Bifidobacteria shape host neural circuits during postnatal development by promoting synapse formation and microglial function

Scientific Reports

Volumn 10, Issue 1, 2020, Pages

  Luck, Berkley ^a,b   Engevik, Melinda A ^a,b   Ganesh, Bhanu Priya ^c   Lackey, Elizabeth P ^b   Lin, Tao ^a,b   Balderas, Miriam ^a,b   Major, Angela ^b   Runge, Jessica ^b   Luna, Ruth Ann ^b   Sillitoe, Roy V ^a,b   Versalovic, James ^a,b  

^a TEXAS CHILDREN S HOSPITAL   (United States)

^b BAYLOR COLLEGE OF MEDICINE   (United States)

^c UNIVERSITY OF TEXAS MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANIMAL; BIFIDOBACTERIUM; CYTOLOGY; GENE EXPRESSION REGULATION; GROWTH, DEVELOPMENT AND AGING; INTESTINE; METABOLISM; MICROBIOLOGY; MICROGLIA; MOUSE; NERVE CELL NETWORK; NEWBORN; PHYSIOLOGY; SYNAPSE;

ANIMALS; ANIMALS, NEWBORN; BIFIDOBACTERIUM; GENE EXPRESSION REGULATION, DEVELOPMENTAL; INTESTINES; MICE; MICROGLIA; NERVE NET; SYNAPSES;

EID: 85084322079     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/s41598-020-64173-3     Document Type: Article

References (112)

1. Diaz Heijtz, R. et al. Normal gut microbiota modulates brain development and behavior. Proc Natl Acad Sci U S A 108, 3047–3052, 10.1073/pnas.1010529108 (2011).
2. Mayer, E. A., Knight, R., Mazmanian, S. K., Cryan, J. F. & Tillisch, K. Gut Microbes and the Brain: Paradigm Shift in Neuroscience. Journal of Neuroscience 34, 15490–15496, 10.1523/jneurosci.3299-14.2014 (2014).
3. Desbonnet, L. et al. Gut microbiota depletion from early adolescence in mice: Implications for brain and behaviour. Brain Behav Immun 48, 165–173, 10.1016/j.bbi.2015.04.004 (2015).
4. Borre, Y. E. et al. Microbiota and neurodevelopmental windows: implications for brain disorders. Trends Mol Med 20, 509–518, 10.1016/j.molmed.2014.05.002 (2014).
5. in Transforming the Workforce for Children Birth Through Age 8: A Unifying Foundation (eds L. R. Allen & B. B. Kelly) (The National Academies Press, 2015).
6. Backhed, F. et al. Dynamics and Stabilization of the Human Gut Microbiome during the First Year of Life. Cell Host Microbe 17, 852, 10.1016/j.chom.2015.05.012 (2015).
7. Di Gioia, D., Aloisio, I., Mazzola, G. & Biavati, B. Bifidobacteria: their impact on gut microbiota composition and their applications as probiotics in infants. Appl Microbiol Biotechnol 98, 563–577, 10.1007/s00253-013-5405-9 (2014).
8. Lim, E. S. et al. Early life dynamics of the human gut virome and bacterial microbiome in infants. Nat Med 21, 1228–1234, 10.1038/nm.3950 (2015).
9. Makino, H. et al. Mother-to-infant transmission of intestinal bifidobacterial strains has an impact on the early development of vaginally delivered infant's microbiota. PLoS One 8, e78331, 10.1371/journal.pone.0078331 (2013).
10. Matsuki, T. et al. A key genetic factor for fucosyllactose utilization affects infant gut microbiota development. Nat Commun 7, 11939, 10.1038/ncomms11939 (2016).
11. Turroni, F. et al. Exploring the diversity of the bifidobacterial population in the human intestinal tract. Appl Environ Microbiol 75, 1534–1545, 10.1128/AEM.02216-08 (2009).
12. Turroni, F. et al. Diversity of bifidobacteria within the infant gut microbiota. PLoS One 7, e36957, 10.1371/journal.pone.0036957 (2012).
13. Favier, C. F., Vaughan, E. E., De Vos, W. M. & Akkermans, A. D. Molecular monitoring of succession of bacterial communities in human neonates. Appl Environ Microbiol 68, 219–226 (2002).
14. Khonsari, S. et al. A comparative study of bifidobacteria in human babies and adults. Biosci Microbiota Food Health 35, 97–103, 10.12938/bmfh.2015-006 (2016).
15. Arboleya, S., Watkins, C., Stanton, C. & Ross, R. P. Gut Bifidobacteria Populations in Human Health and Aging. Front Microbiol 7, 1204, 10.3389/fmicb.2016.01204 (2016).
16. Odamaki, T. et al. Age-related changes in gut microbiota composition from newborn to centenarian: a cross-sectional study. BMC Microbiol 16, 90, 10.1186/s12866-016-0708-5 (2016).
17. Ringel-Kulka, T. et al. Intestinal microbiota in healthy U.S. young children and adults–a high throughput microarray analysis. PLoS One 8, e64315, 10.1371/journal.pone.0064315 (2013).
18. Davis, L. M., Martinez, I., Walter, J., Goin, C. & Hutkins, R. W. Barcoded pyrosequencing reveals that consumption of galactooligosaccharides results in a highly specific bifidogenic response in humans. PLoS One 6, e25200, 10.1371/journal.pone.0025200 (2011).
19. Gueimonde, M., Debor, L., Tolkko, S., Jokisalo, E. & Salminen, S. Quantitative assessment of faecal bifidobacterial populations by real-time PCR using lanthanide probes. J Appl Microbiol 102, 1116–1122, 10.1111/j.1365-2672.2006.03145.x (2007).
20. Matsuki, T. et al. Quantitative PCR with 16S rRNA-gene-targeted species-specific primers for analysis of human intestinal bifidobacteria. Appl Environ Microbiol 70, 167–173 (2004).
21. Chaplin, A. V. et al. [Species Diversity of Bifidobacteria in the Intestinal Microbiota Studied Using MALDI-TOF Mass-Spectrometry]. Vestn Ross Akad Med Nauk, 435-440 (2015).
22. Chu, D. M. et al. Maturation of the infant microbiome community structure and function across multiple body sites and in relation to mode of delivery. Nat Med 23, 314–326, 10.1038/nm.4272 (2017).
23. Yatsunenko, T. et al. Human gut microbiome viewed across age and geography. Nature 486, 222–227, 10.1038/nature11053 (2012).
24. Luk, B. et al. Postnatal colonization with human "infant-type" Bifidobacterium species alters behavior of adult gnotobiotic mice. PLoS One 13, e0196510, 10.1371/journal.pone.0196510 (2018).
25. Ait-Belgnaoui, A. et al. Probiotic gut effect prevents the chronic psychological stress-induced brain activity abnormality in mice. Neurogastroenterol Motil 26, 510–520, 10.1111/nmo.12295 (2014).
26. Bercik, P. et al. The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice. Gastroenterology 141(599-609), 609 e591–593, 10.1053/j.gastro.2011.04.052 (2011).
27. Desbonnet, L., Garrett, L., Clarke, G., Bienenstock, J. & Dinan, T. G. The probiotic Bifidobacteria infantis: An assessment of potential antidepressant properties in the rat. J Psychiatr Res 43, 164–174, 10.1016/j.jpsychires.2008.03.009 (2008).
28. Desbonnet, L. et al. Effects of the probiotic Bifidobacterium infantis in the maternal separation model of depression. Neuroscience 170, 1179–1188, 10.1016/j.neuroscience.2010.08.005 (2010).
29. Nishino, R. et al. Commensal microbiota modulate murine behaviors in a strictly contamination-free environment confirmed by culture-based methods. Neurogastroenterol Motil 25, 521–528, 10.1111/nmo.12110 (2013).
30. Savignac, H. M., Kiely, B., Dinan, T. G. & Cryan, J. F. Bifidobacteria exert strain-specific effects on stress-related behavior and physiology in BALB/c mice. Neurogastroenterol Motil 26, 1615–1627, 10.1111/nmo.12427 (2014).
31. Savignac, H. M., Tramullas, M., Kiely, B., Dinan, T. G. & Cryan, J. F. Bifidobacteria modulate cognitive processes in an anxious mouse strain. Behav Brain Res 287, 59–72, 10.1016/j.bbr.2015.02.044 (2015).
32. Erny, D. et al. Host microbiota constantly control maturation and function of microglia in the CNS. Nat Neurosci 18, 965–977, 10.1038/nn.4030 (2015).
33. Tillisch, K. et al. Consumption of fermented milk product with probiotic modulates brain activity. Gastroenterology 144, 1394-1401, 1401 e1391–1394, 10.1053/j.gastro.2013.02.043 (2013).
34. Schroeder, B. O. et al. Bifidobacteria or Fiber Protects against Diet-Induced Microbiota-Mediated Colonic Mucus Deterioration. Cell Host Microbe 23, 27-40 e27, 10.1016/j.chom.2017.11.004 (2018).
35. Wilson, B. C., Vatanen, T., Cutfield, W. S. & O'Sullivan, J. M. The Super-Donor Phenomenon in Fecal Microbiota Transplantation. Front Cell Infect Microbiol 9, 2, 10.3389/fcimb.2019.00002 (2019).
36. Hsueh, Y. P. Synaptic Formation, Neural Circuits and Neurodevelopmental Disorders Controlled by Signaling, Translation, and Epigenetic Regulation. Dev Neurobiol 79, 2–7, 10.1002/dneu.22655 (2019).
37. Tay, T. L., Savage, J. C., Hui, C. W., Bisht, K. & Tremblay, M. E. Microglia across the lifespan: from origin to function in brain development, plasticity and cognition. J Physiol 595, 1929–1945, 10.1113/JP272134 (2017).
38. Gautier, E. L. et al. Gene-expression profiles and transcriptional regulatory pathways that underlie the identity and diversity of mouse tissue macrophages. Nat Immunol 13, 1118–1128, 10.1038/ni.2419 (2012).
39. Zhan, Y. et al. Deficient neuron-microglia signaling results in impaired functional brain connectivity and social behavior. Nat Neurosci 17, 400–406, 10.1038/nn.3641 (2014).
40. Schafer, D. P. et al. Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron 74, 691–705, 10.1016/j.neuron.2012.03.026 (2012).
41. Paolicelli, R. C. et al. Synaptic pruning by microglia is necessary for normal brain development. Science 333, 1456–1458, 10.1126/science.1202529 (2011).
42. Rangaraju, S. et al. Differential Phagocytic Properties of CD45(low) Microglia and CD45(high) Brain Mononuclear Phagocytes-Activation and Age-Related Effects. Front Immunol 9, 405, 10.3389/fimmu.2018.00405 (2018).
43. Rothhammer, V. et al. Microglial control of astrocytes in response to microbial metabolites. Nature 557, 724–728, 10.1038/s41586-018-0119-x (2018).
44. Ransohoff, R. M. & Perry, V. H. Microglial physiology: unique stimuli, specialized responses. Annu Rev Immunol 27, 119–145, 10.1146/annurev.immunol.021908.132528 (2009).
45. Inoue, K., Koizumi, S., Kataoka, A., Tozaki-Saitoh, H. & Tsuda, M. P2Y(6)-Evoked Microglial Phagocytosis. Int Rev Neurobiol 85, 159–163, 10.1016/S0074-7742(09)85012-5 (2009).
46. Koizumi, S. et al. UDP acting at P2Y6 receptors is a mediator of microglial phagocytosis. Nature 446, 1091–1095, 10.1038/nature05704 (2007).
47. Davis, B. M., Salinas-Navarro, M., Cordeiro, M. F., Moons, L. & De Groef, L. Characterizing microglia activation: a spatial statistics approach to maximize information extraction. Sci Rep 7, 1576, 10.1038/s41598-017-01747-8 (2017).
48. Tremblay, M. E., Lowery, R. L. & Majewska, A. K. Microglial interactions with synapses are modulated by visual experience. PLoS Biol 8, e1000527, 10.1371/journal.pbio.1000527 (2010).
49. Wake, H., Moorhouse, A. J., Jinno, S., Kohsaka, S. & Nabekura, J. Resting microglia directly monitor the functional state of synapses in vivo and determine the fate of ischemic terminals. J Neurosci 29, 3974–3980, 10.1523/JNEUROSCI.4363-08.2009 (2009).
50. Hristovska, I. & Pascual, O. Deciphering Resting Microglial Morphology and Process Motility from a Synaptic Prospect. Front Integr Neurosci 9, 73, 10.3389/fnint.2015.00073 (2015).
51. Booth, P. L. & Thomas, W. E. Evidence for motility and pinocytosis in ramified microglia in tissue culture. Brain Res 548, 163–171, 10.1016/0006-8993(91)91118-k (1991).
52. Fernandez-Arjona, M. D. M., Grondona, J. M., Granados-Duran, P., Fernandez-Llebrez, P. & Lopez-Avalos, M. D. Microglia Morphological Categorization in a Rat Model of Neuroinflammation by Hierarchical Cluster and Principal Components Analysis. Front Cell Neurosci 11, 235, 10.3389/fncel.2017.00235 (2017).
53. Ford, A. L., Goodsall, A. L., Hickey, W. F. & Sedgwick, J. D. Normal adult ramified microglia separated from other central nervous system macrophages by flow cytometric sorting. Phenotypic differences defined and direct ex vivo antigen presentation to myelin basic protein-reactive CD4+ T cells compared. J Immunol 154, 4309–4321 (1995).
54. Aloisi, F., De Simone, R., Columba-Cabezas, S., Penna, G. & Adorini, L. Functional maturation of adult mouse resting microglia into an APC is promoted by granulocyte-macrophage colony-stimulating factor and interaction with Th1 cells. J Immunol 164, 1705–1712, 10.4049/jimmunol.164.4.1705 (2000).
55. Greter, M., Lelios, I. & Croxford, A. L. Microglia Versus Myeloid Cell Nomenclature during Brain Inflammation. Front Immunol 6, 249, 10.3389/fimmu.2015.00249 (2015).
56. Bennett, M. L. et al. New tools for studying microglia in the mouse and human CNS. Proc Natl Acad Sci U S A 113, E1738–1746, 10.1073/pnas.1525528113 (2016).
57. Sousa, C., Biber, K. & Michelucci, A. Cellular and Molecular Characterization of Microglia: A Unique Immune Cell Population. Front Immunol 8, 198, 10.3389/fimmu.2017.00198 (2017).
58. Stratoulias, V., Venero, J. L., Tremblay, M. E. & Joseph, B. Microglial subtypes: diversity within the microglial community. EMBO J 38, e101997, 10.15252/embj.2019101997 (2019).
59. Madry, C. et al. Microglial Ramification, Surveillance, and Interleukin-1beta Release Are Regulated by the Two-Pore Domain K(+) Channel THIK-1. Neuron 97, 299–312 e296, 10.1016/j.neuron.2017.12.002 (2018).
60. Round, J. L. & Mazmanian, S. K. The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol 9, 313–323, 10.1038/nri2515 (2009).
61. Macpherson, A. J. & Harris, N. L. Interactions between commensal intestinal bacteria and the immune system. Nat Rev Immunol 4, 478–485, 10.1038/nri1373 (2004).
62. Bouskra, D. et al. Lymphoid tissue genesis induced by commensals through NOD1 regulates intestinal homeostasis. Nature 456, 507–510, 10.1038/nature07450 (2008).
63. Tseng, C. Y., Ling, E. A. & Wong, W. C. Light and electron microscopic and cytochemical identification of amoeboid microglial cells in the brain of prenatal rats. J Anat 136, 837–849 (1983).
64. Ling, E. A. & Tan, C. K. Amoeboid microglial cells in the corpus callosum of neonatal rats. Arch Histol Jpn 36, 265–280, 10.1679/aohc1950.36.265 (1974).
65. Ling, E. A. & Wong, W. C. The origin and nature of ramified and amoeboid microglia: a historical review and current concepts. Glia 7, 9–18, 10.1002/glia.440070105 (1993).
66. Shapiro, L. A., Perez, Z. D., Foresti, M. L., Arisi, G. M. & Ribak, C. E. Morphological and ultrastructural features of Iba1-immunolabeled microglial cells in the hippocampal dentate gyrus. Brain Res 1266, 29–36, 10.1016/j.brainres.2009.02.031 (2009).
67. Ito, D. et al. Microglia-specific localisation of a novel calcium binding protein, Iba1. Brain Res Mol Brain Res 57, 1–9, 10.1016/s0169-328x(98)00040-0 (1998).
68. Okere, C. O. & Kaba, H. Heterogenous immunohistochemical expression of microglia-specific ionized calcium binding adaptor protein (Iba1) in the mouse olfactory bulb. Brain Res 877, 85–90, 10.1016/s0006-8993(00)02656-1 (2000).
69. Shapiro, L. A., Wang, L. & Ribak, C. E. Rapid astrocyte and microglial activation following pilocarpine-induced seizures in rats. Epilepsia 49(Suppl 2), 33–41, 10.1111/j.1528-1167.2008.01491.x (2008).
70. Hendrickx, D. A. E., van Eden, C. G., Schuurman, K. G., Hamann, J. & Huitinga, I. Staining of HLA-DR, Iba1 and CD68 in human microglia reveals partially overlapping expression depending on cellular morphology and pathology. J Neuroimmunol 309, 12–22, 10.1016/j.jneuroim.2017.04.007 (2017).
71. Kuno, R. et al. Autocrine activation of microglia by tumor necrosis factor-alpha. J Neuroimmunol 162, 89–96, 10.1016/j.jneuroim.2005.01.015 (2005).
72. Welser-Alves, J. V. & Milner, R. Microglia are the major source of TNF-alpha and TGF-beta1 in postnatal glial cultures; regulation by cytokines, lipopolysaccharide, and vitronectin. Neurochem Int 63, 47–53, 10.1016/j.neuint.2013.04.007 (2013).
73. Riazi, K. et al. Microglial activation and TNFalpha production mediate altered CNS excitability following peripheral inflammation. Proc Natl Acad Sci U S A 105, 17151–17156, 10.1073/pnas.0806682105 (2008).
74. Zhang, Y. et al. An RNA-sequencing transcriptome and splicing database of glia, neurons, and vascular cells of the cerebral cortex. J Neurosci 34, 11929–11947, 10.1523/JNEUROSCI.1860-14.2014 (2014).
75. Cahoy, J. D. et al. A transcriptome database for astrocytes, neurons, and oligodendrocytes: a new resource for understanding brain development and function. J Neurosci 28, 264–278, 10.1523/JNEUROSCI.4178-07.2008 (2008).
76. Werneburg, S., Feinberg, P. A., Johnson, K. M. & Schafer, D. P. A microglia-cytokine axis to modulate synaptic connectivity and function. Curr Opin Neurobiol 47, 138–145, 10.1016/j.conb.2017.10.002 (2017).
77. Stellwagen, D. & Malenka, R. C. Synaptic scaling mediated by glial TNF-alpha. Nature 440, 1054–1059, 10.1038/nature04671 (2006).
78. Stellwagen, D., Beattie, E. C., Seo, J. Y. & Malenka, R. C. Differential regulation of AMPA receptor and GABA receptor trafficking by tumor necrosis factor-alpha. J Neurosci 25, 3219–3228, 10.1523/JNEUROSCI.4486-04.2005 (2005).
79. Gilmore, J. H., Fredrik Jarskog, L., Vadlamudi, S. & Lauder, J. M. Prenatal infection and risk for schizophrenia: IL-1beta, IL-6, and TNFalpha inhibit cortical neuron dendrite development. Neuropsychopharmacology 29, 1221–1229, 10.1038/sj.npp.1300446 (2004).
80. Lee, R. H. et al. Neurodevelopmental effects of chronic exposure to elevated levels of pro-inflammatory cytokines in a developing visual system. Neural Dev 5, 2, 10.1186/1749-8104-5-2 (2010).
81. Konefal, S. C. & Stellwagen, D. Tumour necrosis factor-mediated homeostatic synaptic plasticity in behavioural models: testing a role in maternal immune activation. Philos Trans R Soc Lond B Biol Sci 372, https://doi.org/10.1098/rstb.2016.0160 (2017).
82. Simpson, J. E. et al. Microglial activation in white matter lesions and nonlesional white matter of ageing brains. Neuropathol Appl Neurobiol 33, 670–683, 10.1111/j.1365-2990.2007.00890.x (2007).
83. Woo, M. S., Yang, J., Beltran, C. & Cho, S. Cell Surface CD36 Protein in Monocyte/Macrophage Contributes to Phagocytosis during the Resolution Phase of Ischemic Stroke in Mice. J Biol Chem 291, 23654–23661, 10.1074/jbc.M116.750018 (2016).
84. Wilkinson, K. & El Khoury, J. Microglial scavenger receptors and their roles in the pathogenesis of Alzheimer's disease. Int J Alzheimers Dis 2012, 489456, 10.1155/2012/489456 (2012).
85. Beckinghausen, J. & Sillitoe, R. V. Insights into cerebellar development and connectivity. Neurosci Lett 688, 2–13, 10.1016/j.neulet.2018.05.013 (2019).
86. D'Angelo, E. & Casali, S. Seeking a unified framework for cerebellar function and dysfunction: from circuit operations to cognition. Front Neural Circuits 6, 116, 10.3389/fncir.2012.00116 (2012).
87. Reeber, S. L., Otis, T. S. & Sillitoe, R. V. New roles for the cerebellum in health and disease. Front Syst Neurosci 7, 83, 10.3389/fnsys.2013.00083 (2013).
88. White, J. J. & Sillitoe, R. V. Development of the cerebellum: from gene expression patterns to circuit maps. Wiley Interdiscip Rev Dev Biol 2, 149–164, 10.1002/wdev.65 (2013).
89. McKay, B. E. et al. Climbing fiber discharge regulates cerebellar functions by controlling the intrinsic characteristics of purkinje cell output. J Neurophysiol 97, 2590–2604, 10.1152/jn.00627.2006 (2007).
90. Xu, D., Liu, T., Ashe, J. & Bushara, K. O. Role of the olivo-cerebellar system in timing. J Neurosci 26, 5990–5995, 10.1523/JNEUROSCI.0038-06.2006 (2006).
91. Grasselli, G., Mandolesi, G., Strata, P. & Cesare, P. Impaired sprouting and axonal atrophy in cerebellar climbing fibres following in vivo silencing of the growth-associated protein GAP-43. PLoS One 6, e20791, 10.1371/journal.pone.0020791 (2011).
92. Grasselli, G. & Strata, P. Structural plasticity of climbing fibers and the growth-associated protein GAP-43. Front Neural Circuits 7, 25, 10.3389/fncir.2013.00025 (2013).
93. Lin, C. Y. et al. Abnormal climbing fibre-Purkinje cell synaptic connections in the essential tremor cerebellum. Brain 137, 3149–3159, 10.1093/brain/awu281 (2014).
94. Pierce, D. R., Hayar, A., Williams, D. K. & Light, K. E. Developmental alterations in olivary climbing fiber distribution following postnatal ethanol exposure in the rat. Neuroscience 169, 1438–1448, 10.1016/j.neuroscience.2010.06.008 (2010).
95. Miyazaki, T., Fukaya, M., Shimizu, H. & Watanabe, M. Subtype switching of vesicular glutamate transporters at parallel fibre-Purkinje cell synapses in developing mouse cerebellum. Eur J Neurosci 17, 2563–2572, 10.1046/j.1460-9568.2003.02698.x (2003).
96. Arancillo, M., White, J. J., Lin, T., Stay, T. L. & Sillitoe, R. V. In vivo analysis of Purkinje cell firing properties during postnatal mouse development. J Neurophysiol 113, 578–591, 10.1152/jn.00586.2014 (2015).
97. White, J. J. & Sillitoe, R. V. Genetic silencing of olivocerebellar synapses causes dystonia-like behaviour in mice. Nat Commun 8, 14912, 10.1038/ncomms14912 (2017).
98. Mosher, K. I. & Wyss-Coray, T. Go with your gut: microbiota meet microglia. Nat Neurosci 18, 930–931, 10.1038/nn.4051 (2015).
99. Sampson, T. R. et al. Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson's Disease. Cell 167, 1469–1480 e1412, 10.1016/j.cell.2016.11.018 (2016).
100. Rodriguez, J. M. et al. The composition of the gut microbiota throughout life, with an emphasis on early life. Microb Ecol Health Dis 26, 26050, 10.3402/mehd.v26.26050 (2015).
101. Weinhard, L. et al. Microglia remodel synapses by presynaptic trogocytosis and spine head filopodia induction. Nat Commun 9, 1228, 10.1038/s41467-018-03566-5 (2018).
102. Soliman, M. L., Smith, M. D., Houdek, H. M. & Rosenberger, T. A. Acetate supplementation modulates brain histone acetylation and decreases interleukin-1beta expression in a rat model of neuroinflammation. J Neuroinflammation 9, 51, 10.1186/1742-2094-9-51 (2012).
103. Brown, A. J. et al. The Orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J Biol Chem 278, 11312–11319, 10.1074/jbc.M211609200 (2003).
104. Werner, K. M., Perez, L. J., Ghosh, R., Semmelhack, M. F. & Bassler, B. L. Caenorhabditis elegans recognizes a bacterial quorum-sensing signal molecule through the AWCON neuron. J Biol Chem 289, 26566–26573, 10.1074/jbc.M114.573832 (2014).
105. Zoghbi, H. Y. & Bear, M. F. Synaptic dysfunction in neurodevelopmental disorders associated with autism and intellectual disabilities. Cold Spring Harb Perspect Biol 4, https://doi.org/10.1101/cshperspect.a009886 (2012).
106. Sillitoe, R. V., Chung, S. H., Fritschy, J. M., Hoy, M. & Hawkes, R. Golgi cell dendrites are restricted by Purkinje cell stripe boundaries in the adult mouse cerebellar cortex. J Neurosci 28, 2820–2826, 10.1523/JNEUROSCI.4145-07.2008 (2008).
107. Holt, G. R., Softky, W. R., Koch, C. & Douglas, R. J. Comparison of discharge variability in vitro and in vivo in cat visual cortex neurons. J Neurophysiol 75, 1806–1814, 10.1152/jn.1996.75.5.1806 (1996).
108. Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat Methods 9, 357–359, 10.1038/nmeth.1923 (2012).
109. Hildebrand, F., Tadeo, R., Voigt, A. Y., Bork, P. & Raes, J. LotuS: an efficient and user-friendly OTU processing pipeline. Microbiome 2 (2014).
110. Wang, Q., Garrity, G. M., Tiedje, J. M. & Cole, J. R. Naive Bayesian classifier for rapid assignment of rRNA sequences into the new bacterial taxonomy. Appl Environ Microbiol 73, 5261–5267, 10.1128/AEM.00062-07 (2007).
111. Quast, C. et al. The SILVA ribosomal RNA gene database project: improved data processing and web-based tools. Nucleic Acids Res 41, D590–596, 10.1093/nar/gks1219 (2013).
112. Caporaso, J. G. et al. QIIME allows analysis of high-throughput community sequencing data. Nat Methods 7, 335–336, 10.1038/nmeth.f.303 (2010).