Table 1.

Effects of probiotics on intestinal permeability or clinical effects in diseases associated with increased permeability

Probiotic	In vitro	Effect	In vivo	Effect	Reference
Effects of probiotics in animal or tissue studies
VSL#3	T84 monolayer	Increased resistance	IL-10 gene-deficient mice	Reduced mannitol flux	Madsen et al. (50)
VSL#3 vs commensal E. coli and vs heat-inactivated VSL#3	T84 monolayer with IFN-γ	Reduced barrier disruption measured by TEER and FITC-dextran permeability; effect of VSL#3 reversed by heat-inactivation			Krishnan et al. (51)
vs#3 vs placebo, healthy			DSS colitis in mice	Reduced disease activity; decreased Evans blue uptake and epithelial apoptosis; increased tight junction protein expression	Mennigen et al. (52)
Ecologic 825	IPAA (UC) pouchitis biopsies; Ussing chamber	Reduced horseradish peroxidase flux and E. coli K12 commensal passage, but no effect on paracellular permeability (51CrEDTA), TEER, or chloride secretion			Persborn et al. (53)

Probiotic	Study design	# Patients, Rx duration	Effect	Reference
Human studies with probiotics including intestinal permeability or barrier
Viable vs sonicated probiotics	DB, PC RCT in critically ill patients	28 patients; 7 d	No significant difference of intestinal permeability measured by lactulose:mannitol ratio	Alberda et al. (54)
Bifidobacterium adolescentis IVS-1 vs Bifidobacterium lactis BB12, + GOS prebiotic, 6 Rx arms	Obese (BMI 30–40), aspirin challenge, DB, RCT, lactose control	94 patients; 3 wk	B. adolescentis IVS-1 but not B. lactis BB-12 reduced permeability (SLR); prebiotic GOS also effective alone; however, no synergistic effect	Krumbeck et al. (38)
L. plantarum WCFS1, CIP104448, TIFN101, or placebo	Healthy; indomethacin stressor; DB, PC, 4-way crossover	7-d oral Rx with 4-wk washouts between each	Indomethacin increased LRR; no difference between baseline and on Rx LRR for any treatment vs placebo; Integrin pathway and actinin α4 gene upregulated by L. plantarum TIFN 101; Claudin 5 gene downregulated by L. plantarum WCFS1; claudin 19 gene downregulated by L. plantarum CIP48	Mujagic et al. (55)
Effect of probiotic on human disease without documented effect on permeability
Nonpathogenic E. coli Nissle 1917	Ulcerative colitis; DB, RCT, PG	116 patients: 59 mesalazine, 57 E coli; 12 mo	Equivalent results vs mesalazine: Time to remission, time to relapse	Rembacken et al. (56)
Combination probiotic, Ecologic 641	Primary sclerosing cholangitis + IBD, RCT, X-O	14 pts; 3 month each Rx + 1 mo washout	6 strains of viable and freeze-dried bacteria: 4 lactobacilli, 2 bifidobacteria: Effect on permeability not studied	Vleggaar et al. (57)
VSL#3 vs placebo	Refractory pouchitis, RCT, PC, PG	36 patients: 20 VSL#3, 16 placebo; daily Rx, 1 yr	Cumulative remission maintenance rate for refractory pouchitis after 12 mo f/u higher in VSL#3 group (85%) vs placebo group (6%) P = 0.0001	Mimura et al. (58)

BMI = body mass index; DOSS = dioctyl sodium sulfosuccinate; FITC = fluorescein isothiocyanate; GOS = galactooligosaccharide; IBD = inflammatory bowel disease; IFN = interferon; IPAA = ileal pouch anal anastomosis; PC = placebo control, PG = parallel group; RCT = randomized controlled trial; Rx = treatment; TEER = transepithelial electrical resistance; UC = ulcerative colitis; X-O = crossover.