Increased Colonic Permeability and Lifestyles as Contributing Factors to Obesity and Liver Steatosis

Domenica Maria Di Palo, Gabriella Garruti, Agostino Di Ciaula, Emilio Molina-Molina, Harshitha Shanmugam, Maria De Angelis, Piero Portincasa, Domenica Maria Di Palo, Gabriella Garruti, Agostino Di Ciaula, Emilio Molina-Molina, Harshitha Shanmugam, Maria De Angelis, Piero Portincasa

Abstract

Intestinal permeability (IP) is essential in maintaining gut-metabolic functions in health. An unequivocal evaluation of IP, as marker of intestinal barrier integrity, however, is missing in health and in several diseases. We aimed to assess IP in the whole gastrointestinal tract according to body mass index (BMI) and liver steatosis. In 120 patients (61F:59M; mean age 45 ± SEM 1.2 years, range: 18-75), IP was distinctively studied by urine recovery of orally administered sucrose (SO, stomach), lactulose/mannitol ratio (LA/MA, small intestine), and sucralose (SA, colon). By triple quadrupole mass-spectrometry and high-performance liquid chromatography, we measured urinary recovery of saccharide probes. Subjects were stratified according to BMI as normal weight, overweight, and obesity, and answered questionnaires regarding dietary habits and adherence to the Mediterranean Diet. Liver steatosis was assessed by ultrasonography. IP at every gastrointestinal tract was similar in both sexes and decreased with age. Stomach and small intestinal permeability did not differ according to BMI. Colonic permeability increased with BMI, waist, neck, and hip circumferences and was significantly higher in obese than in lean subjects. As determined by logistic regression, the odds ratio (OR) of BMI increment was significantly higher in subjects in the highest tertile of sucralose excretion, also after adjusting for age and consumption of junk food. The presence of liver steatosis was associated with increased colonic permeability. Patients with lower score of adherence to Mediterranean diet had a higher score of 'junk food'. Intestinal permeability tended to increase in subjects with a lower adherence to Mediterranean diet. In conclusion, colonic (but not stomach and small intestinal) permeability seems to be linked to obesity and liver steatosis independently from dietary habits, age, and physical activity. The exact role of these last factors, however, requires specific studies focusing on intestinal permeability. Results should pave the way to both primary prevention measures and new therapeutic strategies in metabolic and liver diseases.

Keywords: body mass index; intestinal permeability; obesity; sugars; urinary recovery.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Chemical and 3-D formulas of the sugar probes used for the study of intestinal permeability at different tracts: Lactulose (A), mannitol (B), sucrose (C) and sucralose (D).
Figure 1
Figure 1
Chemical and 3-D formulas of the sugar probes used for the study of intestinal permeability at different tracts: Lactulose (A), mannitol (B), sucrose (C) and sucralose (D).
Figure 2
Figure 2
Correlation between body mass index (BMI) and waist circumference according to: International Diabetes Federation (IDF) (A), Adult Treatment Panel III (ATPIII) (B), neck circumference (C), and hip circumference (D).
Figure 3
Figure 3
Intestinal permeability by tract and age groups: Stomach permeability (A), small intestinal permeability (B), colonic permeability (C), and correlation between small intestinal permeability and age (D).
Figure 4
Figure 4
Correlation between sucralose recovery and BMI in all subjects (A), females (B), and males (C).
Figure 5
Figure 5
(A) shows odds ratios and 95 % confidence intervals of BMI variations (kg/m2) in subjects grouped according to tertiles of sucralose urinary excretion. Values were calculated by logistic regression models, with BMI as the dependent variable and tertiles of sucralose recovery as the independent variable, after adjusting for covariates (age, junk score). (B) indicates average BMI (kg/m2) in subjects grouped according to tertiles of sucralose recovery. Data are mean ± SE. *p = 0.02 vs. reference group and subjects in the second tertile (ANOVA followed by Fisher’s LSD multiple comparison test).
Figure 6
Figure 6
Correlation between sucralose recovery and waist, neck, and hip circumferences in: All subjects (A) and in females (B).
Figure 7
Figure 7
Differences in ‘Junk Score’ (A) and small intestinal permeability (B) according to adherence to Mediterranean Diet.

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Source: PubMed

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