Modulation of immunity and inflammatory gene expression in the gut, in inflammatory diseases of the gut and in the liver by probiotics

Table 1 Regulation of immunity and inflammatory gene expression in the gut by probiotics

Study	Probiotic strain	Genes involved
Intestinal cultured cells
Enterocytes
Ghadimi et al[14]	DNA from L. rhamnosus GG and B. longum	TLR-9 and IL-8
Otte et al[17]	E. coli Nissle 1917 and VSL#3	Mucins genes
Mack et al[18]	L. plantarum 299v and L. rhamnosus GG	MUC2 and MUC3
Anderson et al[19]	L. plantarum MB452	Tight junction-related genes
Audy et al[20]	Lactobacilli and bifidobacteria strains	MAPK signaling pathway
Riedel et al[21]	Bifidobacteria strains	NF-κB activation, IL-8, TNF-α, COX-2, and ICAM-1
Ruiz et al[22]	B. lactis BB12	NF-κB, MAPK signaling, and IL-6
Liu et al[23]	B. lactis HN019	IL-8
Okada et al[24]	Bifidobacteria	IL12p40, IL-1β, TNF-α, and SOCS1
Imaoka et al[25]	B. breve strain Yakult and B. bifidum strain Yakult	IL-8 and IκB-zeta
Boesten et al[26]	B. breve strains M-16V, NR246 and UCC2003	CASP7, IRF3, A4, APBA1, NOX5, and LIFR
Nishitani et al[27]	L. lactis subsp. cremoris FC	IL-8
O'Flaherty et al[28]	L. acidophilus	NF-κB signaling
Oksaharju et al[29]	Bifidobacteria, lactobacilli, and P. freudenreichii	FCER1A, FCER1G, IL-8, TNF-α, and IL-10
Paszti-Gere et al[30]	L. plantarum 2142 and bifidobacteria	IL-8 and TNF-α
Zanello et al[31]	Saccharomyces cerevisiae CNCM I-3856	PPAR-γ
Latvala et al[32]	Lactobacillus and Streptococcus species	SOCS3
Ukena et al[33]	E. coli Nissle 1917	MCP-1, MIP-2alpha and MIP-2beta
Wang et al[34]	L. casei Zhang	TLR2, TLR3, TLR4, and TLR9
Kim et al[35]	L. plantarum genomic DNA	TLR2, TLR4, and TLR9
Cammarota et al[36]	L. plantarum DSMZ 12028	TLR2 and TLR4
Tomosada et al[37]	Eleven different probiotic strains	MAPK and NF-κB pathways
Gao et al[38]	C. butyricum	IL-8, IL-6, and TNF-α
Isono et al[39]	C. butyricum TO-A	TLR-4
Huang et al[40]	Bacillus species	TLR-2 and TLR-4
Dendritic cells
Bermudez-Brito et al[7]	L. paracasei CNCM I-4034	TLR9, CASP8, and TOLLIP
Weiss et al[48]	L. acidophilus	Genes encoding IFN, TLR-3, and IL-12
Rajput et al[49]	S. boulardii and B. subtillis B10	MyD88, NF-κB, TLR-1, 2, 4, and 15
Latvala et al[50]	Bifidobacteria, lactobacilli, and S. thermophilus THS	TNF-α, IL-1β, IL-6, IL-10, IL-12, and IFN-γ
Evrard et al[52]	L. rhamnosus 35	IL12, TNF-α, IL1B, IL6, TGFB1, IL-23, and IL-8
Bermudez-Brito et al[55]	B. breve CNCM I-4035	TLR-9 and TOLLIP
Ayehunie et al[56]	L. delbrueckii subsp. bulgaricus	TLR-4, p38, and IκB
Animal studies
Matsumoto et al[57]	B. animalis subsp. lactis LKM512	Aging-associated and inflammation-associated genes
Ohtsuka et al[58]	B. breve M-16V	LBP
Trevisi et al[59]	B. animalis	TLR-2 and TLR-4
Dykstra et al[60]	Bifidobacteria and lactobacilli	MUC2, MUC3, NAIP, HIAP1/cIAP2, and HIAP2/cIAP1
Foye et al[62]	L. acidophilus	IL-10 and TGF-β
Deng et al[63]	B. subtillis RJGP16 and L. salivarius B1	IL-6 and pBD-2
Jain et al[64]	L. casei	IFN-γ and IL-2
Pérez-Sánchez et al[65]	L. plantarum, L. lactis, and L. mesenteroides	IL-1β, IL-8, IL-10, TNF-α, IL-8, TLR5, and IgT
Pirarat et al[66]	L. rhamnosus GG	TNF-α and IL-1
Human studies
van Baarlen et al[67]	L. acidophilus, L. casei, and L. rhamnosus	Gene-regulatory networks and pathways in human mucosa
Lammers et al[68]	VSL#3	IL-1β, IL-6, IFN-γ, TNF-α, IL-12, IL-10, TGF-β, and IL-8
Di Caro et al[69]	B. clausii	Genes involved in the immune response and inflammation

A4: Amyloid beta; APBA1: Precursor protein-binding family A member 1; CASP7: Cysteine protease caspase 7; COX2: Cyclooxygenase 2; FCER1A: Allergy-related high-affinity IgE receptor subunits α; FCER1G: Allergy-related high-affinity IgE receptor subunits γ; HIAP1/cIAP2: Human inhibitor of apoptosis protein 1/cellular inhibitor of apoptosis 2; HIAP2/cIAP1: Human inhibitor of apoptosis protein 2/cellular inhibitor of apoptosis 1; ICAM-1: Intercellular adhesion molecule 1; IFN-γ: Interferon gamma; IL: Interleukin; IRF3: Interferon regulatory factor 3; LBP: Lipopolysaccharide-binding protein; LIFR: Leukemia inhibitory factor receptor; MAPK: Mitogen-activated protein kinases; MCP-1: Monocyte chemo-attractant protein-1; MIP-2α: Macrophage inflammatory protein-2 alpha; MIP-2β: Macrophage inflammatory protein-2 beta; MUC: Mucins; MyD88: Myeloid differentiation primary response protein 88; NAIP: Neuronal apoptosis inhibitor protein; NF-κB: Nuclear factor-kappa beta; NOX5: NADPH oxidase; PPAR-γ: Peroxisome proliferator-activated receptor gamma; SOCS: Suppressor of cytokine signaling; p-BD2: Porcine beta-defensins 2; TGF-β: Transforming growth factor beta; TLR: Toll-like receptor; TNF- α: Tumor necrosis factor-alpha; TOLLIP: Toll-interacting protein; VSL#3: mixture of Bifidobacterium longum, Bifidobacterium infantis, Bifidobacterium breve, Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus delbrueckii subsp. bulgaricus, Lactobacillus plantarum, and Streptococcus salivarius subsp, thermophilus.

Table 2 Regulation of gene expression by probiotics in inflammatory diseases of the gut

Study	Probiotic strain	Genes involved
Inflammatory bowel disease
Disfrutti et al[71]	VSL#3	IL-10, TNFRSF1B
Ghadimi et al[72]	B. breve (DSMZ 20213) and L. rhamnosus GG	IL-17 and IL-23
Grimoud et al[73]	B. breve and L. lactis	TLR-4
Chen et al[74]	Saccharomyces boulardii	VEGF
Bassaganya-Riera et al[75]	VSL#3	TNF-α, COX-2, and PPAR-γ
Ulcerative colitis
Garrido-Mesa et al[76]	E. coli Nissle 1917	TNF-α, IL-1β, IL2, MIP-2, MCP-1, ICAM-1, MUC3, and ZO-1
Claes et al[77]	L. rhamnosus GG wild type and mutant	TLR-2
Miyauchi et al[78]	L. rhamnosus OLL2838	ZO-1
Mariman et al[79]	L. plantarum NCIMB8826 and VSL#3	Inflammation and immune genes
Amit-Romach et al[80]	L. rhamnosus GG and a mixture of probiotics	MUC2, IL-6, and TNF-α
Duary et al[81]	L. plantarum Lp91	IL-4, IL-6,COX-1, COX-2, and TNF-α
Grompone et al[82]	L. rhamnosus CNCM I-3690	DAF-16/insulin-like pathway
Furrie et al[83]	B. longum	Human beta defensins 2, 3, and 4, TNF-α, and IL-1α
Necrotizing enterocolitis
D'Souza et al[84]	S. boulardii	Caveolin-1 and NOS-isoforms
Lin et al[85]	L. rhamnosus GG	Genes with cytoprotective effects
Other inflammatory disorders
Gomi et al[86]	B. bifidum BF-1	MUC5
Mirpuri et al[87]	L. rhamnosus GG	IL-10, MIP-2, and TNF-α

COX1: Cyclooxygenase 1; COX2: Cyclooxygenase 2; ICAM-1: Intercellular adhesion molecule 1; IL: Interleukin; MCP-1: Monocyte chemo-attractant protein-1; MIP-2: Macrophage inflammatory protein-2 alpha; MUC: Mucins; NOS isoforms: Constitutional neuronal isoform (nNOS), the inducible isoform (iNOS), and the endothelial isoform (eNOS); PPAR-γ: Peroxisome proliferator-activated receptor gamma; TLR: Toll-like receptor; TNF-α: Tumor necrosis factor-alpha; TNFRSF1B: Tumor necrosis factor receptor superfamily, member 1b; TOLLIP: Toll-interacting protein; VEGF: Vascular endothelial growth factor; VSL#3: Mixture of Bifidobacterium longum, Bifidobacterium infantis, Bifidobacterium breve, Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus delbrueckii subsp. bulgaricus, Lactobacillus plantarum, and Streptococcus salivarius subsp, thermophilus; ZO: Zona occludens.

Table 3 Regulation of immunity and inflammation gene expression in the liver by probiotics

Study	Probiotic strain	Genes involved
Sepsis
Bu et al[101]	Lactobacillus spp.	CRAMP
Inflammation
Mair et al[102]	E. faecium, L. salivarius, L. reuteri and B. thermophilum	CDK-4 and TGF-β
Angelakis et al[103]	L. ingluviei	TNF-α
Experimental liver disease
D'Argenio et al[104]	L. paracasei B21060	TNF-α, TGF-β, IL-10, TLR4, TLR2, iNOS, eNOS, and αSMA
Zuo et al[105]	L. casei, B. subtillis, and Pichia anomala	Genes involved in immunity

CDK-4: Cyclin-dependent kinase-4; CRAMP: Cathelicidin-related peptide; IL: Interleukin; TGF-β: Transforming growth factor beta; iNOS: Inducible isoform; eNOS: Endothelial isoform; TLR: Toll-like receptor; TNF-α: Tumor necrosis factor-alpha.