Transplantation of gut microbiota from old mice into young healthy mice reduces lean mass but not bone mass

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.

Keywords: Gut microbiota; HUNT cohort; bacteroides ovatus; bone mass; germ-free mice; gut microbiota transplantation; lean mass; osteoporosis; sarcopenia.

Figure 1.

Old donor mice have lower lean mass and bone mass compared with young adult donor mice.

Figure 2.

Old donor mice have altered GM composition compared with young adult donor mice.

Figure 3.

GM transplantation to recipient GF mice.

Figure 4.

The GM from old mice reduces relative lean mass but not bone mass in young healthy still growing recipient mice compared with the GM from young adult donors.