The gut microbiome regulates astrocyte reaction to Aβ amyloidosis through microglial dependent and independent mechanisms
Open accessAbstract
Background: Previous studies show that antibiotic-mediated (abx) alteration of the gut microbiome (GMB) results in a reduction of amyloid beta (Aβ) plaques and proinflammatory microglial phenotype in male APPPS1-21 mice. However, the effect of GMB perturbation on astrocyte phenotypes and microglial-astrocyte communication in the context of amyloidosis has not been examined. Methods: To study whether the GMB modulates astrocyte phenotype in the context of amyloidosis, APPPS1-21 male and female mice were treated with broad-spectrum abx leading to GMB perturbation. GFAP + astrocytes, plaque-associated astrocytes (PAA), PAA morphological parameters, and astrocyte complement component C3 levels were quantified using a combination of immunohistochemistry, immunoblotting, widefield microscopy, and confocal microscopy. Furthermore, these same astrocyte phenotypes were assessed in abx-treated APPPS1-21 male mice that received either fecal matter transplant (FMT) from untreated APPPS1-21 male donors to restore their microbiome or vehicle control. To assess complete absence of the GMB on astrocyte phenotypes, the same astrocyte phenotypes were quantified in APPPS1-21 male mice raised in germ-free (GF) or specific-pathogen free conditions (SPF). Lastly, we assessed whether microglia are necessary for abx-induced astrocyte phenotypes by depleting microglia in APPPS1-21 male mice via treatment with a colony-stimulating factor 1 receptor (CSF1R) inhibitor (PLX5622) and vehicle control or PLX5622 and abx. Results: Herein, we demonstrate that postnatal treatment of male APPPS1-21 mice with broad-spectrum abx leading to GMB perturbation reduces GFAP + reactive astrocytes and PAAs, suggesting that the GMB plays a role in regulating reactive astrocyte induction and recruitment to Aβ plaques. Additionally, we show that compared to controls, PAAs in abx-treated male APPPS1-21 mice exhibit an altered morphology with increased number and length of processes and reduced astrocytic complement C3, consistent with a homeostatic phenotype. GFAP + astrocyte reduction, PAA reduction, astrocyte morphological changes, and C3 levels are restored when abx-treated mice are subject to FMT from untreated APPPS1-21 male donor mice. Next, we found that APPPS1-21 male mice raised in GF conditions have similar astrocyte phenotypes as abx-treated male APPPS1-21 male mice. Correlational analysis revealed that pathogenic bacteria depleted by abx correlate with GFAP + astrocytosis, PAAs, and astrocyte morphological changes. Finally, we determined that abx-mediated reduction in GFAP + astrocytosis, PAAs, and astrocytic C3 expression is independent of microglia. However, abx-induced astrocyte morphological alterations are dependent on the presence of microglia, suggesting that there is both microglial independent and dependent GMB control of reactive astrocyte phenotypes. Conclusions: We show for the first time, in the context of amyloidosis, that the GMB plays an important role in controlling reactive astrocyte induction, morphology, and astrocyte recruitment to Aβ plaques. GMB regulation of these astrocytic phenotypes is both independent and dependent on microglia.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The microbiota-gut-brain axis represents an important regulator of glial functions, making it an actionable target to ameliorate the development and progression of neurodegenerative diseases.
“The microbiota–gut–brain axis represents an important regulator of glial functions, making it an actionable target to ameliorate the development and progression of neurodegenerative diseases.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [61]
SCFA supplementation restores gliosis and tau pathology in GF TE4 mice.
“In particular, FMT from age-matched control mice restored astrogliosis in antibiotic-treated APP/PS1-21 mice, while SCFAs supplementation restored the gliosis and tau pathology in GF TE4 mice.56,61”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [61]
Gut microbiota perturbation reduces reactive astrogliosis, promotes a shift in astrocytes toward a more homeostatic-like state, and protects against amyloidosis and tau-mediated neurodegeneration.
“Gut microbiota perturbation has also been shown to reduce reactive astrogliosis, promote a shift in astrocytes towards a more homeostatic-like state, and protect against amyloidosis and tau-mediated neurodegeneration.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [61]
The effects of gut microbiota perturbation on astrocytes appear more prominent in male mice.
“Interestingly, these effects appear to be more prominent in male mice.56,61”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [61]
The neuroprotective effects of gut microbiota depletion are diminished following microbiota restoration and SCFA supplementation.
“However, the neuroprotective effects of gut microbiota depletion were diminished following microbiota restoration and SCFA supplementation.”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [61]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing
Benjamini, Y., & Hochberg, Y. (1995) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1995.tb02031.x · Cited by 109,482 · see citing works
DADA2: High–resolution sample inference from Illumina amplicon data
Callahan, B. J., McMurdie, P. J., Rosen, M. J., Han, A. W., Johnson, A. J. A., & Holmes, S. P. (2016) · Nature Methods · doi:10.1038/nmeth.3869 · Cited by 35,698 · see citing works
Cutadapt removes adapter sequences from high-throughput sequencing reads
Martin, M. (2011) · EMBnet.journal · doi:10.14806/ej.17.1.200 · Cited by 33,889 · see citing works
Search and clustering orders of magnitude faster than BLAST
Edgar, R. C. (2010) · Bioinformatics · doi:10.1093/bioinformatics/btq461 · Cited by 20,617 · see citing works
Neurotoxic reactive astrocytes are induced by activated microglia
Liddelow, S. A., Guttenplan, K. A., Clarke, L. E., Bennett, F. C., Bohlen, C. J., Schirmer, L., Bennett, M. L., Münch, A. E., Chung, W.-S., Peterson, T. C., et al. (2017) · Nature · doi:10.1038/nature21029 · Cited by 7,971 · see citing works
Sex differences in immune responses
Klein, S. L., & Flanagan, K. L. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2016.90 · Cited by 6,370 · see citing works
McCarthy, D. J., Chen, Y., & Smyth, G. K. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks042 · Cited by 5,195 · see citing works
PEAR: a fast and accurate Illumina Paired-End reAd mergeR
Zhang, J., Kobert, K., Flouri, T., & Stamatakis, A. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btt593 · Cited by 4,497 · see citing works
Meta-Analysis of 74,046 Individuals Identifies 11 New Susceptibility Loci for Alzheimer’s Disease
(EADI), E. A. D. I., Lambert, J.-C., (GERAD), G. A. E. R. I. A. D., Alzheimer's Disease Genetic Consortium (ADGC), (CHARGE), C. F. H. A. A. R. I. G. E., Ibrahim-Verbaas, C. A., Harold, D., Naj, A. C., Sims, R., Bellenguez, C., et al. (2013) · Nature Genetics · doi:10.1038/ng.2802 · Cited by 4,336 · see citing works
Gut microbiota regulate motor deficits and neuroinflammation in a model of Parkinson's disease
Sampson, T. R., Debelius, J. W., Thron, T., Janssen, S., Shastri, G. G., Ilhan, Z. E., Challis, C., Schretter, C. E., Rocha, S., Gradinaru, V., et al. (2016) · Cell · doi:10.1016/j.cell.2016.11.018 · Cited by 3,622 · see citing works
The neuropathological diagnosis of Alzheimer's disease
DeTure, M. A., & Dickson, D. W. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0333-5 · Cited by 3,329 · see citing works
Alzheimer Disease: An Update on Pathobiology and Treatment Strategies
Long, J. M., & Holtzman, D. M. (2019) · Cell · doi:10.1016/j.cell.2019.09.001 · Cited by 3,204 · see citing works
<i>TREM2</i> Variants in Alzheimer's Disease
Guerreiro, R., Wojtas, A., Bras, J., Carrasquillo, M., Rogaeva, E., Majounie, E., Cruchaga, C., Sassi, C., Kauwe, J. S. K., Younkin, S., et al. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1211851 · Cited by 3,020 · see citing works
Reactive astrocyte nomenclature, definitions, and future directions
Escartin, C., Galea, E., Lakatos, A., O’Callaghan, J. P., Petzold, G. C., Serrano-Pozo, A., Steinhäuser, C., Volterra, A., Carmignoto, G., Agarwal, A., et al. (2021) · Nature Neuroscience · doi:10.1038/s41593-020-00783-4 · Cited by 2,533 · see citing works
New insights into the genetic etiology of Alzheimer’s disease and related dementias
Bellenguez, C., Küçükali, F., Jansen, I. E., Kleineidam, L., Moreno-Grau, S., Amin, N., Naj, A. C., Campos-Martin, R., Grenier-Boley, B., Andrade, V., et al. (2022) · Nature Genetics · doi:10.1038/s41588-022-01024-z · Cited by 2,498 · see citing works
Self-citationGenomic analysis of reactive astrogliosis
Zamanian, J. L., Xu, L., Foo, L. C., Nouri, N., Zhou, L., Giffard, R. G., & Barres, B. A. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.6221-11.2012 · Cited by 2,404 · see citing works
Gut microbiome alterations in Alzheimer’s disease
Vogt, N. M., Kerby, R. L., Dill-McFarland, K. A., Harding, S. J., Merluzzi, A. P., Johnson, S. C., Carlsson, C. M., Asthana, S., Zetterberg, H., Blennow, K., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-13601-y · Cited by 2,137 · see citing works
Sex differences in the gut microbiome drive hormone-dependent regulation of autoimmunity
Markle, J. G. M., Frank, D. N., Mortin-Toth, S., Robertson, C. E., Feazel, L. M., Rolle-Kampczyk, U., von Bergen, M., McCoy, K. D., Macpherson, A. J., & Danska, J. S. (2013) · Science · doi:10.1126/science.1233521 · Cited by 2,025 · see citing works
Naj, A. C., Jun, G., Beecham, G. W., Wang, L.-S., Vardarajan, B. N., Buros, J., Gallins, P. J., Buxbaum, J. D., Jarvik, G. P., Crane, P. K., et al. (2011) · Nature Genetics · doi:10.1038/ng.801 · Cited by 1,901 · see citing works
Jankowsky, J. L., Fadale, D. J., Anderson, J., Xu, G. M., Gonzales, V., Jenkins, N. A., Copeland, N. G., Lee, M. K., Younkin, L. H., Wagner, S. L., et al. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh019 · Cited by 1,575 · see citing works
Rothhammer, V., Mascanfroni, I. D., Bunse, L., Takenaka, M. C., Kenison, J. E., Mayo, L., Chao, C.-C., Patel, B., Yan, R., Blain, M., et al. (2016) · Nature Medicine · doi:10.1038/nm.4106 · Cited by 1,559 · see citing works
Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS)
Constantinescu, C. S., Farooqi, N., O'Brien, K., & Gran, B. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01302.x · Cited by 1,523 · see citing works
Cattaneo, A., Cattane, N., Galluzzi, S., Provasi, S., Lopizzo, N., Festari, C., Ferrari, C., Guerra, U. P., Paghera, B., Muscio, C., et al. (2017) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.08.019 · Cited by 1,382 · see citing works
Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination
Berer, K., Mues, M., Koutrolos, M., Rasbi, Z. A., Boziki, M., Johner, C., Wekerle, H., & Krishnamoorthy, G. (2011) · Nature · doi:10.1038/nature10554 · Cited by 1,251 · see citing works
Normal aging induces A1-like astrocyte reactivity
Clarke, L. E., Liddelow, S. A., Chakraborty, C., Münch, A. E., Heiman, M., & Barres, B. A. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1800165115 · Cited by 1,237 · see citing works
Block of A1 astrocyte conversion by microglia is neuroprotective in models of Parkinson’s disease
Yun, S. P., Kam, T.-I., Panicker, N., Kim, S., Oh, Y., Park, J.-S., Kwon, S.-H., Park, Y. J., Karuppagounder, S. S., Park, H., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0051-5 · Cited by 1,123 · see citing works
Microglial control of astrocytes in response to microbial metabolites
Rothhammer, V., Borucki, D. M., Tjon, E. C., Takenaka, M. C., Chao, C.-C., Ardura-Fabregat, A., de Lima, K. A., Gutiérrez-Vázquez, C., Hewson, P., Staszewski, O., et al. (2018) · Nature · doi:10.1038/s41586-018-0119-x · Cited by 1,051 · see citing works
Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease
Guo, T., Zhang, D., Zeng, Y., Huang, T. Y., Xu, H., & Zhao, Y. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00391-7 · Cited by 994 · see citing works
Aβ42‐driven cerebral amyloidosis in transgenic mice reveals early and robust pathology
Radde, R., Bolmont, T., Kaeser, S. A., Coomaraswamy, J., Lindau, D., Stoltze, L., Calhoun, M. E., Jäggi, F., Wolburg, H., Gengler, S., et al. (2006) · The EMBO Reports · doi:10.1038/sj.embor.7400784 · Cited by 986 · see citing works
Akbari, E., Asemi, Z., Daneshvar Kakhaki, R., Bahmani, F., Kouchaki, E., Tamtaji, O. R., Hamidi, G. A., & Salami, M. (2016) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2016.00256 · Cited by 946 · see citing works
Spangenberg, E., Severson, P. L., Hohsfield, L. A., Crapser, J., Zhang, J., Burton, E. A., Zhang, Y., Spevak, W., Lin, J., Phan, N. Y., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11674-z · Cited by 939 · see citing works
25 years of serving the community with ribosomal RNA gene reference databases and tools
Glöckner, F. O., Yilmaz, P., Quast, C., Gerken, J., Beccati, A., Ciuprina, A., Bruns, G., Yarza, P., Peplies, J., Westram, R., et al. (2017) · Journal of Biotechnology · doi:10.1016/j.jbiotec.2017.06.1198 · Cited by 936 · see citing works
Reduction of Abeta amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota
Harach, T., Marungruang, N., Duthilleul, N., Cheatham, V., Mc Coy, K. D., Frisoni, G., Neher, J. J., Fåk, F., Jucker, M., Lasser, T., et al. (2017) · Scientific Reports · doi:10.1038/srep41802 · Cited by 901 · see citing works
Identification of region-specific astrocyte subtypes at single cell resolution
Batiuk, M. Y., Martirosyan, A., Wahis, J., de Vin, F., Marneffe, C., Kusserow, C., Koeppen, J., Viana, J. F., Oliveira, J. F., Voet, T., et al. (2020) · Nature Communications · doi:10.1038/s41467-019-14198-8 · Cited by 805 · see citing works
Lian, H., Yang, L., Cole, A., Sun, L., Chiang, A. C.-A., Fowler, S. W., Shim, D. J., Rodriguez-Rivera, J., Taglialatela, G., Jankowsky, J. L., et al. (2015) · Neuron · doi:10.1016/j.neuron.2014.11.018 · Cited by 697 · see citing works
Function and therapeutic value of astrocytes in neurological diseases
Lee, H.-G., Wheeler, M. A., & Quintana, F. J. (2022) · Nature Reviews Drug Discovery · doi:10.1038/s41573-022-00390-x · Cited by 662 · see citing works
Vainchtein, I. D., Chin, G., Cho, F. S., Kelley, K. W., Miller, J. G., Chien, E. C., Liddelow, S. A., Nguyen, P. T., Nakao-Inoue, H., Dorman, L. C., et al. (2018) · Science · doi:10.1126/science.aal3589 · Cited by 657 · see citing works
Minter, M. R., Zhang, C., Leone, V., Ringus, D. L., Zhang, X., Oyler-Castrillo, P., Musch, M. W., Liao, F., Ward, J. F., Holtzman, D. M., et al. (2016) · Scientific Reports · doi:10.1038/srep30028 · Cited by 655 · see citing works
Self-citationKennedy, E. A., King, K. Y., & Baldridge, M. T. (2018) · Frontiers in Physiology · doi:10.3389/fphys.2018.01534 · Cited by 602 · see citing works
Lian, H., Litvinchuk, A., Chiang, A. C.-A., Aithmitti, N., Jankowsky, J. L., & Zheng, H. (2016) · The Journal of Neuroscience · doi:10.1523/jneurosci.2117-15.2016 · Cited by 597 · see citing works
Complement C3 deficiency protects against neurodegeneration in aged plaque-rich APP/PS1 mice
Shi, Q., Chowdhury, S., Ma, R., Le, K. X., Hong, S., Caldarone, B. J., Stevens, B., & Lemere, C. A. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aaf6295 · Cited by 593 · see citing works
Neuroinflammatory astrocyte subtypes in the mouse brain
Hasel, P., Rose, I. V. L., Sadick, J. S., Kim, R. D., & Liddelow, S. A. (2021) · Nature Neuroscience · doi:10.1038/s41593-021-00905-6 · Cited by 586 · see citing works
Neurotoxic reactive astrocytes induce cell death via saturated lipids
Guttenplan, K. A., Weigel, M. K., Prakash, P., Wijewardhane, P. R., Hasel, P., Rufen-Blanchette, U., Münch, A. E., Blum, J. A., Fine, J., Neal, M. C., et al. (2021) · Nature · doi:10.1038/s41586-021-03960-y · Cited by 578 · see citing works
Late onset Alzheimer’s disease genetics implicates microglial pathways in disease risk
Efthymiou, A. G., & Goate, A. M. (2017) · Molecular Neurodegeneration · doi:10.1186/s13024-017-0184-x · Cited by 562 · see citing works
Molecular basis of astrocyte diversity and morphology across the CNS in health and disease
Endo, F., Kasai, A., Soto, J. S., Yu, X., Qu, Z., Hashimoto, H., Gradinaru, V., Kawaguchi, R., & Khakh, B. S. (2022) · Science · doi:10.1126/science.adc9020 · Cited by 560 · see citing works
Sun, J., Xu, J., Ling, Y., Wang, F., Gong, T., Yang, C., Ye, S., Ye, K., Wei, D., Song, Z., et al. (2019) · Translational Psychiatry · doi:10.1038/s41398-019-0525-3 · Cited by 532 · see citing works
Reactive Glia not only Associates with Plaques but also Parallels Tangles in Alzheimer’s Disease
Serrano-Pozo, A., Mielke, M. L., Gómez-Isla, T., Betensky, R. A., Growdon, J. H., Frosch, M. P., & Hyman, B. T. (2011) · The American Journal of Pathology · doi:10.1016/j.ajpath.2011.05.047 · Cited by 488 · see citing works
Altered Gut Microbiota in a Mouse Model of Alzheimer’s Disease
Zhang, L., Wang, Y., Xiayu, X., Shi, C., Chen, W., Song, N., Fu, X., Zhou, R., Xu, Y.-F., Huang, L., et al. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-170020 · Cited by 449 · see citing works
The role of astrocytes in amyloid production and Alzheimer's disease
Frost, G. R., & Li, Y. (2017) · Open Biology · doi:10.1098/rsob.170228 · Cited by 435 · see citing works
Aho, V. T. E., Houser, M. C., Pereira, P. A. B., Chang, J., Rudi, K., Paulin, L., Hertzberg, V., Auvinen, P., Tansey, M. G., & Scheperjans, F. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00427-6 · Cited by 435 · see citing works
Reitz, C., Jun, G., Naj, A., Rajbhandary, R., Vardarajan, B. N., Wang, L.-S., Valladares, O., Lin, C.-F., Larson, E. B., Graff-Radford, N. R., et al. (2013) · JAMA · doi:10.1001/jama.2013.2973 · Cited by 431 · see citing works
Sadick, J. S., O’Dea, M. R., Hasel, P., Dykstra, T., Faustin, A., & Liddelow, S. A. (2022) · Neuron · doi:10.1016/j.neuron.2022.03.008 · Cited by 415 · cited 1× · see citing works
“of male APPPS1‐21 mice Astrocytes change their morphology and upregulate complement component C3 expression in the context of inflammatory stimuli, including Aβ deposits [11, 17, 18, 58, 60, 63].”
BackgroundHaran, J. P., Bhattarai, S. K., Foley, S. E., Dutta, P., Ward, D. V., Bucci, V., & McCormick, B. A. (2019) · mBio · doi:10.1128/mbio.00632-19 · Cited by 412 · see citing works
Reactive astrocytes function as phagocytes after brain ischemia via ABCA1-mediated pathway
Morizawa, Y. M., Hirayama, Y., Ohno, N., Shibata, S., Shigetomi, E., Sui, Y., Nabekura, J., Sato, K., Okajima, F., Takebayashi, H., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-00037-1 · Cited by 411 · see citing works
Astrocyte Heterogeneity: Impact to Brain Aging and Disease
Matias, I., Morgado, J., & Gomes, F. C. A. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00059 · Cited by 387 · see citing works
The innate immunity protein IFITM3 modulates γ-secretase in Alzheimer’s disease
Hur, J.-Y., Frost, G. R., Wu, X., Crump, C., Pan, S. J., Wong, E., Barros, M., Li, T., Nie, P., Zhai, Y., et al. (2020) · Nature · doi:10.1038/s41586-020-2681-2 · Cited by 382 · see citing works
Self-citationRojo, R., Raper, A., Ozdemir, D. D., Lefèvre, L., Grabert, K., Wollscheid-Lengeling, E., Bradford, B. M., Caruso, M., Gažová, I., Sánchez, A., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11053-8 · Cited by 372 · see citing works
Zhao, J. J., O’Connor, T., & Vassar, R. J. (2011) · Journal of Neuroinflammation · doi:10.1186/1742-2094-8-150 · Cited by 370 · see citing works
Self-citationIL-33 ameliorates Alzheimer's disease-like pathology and cognitive decline
Fu, A. K. Y., Hung, K.-W., Yuen, M. Y. F., Zhou, X., Mak, D. S. Y., Chan, I. C. W., Cheung, T. H., Zhang, B., Fu, W.-Y., Liew, F. Y., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1604032113 · Cited by 369 · see citing works
SOX9 Is an Astrocyte-Specific Nuclear Marker in the Adult Brain Outside the Neurogenic Regions
Sun, W., Cornwell, A., Li, J., Peng, S., Osorio, M. J., Aalling, N., Wang, S., Benraiss, A., Lou, N., Goldman, S. A., et al. (2017) · The Journal of Neuroscience · doi:10.1523/jneurosci.3199-16.2017 · Cited by 357 · see citing works
Inhibition of Stat3‐mediated astrogliosis ameliorates pathology in an Alzheimer's disease model
Reichenbach, N., Delekate, A., Plescher, M., Schmitt, F., Krauss, S., Blank, N., Halle, A., & Petzold, G. C. (2019) · EMBO Molecular Medicine · doi:10.15252/emmm.201809665 · Cited by 343 · see citing works
Gut-licensed IFNγ+ NK cells drive LAMP1+TRAIL+ anti-inflammatory astrocytes
Sanmarco, L. M., Wheeler, M. A., Gutiérrez-Vázquez, C., Polonio, C. M., Linnerbauer, M., Pinho-Ribeiro, F. A., Li, Z., Giovannoni, F., Batterman, K. V., Scalisi, G., et al. (2021) · Nature · doi:10.1038/s41586-020-03116-4 · Cited by 331 · see citing works
Lei, F., Cui, N., Zhou, C., Chodosh, J., Vavvas, D. G., & Paschalis, E. I. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1922788117 · Cited by 322 · see citing works
Astrocytic interleukin-3 programs microglia and limits Alzheimer’s disease
McAlpine, C. S., Park, J., Griciuc, A., Kim, E., Choi, S. H., Iwamoto, Y., Kiss, M. G., Christie, K. A., Vinegoni, C., Poller, W. C., et al. (2021) · Nature · doi:10.1038/s41586-021-03734-6 · Cited by 322 · see citing works
Altered Gut Microbiome Composition and Tryptic Activity of the 5xFAD Alzheimer’s Mouse Model
Brandscheid, C., Schuck, F., Reinhardt, S., Schäfer, K.-H., Pietrzik, C. U., Grimm, M., Hartmann, T., Schwiertz, A., & Endres, K. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-160926 · Cited by 318 · see citing works
Microbiota in neuroinflammation and synaptic dysfunction: a focus on Alzheimer’s disease
Bairamian, D., Sha, S., Rolhion, N., Sokol, H., Dorothée, G., Lemere, C. A., & Krantic, S. M. (2022) · Molecular Neurodegeneration · doi:10.1186/s13024-022-00522-2 · Cited by 318 · see citing works
Regulation of beta-amyloid production in neurons by astrocyte-derived cholesterol
Wang, H., Kulas, J. A., Wang, C., Holtzman, D. M., Ferris, H. A., & Hansen, S. B. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2102191118 · Cited by 294 · see citing works
Minter, M. R., Hinterleitner, R., Meisel, M., Zhang, C., Leone, V., Zhang, X., Oyler-Castrillo, P., Zhang, X., Musch, M. W., Shen, X., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-11047-w · Cited by 292 · see citing works
Self-citationSex-specific effects of microbiome perturbations on cerebral Aβ amyloidosis and microglia phenotypes
Dodiya, H. B., Kuntz, T., Shaik, S. M., Baufeld, C., Leibowitz, J., Zhang, X., Gottel, N., Zhang, X., Butovsky, O., Gilbert, J. A., et al. (2019) · Journal of Experimental Medicine · doi:10.1084/jem.20182386 · Cited by 288 · see citing works
Self-citationBarcoded viral tracing of single-cell interactions in central nervous system inflammation
Clark, I. C., Gutiérrez-Vázquez, C., Wheeler, M. A., Li, Z., Rothhammer, V., Linnerbauer, M., Sanmarco, L. M., Guo, L., Blain, M., Zandee, S. E. J., et al. (2021) · Science · doi:10.1126/science.abf1230 · Cited by 285 · see citing works
Shen, L., Liu, L., & Ji, H. (2016) · Journal of Alzheimer s Disease · doi:10.3233/jad-160884 · Cited by 280 · see citing works
The gut microbiome in Alzheimer’s disease: what we know and what remains to be explored
Chandra, S., Sisodia, S. S., & Vassar, R. J. (2023) · Molecular Neurodegeneration · doi:10.1186/s13024-023-00595-7 · Cited by 278 · see citing works
Self-citationLavialle, M., Aumann, G., Anlauf, E., Pröls, F., Arpin, M., & Derouiche, A. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1100957108 · Cited by 267 · see citing works
Astrocytic LRP1 Mediates Brain Aβ Clearance and Impacts Amyloid Deposition
Liu, C.-C., Hu, J., Zhao, N., Wang, J., Wang, N., Cirrito, J. R., Kanekiyo, T., Holtzman, D. M., & Bu, G. (2017) · The Journal of Neuroscience · doi:10.1523/jneurosci.3442-16.2017 · Cited by 267 · see citing works
Ceyzériat, K., Ben Haim, L., Denizot, A., Pommier, D., Matos, M., Guillemaud, O., Palomares, M.-A., Abjean, L., Petit, F., Gipchtein, P., et al. (2018) · Acta Neuropathologica Communications · doi:10.1186/s40478-018-0606-1 · Cited by 256 · see citing works
Seo, D.-O., O’Donnell, D., Jain, N., Ulrich, J. D., Herz, J., Li, Y., Lemieux, M., Cheng, J., Hu, H., Serrano, J. R., et al. (2023) · Science · doi:10.1126/science.add1236 · Cited by 254 · see citing works
Self-citationAssociation of Infant Antibiotic Exposure With Childhood Health Outcomes
Aversa, Z., Atkinson, E. J., Schafer, M. J., Theiler, R. N., Rocca, W. A., Blaser, M. J., & LeBrasseur, N. K. (2020) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2020.07.019 · Cited by 235 · see citing works
Den, H., Dong, X., Chen, M., & Zou, Z. (2020) · Aging · doi:10.18632/aging.102810 · Cited by 230 · see citing works
Jiwaji, Z., Tiwari, S. S., Avilés-Reyes, R. X., Hooley, M., Hampton, D., Torvell, M., Johnson, D. A., McQueen, J., Baxter, P., Sabari-Sankar, K., et al. (2022) · Nature Communications · doi:10.1038/s41467-021-27702-w · Cited by 223 · see citing works
Neurotoxic Reactive Astrocytes Drive Neuronal Death after Retinal Injury
Guttenplan, K. A., Stafford, B. K., El-Danaf, R. N., Adler, D. I., Münch, A. E., Weigel, M. K., Huberman, A. D., & Liddelow, S. A. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.107776 · Cited by 221 · see citing works
Xiao, J., Katsumata, N., Bernier, F., Ohno, K., Yamauchi, Y., Odamaki, T., Yoshikawa, K., Ito, K., & Kaneko, T. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-200488 · Cited by 206 · see citing works
Chen, C., Ahn, E. H., Kang, S. S., Liu, X., Alam, A., & Ye, K. (2020) · Science Advances · doi:10.1126/sciadv.aba0466 · Cited by 205 · see citing works
Human gut microbiota and healthy aging: Recent developments and future prospective
Kumar, M., Babaei, P., Ji, B., & Nielsen, J. (2016) · Nutrition and Healthy Aging · doi:10.3233/nha-150002 · Cited by 201 · see citing works
Basak, J. M., Verghese, P. B., Yoon, H., Kim, J., & Holtzman, D. M. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.288746 · Cited by 192 · see citing works
Park, J.-S., Kam, T.-I., Lee, S., Park, H., Oh, Y., Kwon, S.-H., Song, J.-J., Kim, D., Kim, H., Jhaldiyal, A., et al. (2021) · Acta Neuropathologica Communications · doi:10.1186/s40478-021-01180-z · Cited by 192 · see citing works
Absence of microglia promotes diverse pathologies and early lethality in Alzheimer’s disease mice
Kiani Shabestari, S., Morabito, S., Danhash, E. P., McQuade, A., Sanchez, J. R., Miyoshi, E., Chadarevian, J. P., Claes, C., Coburn, M. A., Hasselmann, J., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.110961 · Cited by 167 · see citing works
Chen, Y., Fang, L., Chen, S., Zhou, H., Fan, Y., Li, L., Li, J., Xu, J., Chen, Y., Ma, Y., et al. (2020) · BioMed Research International · doi:10.1155/2020/8456596 · Cited by 150 · see citing works
Astroglial atrophy in Alzheimer’s disease
Verkhratsky, A., Rodriguez, J. J., Pivoriūnas, A., Zorec, R., & Semyanov, A. V. (2019) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-019-02310-2 · Cited by 140 · see citing works
Astrocyte-secreted IL-33 mediates homeostatic synaptic plasticity in the adult hippocampus
Wang, Y., Fu, W., Cheung, K., Hung, K.-W., Chen, C., Geng, H.-Y., Yung, W., Qu, J. Y., Fu, A. K. Y., & Ip, N. Y. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2020810118 · Cited by 133 · see citing works
Kummer, M. P., Ising, C., Kummer, C., Sarlus, H., Griep, A., Vieira‐Saecker, A., Schwartz, S., Halle, A., Brückner, M., Händler, K., et al. (2021) · The EMBO Journal · doi:10.15252/embj.2021108662 · Cited by 127 · see citing works
Sompol, P. M., Furman, J. L., Pleiss, M. M., Kraner, S. D., Artiushin, I. A., Batten, S. R., Quintero, J. E., Simmerman, L. A., Beckett, T. L., Lovell, M. A., et al. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.0877-17.2017 · Cited by 122 · see citing works
Mezö, C., Dokalis, N., Mossad, O., Staszewski, O., Neuber, J., Yilmaz, B., Schnepf, D., de Agüero, M. G., Ganal-Vonarburg, S. C., Macpherson, A. J., et al. (2020) · Acta Neuropathologica Communications · doi:10.1186/s40478-020-00988-5 · Cited by 120 · see citing works
Gut microbiota–driven brain Aβ amyloidosis in mice requires microglia
Dodiya, H. B., Lutz, H. L., Weigle, I. Q., Patel, P., Michalkiewicz, J., Roman-Santiago, C. J., Zhang, C. M., Liang, Y., Srinath, A., Zhang, X., et al. (2022) · Journal of Experimental Medicine · doi:10.1084/jem.20200895 · Cited by 120 · see citing works
Self-citationDroplet-based forward genetic screening of astrocyte–microglia cross-talk
Wheeler, M. A., Clark, I. C., Lee, H., Li, Z., Linnerbauer, M., Rone, J. M., Blain, M., Akl, C. F., Piester, G., Giovannoni, F., et al. (2023) · Science · doi:10.1126/science.abq4822 · Cited by 117 · see citing works
Microbial involvement in Alzheimer disease development and progression
Bulgart, H. R., Neczypor, E. W., Wold, L. E., & Mackos, A. R. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00378-4 · Cited by 116 · see citing works
Lu, Y., Sareddy, G. R., Wang, J., Zhang, Q., Tang, F., Pratap, U. P., TEKMAL, R. R., Vadlamudi, R. K., & Brann, D. W. (2020) · Journal of Neuroscience · doi:10.1523/jneurosci.0115-20.2020 · Cited by 109 · see citing works
Doron, H., Amer, M., Ershaid, N., Blazquez, R., Shani, O., Lahav, T. G., Cohen, N., Adler, O., Hakim, Z., Pozzi, S., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.07.033 · Cited by 87 · see citing works
Dodiya, H. B., Frith, M., Sidebottom, A. M., Cao, Y., Koval, J., Chang, E. B., & Sisodia, S. S. (2020) · Scientific Reports · doi:10.1038/s41598-020-64797-5 · Cited by 84 · see citing works
Self-citationSpichak, S., Donoso, F., Moloney, G. M., Gunnigle, E., Brown, J. R.-M., Codagnone, M. G., Dinan, T. G., & Cryan, J. F. (2021) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2021.100318 · Cited by 73 · see citing works
Katsouri, L., & Georgopoulos, S. (2011) · PLoS ONE · doi:10.1371/journal.pone.0021880 · Cited by 72 · see citing works
Boztuǧ, K., Carson, M. J., Pham-Mitchell, N., Asensio, V. C., DeMartino, J. A., & Campbell, I. L. (2002) · The Journal of Immunology · doi:10.4049/jimmunol.169.3.1505 · Cited by 71 · see citing works
Preman, P., Julia, T. C. W., Calafate, S., Snellinx, A., Alfonso-Triguero, M., Corthout, N., Munck, S., Thal, D. R., Goate, A., Strooper, B. D., et al. (2021) · Molecular Neurodegeneration · doi:10.1186/s13024-021-00487-8 · Cited by 71 · see citing works
Cuervo-Zanatta, D., Garcı́a-Mena, J., & Perez‐Cruz, C. (2021) · Journal of Alzheimer s Disease · doi:10.3233/jad-201367 · Cited by 60 · see citing works
Synergistic effects of APOE and sex on the gut microbiome of young EFAD transgenic mice
Weng, J. E. M., Parikh, I. J., Naqib, A., York, J., Green, S., Estus, S., & LaDu, M. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0352-2 · Cited by 59 · see citing works
Don't forget astrocytes when targeting Alzheimer's disease
Sadick, J. S., & Liddelow, S. A. (2019) · British Journal of Pharmacology · doi:10.1111/bph.14568 · Cited by 58 · see citing works
Du, J., Yi, M., Zhou, F., He, W., Yang, A., Qiu, M., & Huang, H. (2021) · Molecular Brain · doi:10.1186/s13041-021-00865-9 · Cited by 57 · see citing works
Sánchez-Tapia, M., Mimenza-Alvarado, A., Granados-Domínguez, L., Flores-López, A., López-Barradas, A., Ortiz, V., Pérez-Cruz, C., Sánchez-Vidal, H., Hernández-Acosta, J., Ávila-Funes, J. A., et al. (2023) · Nutrients · doi:10.3390/nu15040932 · Cited by 47 · see citing works
Neuroprotective effect of astrocyte-derived IL-33 in neonatal hypoxic-ischemic brain injury
Jiao, M.-Y., Li, X.-Y., Chen, L., Wang, X.-D., Yuan, B., Liu, T., Dong, Q., Mei, H., & Yin, H. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-020-01932-z · Cited by 46 · see citing works
Still, K., Batista, S. J., O'Brien, C. A., Oyesola, O., Früh, S. P., Webb, L., Smirnov, I., Kovacs, M. A., Cowan, M., Hayes, N., et al. (2018) · PLoS Pathogens · doi:10.1371/journal.ppat.1009027 · Cited by 41 · see citing works
Bello-Medina, P. C., Corona-Cervantes, K., Zavala-Torres, N. G., González, A., Pérez-Morales, M., González-Franco, D. A., Gómez, A., Garcı́a-Mena, J., Díaz-Cintra, S. Y., & Pacheco‐López, G. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23158209 · Cited by 31 · see citing works
Impact of Acute and Chronic Amyloid-β Peptide Exposure on Gut Microbial Commensals in the Mouse
Guilherme, M. D. S., Todorov, H., Osterhof, C., Möllerke, A., Cub, K., Hankeln, T., Gerber, S., & Endres, K. (2020) · Frontiers in Microbiology · doi:10.3389/fmicb.2020.01008 · Cited by 29 · see citing works
Schacke, S., Kirkpatrick, J. M., Stocksdale, A., Bauer, R., Hagel, C., Riecken, L. B., & Morrison, H. (2022) · Glia · doi:10.1002/glia.24253 · Cited by 27 · see citing works
Engulfment of Toxic Amyloid β-protein in Neurons and Astrocytes Mediated by MEGF10
Fujita, Y., Maeda, T., Sato, C., Sato, M., Hatakeyama, H., Ota, Y., Iwabuchi, N., Tatesawa, K., Nomura, A., Zou, K., et al. (2020) · Neuroscience · doi:10.1016/j.neuroscience.2020.07.016 · Cited by 17 · see citing works
Cavieres-Lepe, J., & Stuardo, N. (2021) · Journal of Neuroscience · doi:10.1523/jneurosci.2352-20.2021 · Cited by 4 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- [78]Dodiya HB Lutz HL Weigle IQ Patel P Michalkiewicz J Roman-Santiago CJ Gut microbiota–driven brain Aβ amyloidosis in mice requires microglia J Exp Med 2021 219 1 e20200895 10.1084/jem.20200895 34854884 PMC8647415 · DOI · Paper page
Cited by
Sorted by citations
Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases
Loh, J. S., Mak, W. Q., Tan, L. K. S., Ng, C. X., Chan, H. H., Yeow, S. H., Foo, J. B., Ong, Y. S., How, C. W., & Khaw, K. Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01743-1 · Cited by 1,193 · see citing works
- Authors
- Chandra, S., Di Meco, A., Dodiya, H. B., Popovic, J., Cuddy, L. K., Weigle, I. Q., Zhang, X., Sadleir, K., Sisodia, S. S., & Vassar, R.
- Affiliations
- Northwestern University (US)
- University of Chicago (US)
- Corresponding author
- Vassar, Robert
- ORCID
- Venue
- Molecular Neurodegeneration
- Published
- 2023-07-06
- Volume
- 18
- Issue
- 1
- Pages
- 45-45
- ISSN
- 1750-1326 (ISSN-L)
- PMC
- PMC10324210
- OpenAlex
- W4383370805
- Cited by
- 58
- References
- 114
- Citations by year
- 2026: 10 · 2025: 27 · 2024: 19 · 2023: 2
- FWCI
- 10.48
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Molecular Neurodegeneration (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Knowledge@UChicago (University of Chicago) (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- University of Chicago (cc-by)
- Funders
- Good Ventures Foundation
- National Institute on Aging (F30AG079577)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- gut microbiota, amyloid plaques, Alzheimer's disease, astrocyte phenotype, reactive astrocytes, microglia, fecal microbiota transplantation, germ-free mice, CSF1R inhibitor, PLX5622, complement C3
- MeSH terms
- Gastrointestinal Microbiome, Alzheimer Disease, Amyloidosis, Animals, Astrocytes, Female, Gliosis, Male, Mice, Transgenic, Organic Chemicals, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Microglia, Mice, Plaque, Amyloid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
