Table 4.
Summary of the studies that investigated the effects of probiotics on intestinal permeability and immunity
| Authors, Year of publication | Location | Age (years) | Studied population | Study design | Intervention/Dose/Duration | Gut effects (intestinal permeability) | Effects on cytokines | Quality score/ degree of trials | Side effects |
|---|---|---|---|---|---|---|---|---|---|
| Kantah et al., (2017) 40 | China, Italy, India, and South Korea | Between 38 and 62 | 120 individuals | A multicenter randomized study | 1. A) given a symbiotic 10 mL t.i.d. for 5 months | Zonulin levels decreased by treatment in the B and C groups. | - | 2/Low | Not reported |
| 2. B) given 1-tab t.i.d of P3T/J (a probiotic mixture) for 5 months | Bacteroidetes/Firmicutes ratio normalized by B and C treatments. | ||||||||
| 3. C) Given the symbiotic 10 mL t.i.d. for 1 month and then shifted to 1 tablet t.i.d of probiotic mixture for 4 months | |||||||||
| 4. Control: Prior study supplemented a marine PUFA extract | |||||||||
| Townsend et al., (2018) 41 | USA | 20.1±1.5 | 25 Division I male baseball athletes | Double-blind, placebo-controlled, randomized study | 1. Probiotics consisted of 1.2 billion CFU/capsule | No effects on the levels of zonulin | TNF-α levels decreased. | 5/High | No adverse effect |
| 2. Placebo capsule consisted of maltodextrin/ 12 weeks | No effects on the levels of IL-10. | ||||||||
| Lamprecht et al., (2012) 22 | Austria | 30-45 | 23 trained men | Randomized, double-blinded, placebo-controlled trial | 1. Multi-species probiotics (1010 CFU/day), | Zonulin levels decreased. | TNF-α levels decreased. | 5/High | Not reported |
| 2. OMNi-BiOTiC (n=11) | No effects on the levels of IL-6. | ||||||||
| 3. Placebo (n=12) /14 weeks | |||||||||
| Liu et al., (2015) 54 | China | 25 and 75 years | 117 participants with colorectal liver metastases | a double-center and double-blind randomized clinical trial | 1. Probiotic 2 g/day, at a total daily dose of 2.6×1014 CFU: Encapsulated admixture of three probiotic bacteria [composed of LP (CGMCC No.1258, cell count ≥1011 CFU/g), LA-11 (cell count ≥7.0×1010 CFU/g) and BL-88 (cell count ≥5.0×1010 CFU/g) every day | Postoperative zonulin levels decreased | - | 5/High | No side effects |
| 2. Placebo encapsulated maltodextrin/6 days preoperatively and 10 days postoperatively | |||||||||
| Stenman et al., (2016) 55 | Finland | 18-65 years old | 224 participants with a BMI between 28.0-34.9 and a waist-to-hip ratio of≥0.88 for males and ≥0.83 for females. | Double-blind, randomized, placebo-controlled, multi-center clinical trial | 1. Placebo, microcrystalline cellulose, 12 g/d | Zonulin levels decreased in the B420 and LU+B420 groups. | No effects on the levels of hs-CRP, IL-6, and sCD4 | 5/High | At least one adverse event (Gastrointestinal symptoms) (133 were potentially product-related) |
| 2. Litesse® Ultra polydextrose (LU), 12 g/d | No effects on the levels of LPS | ||||||||
| 3. Bifidobacterium animalis ssp. lactis. 420 (B420), 1010 CFU/d in microcrystalline cellulose, 12 g/d | |||||||||
| 4. LU+B420, 12 g+1010 CFU/d, 6 months | |||||||||
| De Roos et al., (2017) 56 | USA | 18-70 | 60 patients (56 women) with migraine | A randomized double-blinded placebo-controlled study | 1. Multispecies probiotic (5×109 colony-forming units) | No effects on the levels of zonulin | No effects on the levels of IL-6, IL-10, TNF-α and hs- CRP | 4/High | Not reported |
| 2. Placebo (maize starch and maltodextrin powder) daily/12 weeks | |||||||||
| Liu et al., (2013) 57 | China | Between 25 and 75 years | 150 patients with colorectal cancer who were scheduled to undergo a radical colectomy | A double-center and double-blind randomized clinical trial | 1. Probiotics, 2 g/d, at a total daily dose of 2.6×1014 CFU. | Zonulin levels decreased | p38 MAPK signaling pathway decreased | 5/High | Not reported |
| 2. Encapsulated maltodextrin daily/ 6 d preoperative and 10 d postoperative | |||||||||
| Mokkal et al., (2017) 58 | Finland | 20-36 | 200 healthy overweight women | A randomized double-blind placebo-controlled clinical trial | 1. One capsule Probiotics (a combination of two bacteria, Bifidobacterium animalis subsp. Lactic 420 and Lactobacillus rhamnosus HN001; it contained 1010 CFU of each in a capsule | No effects on levels of zonulin and LPS | - | 4/High | Not reported |
| 2. LC-PUFA (consisted of 1.2 g of n-3 LC-PUFA (79.6% DHA and 9.7% EPA), two capsules consumed per day to give a total daily dose of 2.4 g | |||||||||
| 3. Probiotics and LC-PUFA | |||||||||
| 4. Placebo for each supplement (for the probiotics consisted of microcrystalline cellulose and for the n-3 LCPUFA, medium chain fatty acids [capric acid C8 54.6% and caprylic acid C10 40.3%]) | |||||||||
| Horvath et al., (2016) 21 | Austria | 50-64 years | 80 patients with liver cirrhosis. | A randomized, double-blind, placebo-controlled study | 1. A daily dose of a probiotic powder containing eight different bacterial strains (Bifidobacterium bifidum W23, Bifidobacterium lactis W52, Lactobacillus acidophilus W37, Lactobacillus brevis W63, Lactobacillus casei W56, Lactobacillus salivarius W24, Lactococcus lactis W19 and Lactococcus lactis W58) | No effects on the levels of zonulin | No effects on the levels of Calprotectin | 5/High | The side effects were mild, and most symptoms were gastrointestinal complaints. |
| 2. Placebo/6 months and were followed up for another 6 months | |||||||||
| Stadlbauer et al., (2015) 63 | Austria | 40-62 | 28 subjects with metabolic syndrome | Randomized controlled pilot study | 1. LcS group: Food supplementation with a milk drink containing LcS (3 bottles a day, 65 mL, containing LcS at a concentration of 108/mL, Yakult light1, Yakult Austria, Vienna, Austria) (n=13, LcS group) | No effects on the levels of zonulin, BA, and Bacteroidetes/Firmicutes ratio Parabacteroides increased (at the level of the genes) | No effects on the levels of Calprotein | 3/High | Not reported |
| 2. No intervention (n=15, standard therapy group)/12 weeks | |||||||||
| Roman, E et al., (2019) 64 | Spain | 60-70 | 35 patients with cirrhosis | Double-blind placebo-controlled randomized trial | 1. Probiotic (probiotic group): 450 billion bacteria twice daily (a mixture of eight strains, namely, Streptococcus thermophilus DSM 24731, Bifidobacterium breve (B. breve) DSM 24732, B. longum DSM 24736, B. infantis DSM 24737, Lactobacillus paracasei (L. paracasei) DSM 24733) | No effects on the levels of zonulin and Microbiota | hs-CRP and TNF-α levels decreased Neutrophil levels increased | 5/High | No side effects |
| 2. Placebo (placebo group): contained maltose and silicon dioxide as inactive agents and was formulated as identical in appearance to the active agent/12 weeks | No effects on the levels of LBP | ||||||||
| Axelrod et al., (2019) 65 | USA | 18-45 years | 7 healthy adults | Randomized, double-blind, placebo-controlled crossover study | 4 weeks’ intake of 200 mg capsules containing the Lactobacillus Salivarius UCC118 (2 9 108 CFU/capsule) | No effects on fecal levels of zonulin Verrucomicrobiota levels decreased Rosebeburia and Lachnospiraceae (butyrate-producing) levels increased | No effects on the levels of IL-6 | 3/High | Not reported |
| 2. 4 weeks’ intake of placebo (corn starch with magnesium stearate) | |||||||||
| After 4 weeks of wash-out period before the crossover assessment period (4 weeks) | |||||||||
| Horvath et al., (2020) 66 | Austria | 45-67 | 58 patients with compensated cirrhosis | Randomized controlled trial | Daily dose of | Fecal zonulin levels decreased. | - | 3/High | Not reported |
| 1. Multispecies probiotics containing 1.5×1010 CFU in 6 g of Powder (Bifidobacterium bifidum W23, Bifidobacterium lactis W51, Bifidobacterium lactis W52, Lactobacillus acidophilus W37, Lactobacillus brevis W63, Lactobacillus casei W56, Lactobacillus salivarius W24, Lactococcus Lactic W19 and Lactococcus lactis W58 in a matrix of maize starch, maltodextrins, vegetable protein, potassium chloride, magnesium sulfate, enzymes (amylases), and manganese sulfate) | The composition of probiotic bacteria, including (Faecalibacterium prausnitzii, Syntrophococcus sucromutans, Bacteroides vulgatus, Alistipes shahii, and Prevotella) increased. | ||||||||
| 2. Placebo consisted of the matrix without bacteria/6 months | No effects on microbiota diversity | ||||||||
| Karim et al., (2022) 67 | Pakistan | 63-73 | 104 patients with COPD | Randomized, double-blind, computer-controlled, multicenter trial | 1. Vivomix 112 billion live bacteria (Streptococcus thermophilus DSM 24731, bifidobacteria (B. longum DSM 24736, B. breve DSM, 24732, DSM 24737), lactobacilli (DSM 24735, DSM 24730, DSM 24733, L. delbrueckii subsp. bulgaricus DSM 24734) along with maltose, anti-caking agent: silicon dioxide 1 capsule a day | Zonulin levels decreased | hs-CRP levels decreased | 5/High | Not reported |
| 2. Placebo (inactive agents in similar capsules) /16 weeks | |||||||||
| Karim et al., (2022) 68 | Pakistan | 58-73 | 92 CHF patients | Randomized controlled trial | 1. Vivomix 112 billion live bacteria (Streptococcus thermophilus DSM 24731), bifidobacteria (B. longum DSM 24736, B. breve DSM, 24732, DSM 24737), lactobacilli (DSM 24735, DSM 24730, DSM 24733, L. delbrueckii subsp. bulgaricus DSM 24734) along with maltose, anti-caking agent: silicon dioxide, 1 capsule a day | Zonulin levels decreased | - | 5/High | Not reported |
| 2. Placebo (inactive agents in similar capsules) /12 weeks | |||||||||
| Ayob et al., (2023) 69 | Malaysia, | 40-68 | 40 Patients with non-alcoholic fatty liver disease | Randomized, double-blind, placebo-controlled trial | 1. Probiotics Each sachet (3 g) consists of a total of 30 billion CFU with six probiotic strains (Lactobacillus acidophilus BCMC® 12130 (107 mg), Lactobacillus casei sub-spp. BCMC® 12313 (107 mg), Lactobacillus lactis BCMC® 12451 (107 mg), Bifidobacterium bifidum BCMC® 02290 (107 mg), Bifidobacterium infantis BCMC® 02129 (107 mg) and Bifidobacterium longum BCMC® 02120 (107 mg) | Zonulin levels increased in both groups. | TNF-α levels decreased IL-6 levels increased | 3/High | Not reported |
| 2. The placebo group received an identical sachet without probiotic strains/6 months | Unclassified-proteobacteria, unclassified-streptococcus, and unclassified-stenotrophomonas decreased. | ||||||||
| Qaisar et al., (2024) 70 | United Arab Emirates | 71.4±3.9 | 123 older adults with agerelated muscle decline | Randomized, controlled-double blinded study | 1. Probiotic: one capsule of Vivomix, 112 included bifidobacteria (B. longum DSM 24736, B. breve DSM 24732, DSM 24737), Streptococcus thermophilus DSM 24731, and lactobacilli (DSM 24735, DSM 24730, DSM 24733, L. delbrueckii subsp. bulgaricus DSM 24734) | Zonulin levels decreased | No effects on levels of hs-CRP | 4/High | Not reported |
| 2. Placebo/ 16 weeks | |||||||||
| Lennon et al., (2024) 71 | USA | 18-50 | 16 runners | Randomized double-blinded crossover clinical trial | 1. Probiotic: daily supplementation with a probiotic cocktail containing P.acidilatici and L.plantarum | No effects on the levels of zonulin, microbiota, SCFA, and LBP | No effects on the levels of IL-1β, IL-6, IL-10, MCP-1, TNF-α, hs-CRP, and Calprotectin | 3/High | Not reported |
| 2. Placebo/ 4 weeks |
CFU: Colony-forming unit; TNF-α: Tumor necrosis factor-α; IL-10: Interleukin-10; IL-6: Interleukin-6; LPS: Lipopolysaccharide; sCD4: Stearoyl-CoA desaturase-4; p38 MAPK: p38 mitogen-activated protein kinase; LC-PUFA: Long-chain polyunsaturated fatty acid; DHA: Docosahexaenoic acid; EPA: Eicosapentaenoic acid; LcS: Lactobacillus casei Shirota; t.i.d: Three times a day; COPD: Chronic obstructive pulmonary disease; CHF: Congestive heart failure; SCFA: Short-chain fatty acids; LBP: Lipopolysaccharide-binding protein