ABSTRACT
Aging is associated with low bone and lean mass as well as alterations in the gut microbiota (GM). In this study, we determined whether the reduced bone mass and relative lean mass observed in old mice could be transferred to healthy young mice by GM transplantation (GMT). GM from old (21-month-old) and young adult (5-month-old) donors was used to colonize germ-free (GF) mice in three separate studies involving still growing 5- or 11-week-old recipients and 17-week-old recipients with minimal bone growth. The GM of the recipient mice was similar to that of the donors, demonstrating successful GMT. GM from old mice did not have statistically significant effects on bone mass or bone strength, but significantly reduced the lean mass percentage of still growing recipient mice when compared with recipients of GM from young adult mice. The levels of propionate in the cecum of mice receiving old donor GM were significantly lower than those in mice receiving young adult donor GM. Bacteroides ovatus was enriched in the microbiota of recipient mice harboring GM from young adult donors. The presence of B. ovatus was not only significantly associated with high lean mass percentage in mice, but also with lean mass adjusted for fat mass in the large human HUNT cohort. In conclusion, GM from old mice reduces lean mass percentage but not bone mass in young, healthy, still growing recipient mice. Future studies are warranted to determine whether GM from young mice improves the musculoskeletal phenotype of frail elderly recipient mice.
Acknowledgments
We thank Ulrika Björklund, Sabrina Wagoner, Martin Meier, Janaki Guruge, and Jiye Cheng for excellent technical assistance. We thank Dave O’Donnell and Maria Karlsson for their assistance with the gnotobiotic mouse husbandry.
Disclosure statement
C.O. and K.S. are listed as inventors of a patent application regarding the impact of probiotics on bone metabolism and have received research funding for probiotic-related research from Probi AB and Solarea Bio.
Data availability statement
Sequencing data are available from the NCBI database under the BioProject number PRJNA949823 in https://www.ncbi.nlm.nih.gov/bioproject/. Other data supporting the findings of this study are available from the corresponding authors upon reasonable request.
Author contribution
Study design: LL, CC, JIG, KS, and CO; Study conduct: LL, CC, KS, JIG and CO; Data Collection: LL, CC, JMS, KHo, CE, JW, LV, AK, JT, and KS; Writing – Original Draft: LL, CC, LG, SA, KS, and CO; Writing – Review & Editing: LL, CC, LG, JMS, KHo, CE, JW, LV, AK, JT, EC, KH, AL, SA, JIG, KS, and CO; Data analysis: LL, CC, LG, AK, JT, SA, JIG, KS, and CO.
The Trøndelag Health Study (HUNT) is a collaboration between the HUNT Research Centre (Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, NTNU), Trøndelag County Council, Central Norway Regional Health Authority, and the Norwegian Institute of Public Health.
Supplementary material
Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2023.2236755
Correction Statement
This article has been corrected with minor changes. These changes do not impact the academic content of the article.