In age-accelerated SAMP8 mouse model, GKM3 groups showed significantly increased latency in the passive avoidance test and time of successful avoidance in the active avoidance test. The TBARS and 8-OHdG from the aged mice brains also showed a significant reduction in the groups treated with GKM3. In addition, lower accumulation of the amyloid-β protein was found in SAMP8 mice brains with the supplement of GKM3. These results indicated that L. plantarum GKM3 delayed the process of aging, alleviated age-related cognitive impairment, and reduced oxidative stress.
1. Introduction
It has been an issue that population-suffered cognitive impairment has become bigger following the growth of the amount of older individuals in the last decade
[1]. According to the report from the World Health Organization (WHO), the number of people with cognitive decline, which was more than 46.8 million in 2015, will reach over 74.7 million in 2030, which is almost increased by half within fifteen years
[2]. Aging, recognized as a strong correlation with cognitive impairment, is generally thought to be associated with oxidative stress, which is involved in the accumulation of free radicals and promoted many physiological dysfunctions especially in the brain, an oxygen-sensitive organ, leading to degenerative symptoms such as memory loss and decline of learning ability
[3][4][5][3,4,5].
As aging is inevitable and its relative negative symptoms are complicated, people pursue treatments for anti-aging, ranging from diet therapies to more than drug treatments
[6][7][6,7]. For example, ginseng (
Panax quinquefolius) root extract demonstrated improved cognitive function and was marked as a favorite by the Koreans
[8].
Ginkgo biloba extract, another example, was loved by the Japanese for its functions in cognitive enhancing and oxidation-reduction
[9]. Although many reports have suggested that the plant-based diets provide antioxidant effects and retard the aging process, there are more interesting focuses on the gut microbiota or even on a group of specific bacteria in the gut that could metabolize these nutraceuticals and provide positive multi-modulation effects to the host, including longevity
[10][11][12][13][14][10,11,12,13,14]. Gut bacteria could produce short-chain fatty acids (SCFAs) such as acetate, propionate, or butyrate from one’s diet
[15]. Children who consumed plant-based enteral nutrition showed higher SCFAs than the normal kids in their stool samples
[16]. These SCFAs can play an important role in the human gastrointestinal epithelium
[17]. Acetate can cross the blood-brain barrier, inducing hypothalamic neuronal activation
[18]. In addition, butyrate has been studied regarding the effect of suppressing colonic inflammation in the human gut
[19]. Therefore, it matters what kind of microbiota or specific bacteria is in the human gut, especially in terms of influencing body health and longevity
[20][21][20,21].
The intestinal microbiota also can impact the gut-brain axis and delay the process of aging, thereby preventing the progress of age-related diseases such as amnesia, dementia, or even Alzheimer’s disease
[22][23][22,23]. The neurotransmitter gamma-aminobutyric acid (GABA), for example, could be produced by certain bacteria strains that have been reported with the proliferation of epithelial stem cells in the gut and the improvement of depressive-like behavior in mice
[24][25][24,25]. With current supportive data, the addition of probiotics as a prevention method has been a trend for these age-related neurological disorders
[26][27][26,27].
Lactobacillus is the most common probiotic that showed a high possibility of developing functional food as it has existed in human food for a long time
[28]. However, individual bacterial species have unique bioactivities, from strains to strains, that require experimental confirmation. In our previous studies, we isolated the probiotic strain
Lactobacillus plantarum GKM3 from pickled leaf (
Brassica juncea), also known as the longevity vegetable in Taiwanese Hakka society, and conducted functional studies on boosting the gastrointestinal tract and immunity in vivo
[29][30][31][29,30,31]. Therefore, we expected the likelihood of
L. plantarum GKM3 alleviating the process of aging and age-related cognitive impairment.
2. Development and Findings
There were no significant difference in the body weight or food intake between the control group and the probiotic groups (
Table 1). This indicates that the probiotic GKM3 is safe and non-toxic to the mammal. Under the same metabolic parameter and energy consumption, the effects of anti-aging in GKM3-fed SAMP8 can be discussed in the following section.
Table 1. Body weight, food intake, and water consumption.
Sex |
Group |
Body Weight (g) |
Food Intake (g/day) |
Water Consumption (mL/day) |
Initial (Week 0) |
Final (Week 14th) |
Gain |
Male |
Control |
28.37 ± 1.03 a |
32.06 ± 1.05 b |
3.69 ± 0.47 c |
4.79 ± 0.06 d |
6.67 ± 0.10 e |
GKM3-L |
28.81 ± 0.78 a |
31.14 ± 1.01 b |
2.33 ± 0.36 c |
4.74 ± 0.07 d |
6.65 ± 0.16 e |
GKM3-H |
28.58 ± 0.76 a |
32.12 ± 1.03 b |
3.55 ± 0.57 c |
4.71 ± 0.08 d |
6.53 ± 0.15 e |
Female |
Control |
27.14 ± 0.95 f |
27.61 ± 0.87 g |
0.47 ± 0.61 h |
4.09 ± 0.04 i |
4.64 ± 0.14 j |
GKM3-L |
27.01 ± 0.73 f |
28.05 ± 0.85 g |
1.49 ± 0.70 h |
3.98 ± 0.11 i |
4.60 ± 0.06 j |
GKM3-H |
26.63 ± 0.39 f |
28.51 ± 0.84 g |
1.88 ± 1.02 h |
4.10 ± 0.14 i |
4.69 ± 0.07 j |