Abstract
The decline of circulating testosterone levels in aging men is associated with adverse health effects. During studies of probiotic bacteria and obesity, we discovered that male mice routinely consuming purified lactic acid bacteria originally isolated from human milk had larger testicles and increased serum testosterone levels compared to their age-matched controls. Further investigation using microscopy-assisted histomorphometry of testicular tissue showed that mice consuming Lactobacillus reuteri in their drinking water had significantly increased seminiferous tubule cross-sectional profiles and increased spermatogenesis and Leydig cell numbers per testis when compared with matched diet counterparts This showed that criteria of gonadal aging were reduced after routinely consuming a purified microbe such as L. reuteri. We tested whether these features typical of sustained reproductive fitness may be due to anti-inflammatory properties of L. reuteri, and found that testicular mass and other indicators typical of old age were similarly restored to youthful levels using systemic administration of antibodies blocking pro-inflammatory cytokine interleukin-17A. This indicated that uncontrolled host inflammatory responses contributed to the testicular atrophy phenotype in aged mice. Reduced circulating testosterone levels have been implicated in many adverse effects; dietary L. reuteri or other probiotic supplementation may provide a viable natural approach to prevention of male hypogonadism, absent the controversy and side-effects of traditional therapies, and yield practical options for management of disorders typically associated with normal aging. These novel findings suggest a potential high impact for microbe therapy in public health by imparting hormonal and gonad features of reproductive fitness typical of much younger healthy individuals.
Highlights
The main cellular source of testosterone in male mammals is the Leydig cell, which resides in clusters within the testicular interstitium
Knowing that age-related hypogonadism has been linked with functional alterations of Leydig cells and low testosterone levels that reduce reproductive fitness and quality of life [1,4,5,9,10,12,13], we examined testes of probiotic microbe-fed mice and found that they had less testicular atrophy coinciding with higher levels of circulating testosterone compared to their age-matched controls
We propose a model whereby probiotic bacteria modulate gastrointestinal immunity resulting in systemic effects on the immune system that activate metabolic pathways that restore tissue homeostasis and overall health
Summary
The main cellular source of testosterone in male mammals is the Leydig cell, which resides in clusters within the testicular interstitium. We have found that the dietary supplementation of aged mice with the probiotic bacterium Lactobacillus reuteri makes them appear to be younger than their matched untreated sibling mice, at least in part by inducing beneficial integumentary effects that manifest as luxuriant hair [18] and inhibition of diet-induced obesity [19]. In another study we discovered that aged mice eating L. reuteri show accelerated healing of skin wounds, which depends upon the suppressive arm of the immune system and the up-regulation of the pituitary gland neuropeptide hormone oxytocin (manuscript submitted for publication) During all these studies we consistently observed that young and aged mice consuming purified L. reuteri organisms had large testes and a dominant male behavior. Given the aggravated controversy about the benefits and sideeffect risks of testosterone replacement therapy [9,10,13,20], dietary L. reuteri may provide an alternative natural approach to the prevention of late-onset male hypogonadism
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