In a recent study published in Nutrition, researchers investigated whether a high-refined carbohydrate (HC) diet and associated metabolic alterations could cause small intestinal dysregulation.
Excessive nutrient intake is a leading cause of adiposity or obesity, marked by the expansion of adipose tissues, metabolic changes, and immunological dysfunctions. High-fat diets reportedly result in obesity with altered gut health; however, similar effects have not been extensively investigated in mild-obesity murine models fed HC diets.
The intestinal barrier comprises epithelial cells, tight junctions, mucus, immunological cells, and the microbiome. The gut is vulnerable to dysfunction caused by excessive dietary intake via increased intestinal permeability and the translocation of intestinal bacteria-derived lipopolysaccharides (LPS) within and beyond the intestines to various organs.
About the study
In the present study, researchers evaluated the effects of HC diets on gut integrity using a murine model.
Ten eight-week-old BALB/c murine animals were randomly allocated to receive either a diet rich in high-refined carbohydrates (the intervention group) or a chow diet (control animals) for eight weeks. The high-refined carbohydrate diet comprised 10.0% refined sugar, 45.0% condensed-type milk, and 45.0% chow, consisting of 30% refined sugar (mainly sucrose).
Body weight and food consumption were measured once and twice weekly, respectively. The animals were sacrificed, and samples of their serum, mesenteric lymphatic nodes, small intestines, and adipose tissues from visceral regions were obtained for further evaluation. The distal portions of the ileum and jejunum were utilized to extract messenger ribonucleic acid (mRNA) and determine myeloperoxidase (MPO) levels. Adiposity index scores were calculated as the proportion of the mesenteric, retroperitoneal, and epididymal adipose tissues by weight to body mass.
Gut permeability and bacterial translocation (BT) assays were assessed. The tissues sampled were inserted into tubes to determine 99m technetium (Tc)-Escherichia coli radioactivity. Oral glucose tolerance tests (OGTTs) were performed. Intestinal (jejunum and ileum) and epididymal adipose tissue samples underwent histopathological examination. MPO levels were monitored using colorimetric assays to measure neutrophil infiltration in the small intestines indirectly.
Further, serological fasting glucose, total cholesterol (TC), triacylglyceride (TG), and leptin levels were also measured. Further, RNA expression of tight junctions in the ileum and jejunum and inflammatory mediators was assessed using reverse transcription polymerase chain reaction (RT-PCR). In addition, the levels of claudin 4 (Cldn4), zonula occludens-1 (Zo1), interferon-gamma (IFN-γ), and tumor necrosis factor-alpha (TNF-α) genes were assessed, and flow cytometry (FC) was performed to analyze mesenteric lymph node samples.
Energy intake and body weight did not significantly differ among the groups; nevertheless, HC-fed mice exhibited mild obesity characterized by increased visceral adiposity in the epididymal, retroperitoneal, and mesenteric tissues in relation to metabolic changes such as increased TC, TG, leptin, and fasting blood glucose levels with reduced glucose tolerance in the HC group compared to controls.
MPO and IFN-γ levels in the ileum were elevated within the small intestines of HC-fed mice, indicating local inflammation. However, the length of intestinal villi, tight junction (Cldn4 and Zo1) expression, TNF-α levels, and intraepithelial lymphocytic proportion in the jejunum and ileum were not significantly different among the two groups. In addition, there were no differences in permeability or BT in the intestines, blood, spleen, liver, lungs, mesenteric adipose tissue (MAT), or mesenteric lymph nodes of HC-fed animals.
Further, no significant changes were observed in the population of neutrophils, macrophages, natural killer (NK) lymphocytes, cytotoxic [cluster of differentiation 8+ (CD8+)] T lymphocytes, T helper (Th)-1, 2, and 17 lymphocytes, regulatory T (Treg) cells, and TNF+ cells in the mesenteric lymph nodes. Only the eosinophilic count was significantly lowered in the HC group.
Overall, the study findings showed that HC diets (comprising mainly sucrose) could induce metabolic changes resulting in mild obesity (increased adiposity with no excessive weight gain) and metabolic dysfunction without significant alterations in gut morphology, integrity, or immune function.
The small intestines showed elevated IFN-γ expression and neutrophil counts without any inflammatory signs, as indicated by the unaltered inflammatory cell counts within the mesenteric lymphatic nodes.
An increase in adiposity could predispose to metabolic changes since adipose tissues are endocrinal organs involved in metabolic control and energy metabolism. A sugar-dense diet can promote metabolic disorders with insulin signaling impairments.
The lowered eosinophil count in the gut of HC-fed animals may have led to mucosal immunoglobulin (Ig)A dysregulation and subsequent changes in innate immunological responses; however, the effects of lowered eosinophilic counts in the mesenteric lymph nodes require further research.