Table 1.
Summary of articles investigating the effect of probiotics on inflammation, n-3 acids, vitamin D and nutraceuticals on inflammation
| Author | Study type | Number of patients | Time | Intervention | Efficacy outcome(s) |
|---|---|---|---|---|---|
| Probiotics | |||||
| Fedorak et al. [27] | CD patients | n = 120 (n = 59 vs. placebo n = 60) | 1 year | VSL#3 (1 sachet 2 times a day) | Lower frequency of relapses in the study group |
| Pathmakanthan et al. [29] | Cells from normal and active mucosa from colon adults with UC | – | – | Lactobacillus plantarum 299 | Macrophages and T cells an increased in IL-10 production and subsequently inflammatory-quenching reaction |
| Wu et al. [30] |
Mice Human intestinal epithelial cells |
n = 12 (n = 6 with VDR and n = 6 without VDR) | 24 days | Lactobacillus rhamnosus (LGG) and Lactobacillus plantarum (LP) |
Increased VDR expression Increased the number of Paneth cells-reduced inflammation |
| Ahn et al. [31] | Rats | n = 47 (control group n = 10; colitis control group n = 9; group with live Lp. plantarum K8 1 × 109 CFU n = 9; group with Lb. plantarum in 1 × 09 CFU n = 10; group with Lb. plantarum in 1 × 1010 CFU n = 9 | 14 days | Lactobacillus plantarum K8 |
Reduced IL-6 and TNF-α in the colon Reduced colon shortening, edema, mucosal damage High-dose of lysate increased colonic expression of receptor-2 mRNA |
| Yin et al. [32] | Mice | n = 18 (control group n = 6; DSS-treated group (n = 6); MIMP-treated group (i = 6) | 14 days | Lactobacillus plantarum |
Reduced proinflammatory cytokines IFN-γ, IL-17 or IL-23 Increased IL-4, IL-10 Improved gut microbiota dysbiosis |
| Levit et al. [33] | Mice | n = 25 (5 groups of 5 animals | 5 days | Lactobacillus plantarum CRL2130 vs control group |
Increased the IL-10 levels Diarrhea incidences’ reduction An intestinal mucosa condition improvement An intestinal villi protective effect |
| Derwa et al. [34] | Systematic review and meta‐analysis | – | – | – |
No advantages over the recommendations for the treatment of placebo in the induction of remission in active UC VSL3 # has demonstrated the benefit of a probiotic over placebo in induced UC remission Probiotics may be as effective as 5-ASA in preventing exacerbations in UC Inducing remission in the active phase of CD: there were no benefits of using probiotics compared to placebo |
| Kruis et al. [35] | Patients with UC | n = 327 (study group n = 162; group with only drugs n = 165) | 12 months |
Study group: 200 mg/day probiotics Second group: 500 mg meslazayny 3xday |
E. coli Nissle 1917 wykazuje potwierdzoną skuteczność i bezpieczeństwo w utrzymaniu remisji UC porównywalnie do wpływu leczenia mesalazyną |
| Bovine immunoglobulin | |||||
| Shafran et al. [37] | Patients with IBD | n = 45 (CD group n = 38; UC group n = 7) | 12 weeks | 5 g SBI/day | Clinical condition improvement |
| Beauerle et al. [38] | Single case study—patient with UC | n = 1 | 2 months |
First week—5 g SBI × 4/day After first week 5 g SBI/day |
Clinical condition improvementin case of a patient resistant for UC standard therapy Improved Mayo UC score |
| Shaw et al. [39] | Survey with IBS/IBD patients | n = 595 (n = 344 IBS; n = 251 = IBD) | – | SBI |
Reduced daily stools’ number Improvement quality of life |
| Liaquat et al. [40] | Patients with IBD (who were refractory to standard treatment) | n = 40 | 6 weeks | 5 g SBI/day | Reduction nausea, diarrhea |
| Soriano et al. [41] | Single case study—pediatric patient with UC | n = 1 | 2 months | 5 g SBI/day |
Blood in the stools, and diarrhea resolved PUCAI score decreased |
| Shafran et al. [42] | Patients with IBD | n = 21 (CD n = 14; UC n = 4) | 2 months | 5 g SBI/day | Possible reductions in the cost of standard care have been demonstrated in IBD patients receiving SBI |
| Vitamin D | |||||
| Blanck et al. [46] | Patients with UC | n = 34 | – | – |
Higher Mayo Score for ulcerative colitis activity in the group with vitamin D deficiency Vitamin D deficiency is associated with a greater need for steroid treatment |
| Jorgensen et al. [48] | Patients with Crohn disease in remission |
n = 94 (46 CD patients/48 CD patients-placebo) |
12 months | 1200 IU vitamin D3/day |
Oral supplementation increased serum vitamin D levels Relapse rates in patients supplementing with vitamin D3 decreased from 29 to 13% |
| Del Pinto et al. [49] | Meta-analysis | – | – | – |
Vitamin D as a therapeutic agent has been shown to be promising in reducing the frequency of relapses and improving the quality of life in IBD IBD patients have been shown to have a twofold higher risk of developing vitamin D deficiencies compared to control |
| Omega-3 acids | |||||
| Charpentier et al. [52] | Rats with induced colitis | n = 50 (divided into 5 groups: TNBS, n-3, n-6, n-9, control) | 4 weeks | Diets with several fatty acid proportions: n-3, n-6, n-9 |
In diet with OMEGA3-reduce iNOS, COX-2 expression in colon; decrease IL-6, TNF-α production In diet with OMEGA9-decrease the colon IL-6 No differences between groups in levels: claudin-1 and occludin |
| Mbodji et al. [53] | Rat with induced colitis | – | 14 days | Omega3 acid (fish oil-rich formula) or isocaloric and isolipidic oil formula + 5-ASA | Combination of omega 3 with 5-ASA treatment—reduction of NF-κB activation (together they are more effective than a higher dose of the drug alone) |
| Turner et al. [54] | Systematic review with IBD patients | CD n = 1039; UC n = 138 | – | – | Insufficient data to order the use of omega-3 to maintain remission of both diseases |
| Eupatilin | |||||
| Joo et al. [56] | Rat with induced colitis | N = 6 w 8 grupach | 48 h |
Artemisia vulgaris L EIE—ekstrakt z Artemisia asiatica (100 mg/kg) lub EIQ—ekstrakt z Rumex aquaticus (30 mg/kg) 5-AS- kwas 5-aminosalicylowy (25 mg/kg) |
Reduced MPO activity, nitric oxide production, TNF-α expression in a dose-dependent manner |
| Zhou et al. [57] | Mice with induced colitis |
5 groups n = 10 animals per group |
7 days | Eupatilin (10 or 20 mg/kg/day) | Inhibits NF-κB activation in both intestinal epithelial cells, in macrophages, and in experimental models where colitis has been induced |
| Apigenin | |||||
| Mascaraque et al. [59] | Rat with induced colitis | 6 groups n = 4–6 per group |
All treatments started 2 d before colitis induction |
apigenin K(1, 3 or 10 mg/kg) |
Reduced inflammation area Decreased: myeloperoxidase, TNF-α and IL-6 |
| Sadraei et al. [60] | Rats with experimental colitis (9 group n = 6 in each group) | 3 grupy dostały rosnące dawki Kotschyi; 3 kolejne apigeninę; kolejne 3 kontrola | 5 days | Apigenin (5, 10, and 20 mg/kg)or Dracocephalum kotschyi Boiss (10, 20, and 40 mg/kg) hydroalcoholic extract—ere administered orally 2 h prior to induction of colitis |
Lower score values of macroscopic and microscopic characters Decreased MPO Reduced the total colitis index Best effect was achived with dose of 5 mg apigenin |
| Ben-Arye et al. [61] | Patients with active UC | n = 23 | 1 month | 100 cm3 wheatgrass juice—Triticum aestivum or placebo |
Reduction in the rate of disease activity Reduction in severity of rectal bleeding |
| Polyphenols | |||||
| Boussena et al. [62] | UC-induced rats | n = 40 (divided into 5 groups) | 21 days | Polyphenol-rich red grape pomace extracts (GPEs) | Reduces the proinflammatory cytokines production and influences the MPO and antioxidant enzymes activities |
| D'Argenio et al. [63] | Rats with TNBS-induced colitis | n = 16 (divided in 2 groups, n = 8 in each group) | 14 days | Apple methanol extract (1 mL/die of APE 10−4 M) | reduction of inflammatory process activity as well as normalization of inflammatory markers values, such as IL-1β, IL-1α, IFN-γ, IL-6, TNF-α |
| Parkar et al. [64] | Caco-2 enterocytes | – | – |
Hydroxycinniaminc acids; flavonoids; glycosides; flavanone; isoflavones; flavonol 10,30, 100 µg/mL After 1 h of incubation of Lactobacillus rhamnosus, Escherichia coli, Staphylococcus aureus and Salomnella typhimurium was added to cells |
All polyphenols inhibited Staphylococcus aureus adhesion The most sensitive to polyphenols is S. aureus High antibacterial activity: flavanone, flavanol Low antibacterial activity: flavonols, isoflavones, glycosides |
| Curcumin | |||||
| Suskind et al. [68] | Children with IBD | n = 11 (UC n = 5, CD n = 6) | 9 weeks |
500 mg capsules (for all patients, no placebo) 2 razy dziennie przez 3 tygodnie 1 g dwa razy dziennie od 3 tygodnia 2 g dwa razy dziennie od 6 tygodnia |
PDCAI, PUCAI was improved, |
| Garg et al. [69] | Patients with UC—review | n = 89 (treatment n = 45 placebo n = 44) | 6 months | 2 g curcumin/day (oral dose) | Lower CAI index compare to placebo group |
| Iqbal et al. [70] | Patients with UC—review | N = 142 (study group n = 71; n = 71 placebo) | – | Curcumin + mesalazine |
Higher incidence of disease remission versus placebo Endoscopic remission |
| Hanai et al. [71] | Patients with UC | n = 89 (n = 45 study group; n = 44 placebo) | 6 months | 45 patients 2 g/day curcumin + mesalazine or sulfalazine/44 patients’ placebo only drug |
Curcumin combinaton with drug-reduced relapses vs placebo Improved CAI, EI |
| Phosphatidylcholine | |||||
| Ehehalt et al. [73] | Rectal mucus of patients with UC and CD (clinical remmision) |
CD n = 7 UC n = 11 Control n = 21 |
– | Mass spectrometric analyses of mucus. Quantitative analyses of phosphatidylcholine (PC) and lysophosphatidylcholine (LPS) | Patients with UC: significant less PC and LPS in mucus compared to CD and control |
| Treede et al. [75] | CaCo2 cells | – | – | Phosphatidylcholine |
Inhibition TNF-alfa Reduced: IL-8, ICAM-1, IP-10, MCP-1, TNF-alpha and MMP-1 |
| Amadei et al. [76] | In vitro intestinal surface model | – | – | Phosphatidylcholine | Sustained the binding capability to enzymatically degraded mucin |
| Stremmel et al. [77] | Patients UC | n = 60 (n = 30 study group, n = 30 placebo group) | 3 months | Phosphatidylcholine (PC) supplement 6 g/day vs placebo |
Induction of clinical remission in study group CAI index improvement Improvement in quality of life |
| Terminalia arjuna | |||||
| Cota et al. [79] | Rat with experimentally induced colitis | n = 48 (6 groups n = 8 in each group (2 control group: noncolitic, untreated colitic and 4 study group) | 28 days | Terminalia arjuna (hydroalcoholic extract TAHA) in various doses (500, 250, 125 mg/kg) |
Reduction macroscopic and histologic score Decreased MPO, NO, IL-6, IL-1beta, TNF-α, MCP-1 |
| Soy protein | |||||
| Metzger et al. [81] | Rats with induced colitis | n = 32 | 28 days | 35% soy protein diet |
TNF-α reduce Improvement histological examinations in intestinal tissue and bone tissue |
| Common nettle | |||||
| Nematgorgani et al. [84] | Patients with IBD | n = 64 (59 ukończyło badanie) (n = 30 study group; n = 29 placebo group) | 3 months | 400 mg per tablet nettle extract 3 times/day or placebo group |
Reduction CRP serum levels Increase SOD Quality of life improved |
| Francišković et al. [82] | Ex vivo human platelets | – | – | 200 mg/mL nettle extract |
Inhibited: thromboxane, LPS production, expression COX-2 Inhibited 12-LOX trail Supports the maintenance of epithelial integrity and intestinal mucosal defensive ability |