The gut microbiome changes with age, losing populations that produce beneficial metabolites, and gaining populations that produce chronic inflammation and other harms. There are many possible contributions to this process of aging, but it is unclear as to which of them are important. It has been shown in animal studies that performing fecal microbiota transplantation from young to old individuals restores a more youthful gut microbiome for an extended period of time, improving health and extending life span. Researchers here add more data for the short term outcomes of fecal microbial transplantation in mice.
Altered gut microbial ecosystems have been associated with increased risk of metabolic and immune disorders. Aging is associated with chronic inflammation, a risk for age-associated pathologies such as atherosclerosis, insulin resistance, diabetes, as well as Alzheimer's disease. Emerging evidence reveals aging-associated changes in the composition, diversity, and function of gut microbiota increases gut permeability and activates innate immune responses. Therefore, microbiome-based interventions against aging-associated health issues should provoke attention.
The microbiota-targeted interventions slow down aging process through preventing insulin resistance, improving immunity, suppressing chronic inflammation, as well as regulating metabolism. Additionally, fecal microbiota transplantation (FMT) extends mouse lifespan. Moreover, donor metabolic characteristics drive the effects of FMT on recipient insulin sensitivity in male adult. Furthermore, feces from lean donors can transiently improve the insulin sensitivity in some obese male patients with metabolic syndrome, and the improvement is driven by baseline intestinal microbiota composition of the recipients. These findings suggested the importance of donor as well as recipient in dictating the transplantation outcomes. Additional studies are needed to understand the sex effect.
Women and men differ substantially regarding the degree of insulin sensitivity, body composition, energy balance, and the incidence of metabolic diseases. Others' and our studies show sex differences in microbiota may account for sex dissimilarity in metabolism and metabolic diseases. However, whether the sex of donor and recipient affect FMT efficacy in metabolism has not been examined.
In the current study, we tested a hypothesis that aging-associated metabolic issues such as insulin resistance may be due to aging-induced structural and functional changes of the gut microbiome in a sex-dependent manner. Thus, we analyzed aging-associated gut microbiota and metabolome on inflammatory signaling and metabolism in both sexes. Our novel data revealed that aging differentially affects metabolic signaling and metabolome in males and females. Additionally, sex difference in insulin sensitivity narrowed as mice age. Because aged male mice were the most insulin resistant group, whereas young female mice were the most insulin sensitive group, FMT were performed by using aged male feces (AFMT) and young female feces (YFMT).
Our data showed that AFMT lead to insulin resistance only in females, which abolished sex difference in insulin sensitivity and colon metabolome. Moreover, YFMT reduced body weight and fasting blood glucose in males and improved insulin sensitivity in females, leading to increased sex differences in insulin sensitivity and colon metabolome. Together, FMT effects on metabolic changes are sex specific.