Distinct Shifts in Microbiota Composition during Drosophila Aging Impair Intestinal Function and Drive Mortality

Alterations in the composition of the intestinal microbiota have been correlated with aging and measures of frailty in the elderly. However, the relationships between microbial dynamics, age-related changes in intestinal physiology, and organismal health remain poorly understood. Here, we show that dysbiosis of the intestinal microbiota, characterized by an expansion of the Gammaproteobacteria, is tightly linked to age-onset intestinal barrier dysfunction in Drosophila. Indeed, alterations in the microbiota precede and predict the onset of intestinal barrier dysfunction in aged flies. Changes in microbial composition occurring prior to intestinal barrier dysfunction contribute to changes in excretory function and immune gene activation in the aging intestine. In addition, we show that a distinct shift in microbiota composition follows intestinal barrier dysfunction, leading to systemic immune activation and organismal death. Our results indicate that alterations in microbiota dynamics could contribute to and also predict varying rates of health decline during aging in mammals. [Display omitted] •Age-related dysbiosis in Drosophila is characterized by Gammaproteobacteria expansion•Dysbiosis predicts age-onset intestinal barrier dysfunction and rapid health decline•Age-related dysbiosis drives changes in excretory function•Loss of commensal control following intestinal barrier dysfunction drives mortality The relationship between microbiota dynamics and age-related changes in organismal health are poorly understood. Using Drosophila, Clark et al. show that dysbiosis of the intestinal microbiota precedes and predicts age-related intestinal barrier dysfunction. Age-related alterations in the microbiota contribute to intestinal immune activation, modulate excretory function, and ultimately lead to mortality.