Upregulation of colonic luminal polyamines produced by intestinal microbiota delays senescence in mice

Abstract

Prevention of quality of life (QOL) deterioration is associated with the inhibition of geriatric diseases and the regulation of brain function. However, no substance is known that prevents the aging of both body and brain. It is known that polyamine concentrations in somatic tissues (including the brain) decrease with increasing age, and polyamine-rich foods enhance longevity in yeast, worms, flies, and mice, and protect flies from age-induced memory impairment. A main source of exogenous polyamines is the intestinal lumen, where they are produced by intestinal bacteria. We found that arginine intake increased the concentration of putrescine in the colon and increased levels of spermidine and spermine in the blood. Mice orally administered with arginine in combination with the probiotic bifidobacteria LKM512 long-term showed suppressed inflammation, improved longevity, and protection from age-induced memory impairment. This study shows that intake of arginine and LKM512 may prevent aging-dependent declines in QOL via the upregulation of polyamines.

Plasma Biomarkers of Poor Muscle Quality in Older Men and Women from the Baltimore Longitudinal Study of Aging

“…Consequently, the activity of ODC was lower in participants with low muscle quality compared to controls, even though the difference between cases and controls did not reach statistical significance. This is consistent with previous studies demonstrating that higher levels of polyamines correlated with reduced inflammation and greater longevity (43,44). No other association between any of the amino acids and biogenic amines was found.…”

Clostridium difficile heterogeneously impacts intestinal community architecture but drives stable metabolome responses

“…This finding again suggests that different diseases (for example, ulcerative colitis, IBS and CDAD) may be associated with not only distinct gut metabolic profiles but also specific measurable metabolic changes in the gut microbiota. The fact that N-acetylputrescine is the result of the metabolic activity of gut microbiota (Murray et al, 1993;Le Gall et al, 2011;Kibe et al, 2014) and that the microbial intracellular concentration of this chemical may be a good estimator of its corresponding concentration in faecal fluids through the action of specific transporters (Kibe et al, 2014) may agree with this hypothesis. In the case of choline, such direct evidence could not be established, as choline is not a direct product of microbial activity.…”

“…Such complex mixtures are commonly investigated in metabolomics studies (Saric et al, 2008;Le Gall et al, 2011;Marcobal et al, 2013;Weir et al, 2013;Walker et al, 2014). Metabolites from intestinal bacteria (rather than dietary or host metabolites) are required to maintain and repair the large intestine and to support human health (Kibe et al, 2014). Therefore, any metabolites that are directly produced or absorbed (from environmental inputs or the host) by gut microbes, and not those present in complex whole faecal fluids, may be relevant and useful indicators not only for investigating gut physiology but also for determining the role of such metabolites in pathophysiologies and human health.…”

“…Both chemicals were found at significantly lower levels in patients with carriage of toxin − C. difficile than in non-colonised control patients (6.1-fold for choline and 7.4-fold for acetylputrescine; P-value ≤ 0.0095), which suggests that the negative effect of C. difficile on the adsorption and/or metabolism of both metabolites is accentuated when toxins are produced by the bacteria. Note that deficiencies in the microbial metabolism of both compounds have been associated with the development of human diseases, including a predisposition to impaired glucose homeostasis, non-alcoholic fatty liver disease (Dumas et al, 2006), inflammation and intestinal mucosa stability (Kibe et al, 2014), immune system and intestinal maturation (Gómez-Gallego et al, 2012). Recently, a high level of N-acetylputrescine was found in the faecal extracts of patients with ulcerative colitis and IBS (Le Gall Figure 3 Box plot of the metabolite abundance levels in the three groups of patients examined.…”

Spermidine: a physiological autophagy inducer acting as an anti-aging vitamin in humans?

“…Therefore, blood levels of spermidine and spermine can be upregulated through oral administration of the polyamine-producing probiotic Bifidobacterium LKM512, resulting in suppressed inflammation and improved longevity in old mice [35]. Interestingly, these effects can be enhanced, if combined with additional supplementation of arginine, a polyamine precursor [36]. Thus, arginine may be considered as a prebiotic for stimulating intestinal spermidine synthesis.…”