title: Lactobacillus rhamnosus accelerates zebrafish backbone calcification and gonadal differentiation through effects on the GnRH and IGF systems.
abstract: Endogenous microbiota play essential roles in the host's immune system, physiology, reproduction and nutrient metabolism. We hypothesized that a continuous administration of an exogenous probiotic might also influence the host's development. Thus, we treated zebrafish from birth to sexual maturation (2-months treatment) with Lactobacillus rhamnosus, a probiotic species intended for human use. We monitored for the presence of L. rhamnosus during the entire treatment. Zebrafish at 6 days post fertilization (dpf) exhibited elevated gene expression levels for Insulin-like growth factors -I and -II, Peroxisome proliferator activated receptors -α and -β, VDR-α and RAR-γ when compared to untreated-10 days old zebrafish. Using a gonadotropin-releasing hormone 3 GFP transgenic zebrafish (GnRH3-GFP), higher GnRH3 expression was found at 6, 8 and 10 dpf upon L. rhamnosus treatment. The same larvae exhibited earlier backbone calcification and gonad maturation. Noteworthy in the gonad development was the presence of first testes differentiation at 3 weeks post fertilization in the treated zebrafish population -which normally occurs at 8 weeks- and a dramatic sex ratio modulation (93% females, 7% males in control vs. 55% females, 45% males in the treated group). We infer that administration of L. rhamnosus stimulated the IGF system, leading to a faster backbone calcification. Moreover we hypothesize a role for administration of L. rhamnosus on GnRH3 modulation during early larval development, which in turn affects gonadal development and sex differentiation. These findings suggest a significant role of the microbiota composition on the host organism development profile and open new perspectives in the study of probiotics usage and application.
authors.affiliation: Department of Life and Environmental Sciences, Polytechnic University of Marche, Ancona, Italy.
authors.forename: Matteo A
authors.initials: MA
authors.lastname: Avella
authors.forename: Allen
authors.initials: A
authors.lastname: Place
authors.forename: Shao-Jun
authors.initials: SJ
authors.lastname: Du
authors.forename: Ernest
authors.initials: E
authors.lastname: Williams
authors.forename: Stefania
authors.initials: S
authors.lastname: Silvi
authors.forename: Yonathan
authors.initials: Y
authors.lastname: Zohar
authors.forename: Oliana
authors.initials: O
authors.lastname: Carnevali
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D049628:Body Size; D001835:Body Weight; D001842:Bone and Bones / Q000378:metabolism*; D002113:Calcification, Physiologic; D005260:Female; D041981:Gastrointestinal Tract / Q000382:microbiology; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D006066:Gonads / Q000378:metabolism*; D052201:Lacticaseibacillus rhamnosus / Q000502:physiology*; D008297:Male; D009132:Muscles / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives* / Q000378:metabolism; D012733:Sex Differentiation / Q000502:physiology; D013002:Somatomedins / Q000378:metabolism*; D013312:Stress, Physiological; D015027:Zebrafish / Q000254:growth & development* / Q000382:microbiology*
chemical_list: D015415:Biomarkers; D013002:Somatomedins; C448022:gonadotropin-releasing hormone-III; D007987:Gonadotropin-Releasing Hormone; D011761:Pyrrolidonecarboxylic Acid