Table 2.

Summary of studies evaluating in animal models the effects of food compounds on the mucus layer.

Food Group/Compounds	Animal Model	Experimental Administration	Study Period	Outcomes and Mechanisms of Action	Reference
Proteins
Total proteins	Adult finishing pigs	Three study groups (16%, normal dietary protein concentration; 13%, low dietary protein concentration; 10%, extremely low dietary protein concentration)	50 days	−Decrease in ileal bacterial richness, levels of intestinal SCFAs and biogenic amines with reduction of protein concentration. −Inhibition of stem cell proliferation, decrease in the expression of biomarkers of intestinal cells (Lgr5 and Bmi1) and alteration of gut bacteria community and ileal morphology in the 10% protein group. −Improvement of ileal and colonic bacterial community and enhancement of tight junction proteins (occludin and claudin) and ileal barrier function in the 13% protein group.	[94]
Total proteins	Growing pigs	Three study groups (18%, normal dietary protein concentration; 15%, low dietary protein concentration; 12%, extremely low dietary protein concentration)	30 days	−Decrease in the levels of most bacterial metabolites with reduction of protein concentration. −Reduction of ileal barrier function and tight junction proteins (occludin, zo-3, claudin-3 and claudin-7) in the 12% protein group. −Deficit in the development of intestinal villi and crypts and increased intestinal LPS-permeability in the low protein groups. −Enhancement of ileal richness, bacterial diversity and expression of intestinal stem cells (Lgr5) in the 15% protein group.	[95]
Chicken and soy proteins	C57BL/6 mice	Chicken or soy protein-based diets	4 weeks	−Increase in the thickness of the colonic mucus layer, the number of goblet cells, the expression of Muc2 mRNA and the abundance of A. muciniphila, in comparison to soy-protein-based diet.	[96]
Milk casein	Rats	Milk casein hydrolysate	8 days	−Stimulation of terminal ileal endogenous nitrogen flow. −Upregulation in the expression of mucin genes Muc3 in the small intestine and Muc4 in the colon.	[97]
Milk casein	Zucker rats	Milk casein hydrolysate	8 weeks	−Rise in the secretion of O-linked glycoproteins in the fecal material. −Upregulation in the expression of mucins genes (Muc3 and Muc4) in the ileal and colonic intestinal regions.	[98]
Milk β-casein	Rats pups	Milk β-casein peptide f(94–123)	9 days	−Increase in the number of goblet cells and crypts containing Paneth cells in the small intestine. −Upregulation in the expression of intestinal mucins (Muc2 and Muc4) and antibacterial factors (defensin-5 and lysozyme).	[99]
Milk β-casein	Indomethacin-induced jejunal injury in rats	Milk β-casein peptide f(94–123)	8 days	−Preventive amelioration of macroscopic and microscopic intestinal damage. −Preventive reduction of goblet cells, increased myeloperoxidase activity and expression of TNF-α and active caspase-3.	[100]
Goat whey	DNBS-induced colitis in CD1 mice	Goat whey proteins, fatty acids and oligosaccharides	16 days	−Reduction of colitis activity index and symptoms and mucosal leukocyte infiltration. −Downregulation in the expression of pro-inflammatory IL-1β, IL-6, IL-17, TNF-α, iNOS, MMP-9 and ICAM-1. −Increase in barrier function and upregulation in the expression of Muc2, Muc3, occludin and zonula occludens-1.	[101]
Hen egg	DSS-induced colitis in piglets	Egg white lysozyme	5 days	−Restoration of colitis symptoms, mucosal inflammation, muscle wall thickening, gastric permeability and mucin gene expression. −Down-regulation of intestinal expression of pro-inflammatory TNF-α, IL-6, IFN-γ, IL-8 and IL-17 and up-regulation of tolerogenic TGF-β and Foxp3.	[102]
Soybean protein	DSS-induced colitis in piglets	Soybean protein derived di- and tri-peptides	5 days	−Decrease in gut permeability, crypt elongation and muscle thickness, colonic expression of pro-inflammatory mediators and myeloperoxidase activity. −Down-regulation of ileal mRNA levels of IFN-γ, TNF-α, IL-12B and IL-17A and up-regulation of FOXP3 expression.	[103]
Pea protein	DSS-induced colitis in C57BL/6J mice	Pea seed protein extracts	23 days	−Amelioration of colitis-induced histological alterations. −Restoration of colonic protein levels related to epithelial barrier function and mRNA expression of pro-inflammatory cytokines, inducible enzymes, metalloproteinases, adhesion molecules and toll-like receptors. −Gut modulation of bacterial abundances towards healthy conditions.	[104]
Lipids
High- and low-fat diets	C57BL/6J mice	Chicken, soy or pork protein-based administration either with low fat (12% kcal) or high fat (60% kcal) diets	12 weeks	−Disruption of crypt depth, numbers of goblet cells and protein and gene expression of Muc2 in the high-fat diet group, regardless of protein diets. −Upregulation of Muc2 gene expression by meat proteins in the low-fat diet group. −Reduction of intestinal barrier, zonula occludens-1 and E-cadherin proteins and increase of colonic IL-1β expression and serum TNF-α and IL-6 by meat proteins in the high-fat diet group.	[93]
High-fat diet	C57BL/6 mice	High-fat diet (56.7 Fat kcal %), in comparison with normal chow diet (12.0 Fat kcal %)	8 weeks	−Reduction of fecal weight, increase of total gastrointestinal transit time and colon transit time and reduction of colonic mucus in the high-fat diet group	[105]
High-fat diet	Spontaneous colitis in Winnie mice	High-fat diet (46% available energy as fat), in comparison with normal chow diet (11% available energy as fat)	9 weeks	−Increase in diarrhea scores, bloody feces, more severe and widespread colonic damage with prominent mucosal erosions and crypt abscesses. −Induction of endoplasmic reticulum stress (Grp78 and sXbp1) and oxidative stress (Nos2) markers. −Down-regulation of goblet cell differentiation (Klf4) and intestinal claudin-1 protein staining.	[106]
Flaxseed oil	LPS-induced intestinal injury in weaned piglets	Supplementation of diets with flaxseed oil in comparison with corn oil (5% weight:weight)	3 weeks	−Restoration of intestinal morphology, jejunal lactase activity, necroptosis signals and claudin-1 protein expression. −Down-regulation of mRNA expression of intestinal toll-like receptors 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear factor kappa B (NF-κB), nucleotide-binding oligomerization domain proteins (NOD1, NOD2) and receptor-interacting protein kinase 2 (RIPK2). −Increased levels of intestinal α-linolenic acid, eicosapentaenoic acid and total n-3 polyunsaturated fatty acids.	[107]
Fiber
Inulin	Western style diet-induced obesity in C57BL/6J mice	1% oligofructose-enriched inulin supplementation in the drinking water	4 weeks	−Alteration of gut microbiota composition with loss of Bifidobacterium taxa and reduced growth rate and higher penetrability of the colonic mucus by the Wester style diet. −Prevention of the penetrability of the inner mucus layer in the fiber inulin group.	[77]
Inulin and cellulose	Western style diet-induced obesity in C57BL/6J mice	Supplementation of high-fat diets (60 kcal% fat) with 20 % fiber	4 weeks	−Protection against diet-induced low-grade inflammation and metabolic syndrome by fermentable inulin fiber, but not insoluble cellulose fiber. −Restoration of epithelial cell proliferation and colon atrophy, microbiota loads, IL-22 production and antimicrobial gene expression. −Suppression of adiposity and improvement of glycemic control.	[108]
Pectin	TNBS- and DSS-induced colitis in C57BL/6J mice	Diet supplemented with characteristically high (5% orange pectin) in comparison to low (5% citrus pectin) side chain content of pectin	10–14 days	−Amelioration of clinical symptoms and colonic damage. −Decrease in levels of colonic IL-1β and IL-6. −Increase in the fecal concentration of propionic acid. −Protective effects against intestinal inflammation even in mice treated with antibiotics.	[109]
Microbiota-accessible carbohydrates	High-fat and fiber-deficient diet in C57BL/6J mice	Supplementation of high-fat (31.5% fat by weight) and fiber-deficient (5% fiber by weight) diet with microbiota-accessible carbohydrates	15 weeks	−Improved intestinal barrier function by increased colonic mucus thickness and tight junction protein expression. −Amelioration of endotoxemia, colonic and systemic inflammation and enhancement of microbiota richness and α-diversity. −Improvement of cognitive impairment via the gut microbiota-brain axis.	[110]

DNBS: dinitrobenzene sulfonic acid; DSS: dextran sulfate sodium; LPS; lipopolysaccharide; TNBS: 2,4,6-trinitrobenzenesulfonic acid.