Table 1.
: The microbiome shapes enteric-, peripheral- and neuro-immune development.
| Species (Strain) | Microbiome Perturbation | Description | Reference |
|---|---|---|---|
| Enteric Immunity | |||
| Mice (C57BL/6) | Abx treatment E15-continuous (ampicillin, gentamycin, metronidazole, vancomycin, neomycin; ampicillin, gentamycin, vancomycin); GF mice | Decreased: small intestine IL-17A transcripts; small intestine IL-17+ ILC3s | Deshmukh et al.,2014 |
| Mice (NOD, H2g7) | Abx treatment E0-continuous (streptomycin, colistin, ampicillin; vancomycin only) | Decreased: colonic and ileal CD45+CD4+TCRαβ+IL-17+ cells; colonic, Peyer’s patches and MLN IL-17A transcript | Candon et al., 2015 |
| Mice (NOD/Caj) | Abx treatment E0-birth (neomycin, polymyxin B, streptomycin) | Decreased: MLN CD4+IFNγ+ and CD8+IFNγ+ cells; T cell IL-17 and IFNγ production; APC tolerance Increased: MLN CD4+CD25+Foxp3+cells |
Hu et al., 2015 |
| Mice (NOD) | Abx treatment E0-E4 + E14-E18 (metronidazole, neomycin, polymyxin) | Decreased: Peyer’s patches CD3+CD4+CD25+, CD4+CD69+CD25+ and CD4+CD62L+ cells Increased: MLN CD3+ and CD3+CD8+ cells; Peyer’s patches CD4+CD62L+ cells |
Tormo-Badia et al., 2014 |
| Mice (C57BL/6J) | Abx treatment E0-continuous (vancomycin; streptomycin) | Decreased: colonic CD4+CD25+Foxp3+ cells (vancomycin) | Russell et al., 2012 |
| Mice (Swiss Webster; C57BL/6) | GF mice; microbe exposure at P0 or P35 | Increased: colonic iNKT cells; colitis-associated colonic IL-4, IL-13, IL-1β; greater colonic Cxcl16* *corrected by microbe exposure at P0 |
Olszak et al., 2012 |
| Mice (C57BL/6J) | GF mice; colonization with non-replicating E. coli HA107 every 4 days E4-E15 | Increased: small intestine lamina propria NKp46+ ILC3s, CD11c+F4/80+ mononuclear cells (following gestation colonization) Altered small intestine qene expression |
Gomez de Aguero et al., 2016 |
| Pigs (Landrace X Large white X Duroc) | Abx treatment P0-continuous (ampicillin, gentamycin, metronidazole) | Decreased: small intestine IL-1β and IL-8; Increased: colonic goblet cells Altered small intestine gene expression |
Jensen et al., 2014 |
| Rats (Sprague-Dawley) | Abx treatment P7-continuous (Clamoxyl solution) | Altered small intestine and colonic gene expression | Schumann et al.,2005 |
| Mice (C57BL/6J) | GF mice; conventionalized (adult) or conventionally raised | Temporal-specific effects of colonization on colonic gene expression | El Aidy et al., 2013 |
| Mice (C57BL/6; Balb/c; Swiss Webster) | GF mice | IgG2b and IgG3 antibodies generated against microbiota and transmitted to offspring | Koch et al., 2016 |
| Peripheral Immunity | |||
| Mice (NOD/Caj) | Abx treatment E0-P0 (neomycin, polymyxin B, streptomycin) | Decreased: splenic CD11c+ IFNγ+ cells, CD11b+IL-12+ and CD11b+IL-17+ cells; splenic APC response to LPS Increased: splenic CD11b+IL-10+ cells |
Hu et al., 2015 |
| Mice (Swiss Webster; C57BL/6) | GF mice; microbe exposure at P0 or P35 | More lung iNKT cells*; more BALF eosinophils and IgE; greater serum CXCL16 and lung Cxcl16* *corrected by microbe exposure during pregnancy |
Olszak et al., 2012 |
| Mice (C57BL/6) | Abx treatment E18-P14 (ampicillin, vancomycin, metronidazole, neomycin) | Decreased: skin IL-1β andTNF-α | Nakamura et al.,2012 |
| Mice (C57/BL6) | Abx treatment E15-continuous (ampicillin, gentamycin, metronidazole, vancomycin, neomycin; ampicillin, gentamycin, vancomycin); GF mice | Decreased: circulating and bone marrow (LY6G+) neutrophils; plasma G-CSF (P3-P14) | Deshmukh et al.,2014 |
| Mice (C57BL/6J) | Abx treatment final 3–5 days of gestation (ampicillin and clindamycin) | Decreased: splenic CD8+IFNγ+ cells; Bcl-2 post-infection; splenic CD11chiMHCIIhi and CD11b−CD103+ cells; reduced splenic NK1.1+CD49b+ cells Increased: PD-1 post-infection |
Gonzalez-Perez et al., 2016 |
| Mice (C57BL/6J) | Abx treatment final 3–5 days of gestation-continuous (ampicillin, streptomycin, clindamycin) | Decreased: frequency of splenic OT-I IFNγ+/TNF-α+ and CD8+Erk2/pErk1/2 cells; CD8+ T cell IFNγ production | Gonzalez-Perez and Lamouse-Smith 2017 |
| Mice (NOD/Caj) | Abx treatment E0-birth (neomycin; vancomycin) | Decreased: splenic CD11b+CD80+, CD11b+CD86+, CD11c+CD80+ and CD11c+CD86+ cells; IFNγ production Differential effects of abx treatment in peripheral APCs, CD4+, CD8+cells | Hu et al., 2016 |
| Rhesus Macaque | Breast-fed versus nursery-fed microbiota | Decreased: circulating Th17 and CD4+CCR4+cells Altered circulating CD4+ and CD8+ T cell gene expression |
Ardeshir et al., 2014 |
| Human | Lactobacillus in vaginal microbiota | Decreased: CD4+CD45RO+ T cells; CBMC culture IL-12 (lacking Lactobacillus in vaginal microbiota) | Stencel-Gabriel et al., 2009 |
| Human | Differential neonatal microbiota compositions | Decreased: TLR4 mRNA in PBMCs (Bacteroides fragilis-containing samples) Increased: salivary IgA (Bifidobacterium-containing samples) |
Sjogren et al., 2009 |
| Human | Caesarean section-delivered neonatal microbiota | Decreased: blood CXCL10 and CXCL11 (Caesarean section birth and reduced Bacteroidetes) | Jakobsson et al.,2014 |
| Mice (C57BL/6) | Abx treatment adult (ampicillin, vancomycin, neomycin, metronidazole) | Decreased: peripheral blood B cells, CD4+ and CD8+ T cells; thymic and splenic weight; bone marrow and common lymphoid progenitors; HSCs; granulocytes and B cells Increased: T cells |
Josefsdottir et al.,2017 |
| Mice (C57BL/6) | GF mice | Decreased: splenic F4/80hiCD11b+ and F4/80loCD11b+ cells; splenic myelopoiesis bone marrow neutrophils | Khosravi et al., 2014 |
| Rats (Wistar, male) | SCFA treatment adult cultured neutrophils (acetate, propionate, butyrate) | Decreased: neutrophil TNF-α, CINC-2αβ and nitrite | Vinolo et al., 2011 |
| Mice (C57BL/6) | Abx treatment adult (metronidazole, vancomycin, ampicillin, kanamycin); SCFA treatment adult (butyrate, acetate, propionate) | Decreased: Foxp3+ Tregs (GF and Abx) Increased: Foxp3+ Tregs and acetylation of Foxp3 locus with SCFA treatment |
Arpaia et al., 2013 |
| Mice (C57BL/6) | SCFA treatment adult cultured bone marrow cells (acetate, propionate, butyrate, nicotinate) | Decreased: bone marrow DCs with SCFA treatment; PU.1 and RelB expression | Singh et al., 2010 |
| Mice (C57BL/6) | Abx treatment adult (metronidazole and vancomycin); n-butyrate treatment adult | Decreased: bone marrow-derived macrophage Nos2, Il6, Il12a and Il12b (butyrate) Increased: bone marrow-derived macrophage H3 acetylation (butyrate) |
Chang et al., 2014 |
| Mice (C57BL/6) | SCFA treatment adult (acetate, propionate) | Decreased: allergic airway inflammation and CD4+CD44+ T cells (propionate); CD11bhi CD40, PD-L2, IL-4, IL-5 and IL-10 expression (propionate) Increased: bone marrow Lin−c-KitloFlt3+ precursors and Lin−c-KithiFlt3+ precursors |
Trompette et al.,2014 |
| Mice (IQI; C57BL/6) | GF mice; SCFA treatment adult naive CD4+ T cells (acetate, propionate, butyrate) | Decreased: colonic neuropilin-1−Foxp3+, neuropilin-1+Foxp3+, CD103−Foxp3+ and CD103+Foxp3+ Tregs Increased: colonic Foxp3+Tregs (propionate, butyrate) Altered Foxp3 locus (butyrate) |
Furusawa et al.,2013 |
| Mice (Balb/c; Swiss Webster) | GF mice; SCFA treatment (acetate, propionate, butyrate) | Decreased: colonic Foxp3+ cells (GF) Increased: colonic Foxp3+ cells and Foxp3 and IL-10 expression (propionate); IL-10+Foxp3+ Tregs (propionate, acetate, butyrate) |
Smith et al., 2013b |
| Mice (C57BL/6J) | GF mice; Abx treatment adult (vancomycin, ampicillin, kanamycin, metronidazole) | Altered intestinal ILC gene transcription and epigenetic landscape | Gury-BenAri et al., 2016 |
| Neuroimmunity | |||
| Mice (C57BL/6) | GF mice | Altered newborn and adult microglial gene expression | Matcovitch-Natan et al., 2016 |
| Mice (C57BL/6) | GF mice adult; SCFA treatment (acetate, propionate, butyrate) | Decreased: response to LPS and LCMV (rescue with SCFAs) Increased: Iba1+ microglia (GF brain) Altered microglial morphology and gene expression profiles |
Erny et al., 2015 |
| Mice (C57BL/6J) | GF mice | Microglial transcriptomic profiles are altered by the microbiome in a temporal- and sex-specific manner; Increased: mid-gestation GF brain Iba1+ microglia; E18.5 GF male brain Iba1+ microglia; P20 GF female brain Iba1+ microglia Altered GF microglia epigenetic landscape |
Thion et al., 2018 |
| Mice (Swiss Webster) | GF mice | Decreased: neonatal brain IL-1β andTNF-α; cell death in neonatal ARC Increased: neonatal PVN and CA1 oriens cell death; neonatal hypothalamus, PVN, CA1 oriens and ARC Iba1+ microglia Altered microglial morphology |
Castillo-Ruiz et al., 2018 |
Abbreviations: Abx, antibiotic; APC, antigen presenting cell; ARC, arcuate nucleus; BALF, bronchioalveolar lavage fluid; Bcl-2, B cell lymphoma 2; CBMC, cord blood mononuclear cells; CINC-2αβ, cytokine-induced neutrophil chemoattractant-2αβ; DC, dendritic cell; Flt3, FMS-related tyrosine kinase 3; G-CSF, granulocyte-colony stimulating factor; GF, germ-free; HSC, hematopoietic stem cells; Iba-1, ionized calcium binding adapter molecule-1; IL, interleukin; ILC3, innate lymphoid cell 3; IFNγ, interferon-gamma; iNKT, invariant natural killer cell; LCMV, lymphocytic choriomeningitis virus; LPS, lipopolysaccharide; MHCII, major histocompatibility complex II; MLN, mesenteric lymph node; PBMC, peripheral blood mononuclear cells; PD-1, programmed cell death protein 1; PVN, paraventricular nucleus; SCFA, short-chain fatty acid; TCR, T cell receptor; TNF-α, tumor necrosis factor-alpha