Table 2.

The effectiveness of probiotics in the treatment of IBD.

Strain	IBD	Research Model and Study Scheme	Results	Ref.
Bifidobacterium infantis (BabyLife, Solaray)	CD-like	Rat model (TNBS) 10 days supplementation with 0.205 g of B. infantis dissolved in 1.0 mL distilled water prior colitis. Colitis was induced by enema of 1.0 mL 5% (w/v) TNBS which lasted for 7 days.	Reduction in the symptoms, weaker damage to the mucosal architecture, protective function for mucus goblet cells and the epithelial cell layer;	[75]
Summary: a beneficial effect was observed
Bifidobacterium bifidum PRL2010	CD-like	Murine model (TNBS) 7 days oral supplementation of 109 of B. bifidum PRL 2010. Colitis (TNBS 2.5 mg/mice) was induced in the 5th day of probiotic strain feeding.	Reduction in the edema, reduction in the macroscopic damage and histological scores, reduction in weight-loss, anti-inflammatory effect;	[76]
Summary: a beneficial effect was observed
Bifidobacterium bifidum 231	CD-like	Rat model (TNBS) Colitis was induced by 31 mg/kg of TNBS. 14 days supplementation of 1.4 × 1011 CFU/rat/day B. bifidum (in saline) after colitis induction	Reduction in the edema, reduction in the macroscopic damage and histological scores, reduction in weight-loss, anti-inflammatory effect;	[77]
Summary: a beneficial effect was observed
Lactobacillus plantarum species 299	CD-like	Rat model (TBSN) Colitis was induced by 30 mg (0.6 mL of 5% aqueous solution) of TNBS. 7 days supplementation of 109 colony forming units (CFU) of Lactobacillus plantarum (in oat fiber) after colitis induction.	No beneficial effects on the rat’s gut permeability, weight changes, colon microscopic scores, and the level of blood albumins;	[78]
Summary: Lack of positive effect
Bifidobacterium animalis subsp. lactis BB12	UC-like	Murine model (DSS) 7 days supplementation (twice a day) with 1.2 × 1010 CFU Bifidobacterium animalis subsp. lactis BB12 by oral gavage prior to colitis. Colitis was induced by 3% DSS added to drinking water for 6 days.	Protection against a reduction in colon length, better picture of the colon histology, reduction in apoptosis in the epithelial layer, decrease in the level of TNF-α;	[79]
Summary: a beneficial effect was observed
Bifidobacterium longum subsp. infantis BB-02	UC-like	Murine model (DSS) 10 days supplementation (by oral gavage) once a day with 0.1 mL of a suspension containing 9.0 log10 CFU/mL in phosphate-buffered saline prior to colitis induction and continued during its development for next 7 days. Colitis was induced by DSS 3.5% (w/v) in drinking water ad libitum for 7 days.	Reduction in the clinical symptoms of the disease, protection of the colonic structure, reduction in edema;	[80]
Summary: a beneficial effect was observed
Bifidobacterium lactis from fermented milk (Activia; Danone)	UC-like	Murine model (T-bet−/−Rag2−/−) 100 mg of diary product was orally instilled daily, and additional 100 mg per mouse in its cage was provided for consumption.	Reduction in severity of colitis and inflammation in an early stage, decrease in the level of Enterobacteriaceae (colitogenic)	[81]
Summary: a beneficial effect was observed
Lactobacillus delbrueckii	UC-like	Murine model (DSS) Colitis was induced by the addition of 3% (w/v) DSS in the drinking water for 7 days. Administration of probiotic (5 × 109 bacteria/mouse/day started 1 day) before colitis induction and lasted until sacrifice.	Modulation of the NF-kB pathway, reduction in the inflammatory state;	[82]
Summary: a beneficial effect was observed
VSL#3 (L. paracasei, L. plantarum, L. acidophilus, L. delbrueckii subspecies bulgaricus, B. longum, B. breve, and B. infantis, Streptococcus thermophilus)	UC-like	Murine model (DSS) 8 days supplementation (by oral gavage) with 0.1 mL of a suspension containing 5 × 1010 probiotic CFU/kg of body weight dissolved in saline solution after colitis induction. Colitis was induced by 5% DSS (w/v) in drinking water for 8 days.	Discrepancy in results (two different batches of VSL#3, contrary data); VSL#3 batch A: reduction in macroscopic scores, intestinal permeability, -reduction in expression of TNFα, IL-1β, IL-6 mRNAs, increase in the expression of TGFβ, IL-10, occludin, zonula occludens-1 (ZO-1) mRNAs, shift of colonic macrophages from a M1 to M2 phenotype- lack of effect in VSL#3 batch B	[84]
	CD-like	Murine model (TBNS) Eight days supplementation (by oral gavage) with 0.1 mL of a suspension containing 5 × 1010 probiotic CFU/kg of body weight dissolved in saline solution after colitis induction. Colitis was induced by 1 mg of TNBS fasted for 12 h.		[84]
Summary: positive effect only one batch of the same product
Bifidobacterium animalis spp. lactis Bl 5764	CD-like	Murine model (TNBS) 5 days supplementation (by oral gavage) of a 5 × 108 CFU/day/mice prior to colitis induction and continued during its development for next 2 days. Colitis was induced by TNBS (110 mg/kg, dissolved in 0.9% NaCl/ethanol (50/50 v/v)).	Lower body weight-loss, better macroscopic indicators of inflammation (Wallace scores), histopathological analysis (Ameho score), and level of lipocalin-2, promotion in the bone marrow-derived dendritic cell maturation and IL-17A secretion	[85]
Lactobacillus reuteri Lr 5454	CD-like	Murine model (TNBS) 5 days supplementation (by oral gavage) of a 5 × 108 CFU/day/mice prior to colitis induction and continued during its development for next 2 days. Colitis was induced by TNBS (110 mg/kg, dissolved in 0.9% NaCl/ethanol (50/50 v/v)).	Lower body weight-loss, better macroscopic indicators of inflammation (Wallace scores), histopathological analysis (Ameho score), and level of lipocalin-2; greater involvement in the development of tolerogenic DC, induce Tregs population and expression of Reg3b in a NOD2-independent manner;	[85]
Summary: a beneficial effect was observed
Saccharomyces boulardii (Floratil®)	CD	Human model Patients with CD in remission (based on Crohn’s disease activity index) were supplemented with S. boulardii about 4 × 108 cells every 8 h as an oral capsule formulation during 3 months.	Help in maintaining remission and bowel sealing;	[86]
Summary: a beneficial effect was observed
Bifidobacterium breve strain Yakult, Bifidobacterium bifidum strain Yakult, Lactobacillus acidophilus strain Yakult (Yakult Co. Ltd. Japan)	UC	Human model Patients with mild to moderate active UC were supplemented with 100 mL/day (10 billion cells) of bifidobacterial-fermented milk for 3 months.	Promising usefulness in sustaining the remission phase, improvement in clinical activity index score and histological scores;	[87]
Summary: a beneficial effect was observed
Escherichia coli Nissle1917 (Mutaflor 100 mg; Ardeypharm GmbH, Herdecke, Germany)	UC	Human model Randomized, double blind, double dummy trial, patients with UC remission were supplemented with 2.5–25 × 109 viable bacteria for 12 months.	Promising behavior in sustaining the remission phase, prevention from inflammatory state;	[88]
Summary: the beneficial effect was demonstrated
Lactobacillus fermentum, Lactobacillus delbruekii. (Lacteol Fort; Rameda, Egypt)	UC	Human model Patients with mild to moderate UC assessed by Mayo score were supplemented with 10 billion CFU of probiotic cells (powder to dissolve in 50 mL fresh water) for 8 weeks.	Decrease in the IL-6 and TNF-alpha levels and lowering regulation of NF-kB;	[89]
Summary: a beneficial effect was observed
Bifidobacterium infantis 35624	UC	Human model Randomized, double-blind placebo-controlled studies, patients with mild to moderate active UC (based on a clinical activity index) were supplemented with 1 × 1010 CFU viable probiotic cells for 8 weeks.	Reduction in the levels CRP and TNF-α in both gastrointestinal and non-gastrointestinal inflammatory disorders, but did not particularly affect UC disease;	[90]
Summary: Lack of effect for UC group, positive effect for gastrointestinal, and non-gastrointestinal inflammatory disorders group
Bifidobacterium breve strain Yakult	UC	Human model Patients with UC (active and inactive) were supplemented with 1 g of the freeze-dried powder containing probiotic (109 CFU/g) for 1 year.	Better endoscopic scores, decrease of MPO level, modulation of luminal environmental factors such as intestinal microflora and pH	[91]
Summary: a beneficial effect was observed
Bifidobacterium breve strain Yakult, Lactobacillus acidophilus strain Yakult (Yakult fermented milk (Mil–Mil))	UC	Human model Multileft, randomized, placebo-controlled, double-blind parallel-group study; patients with UC in remission were supplemented with 100 mL/day (10 billion cells of Bifidobacterium and 1 billion of cells of Lactobacillus) of fermented milk for 12 months.	No beneficial effect	[92]
Summary: no beneficial effect was observed, the study was discontinued
Lactobacillus acidophilus strain LA-5 and Bifidobacterium animalis subsp. lactis BB12 (Probio-Tec AB25)	UC	Human model Randomized, double blind, placebo-controlled study; patients with UC in remission were supplemented with 1.5 × 1011 CFU daily (2 capsules 3 times daily) for 52 weeks.	Maintaining remission in colitis	[93]
Summary: a beneficial effect was observed
Bifidobacterium longum 536 (Morinaga Milk Industry Co. Ltd, Tokyo, Japan)	UC	Human model A randomized, double-blinded, placebo-controlled multileft trial study; patients with mild to moderate UC (based on disease activity index) were supplemented with 2–3 × 1011 freeze-dried viable probiotic capsule 3 times daily for 8 weeks.	Decrease in the disease activity index and downscale the rectal bleeding, clinical remission;	[94]
Summary: a beneficial effect was observed
Lactobacillus salivarius, Lactobacillus acidophilus, Bifidobacterium bifidum strain BGN4; Acronelle®, Bromatech SRL, Milan, Italy)	UC	Human model Patients with moderate to severe UC (based on disease activity index) were supplemented with probiotic blend for 24 months.	Reduction in recovery time, weaker activity of the disease, better endoscopic picture;	[95]
Summary: a beneficial effect was observed
VSL#3	UC	Murine model UC associated carcinogenesis model was based on a single injection of 12.5 mg/kg body weight azoxymethane intraperitoneally, 1 week later 2.5% DSS was added to drinking water for 5 days, followed by 10 weeks and 2 days of regular drinking water. Probiotic mixture (1.5 × 109 CFU/mice) was supplemented alone or together with mesalazine.	Decrease in the level of TNF-α and IL-6, reduction of number of pathogenic microbiota, increase in the population of Bifidobacterium and other non-pathogenic species in the intestinal mucosa;	[96]
Summary: preventive effect for UC associated carcinogenesis
VSL#3	UC	Human model Patients with mild to moderate, active UC (based on Activity Index) were supplemented with the probiotic mixture twice daily for 12 weeks.	Improvement in rectal bleeding and stool frequency, mucosal appearance and overall physician’s evaluation;	[97]
Summary: a beneficial effect was observed
VSL#3	UC	Human model A multileft, double-blind, randomized, placebo-controlled, parallel study, patients with mild to moderately active UC (based on Activity Index) were supplemented with the probiotic mixture for 8 weeks in addition to standard therapy.	Reduction in UCDAI scores and frequency of rectal bleeding; - no differences in parameters such as the physician’s rate of disease activity, or endoscopic scores;	[98]
Summary: a beneficial effect was observed
VSL#3	UC	Human model, children population Patients with mild to moderately active UC (based on activity index) were supplemented with the probiotic twice daily for 8 weeks with a dose of probiotic based on their age (from one-half sachet to two and one-half).	Remission in colitis, improvement in microbiota composition, decrease in level of IFN-γ, TNF-α, CRP, ESR;	[100]
Summary: a beneficial effect was observed
Faecalibacterium prausnitzii	CD n.a	Murine model (TNBS) A double-blind controlled trial study, 5 days before colitis induction mice were supplemented with 109–1010 CFU bacterial suspension or bacterial medium. Colitis was induced by TNBS (100 mg/kg body weight), which was administrated intrarectally. The observation took 20 days.Cell line CaCo-2	Anti-inflammatory effect, blocking of NF-kB pathway and IL-8 production, anti-inflammatory effect;	[103]
Summary: a beneficial effect was observed
Bifidobacterium lactis	Cancer model	Murine model 6 days of supplementation with probiotic (in different dose) prior to colitis. An acute colitis was induced by 3.5% DSS in drinking water for 7 days. Colitis associated cancer was induced by azoxymethane (10 mg/kg) prior to 5 days DSS challenge. Cell line model (HT-29) Cell line HT-29 was incubated with the different concentration of Bifidobacterium lactis.	Inhibition of NF-kB and NF-kB-regulated genes in epithelial cells and prevention meaning for the acute colitis and cancer model, reduction in number and size of the tumors;	[108]
Summary: a beneficial effect was observed
Lactobacillus acidophilus Lactobacillus fermentum	Cancer model	Murine cancer model 12 weeks supplementation with probiotic (0.5 × 1010 CFU of each strain)among ApcMin/+ mice. Cell line model (CaCo-2) Bacteria (alone and as a mixture) prepared in simulated artificial intestinal juice were incubated with Caco-2 (up to 72 h).	Reduction in cancer cells proliferation, increase in apoptosis level, protection of normal colon cell growth from toxic treatment;	[110]
Summary: a beneficial effect was observed
VSL#3	Cancer model	Murine cancer model (IL10−/−) Supplementation with 1.2 billion bacteria per mouse/day) or conjugated linoleic acid. Cancer was induced by azoxymethane, DSS (the first step) and a single dose of 5 × 107 CFU Helicobacter typhlonius by oral gavage (the second step cancer induction). Observation took 68 days.	Shorter recovery time, lower disease severity in an active phase of cancer; VSL#3 treatment- higher mRNA expression of TNF-α, increase in the angiostatin level and Tcells subpopulations; CLA treatment- decreased the level of COX-2;	[109]
Summary: a beneficial effect was observed
VSL#3	Cancer model	Murine cancer model/IL-10−/− Mice with IL-10 deficient were supplemented by VSL# from the day of cancer induction for 17 weeks (once a day without the weekends). Cell line model (CaCo-2) Bacteria (alone and as a mixture) prepared in simulated artificial intestinal juice were incubated with Caco-2 (up to 72 h).	No protection against inflammatory processes and tumor development, increase in the tumor penetrance, worsening histologic dysplasia scores, extension of Clostridium population;	[112]
Summary: lack of beneficial effect, worsening of the neoplastic processes
VSL#3	Cancer model	Rat cancer model (TNBS) Supplementation with VSL#3 1 week before the colorectal cancer induction by TNBS. Then rats were supplemented with probiotic in drinking water until end of experiment (17 weeks).	Delay in the carcinoma growing processes, improvement in the histological picture of the colon, increase in the level of angiostatin vitamin D receptor (VDR);	[111]
Summary: a beneficial effect was observed
Propionibacterium freudenreichii, Isolated: SlpB, SlpE, two proteins with SLH domains, HsdM3	n.a	Proteomic and transcriptomic study	Potential connection with IL-10 increase and anti-inflammatory value	[116]
Summary: anti-inflammatory effect as a results of combination cytoplasmatic and surface protein
Lactobacillus rhamnosus GG, isolated antigens: surface layer protein, genomic DNA and unmethylated cytosine-phosphate-guanine-containing oligodeoxynucleotides, alone or in combination.	n.a	Cell line RAW 264.7 Cell line was incubated with bacterial cells, components, or their combination (2 h), then was challenged with lipopolysaccharide (0.5 h).	Suppression in the inflammatory paths, inhibition of TLR, MAPK and NF-κB signaling pathways	[117]
Summary: anti-inflammatory properties were observed
bacteria’s cells-free growth medium, Lactobacillus acidophilus, Lactobacillus casei, Lactococcus lactis, Lactobacillus reuteri, and Saccharomyces boulardii	n.a	Cell line HT-29 After LPS challenge (4 h), cell line was incubated with cell free bacterial medium (18 h.)	Anti-inflammatory properties, modulation of the level of IL-10, IL-1β, TNF-α, PGE-2, IL-8;	[118]
Summary: anti-inflammatory properties were observed
Bifidobacterium, Lactobacillus acidophilus, Enterococcus (Bifico, Shanghai Sine Pharmaceutical)	CD-like	Murine model (IL-10-deficient, DSS) Colitis was induced by 4% DSS in drinking water by 14 days. Mice were supplemented with 3 × 107 CFU probiotic in all study groups (with colitis or not) for 14 days.	Increase in the number of Treg, decrease in the total number of T cells in the colon and the peripheral blood, positive influence on the tight junctions;	[119]
Summary: a beneficial effect was observed
Lactobacillus rhamnosus GG.	UC	Case report A female patient affected by UC with severe active pancolonic involvement.	Symptoms of bacteremia;	[120]
Summary: probiotic strain as a cause of bacteremia
VSL#3 (Seaford Pharmaceuticals)	n.a	Rat model 7 days intragastrical supplementation with 3 × 109 bacteria.	Influence on the mucus structure, stimulation of expression of the Muc2 gene, increase in secretion of the non-mucin glycoprotein, improvement in the permeability of the intestinal barrier;	[99]
Summary: a beneficial effect on secretion and mucus within epithelial barrier
VSL#3	UC-like	Murine model (Muc2−/− and Muc2+/+; DSS) 15 days of supplementation with VSL#3. Colitis among Muc2−/− group was induced by 1% DSS added to drinking water for 3 days.	Induction of mucus secretion in the crypts’ goblet cells in the colon, reduction in the wall thickness and MPO level - lack of protection from colitis severity	[121]
Summary: a beneficial effect on mucus secretion and oblet cells, lack of usage in colitis severity protection
VSL#3	n.a	Cell line Caco-2 Cell line monolayer incubated with 108 CFU/mL (4 h).	Discrepancy in results (two different manufacturers of VSL#3, contrary data) - Italy-made product: increased the permeability of the barrier, and decreased the ZO-1/occludin expression - US-made product: increased the occludin level, pretreatment with VSL#3 prevented the heat-induced epithelial barrier integrity loss	[122]
Summary: different usefulness of the same product but produced by two different manufacturers
Lactobacillus casei DN-114 001, lysate	CD-like	Murine model (DSS) Mice were supplemented with 6 x 108 CFU of heat-killed bacteria, by gavage. The administration of bacteria was repeated every 7 days (4 doses together) prior to colitis. Colitis was induced 7 days later by 3% DSS dissolved in tap water for 7 days.	Protective behavior of probiotic only on the BALB/c mice, increase in the barrier function by the upregulation of ZO-1, increase in the amount of Treg, decrease in the level of proinflammatory factors, TNF-α, INF-γ, IL-10, influence on microbiota composition;	[124]
Summary: a beneficial effect was observed
Lactobacillus rhamnosus GG, surface layer protein HM0539	n.a	Cell line CaCo-2 Caco-2 cell line was incubated with HM0539 (50 ng/mL) for 12 h, then cell line was stimulated using TNF-a, (10 ng/mL) or lipopolysaccharide (1 mg/mL) for 6 h.	Increase in the level of the tight junction, increase in mucin secretion;	[125]
Summary: a beneficial effect was observed
Lactobacillus plantarum, isolated MIMP	n.a	Murine model (DSS) Mice were supplemented with MIMP (0.1 μg/20 g) for 7 days prior colitis. Colitis was induced by DSS administered in drinking water for 7 days. Cell line Caco-2 Cell line was incubated with MIMP in different concentrations for 48 h.	Reduction in the permeability, increase in expression of JAM-1, occludin, ZO-1;	[126]
Summary: a beneficial effect was observed