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. 2022 Nov 7;14(21):4699. doi: 10.3390/nu14214699

Table 1.

Microbiota-dependent and independent effects of FOS on paracellular permeability and/or TJs.

Treatment Characteristics [FOS] Model/Experimental Setup Type of Study Observed Effects on PP and/or TJs Type of Effect References
FOS (Sigma-Aldrich, St. Louis, MO, USA) 0.1 mg/mL T84 monolayers In vitro Ca2+ switch assay under normal and LPS-challenged conditions: ↑ TEER/acceleration of TJ re-assembly (better effect with basolateral application) MID [166]
Re-localization of ZO-1, occludin and claudin-1, no alterations on TJ proteins expression
FOS (Nutraflora®, Nutrition GTC, Golden, CO, USA ), DP 2–9 10% w/v EHEC-exposed Caco-2Bbe1 monolayers In vitro Pre-incubation/
challenged cells: ↑ TEER, redistribution of ZO-1,
↑ mRNA ZO-1, ↑ occludin protein but not mRNA
MID [81]
Unchallenged cells: no effect on TEER, ↑ mRNA & protein ZO-1, ↑ occludin protein but not mRNA, no effect on claudin-1
FOS (Nutraflora®), DP 2–9 10% w/v Duodenal organoids In vitro Pre-incubation/challenged organoids: ↑ TEER, ↓ PP of FITC-D MID [81]
Unchallenged organoids: ↑ TEER
FOS Frutalose (OFP; Sensus), DP ≤ 10 100 mg/L PMA-exposed T84 monolayers In vitro Pre-incubation: ↑ TEER MID [179]
FOS Orafti® L95, 75% w/w syrup, FOS:94.8 w/w ds 2% v/v Caco-2 monolayers In vitro ↑ TEER, no effect on TJ gene or mRNA expression MID [171]
FOS (Orafti®, Beneo Orafti, Tienen, Belgium) P95, DP 7–8 2% DON-exposed Caco-2 monolayers In vitro Apical & basolateral pre-treatment: ↑ TEER, ↓ PP of LY dose-dependently MID [23]
Total treatment: ↑ TEER during calcium-switch assay at highest C
FOS (Nutraflora®), DP 2–9 10% w/v Caco-2Bbe1 monolayers In vitro Pre-incubation/challenged cells: unsuccessful attenuation of F-actin microfilaments rearrangement, no effect on TEER, PP of FITC-D and ZO-1 redistribution MID [180]
Unchallenged cells: no effect on FITC-D PP
FOS (34% 1-kestose, 53% nystose, 9% 1F-β-fructofuranosylnystose) 100 mmol/L Caco-2 monolayers In vitro ↓ TEER, ↑ PP of LY MID [175]
FOS (Meioligo W, Meiji Co., Tokyo, Japan) 5% MCD mice (NASH) In vivo Improvement of ZO-1 abundance MD [184]
FOS (Nutraflora®) 6% 5′FU-exposed mice (Mucositis) In vivo Pretreatment and total treatment: ↑ mRNA ZO-1 & occludin, ↓ PP of 99mTc-DTPA MD [185]
FOS (Nutraflora®) 6% 5′FU-exposed mice (Mucositis) In vivo ↓ PP of 99mTc-DTPA MD [186]
FOS (P95S, Quantum Hi-Tech Biological Co. Ltd., Guangdong, China) 1.2% Chronic stress exposed mice In vivo ↑ mRNA & proteins Claudin-1, Occludin & ZO-1 MD [187]
FOS 4 g/kg/day HFD-fed mice (NAFLD) In vivo FOS alone and as synbiotic (Lactobacillus paracasei N111): ↑ occludin-1 & claudin-1 proteins MD [188]
FOS (Solarbio Biotechnology, Beijing, China), 95.93% 2%/day OVA-exposed mice (Food allergy) In vivo Enhancement of TJ complex- electron density MD [189]
PB (Center for Anti-aging Research, Nu Skin Enterprises, Shanghai, China) composed of GOS, FOS, inulin, and anthocyanins 1.26 mg/g/day Trichinella spiralis-exposed mice (IBS) In vivo Pretreatment and total treatment: ↑ occludin MD [163]
FOS (Nutraflora®), DP 2–9 10% w/v Citrobacter rodentium-exposed mice In vivo No effect on FITC-D PP MD [180]
FOS (Meiji Seika Kaisha, Ltd., Tokyo, Japan), 6.5% GF5, 43.4% GF4, 40.9% GF3, 7.1% 1-kestose GF2, 2.1% glucose and fructose. 4 g/kg/day Healthy weaned piglets In vivo ↑ mRNA ZO-1, occludin & claudin-1 MD [170]
Shanghai Lanpu Biotechnology Co., Ltd., Shanghai, China; FOS ≥ 20% 2.5 mg/kg/day ETEC-exposed weaned piglets In vivo ↑ mRNA ZO-1 & occludin (exceeding control) MD [190]
FOS, GOS, MFGM 7.5 g/L/day Weaned piglets In vivo ↑ mRNA ZO-1, claudin-1, occludin & E-cadherin MD [191]
FOS purity 93%g; Raftilose P95, Orafti® 60 g/kg/day Salmonella enterica-exposed rats In vivo ↑ urinary CrEDTA excretion (through TJ) MD [195]
FOS purity 93%g; Raftilose P95, Orafti® 60 g/kg/day Healthy rats In vivo ↑ urinary CrEDTA excretion (through TJ), no alterations on cadherins, ZO-1 claudin 2 & 4 genes expression MD [196]
Enzymatically synthesized FOS, DP 3.5, MW 550Da 5 g/day SHIME® inoculated with fecal sample from IBD patient and coupled with co-cultures of Caco-2 cells and THP1 macrophages In vitro ↑ TEER MD [192]
FOS Orafti® were boiled for 20min, following in vitro digestion and human fecal fermentation 50 mg of an equivalent carbohydrate was fermented using 5% of fecal inoculum Caco-2 cells incubated with FOS ferment supernatant In vitro ↑ TEER MD [193]
FOS (Sigma-Aldrich), chicory root-originated, ≥90% 5g/L SHIME® inoculated with fecal sample from healthy donors and coupled with co-cultures of Caco2:HT29-MTX-E12 In vitro ↑ TEER MD [194]

99mTc-DTPA, Technetium-99mTc-DTPA; DON, Mycotoxin deoxynivalenol; EHEC, Enterohemorrhagic E. coli; ETEC, Enteropathogenic E. coli; FITC-D, Fluorescein isothiocyanate–dextran; FOS, Fructooligosaccharides; FU, Fluorouracil; GOS, Galactooligosaccharides; LY, Lucifer yellow; IBS, Irritable bowel syndrome; MCD, Methionine-choline-deficient; MD, Microbiota-dependent; MID, Microbiota-independent; NASH, Non-alcoholic steatohepatitis; OVA, Ovalbumin; PMA, Phorbol 12-myristate 13-acetate; PP, Paracellular permeability; SHIME, Simulator of the Human Intestinal Microbial Ecosystem; TEER, Transepithelial electrical resistance; TJ, Tight junction.