Table 3.

Summary of the studies that investigated the effects of prebiotic dietary fibers on intestinal permeability and immunity

Authors, Year of publication	Location	Age (years)	Studied Population	Study Design	Intervention/Dose/Duration	Gut effects	Effects on cytokines	Quality score/ degree of trials	Side effects
Bloomer et al., (2020) 44	USA	20-65	75 healthy men and women	Double-blind, placebo-controlled, randomized trial	1. Prebiotic: AA at 2 or 4 g daily	No effects on the levels of zonulin	No effects on the levels of IL-6, IL-10, IL-1β, and TNF-α	3/ High	No side effects
					2. AL at 2 or 4 g daily
					3. Placebo (maltodextrin)/ 8 weeks
Ranaivo et al., (2022) 45	France	44	15 subjects with cardiometabolic risk (9 men, 6 women)	Double-blind, placebo-controlled, randomized, crossover exploratory trial	1. Prebiotic: 4.5 g of CG	A family belonging to the Actinobacteria Phylum decreased 3 Bacterial taxa: Erysipelotrichaceae UCG.003, Ruminococcaceae UCG.005, and Eubacterium ventriosum group increased.	No effects on the levels of hs-CRP and Calprotectin	4/High	No side effects
					2. Placebo (maltodextrin)/ 3 weeks	No effects on zonulin, LBP, BA, LCFAs, and SCFAs levels
Ramos et al., (2018) 46	Brazil	18-80	46 chronic kidney disease patients	Double-blind, placebo-controlled, randomized trial	1. Prebiotic: FOS, 12 g/day 2. Placebo (maltodextrin)	No effects on the levels of Zonulin and GLP-2	No effects on the levels of hs-CRP and IL-6	5/High	Abdominal discomfort (one participant)
Vaghef-Mehrabani et al., (2022) 47	Iran	20-50	45 women with obesity and major depressive disorder (MDD)	Double-blind, placebo-controlled, randomized trial	1. Prebiotic: 10 g/d of inulin 2. Placebo (maltodextrin)/ 8 weeks	No effects on the levels of zonulin and LPS	No impact on the levels of TNF-α, IL-10, MCP-1, TLR-4, and hs-CRP	5/ High	Gastrointestinal complaints (five patients)
Krawczyk et al., (2018) 48	Poland	48.03±13.13	32 (22 males and 10 females) individuals with NAFLD	randomized controlled intervention trial	1. Diet with 30 -35 g/day dietary fiber (3 portions of vegetables and two portions of fruit)/ 6 months	Zonulin levels decreased	-	3/High	Not reported
Drabińska et al., (2020) 49	Poland	Not reported	30 children with celiac	A pilot, randomized, placebo-controlled nutritional intervention	1. GFD with prebiotic oligofructose-enriched inulin (10 g per day)	Zonulin levels increased.	No effects on the levels of Calprotectin	3/ High	Not reported
					2. Placebo (maltodextrin)/ 12 weeks	No effects on the levels of GLP-2
Russo et al., (2012) 50	Italy	18.8±0.7	20 healthy males	Randomized double-blind crossover design	1. 11% Inulin-enriched pasta or control pasta diet: 100 g/d=11.0 and 1.4 g/d of fructans, respectively/ Two 5-week study periods with a washout period (8 weeks) in between and a 2-week run-in period	Zonulin levels decreased GLP-2 levels increased	-	2/Low	No adverse effects
Czerwi´nska-Rogowska et al., (2022) 51	Poland	-	59 patients suffering ischemic stroke	Randomized clinical trial	1. The kitchen diet (n=32; 1.2 g fiber in 100 mL)	Zonulin levels decreased.	No effects on the levels of Calprotectin, but hs-CRP levels increased with the kitchen diet.	1/Low	Not reported
					2. Nutrison Energy® (n=14; 0.02 g fiber in 100 mL)	Propionic acid and butyric acid with a kitchen diet increased SCFAs levels and decreased with an industrial diet without fiber.
					3. Nutrison Diason Energy HP® (n=13; 1.8 g fiber in 100 mL)/7 days
Riviere et al., (2022) 38	USA	50±14	20 males and females with obesity	Controlled-randomized clinical trial	1. Immediate intervention (Frozen GLV) during the first 4 weeks	No effects on the levels of zonulin, LBP, and microbiota	No effects on the levels of TNF-α, IL-6, and hs-CRP	3/ High	Not reported
					2. Delayed intervention (Frozen GLV during the last 4 weeks)/ 12-week trial	Change in serum zonulin was associated with a change in Proteobacteria in females and Bifidobacterium and Bacteroidaceae in males
Neyrinck et al., (2021) 52	Belgium	18-65	24 Obese patients	Single-blind, placebo-controlled trial	1. Prebiotic: 16 g/d native inulin	No effects on the levels of zonulin and SCFAs	Calprotectin levels decreased	2/Low	Not reported
					2. Placebo (maltodextrin), coupled with dietary advice to consume inulin-rich versus inulin-poor vegetables for 3 months, in addition to dietary caloric restriction
Lee et al., (2023) 53	Singapore	50-75	15 Healthy middle-aged and older men and women	Randomized controlled crossover trial	1. Control (C)	SCFAs levels increased No effects on the levels of zonulin AOK decreased the levels of Clostridiales RO increased the levels of Bifidobacteria	-	4/High	Not reported
					2. Prebiotic: 20% flour-substituted okara (AOK)
					3. Prebiotic: 20% flour-substituted bio-valorized okara (RO) biscuits/ 3 weeks
Hiel et al., (2020) 43	Belgium	18 to 65	110 obese patients with at least one obesity-related metabolic disorder	A randomized, single-blinded, multicentric, placebo-controlled trial	1. Preboptic:16 g/d native inulin	Desulfovibrio and Clostridium levels decreased.	-	4/High	Flatulence and bloating, especially at the start of the intervention, which decreased with the duration of the treatment
					2. Placebo (maltodextrin) coupled with dietary advice to consume inulin-rich versus-poor vegetables /3 months	Bifidobacteria levels increased
Vuholm et al., (2017) 39	Denmark	51.0±9.4	70 healthy adults	A single-blinded randomized controlled trial	Replace all cereal products in their habitual diet with:	No effects on the levels of zonulin	-	3/High	Not reported
				1. WGW	Fecal butyrate concentration increased by WGR and WGW.
				2. WGR
				3. RW
Petelin et al., (2022) 62	Slovenia	NR	27 patients (19 women and 8 men) with metabolic syndrome	Randomized, double-blind comparative trial	Drink 200 mL of either	Zonulin levels decreased by HI.	IL-6 levels decreased by HI at week 4	4/High	NR
					1. HA or	HA had no effects on the levels of Zonulin.
					2. HI	Some generations of Firmicutes decreased by both HI and HA.
					tea filter bags containing 1 g of dried plant material every evening, 2 hours after dinner; and a 2-week follow-up phase without any supplementation/4 weeks	α-diversity decreased by both HI and HA.
						Proteobacteria decreased by both HI and HA.

AA: Ambrotose advanced; AL: Ambrotose LIFE; IL-6: Interleukin 6; IL-10: Interleukin-10; IL-1β: Interleukin-1β; TNF-α: Tumor necrosis factor-α; CG: Chitin-Glucan; hs-CRP: High sensitivity C-reactive protein; LBP: Lipopolysaccharide binding protein; BA: Bile acids; LCFA: Long-chain fatty acids; SCFA: Short-chain fatty acids; FOS: Fructooligosaccharide; GLP-2: Glucagon-Like Peptide-2; LPS: Lipopolysaccharide; MCP-1: Monocyte chemoattractant protein-1; TLR-4: Toll-like Receptor 4; GFD: Gluten-free diet; WGW: Whole-grain wheat; WGR: Whole-grain rye; RW: Refined wheat; GLV: Green leafy vegetable; HI: Helichrysum italicum (Roth) G. Don; HA: Helichrysum arenarium (L.) Moench; NAFLD: Nonalcoholic fatty liver disease; AOK: 20% Flour-substituted okara; RO: 20% flour-substituted bio-valorized okara