Distinct Shifts in Microbiota Composition during Drosophila Aging Impair Intestinal Function and Drive Mortality
Open accessAbstract
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.
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The phenomenon of age-related gut microbiota change exists simultaneously in species such as Drosophila, fish, mice, rats, and humans.
“Moreover, this phenomenon exists simultaneously in species such as Drosophila,219 fish,220 mice,221 rats,222 and humans.223”
From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [219]
Young flies fed homogenates from aged flies had significantly decreased lifespan and increased incidence of intestinal barrier dysfunction compared with flies fed homogenates from young animals.
“Young flies fed homogenates from aged flies had significantly decreased lifespan and increased incidence of intestinal barrier dysfunction, compared with flies fed homogenates from young animals [27].”
From Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain (2022) · cites this paper as [27]
Changes in the aging intestinal microbiota can adversely affect host metabolism and immunity and are associated with development of cardiovascular, autoimmune, metabolic, and neurodegenerative disorders.
“These changes can adversely affect the host metabolism and immunity [25–27, 40, 64, 86, 110, 112, 118] and are associated with the development of cardiovascular, autoimmune, metabolic, and neurodegenerative disorders [17, 90, 122, 132].”
From Fecal microbiota transfer between young and aged mice reverses hallmarks of the aging gut, eye, and brain (2022) · cites this paper as [27]
In Drosophila, dysfunction of the gut and skeletal muscle appear to be primary drivers of aging and mortality.
“In Drosophila, dysfunction of the gut and skeletal muscle appear to be primary drivers of aging and mortality.39,40,41,42”
From Asynchronous, contagious and digital aging (2021) · cites this paper as [40]
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- Authors
- Clark, R. I., Salazar, A., Yamada, R., Fitz-Gibbon, S., Morselli, M., Alcaraz, J., Rana, A., Rera, M., Pellegrini, M., Ja, W. W., & Walker, D. W.
- Affiliations
- University of California, Los Angeles (US)
- Scripps Research Institute (US)
- Corresponding author
- Clark, Rebecca I.
- Walker, David W.
- ORCID
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2015-09
- Volume
- 12
- Issue
- 10
- Pages
- 1656-1667
- ISSN
- 2211-1247 (ISSN-L)
- PMC
- PMC4565751
- OpenAlex
- W1930889025
- Cited by
- 510
- References
- 53
- Citations by year
- 2026: 33 · 2025: 41 · 2024: 51 · 2023: 56 · 2022: 62 · 2021: 58 · 2020: 40 · 2019: 44 · 2018: 58 · 2017: 36 · 2016: 28 · 2015: 2
- FWCI
- 16.56
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cell Reports (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Durham Research Online (Durham University) (acceptedVersion, other-oa)
- Durham Research Online (Durham University) (submittedVersion, cc-by)
- HAL (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- National Institutes of Health (NIH P40OD018537, P40OD018537)
- National Institute on Aging (R01AG040288, R01AG045036, R00AG030493, R01AG049157, R01AG037514)
- National Institute of General Medical Sciences (R01GM095656, R24GM092473)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Agricultural and Biological Sciences › Insect Science › Insect symbiosis and bacterial influences
- Keywords
- gut microbiota, aging, dysbiosis, Gammaproteobacteria, intestinal barrier dysfunction, Drosophila, mortality, systemic immune activation, excretory function, immune gene expression, frailty
- MeSH terms
- Gastrointestinal Microbiome, Aging, Animals, Drosophila melanogaster, Intercellular Junctions, Intestines, Longevity, Gammaproteobacteria
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