism [42
], musculoskeletal fitness [34
] and the immune system [5
], establishing its role as a global regulatory hormone.
These diverse probiotic microbe–induced phenotypes impart perinatal impact that may span generations. Oxytocin, for example, is inversely linked with post-partum depression and maternal neglect in human females [44
]. While oxytocin enhances cooperation within kin groups, it promotes aggression towards competitors [45
]. These inter-related roles for oxytocin may impact a natural selection process favoring complex social organizations required for mutual evolutionary success. Through actions of microbe-induced hormones such as oxytocin, gut bacteria may influence our desires and identity as human beings. Harnessing microbes for healthful longevity
In adulthood, these micro-organisms stimulate immune tolerance and the hypothalamic-pituitary axis to improve host fitness and lessen impairments of aging. Features typical of superb physical fitness and youth include mucocutaneous hyperacidity and follicular anagenesis [46
]. All of this is well reasoned from an evolutionary perspective, in that symbiotic microbes co-evolved with mammals by exploiting host immunity and endocrinology for mutual gain [46
]. During periods of fertility, immune and hormonal effects of probiotic organisms dominate environmental interfaces and facilitate host survival and reproductive success [46
]. Probiotic-enhanced immune tolerance permits prolonged placental pregnancy [40
], while hyperacidic mucus inhibits pathogens that otherwise impedes GI tract health, fertilization and pregnancy. Breaking this natural symbiotic cycle with compulsive social hygiene practices leads to insufficient levels of mucosal IL-10 [24
], contributing to immune dysregulation with elevated risk for premature death under favorable conditions, these probiotic bacteria are then passed from mother to naïve offspring during vaginal birth and nursing, imparting evolutionary success to both the symbiotic bacteria and their mammalian hosts.
In conclusion, orally administered microbes may lessen impairments of aging and impart healthful resiliency typical of much younger individuals [5
], providing the psychological and physiological cornerstones of healthful longevity. Microbes have been shown in preclinical models to ablate age-associated weight gain [6
] and cancer burden [28
] that contributes to premature aging. Quantifiable benefits in wound healing capacity directly translate to nearly every aspect of traditional health and medicine [42
], simultaneously unifying social support networks with improved injury repair for a healthy and meaningful life [49
]. In practical terms, this microbe-endocrine-immune linkage
has the potential to reduce hospitalizations, improve healing, lower risk for certain cancers, and bestow wellness and active participation in society throughout life. It’s unknown with certainty whether findings in animal models will translate directly to human subjects. Nonetheless, peoples around the world have cultivated and consumed similar food-grade organisms in fermented beverages and active yogurt drinks for thousands of years, supporting a low-risk population-based approach for a long, healthy, and meaningful life.
Funding: This work was supported by National Institutes of Health grants P30-ES002109 (pilot project award to S.E.E), U01 CA164337 (to S.E.E.), and RO1CA108854 (to S.E.E).