title: Distinct Shifts in Microbiota Composition during Drosophila Aging Impair Intestinal Function and Drive Mortality.
abstract: 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.
authors: Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: rebecca.clark2@durham.ac.uk.
authors: Rebecca I
authors: RI
authors: Clark
authors: Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors: Anna
authors: A
authors: Salazar
authors: Department of Metabolism and Aging, The Scripps Research Institute, Jupiter, FL 33458, USA.
authors: Ryuichi
authors: R
authors: Yamada
authors: Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Institute for Genomics and Proteomics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors: Sorel
authors: S
authors: Fitz-Gibbon
authors: Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors: Marco
authors: M
authors: Morselli
authors: Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors: Jeanette
authors: J
authors: Alcaraz
authors: Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors: Anil
authors: A
authors: Rana
authors: Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors: Michael
authors: M
authors: Rera
authors: Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Institute for Genomics and Proteomics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors: Matteo
authors: M
authors: Pellegrini
authors: Department of Metabolism and Aging, The Scripps Research Institute, Jupiter, FL 33458, USA.
authors: William W
authors: WW
authors: Ja
authors: Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: davidwalker@ucla.edu.
authors: David W
authors: DW
authors: Walker
mesh_terms: D000375:Aging; D000818:Animals; D004331:Drosophila melanogaster / Q000382:microbiology* / Q000502:physiology; D020563:Gammaproteobacteria / Q000254:growth & development; D000069196:Gastrointestinal Microbiome; D007365:Intercellular Junctions / Q000378:metabolism; D007422:Intestines / Q000382:microbiology / Q000502:physiology*; D008136:Longevity