Regular fecal microbiota transplantation to Senescence Accelerated Mouse-Prone 8 (SAMP8) mice delayed the aging of locomotor and exploration ability by rejuvenating the gut microbiota

Abstract

Recent evidence points out the role of the gut microbiota in the aging process. However, the specific changes and relevant interventions remain unclear. In this study, Senescence Accelerated Mouse-Prone 8 (SAMP8) mice were divided into four groups; young-FMT-group transplanted fecal microbiota from young donors (2–3°months old) and old-FMT-group transplanted from old donors (10–11°months old); additionally, other two groups either adult mice injected with saline solution or untreated mice served as the saline and blank control groups, respectively. All mice were intervened from their 7-months-old until 13-months-old. The open field test at 9 and 11°months of age showed that the mice transplanted with gut microbiota from young donors had significantly better locomotor and exploration ability than those of transplanted with old-donors gut microbiota and those of saline control while was comparable with the blank control. 16S rRNA gene sequencing showed that the gut microbiome of recipient mice of young donors was altered at 11°months of age, whereas the alternation of the gut microbiome of old-donor recipient mice was at 9°months. For comparison, the recipient mice in the blank and saline control groups exhibited changes in the gut microbiome at 10°months of age. The hallmark of aging-related gut microbiome change was an increase in the relative abundance of Akkermansia, which was significantly higher in the recipients transplanted with feces from older donors than younger donors at 9°months of age. This study shows that fecal microbiota transplantation from younger donors can delay aging-related declines in locomotor and exploration ability in mice by changing the gut microbiome.

Bazi Bushen capsule improves the deterioration of the intestinal barrier function by inhibiting NLRP3 inflammasome-mediated pyroptosis through microbiota-gut-brain axis

“…SAMP8 is a common model for studying accelerated aging ( Morley et al, 2012 ; Cheng et al, 2014 ). In line with previous studies, we found that the SAMP8 mice had significantly fewer neurons, as shown by Nissl staining ( Figures 1A , B ) ( Yang X. et al, 2020 ; Yang H. H. et al, 2020 ; Zhang N. et al, 2022 ; Zhang Y. et al, 2022 ). This result, together with the two-photon analysis, indicated that the SAMP8 mice show significant neuroinflammation and BBB disruption ( Figure 1C ).…”

“…SAMP8 mice are a common model of accelerated aging that have cognitive and intestinal problems as they age ( Yamamoto et al, 2015 ; Ben Othman et al, 2020 ; Chen et al, 2021 ). The gut-brain axis, which is the bidirectional communication between the gut and the brain ( Xie et al, 2020 ; Chen et al, 2021 ; Zhang N. et al, 2022 ; Zhang Y. et al, 2022 ), may be involved in these problems ( Xie et al, 2020 ; Yang X. et al, 2020 ; Yang H. H. et al, 2020 ; Yang D. et al, 2023 ; Yang X. Q. et al, 2023 ). Many studies have shown that gut dysbiosis, which is the imbalance of the gut microbiota, is associated with not only gastrointestinal diseases, but also the physiology and inflammation of the central nervous system ( Ma et al, 2019 ; Rutsch et al, 2020 ; Morais et al, 2021 ).…”

“…Considering that gut dysbiosis causes central nervous inflammation through the gut-brain axis, we prioritized the detection of gut microbiota changes in the SAMP8 mice, finding a decrease in the ratio of Firmicutes to Bacteroides (F/B) with aging ( Vaiserman et al, 2017 ). Compelling evidence shows that the ratio imbalance of F/B may activate inflammasome in the intestine by increasing the level of LPS, a bacterial toxin ( Yu et al, 2017 ; Paik et al, 2021 ; Zhang N. et al, 2022 ; Zhang Y. et al, 2022 ). Furthermore, the activated inflammasome induces pyroptosis, a type of cell death that releases inflammatory cytokines, and causes intestinal injuries ( Kovacs and Miao, 2017 ).…”

Microbiome Taxonomic and Functional Differences in C3H/HeJ Mice Fed a Long-Term High-Fat Diet with Beef Protein ± Ammonium Hydroxide Supplementation

“…Still, the rate of Akkermansia in older mice is typically not more than ~10% on healthy diets [ 78 ]. However, at least one study showed that under fecal transplantation conditions, Akkermansia can dramatically rise with age [ 79 ] and reduce senescence. Perhaps most relevant to our findings is a study showing Akkermansia levels in mice fed beef protein diets averaging 12.68%, but with ranges of up to 52% in some individuals, suggesting a potentially significant effect of protein type [ 80 ].…”