Protein Malnutrition During Juvenile Age Increases Ileal and Colonic Permeability in Rats

Abstract

Protein malnutrition can lead to morphological and functional changes in jejunum and ileum, affecting permeability to luminal contents. Regarding the large intestine, data are scarce, especially at juvenile age. We investigated whether low-protein (LP) diet could modify ileal and colonic permeability and epithelial morphology in young rats. Isocaloric diets containing 26% (control diet) or 4% protein were given to male rats between postnatal days 40 and 60. LP-diet animals failed to gain weight and displayed decreased plasma zinc levels (a marker of micronutrient deficiency). In addition, transepithelial electrical resistance and occludin expression were reduced in their ileum and colon, indicating increased gut permeability. Macromolecule transit was not modified. Finally, LP diet induced shortening of colonic crypts without affecting muscle thickness. These data show that protein malnutrition increases not only ileum but also colon permeability in juvenile rats. Enhanced exposure to colonic luminal entities may be an additional component in the pathophysiology of protein malnutrition.

Modeling undernutrition with enteropathy in mice

“…In the present study, the combination of 3 weeks LP diet with chronic oral gavage of indomethacin significantly decreased Cldn2 and Ocln mRNA levels. These results are in accordance previous studies showing a reduced ileal and colonic occludin protein expression in protein-deprived rats 10,11 .…”

“…Dietary protein restriction is used from 0 to 7% of proteins and are associated with gut barrier dysfunction, only in the case of drastic dietary protein restriction 8 . Similarly, rats fed with LP diet (4% protein) for 20 days had growth retardation without effect on colonic or ileum permeability to macromolecules 10 . Brown et al study showed no impact of 3 weeks of LP diet (7%) in weaning mice on fecal calprotectin levels 9 while it increased intestinal permeability 9 .…”

“…Mice exposed to both depletions exhibit weight loss and growth faltering 9 – 12 . These models share features of undernutrition related to anthropometric measures observed in humans but their effects on gut barrier function are more debated 6 , 9 , 10 . To impact gut barrier function on murine models, depleted diets has been combined with microbial infections to reflect environmental exposures experienced by malnourished children.…”

Investigating Gut Permeability in Animal Models of Disease

“…However, tissue viability is a major concern and therefore incubation times no longer than 3 h are recommended (Clarke, 2009). The use of everted gut sacs to measure the transit of fluorescent probes has the advantage of not demanding specialized equipment, but larger amounts of tissue are required (3–4 cm 2 ) (Moyano-Porcile et al, 2015; Eyzaguirre-Velasquez et al, 2017). In the Ussing chamber, ion transport across the intestinal wall can be measured in very small segments of tissue (1 cm 2 ) but a more expensive setup is necessary.…”

“…Dietary and microbiota changes can protect the intestinal barrier function, which is the case for glutamine (Li et al, 1994), bacteria-derived lactic acid (Ren et al, 2018) and butyrate (Kelly et al, 2015). Other interventions disrupt the gut barrier, as in the case of DSS (Poritz et al, 2007), TNBS (Bregeon et al, 2016; Xu et al, 2018) or heavy metal supplementation (Zhai et al, 2016), low protein (Eyzaguirre-Velasquez et al, 2017) or high fat diet (Hamilton et al, 2015), infection (Guttman et al, 2006; Goossens et al, 2018) or CLP (Parida et al, 2015). These models can be considered to have good construct validity for organic diseases (i.e., those where morphological and/or biochemical features are altered) where barrier function is compromised.…”