Small intestinal permeability in older adults

Abstract

Abstract It is not yet clear whether intestinal mucosal permeability changes with advancing age in humans. This question is of high importance for drug and nutrition approaches for older adults. Our main objective was to answer the question if small intestinal barrier integrity deteriorates with healthy aging. We conducted a cross-sectional study including the pooled data of 215 nonsmoking healthy adults (93 female/122 male), 84 of whom were aged between 60 and 82 years. After a 12-h fast, all participants ingested 10 g of lactulose and 5 g of mannitol. Urine was collected for 5 h afterwards and analyzed for test sugars. The permeability index (PI = lactulose/mannitol) was used to assess small intestinal permeability. Low-grade inflammation defined by high-sensitivity C-reactive protein ≥1 mL/L and kidney function (estimated glomerular filtration rate) were determined in the older age group. The PI was similar in older compared to younger adults (P = 0.887). However, the urinary recovery of lactulose and mannitol was lower in the older adults and this change was neither associated with urinary volume nor glomerular filtration rate. The PI was not significantly correlated with low-grade inflammation or presence of noninsulin-dependent type 2 diabetes. However, it significantly deteriorated in the copresence of both conditions compared to low-grade inflammation alone (P = 0.043) or type 2 diabetes alone (P = 0.015). Small intestinal mucosal barrier does not deteriorate with age per se. But low-grade inflammation coupled with minor disease challenges, such as type 2 diabetes, can compromise the small intestinal barrier.

Keywords: Aging; cardiovascular risk; gut leakiness; small intestine; sugar test.

Figure 1.

Permeability parameters with advancing age. The permeability index (= % lactulose/% mannitol) and the fractional urinary recovery of lactulose and mannitol are depicted with advancing age along with regression lines. Both lactulose and mannitol but not the permeability index trended to decrease with increasing age. Mildly impaired kidney function (glomerular filtration rate ≤ 60 mL/min) did not consistently lead to low recovery of test sugars as depicted by the black dots.

Figure 2.

Bivariate correlation of sugar probes with glomerular filtration rate. No association was observed between the glomerular filtration rate and the fractional recovery of mannitol (ρ = −0.062, P =0.627) or lactulose (ρ = −0.102, P =0.426). The permeability index (ρ = −0.030, P =0.818) did also not correlate with the glomerular filtration rate in the bivariate Spearman rank‐order correlation. GFR: glomerular filtration rate, MDRD. Formula according to the Modification of Diet in Renal Disease Study (Levey et al. 1999).

Figure 3.

Small intestinal permeability in older people with and without low‐grade inflammation. Panel A: Proportion of participants above the reference range for permeability index (perm, >0.030) or lactulose recovery (lact > 0.44%) depending on the absence or presence of low‐grade inflammation. Panel B: ND: no diabetes, D = diabetes. Intestinal permeability is significantly increased in the copresence of type 2 diabetes with low‐grade inflammation (n =11) compared to low‐grade inflammation (n =35) or type 2 diabetes alone (n =7), or in the absence of both (n =28).