Table 2.
: The microbiome modulates canonical immune factors and neurodevelopment.
| Species (Strain) | Microbiome Perturbation | Effect on Host Brain | Reference |
|---|---|---|---|
| Toll-like receptor (TLR)/Neurogenesis | |||
| Mice (C57BL/6) | GF mice | Decreased: NF-κB signaling in HEK293T cells with GF serum | Clarke et al, 2010 |
| Mice (C57BL/6) | Peptidogylcan-teichoic acid injected at E10 or E15 | Decreased: Spatial- and novel object-recognition (E10) Increased: cortical neuroproliferation; NPC neuroproliferation |
Humann et al, 2016 |
| Mice (Swiss Webster) | GF mice; conventionalization at P21 | Increased: hippocampal neurogenesis (GF and GF-conventionalized) | Ogbonnaya et al, 2015 |
| Mice (C57BL/6) | Abx treatment adult (ampicillin + sulbactum, vancomycin, imipenem + cilastatin, metronidazole) | Decreased: hippocampal neurogenesis; novel object recognition; brain CCR2+Ly6Chi monocytes | Mohle et al, 2016 |
| Cytokines | |||
| Mice (Balb/c) | Abx treatment E0.5-P21 | Increased: brain transcripts arginine vasopressin receptor 1b), IL-6, Cxcl15 and IL-10 (females only) Sex-specific alterations of behavior | Leclercq et al, 2017 |
| Mice (C57BL/6J) | GF mice colonized with pre-term human microbiota at E15 | Decreased: brain NeuN expression (GF, low-weight pre-term colonization), brain Olg2 expression (GF), brain MBP (low-weight colonization), brain IGF-1 (GF, low-weight pre-term colonization, 4 weeks) Increased: brain transcripts IL1β and TNFα(GF), brain IGF-1 (GF, 2 weeks) Altered brain gene expression |
Lu et al, 2018 |
| Mice (C57BL/6) | GF mice; MIA induced E12.5 (poly(I:C)) | Decreased: MIA-associated behavioral deficits; Th17 cell-dependent behavioral phenotypes Increased: SFB-dependent plasma and ileal IL-17a |
Kim et al, 2017 |
| Mice (C57BL/6) | GF mice; MIA induced E12.5 (poly(I:C)) |
Cortical patches associated with MIA | Shin Yim et al, 2017 |
| Mice (C57BL/6) | MIA induced E11.5 and E12.5 (poly(I:C)); co-housing | Taconic-associated microbiota associated with MIA-induced behavioral deficits and serum IL-17a | Lammert et al, 2018 |
| Mice (C57BL/6J) | E12.5 injection of IL-6or IFNγ | IL-6 induced behavioral abnormalities and gene expression changes | Smith et al, 2007 |
| Mice (C57BL/6N) | MIA induced at E12.5 (poly(I:C)) | Increased: MIA-induced fetal brain II6, Stat3 and Myc expression; MIA-induced fetal brain IL-4, IL-6 and IP-10 | Wu et al, 2017 |
| Mice | GF mice; colonization with human microbiota | Differential expression of cecal cytokines in GF mice colonized with human first-trimester or third-trimester fecal samples | Koren et al, 2012 |
| Complement System | |||
| Mice (C57BL/6) | GF mice (neonatal and adult) | Altered microglial gene expression, including complement factors C3ar1, C1qbp and Itgax *supplemental data | Matcovitch-Natan et al., 2016 |
| Mice (NMRI) | GF mice adult | Decreased: anxiety-like behavior; brain BDNF, synaptophysin and PSD-95 Increased: spontaneous motor activity Altered brain gene expression |
Diaz Heijtz et al., 2011 |
| Human | Ulcerative colitis microbiota | Increased: IL-12 and complement genes with ulcerative colitis microbiota | Morgan et al., 2015 |
| Mice (C57BL/6J) | Abx treatment P28-P56 (ampicillin, vancomycin, neomycin, metronidazole; mesenteric ischemia/reperfusion | Decreased: mesenteric ischemia/reperfusion associated intestinal C3 | Yoshiya et al., 2011 |
| Mice (C57BL/6) | GF mice adult | Decreased: skin gene expression C3, C1qa, C1qb and C3ar1 | Meisel et al., 2018 |
| Mice (C57BL/6 and DBA/2J) | Subcutaneous LPS adult | Increased: retinal gene expression of TLR-4, Myd88, c-JUN, TRIF, IRF3 and C1qb following LPS | Astafurov et al., 2014 |
Abbreviations: Abx, antibiotic; BDNF, brain-derived neurotrophic factor; GF, germ-free; IFNγ, interferon-gamma; IGF-1, insulin-like growth factor-1; IL, interleukin; IRF3, interferon transcription regulatory factor 3; LPS, lipopolysaccharide; MBP, myelin basic protein; MIA, maternal immune activation; NPC, neural progenitor cell; Olg2, oligodendrocyte transcription factor 2; PSD-95, post-synaptic density protein-95; SFB, segmented filamentous bacteria; TLR-4, toll-like receptor 4; TNF-α, tumor necrosis factor-alpha; TRIF, TIR-domain-containing adapter-inducing interferon-β