The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index.
Gut Microbiota–Derived Short-Chain Fatty Acids Promote Poststroke Recovery in Aged Mice
Open accessAbstract
Rationale: The elderly experience profound systemic responses after stroke, which contribute to higher mortality and more severe long-term disability. Recent studies have revealed that stroke outcomes can be influenced by the composition of gut microbiome. However, the potential benefits of manipulating the gut microbiome after injury is unknown. Objective: To determine if restoring youthful gut microbiota after stroke aids in recovery in aged subjects, we altered the gut microbiome through young fecal transplant gavage in aged mice after experimental stroke. Further, the effect of direct enrichment of selective bacteria producing short-chain fatty acids (SCFAs) was tested as a more targeted and refined microbiome therapy. Methods and Results: Aged male mice (18–20 months) were subjected to ischemic stroke by middle cerebral artery occlusion. We performed fecal transplant gavage 3 days after middle cerebral artery occlusion using young donor biome (2–3 months) or aged biome (18–20 months). At day 14 after stroke, aged stroke mice receiving young fecal transplant gavage had less behavioral impairment, and reduced brain and gut inflammation. Based on data from microbial sequencing and metabolomics analysis demonstrating that young fecal transplants contained much higher SCFA levels and related bacterial strains, we selected 4 SCFA-producers ( Bifidobacterium longum , Clostridium symbiosum , Faecalibacterium prausnitzii , and Lactobacillus fermentum ) for transplantation. These SCFA-producers alleviated poststroke neurological deficits and inflammation, and elevated gut, brain and plasma SCFA concentrations in aged stroke mice. Conclusions: This is the first study suggesting that the poor stroke recovery in aged mice can be reversed via poststroke bacteriotherapy following the replenishment of youthful gut microbiome via modulation of immunologic, microbial, and metabolomic profiles in the host.
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Cites
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Cited by
A Comprehensive Review on the Role of the Gut Microbiome in Human Neurological Disorders
Sorboni, S. G., Moghaddam, H. S., Jafarzadeh-Esfehani, R., & Soleimanpour, S. (2022) · Clinical Microbiology Reviews · doi:10.1128/cmr.00338-20 · Cited by 522
Understanding the gut microbiota and sarcopenia: a systematic review
Liu, C., Cheung, W., Li, J., Chow, S. K., Yu, J., Wong, S. H., Ip, M., Sung, J. J. Y., & Wong, R. M. Y. (2021) · Journal of Cachexia, Sarcopenia and Muscle · doi:10.1002/jcsm.12784 · Cited by 363
Inflammatory Responses After Ischemic Stroke
DeLong, J. H., Ohashi, S. N., O’Connor, K. C., & Sansing, L. H. (2022) · Seminars in Immunopathology · doi:10.1007/s00281-022-00943-7 · Cited by 319
Systemic inflammation after stroke: implications for post‐stroke comorbidities
Simats, A., & Liesz, A. (2022) · EMBO Molecular Medicine · doi:10.15252/emmm.202216269 · Cited by 276
Xiao, W., Su, J., Gao, X., Yang, H., Weng, R., Ni, W., & Gu, Y. (2022) · Microbiome · doi:10.1186/s40168-022-01255-6 · Cited by 252
Metadata
- Authors
- Lee, J., d’Aigle, J., Atadja, L., Quaicoe, V., Honarpisheh, P., Ganesh, B. P., Hassan, A., Graf, J., Petrosino, J., Putluri, N., Zhu, L., Durgan, D. J., Bryan, R. M., McCullough, L. D., & Venna, V. R.
- Venue
- Circulation Research
- Published
- 2020-07-31
- Volume
- 127
- Issue
- 4
- Pages
- 453-465
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W3022747103
- Cited by
- 554
- References
- 53
- FWCI
- 17.29
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Lee, J., d’Aigle, J., Atadja, L., Quaicoe, V., Honarpisheh, P., Ganesh, B. P., Hassan, A., Graf, J., Petrosino, J., Putluri, N., Zhu, L., Durgan, D. J., Bryan, R. M., McCullough, L. D., & Venna, V. R. (2020). Gut Microbiota–Derived Short-Chain Fatty Acids Promote Poststroke Recovery in Aged Mice. Circulation Research. https://doi.org/10.1161/circresaha.119.316448
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