Abstract
In the intestine, a single layer of epithelial cells sealed together at their apical surfaces by tight junctions helps to prevent the luminal commensal and pathogenic micro-organisms and their toxins from entering host tissues. The intestinal epithelium also helps to maintain homoeostasis in the mucosal immune system by expressing anti-inflammatory cytokines in the steady state and inflammatory cytokines in response to pathogens. Although the function of the mucosal immune system is impaired in elderly humans, the molecular mechanisms which cause this dramatic functional decline are poorly understood. Our current understanding of the effects of aging on the physical and immunological properties of the intestinal epithelial barrier is also very limited. In this issue of Clinical Science, Man et al. provide further insight into the effects of aging on small intestinal barrier function in humans and the influence that gut luminal micro-organisms may have on it. Using human terminal ileal biopsy tissues they show that intestinal permeability to solutes, but not macromolecules, was significantly increased in the intestines of elderly humans. This was accompanied by elevated expression of the pro-inflammatory cytokine interleukin (IL)-6 which appeared to modulate claudin-2 expression and solute permeability in the epithelium. Conversely, IL-8 synthesis in response to flagellin stimulation was reduced in intestines of the elderly subjects, but was not associated with effects on Toll-like receptor 5 (TLR5) expression. These data provide an important advance in our understanding on the effects of aging on intestinal permeability and innate mucosal immune responsiveness in elderly humans.
Highlights
The mammalian intestine contains a huge burden of commensal micro-organisms which in the lumen of the human colon are estimated to be as high as 3 × 1011/g of contents
These commensal micro-organisms are prevented from entering host tissues by a single layer of epithelial cells sealed together at their apical surfaces by tight junctions
The intestinal epithelium plays a significant role in homoeostasis of the mucosal immune system by the expression of anti-inflammatory cytokines in the steady state and inflammatory cytokines in response to certain pathogenic stimuli
Summary
The mammalian intestine contains a huge burden of commensal micro-organisms which in the lumen of the human colon are estimated to be as high as 3 × 1011/g of contents. The intestinal epithelium plays a significant role in homoeostasis of the mucosal immune system by the expression of anti-inflammatory cytokines in the steady state and inflammatory cytokines in response to certain pathogenic stimuli. In this issue of Clinical Science, Man et al [4] provide further insight into the effects of aging on the small intestinal barrier function in humans and the influence that gut luminal micro-organisms may have on it.
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