Differential in vivo and in vitro intestinal permeability to lactulose and mannitol in animals and humans: A hypothesis

Bijlsma, P.B.; Peeters, Roger A.; Groot, J.A.; Dekker, P.R.; Taminiau, J. A. J. M.; Meer, Roelof van der

doi:10.1016/0016-5085(95)90440-9

Cited by 123 publications

(78 citation statements)

References 41 publications

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“…The decrease in absorption of paracellular probes with increasing probe size that we observed in rodents is consistent with a sizesieving effect of the tight junction channels, a phenomenon that has been documented in a variety of species (Delahunty and Hollander, 1987;Bijlsma et al, 1995;Chediack et al, 2003;Lavin et al, 2007;Anderson and Van Itallie, 2009;Fasulo et al, 2013a;Fasulo et al, 2013b;Price et al, 2013a). This size-sieving effect seems to diminish at smaller molecule sizes, such that absorption of arabinose and creatinine was similar in M. lucifugus.…”

Section: Whole Animal Paracellular Nutrient Absorptionsupporting

confidence: 89%

Paracellular nutrient absorption is higher in bats than rodents: integrating from intact animals to the molecular level

Price

Rott

Caviedes‐Vidal

et al. 2014

Journal of Experimental Biology

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Flying vertebrates have been hypothesized to rely heavily on paracellular absorption of nutrients to compensate for having smaller intestines than non-flyers. We tested this hypothesis in an insectivorous bat (Myotis lucifugus) and two insect-eating rodents (Onychomys leucogaster and Peromyscus leucopus). In intact animals, the fractional absorption of orally dosed L-arabinose (M r 150) was 82% in M. lucifugus, which was more than twice that of the rodents. Absorption of creatinine (M r 113) was greater than 50% for all species and did not differ between M. lucifugus and the rodents. We also conducted intestinal luminal perfusions on anesthetized animals. Absorption of L-arabinose per nominal surface area in M. lucifugus was nearly double that of the rodents, while absorption of creatinine was not different among species. Using an everted sleeve preparation, we demonstrated that high concentrations of L-arabinose and creatinine did not inhibit their own uptake, validating their use as passive, paracellular probes. Histological measurements indicated that M. lucifugus has more cells, and presumably more tight junctions, per nominal surface area than P. leucopus. This seems unlikely to explain entirely the higher absorption of L-arabinose in M. lucifugus during perfusions, because L-arabinose absorption normalized to the number of enterocytes was still double that of P. leucopus. As an alternative, we investigated tight junction gene expression. M. lucifugus had higher expression of claudin-1 and claudin-15, and lower expression of claudin-2 relative to P. leucopus. Expression of claudin-7 and occludin did not differ among species. Taken together, our results support the hypothesis that bats have evolved higher paracellular nutrient absorption than non-flying animals, and that this phenomenon might be driven by both histological characteristics and differences in tight junction gene expression.

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Section: Whole Animal Paracellular Nutrient Absorptionsupporting

confidence: 89%

Paracellular nutrient absorption is higher in bats than rodents: integrating from intact animals to the molecular level

Price

Rott

Caviedes‐Vidal

et al. 2014

Journal of Experimental Biology

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“…Reports on intestinal permeability measurements (11,12) have considered the lactulose/mannitol ratio a primary parameter for the normal functioning of intestinal epithelial cells. We have previously evaluated this parameter in human immunodeficiency virus infection (1).…”

Section: Discussionmentioning

confidence: 99%

Measurement of intestinal permeability using mannitol and lactulose in children with diarrheal diseases

Barboza

Silva

Guerrant

et al. 1999

Braz J Med Biol Res

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The excretion ratio of lactulose/mannitol in urine has been used to assess the extension of malabsorption and impairment of intestinal permeability. The recovery of lactulose and mannitol in urine was employed to evaluate intestinal permeability in children with and without diarrhea. Lactulose and mannitol probes were measured using high-performance liquid chromatography with pulsed amperometric detection (HPLC-PAD). Two groups of solutions containing 60 µM sugars were prepared. Group I consisted of glucosamine, mannitol, melibiose and lactulose, and group II of inositol, sorbitol, glucose and lactose. In the study of intra-experiment variation, a sample of 50 µl from each group was submitted to 4 successive determinations. The recovered amounts and retention times of each sugar showed a variation <2 and 1%, respectively. The estimated recovery was >97%. In the study of inter-experiment variation, we prepared 4 independent samples from groups I and II at the following concentrations: 1.0, 0.3, 0.1, 0.03 and 0.01 mM. The amounts of the sugars recovered varied by <10%, whereas the retention times showed an average variation <1%. The linear correlation coefficients were >99%. Retention (k'), selectivity (=) and efficiency (N) were used to assess the chromatographic conditions. All three parameters were in the normal range. Children with diarrhea presented a greater lactulose/mannitol ratio compared to children without diarrhea. Correspondence

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“…In vivo recovery of mannitol is about 50 times that of lactulose, which suggests transcellular permeation. 12,18 Reduced mannitol excretion indicates villous atrophy. [19][20][21][22][23] In alcoholic liver disease, villous atrophy is frequently observed; reduction in villous height in relation to crypt depth and lower mucosal surface have been detected by light microscopy in alcoholics, even in the absence of cirrhosis.…”

Section: Discussionmentioning

confidence: 99%

Increased intestinal permeability in malnourished patients with liver cirrhosis

Norman

Pirlich

et al. 2012

Eur J Clin Nutr

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BACKGROUND/OBJECTIVE: Malnutrition is a prominent feature in liver cirrhosis, with deleterious impact on clinical outcome. The objective of this study is to investigate whether malnutrition is associated with increased gastrointestinal permeability in liver cirrhosis reflected by altered urinary excretion of non-metabolizable sugar probes. SUBJECTS/METHODS: Patients with advanced liver cirrhosis (Child Pugh Score B or C) were recruited. Nutritional status was determined according to the Subjective Global Assessment. Intestinal permeability was assessed by measuring the urinary excretion of orally administered, non-metabolized sugar probe molecules. The lactulose/mannitol ratio served as marker for intestinal permeability and reflects non-carrier-mediated transcellular and paracellular transport of the small intestine during the first 5 h. Sucrose recovery in urine within the first 5 h reflects gastroduodenal permeability; sucralose recovery in urine 5-26 h after consumption reflects colonic permeability. RESULTS: Sixty-four patients (56.7±10.8 years; 33% female) were included in the study. Twenty-one patients were considered well nourished according to the Subjective Global Assessment, 23 moderately nourished and 20 patients severely malnourished; 74% had alcoholic liver disease and 67% had cirrhosis stage Child C. Gastroduodenal and colonic permeability was significantly increased in patients with liver cirrhosis compared with 63 healthy controls (0.23±0.22 and 1.37±1.42% vs 0.14±0.10 and 0.41±0.72% in controls), but not different between well and malnourished subjects. Small intestinal permeability (lactulose/ mannitol ratio) was increased in all patients (0.069 ± 0.055%) and further increased in malnourished patients (0.048 ± 0.031% vs 0.084 ± 0.061%, P ¼ 0.004) due to decreased mannitol recovery only. CONCLUSIONS: Gastric, small intestinal and even colonic permeability was altogether increased in liver cirrhosis, and malnutrition was associated with further increased small intestinal permeability indicative of villous atrophy.

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Differential in vivo and in vitro intestinal permeability to lactulose and mannitol in animals and humans: A hypothesis

Cited by 123 publications

References 41 publications

Paracellular nutrient absorption is higher in bats than rodents: integrating from intact animals to the molecular level

Paracellular nutrient absorption is higher in bats than rodents: integrating from intact animals to the molecular level

Measurement of intestinal permeability using mannitol and lactulose in children with diarrheal diseases

Increased intestinal permeability in malnourished patients with liver cirrhosis

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