Abstract

Although it is clear that probiotics improve intestinal barrier function, little is known about the effects of probiotics on the aging intestine. We investigated effects of 10-week bacterial supplementation of Lactobacillus plantarum WCFS1, Lactobacillus casei BL23, or Bifidobacterium breve DSM20213 on gut barrier and immunity in 16-week-old accelerated aging Ercc1−/Δ7 mice, which have a median lifespan of ~20 weeks, and their wild-type littermates. The colonic barrier in Ercc1−/Δ7 mice was characterized by a thin (< 10 μm) mucus layer. L. plantarum prevented this decline in mucus integrity in Ercc1−/Δ7 mice, whereas B. breve exacerbated it. Bacterial supplementations affected the expression of immune-related genes, including Toll-like receptor 4. Regulatory T cell frequencies were increased in the mesenteric lymph nodes of L. plantarum- and L. casei-treated Ercc1−/Δ7 mice. L. plantarum- and L. casei-treated Ercc1−/Δ7 mice showed increased specific antibody production in a T cell-dependent immune response in vivo. By contrast, the effects of bacterial supplementation on wild-type control mice were negligible. Thus, supplementation with L. plantarum – but not with L. casei and B. breve – prevented the decline in the mucus barrier in Ercc1−/Δ7 mice. Our data indicate that age is an important factor influencing beneficial or detrimental effects of candidate probiotics. These findings also highlight the need for caution in translating beneficial effects of probiotics observed in young animals or humans to the elderly.

Highlights

  • Aging is accompanied by multiple age-related diseases [1], posing a major burden to public health care [2]

  • To determine the effects of the three selected bacterial strains in the young intestine, we analyzed proximal colon tissues of WT mice that were treated with L. plantarum WCFS1, L. casei BL23, or B. breve DSM20213 for 10 weeks

  • The effects of bacterial supplementations on the intestinal barrier and cellular parameters of immunity were studied in fast aging

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Summary

Introduction

Aging is accompanied by multiple age-related diseases [1], posing a major burden to public health care [2]. A decline in the regenerative potential of tissues due to stem cell exhaustion occurs [3]. Turnover in epithelial cells is rapid, and mounting evidence indicates that intestinal stem cells are compromised with aging [4]. A crucial component of the intestinal barrier is mucus secreted by goblet cells [5]. The Muc glycoprotein regulates immunity by inducing tolerogenic signals in mucosal dendritic cells [6] and is important in host–microbe interactions [7]. Changes in mucus quantity and integrity influence immunity [6, 8]

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