Establishment and Resilience of Transplanted Gut Microbiota in Aged Mice

Abstract

The maintenance of healthy and resilient gut microbiota is critical for the life quality and healthspan of the elderly. Many gastrointestinal diseases which are more prevalent in the aged population are believed to be associated with gut microbiota disruption and dysbiosis. Fecal microbiota transplantation (FMT), a procedure in which fecal material is transferred from a donor to a recipient, has been increasingly used as a treatment to restore healthy gut microbiota. However, little is known about the establishment and long-term stability of transplanted microbiota or their resilience to further disruption, especially in aged hosts. In the present investigation, we aimed to study the establishment and resilience of transplanted microbiota after autologous versus heterologous FMT in aged recipients. We demonstrated that gut microbiota of aged mice (20 months old) treated with a broad-spectrum antibiotic cocktail failed to restore its original diversity and composition over 8 weeks via spontaneous recovery; in contrast, FMT using either autologous or heterologous (2 months old from a different vendor) donors facilitated the recovery of gut microbiota diversity. Both autologous and heterologous FMT successfully established donor-like microbiota states and affects the gene expression profile of the aged host for as long as 8 weeks. Furthermore, we evaluated the resilience of transplanted microbiota during further colon environment changes. The transplanted microbiota established by heterologous FMT is not resilient during chemical-induced colonic inflammation, in contrast to that of autologous FMT. Our findings systematically examined the effects of FMT on the gut homeostasis of aged hosts, highlighted the need to monitor the long-term stability of transplanted gut microbiota and to perform multiple FMT when necessary.