title: 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.
authors.affiliation: Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America ; Laboratory of Pathology, Faculty of Veterinary Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Theofilos
authors.initials: T
authors.lastname: Poutahidis
authors.affiliation: Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America ; Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
authors.forename: Alex
authors.initials: A
authors.lastname: Springer
authors.affiliation: Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Levkovich
authors.affiliation: Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
authors.forename: Peimin
authors.initials: P
authors.lastname: Qi
authors.affiliation: Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
authors.forename: Bernard J
authors.initials: BJ
authors.lastname: Varian
authors.affiliation: Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Lakritz
authors.affiliation: Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
authors.forename: Yassin M
authors.initials: YM
authors.lastname: Ibrahim
authors.affiliation: Laboratory of Pathology, Faculty of Veterinary Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Antonis
authors.initials: A
authors.lastname: Chatzigiagkos
authors.affiliation: Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America ; Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Alm
authors.affiliation: Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Erdman
mesh_terms: D000367:Age Factors; D000818:Animals; D001284:Atrophy; D004032:Diet; D020381:Interleukin-17 / Q000378:metabolism; D052200:Limosilactobacillus reuteri / Q000502:physiology; D007985:Leydig Cells / Q000166:cytology; D008297:Male; D051379:Mice; D009929:Organ Size; D019936:Probiotics / Q000008:administration & dosage*; D012671:Seminiferous Tubules / Q000166:cytology; D013091:Spermatogenesis; D013737:Testis / Q000033:anatomy & histology* / Q000473:pathology; D013739:Testosterone / Q000097:blood*
chemical_list: D020381:Interleukin-17; D013739:Testosterone