Probiotic Microbes Sustain Youthful Serum Testosterone Levels and Testicular Size in Aging Mice

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.

The Gut Microbiota and Developmental Programming of the Testis in Mice

“…An earlier study reported that the absence of gut microbiota influenced testosterone levels [41] in accordance with our observation of a lower intratesticular level of testosterone in GF mice compared to SPF and CBUT mice. A recent study demonstrated that dietary supplementation of the probiotics Lactobacillus reuteri increased and restored testosterone levels in aging mice [42]. We could not detect any differences in the expression levels of genes specific for Leydig cell or the levels of mRNA encoding enzymes involved in testosterone production (e.g., Insl3, Hsd3b1, Hsd17b11, cyp11a1 and cyp19a ).…”

Probiotics to improve testicular function (Andrology 5:439–444, 2017) – a comment on mechanism of action and therapeutic potential of probiotics beyond reproduction

“…The consumption of Lactobacillus paracasei probiotic bacteria, and their preferred food source (FOS, fibre) present within the Flortec supplement, is known to enhance intestinal barrier function, thereby reducing levels of endotoxin exposure and inflammation. We believe that this is a likely mechanism behind the improvement in testicular function seen in these men, especially as earlier reports have shown that Lactobacillus probiotic primarily mediates its beneficial effect on testicular function via modulation of the immune system (Poutahidis et al, 2014).…”

Immunization with a heat-killed preparation of the environmental bacterium Mycobacterium vaccae promotes stress resilience in mice

“…Interestingly, the microbiome generally (63) and the probiotic Lactobacillus reuteri specifically have been shown to increase testosterone in mice, effects that could be mimicked by interfering with IL-17A signaling, a proinflammatory cytokine (64). Immunoregulatory microbes act on regulatory dendritic cells, which in turn bias T-cell differentiation toward Treg and away from IL-17-producing T helper 17 (Th17) cells (65,66).…”