Abstract
BackgroundChronic low-grade inflammation is recognized as an important factor contributing to senescence and age-related diseases. In mammals, levels of polyamines (PAs) decrease during the ageing process; PAs are known to decrease systemic inflammation by inhibiting inflammatory cytokine synthesis in macrophages. Reductions in intestinal luminal PAs levels have been associated with intestinal barrier dysfunction. The probiotic strain Bifidobacterium animalis subsp. lactis LKM512 is known to increase intestinal luminal PA concentrations.Methodology/Principal FindingsWe supplemented the diet of 10-month-old Crj:CD-1 female mice with LKM512 for 11 months, while the controls received no supplementation. Survival rates were compared using Kaplan–Meier survival curves. LKM512-treated mice survived significantly longer than controls (P<0.001); moreover, skin ulcers and tumors were more common in the control mice. We then analyzed inflammatory and intestinal conditions by measuring several markers using HPLC, ELISA, reverse transcription-quantitative PCR, and histological slices. LKM512 mice showed altered 16S rRNA gene expression of several predominant intestinal bacterial groups. The fecal concentrations of PAs, but not of short-chain fatty acids, were significantly higher in LKM512-treated mice (P<0.05). Colonic mucosal function was also better in LKM512 mice, with increased mucus secretion and better maintenance of tight junctions. Changes in gene expression levels were evaluated using the NimbleGen mouse DNA microarray. LKM512 administration also downregulated the expression of ageing-associated and inflammation-associated genes and gene expression levels in 21-month-old LKM512-treated mice resembled those in 10-month-old untreated (younger) mice.Conclusion/SignificanceOur study demonstrated increased longevity in mice following probiotic treatment with LKM512, possibly due to the suppression of chronic low-grade inflammation in the colon induced by higher PA levels. This indicates that ingestion of specific probiotics may be an easy approach for improving intestinal health and increasing lifespan. Further studies are required to clarify its effectiveness in humans.
Highlights
More than 100 years have passed since Metchnikoff introduced oral bacteriotherapy to prevent intestinal putrefaction and ageing [1]
We have shown that the lifespan of mammals can be increased by probiotic treatment; we have proposed that the mechanism by which this longevity was achieved is the suppression of chronic low-grade inflammation resulting from improvements in the intestinal luminal environment and the maintenance of colon tissue
It is generally believed that intestinal bacterial components are recognized by Toll-like receptors under normal steady-state conditions, and this interaction plays a crucial role in host immunity [33]
Summary
More than 100 years have passed since Metchnikoff introduced oral bacteriotherapy to prevent intestinal putrefaction and ageing [1]. Many mechanisms have been shown to contribute to the process of senescence, such as telomere shortening in replicative cells, cumulative damage to DNA leading to genomic instability, oxidative damage to critical molecules by reactive oxygen species (ROS), and so on [2]. These mechanisms comprise chronic low-grade inflammation, a major risk factor for ageing and agerelated diseases, such as Alzheimer’s disease and type II diabetes [3,4]. Chronic low-grade inflammation is recognized as an important factor contributing to senescence and agerelated diseases. The probiotic strain Bifidobacterium animalis subsp. lactis LKM512 is known to increase intestinal luminal PA concentrations
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