Gut Microbiota Predicts Healthy Late-Life Aging in Male Mice.
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ABSTRACT:
SUBMITTER: Ke S
PROVIDER: S-EPMC8467910 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The constitutive inflammation that characterizes advanced age is termed inflamm-aging. This process is associated with age-related changes to immune homeostasis and gut microbiota. We investigated the relationship between aging and gut microbiota lipopolysaccharide (LPS)-inducible inflammation.A taxonomy-based analysis showed that aging resulted in increased prevalence of the phyla Firmicutes and Actinobacteria and a reduced prevalence of Bacteroidetes and Tenericutes, resulting in an increase in the Firmicutes to Bacteroidetes ratio. The levels of plasmatic and fecal lipopolysaccharides were higher in aged mice. Aging induced the expression of p16 and the activation of nuclear factor-kappa B (NF-?B) in the colon of aged mice. Interestingly, the expression level of sterile ?-motif domain- and HD domain-containing protein 1 (SAMHD1) in the colon was higher in aged mice than in young mice, while cyclin-dependent kinase-2 and cyclin E levels were lower in aged mice than in young mice. The lipopolysaccharide fraction of fecal lysates (LFL) from young or aged mice increased p16 and SAMHD1 expression and NF-?B activation in peritoneal macrophages from wild-type mice, in a TLR4-dependent manner. However, LFLs did not induce NF-?B activation and SAMHD1 expression in peritoneal macrophages from TLR4-deificent mice, whereas they significantly induced p16 expression. Nevertheless, p16 expression was induced more potently in macrophages from WT mice than in macrophages from TLR4-deficient mice.Aging increased p16 and SAMHD1 expression, gut microbiota LPS production, and NF-?B activation; thereby, signifying that gut microbiota LPS may accelerate inflamm-aging and SAMHD1 may be an inflamm-aging marker.
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Project description:In defiance of the paradigm that calories from all sources are equivalent, we and others have shown that dietary protein is a dominant regulator of healthy aging. The restriction of protein or the branched-chain amino acid isoleucine promotes healthspan and extends lifespan when initiated in young or adult mice. However, many interventions are less efficacious or even deleterious when initiated in aged animals. Here, we investigate the physiological, metabolic, and molecular consequences of consuming a diet with a 67% reduction of all amino acids (Low AA), or of isoleucine alone (Low Ile), in male and female C57BL/6J.Nia mice starting at 20 months of age. We find that both diet regimens effectively reduce adiposity and improve glucose tolerance, which were benefits that were not mediated by reduced calorie intake. Both diets improve specific aspects of frailty, slow multiple molecular indicators of aging rate, and rejuvenate the aging heart and liver at the molecular level. These results demonstrate that Low AA and Low Ile diets can drive youthful physiological and molecular signatures, and support the possibility that these dietary interventions could help to promote healthy aging in older adults.
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Project description:In recent years, the first-line anti-diabetic drug metformin has been shown to be also useful for the treatment of other diseases like cancer. To date, few reports were about the impact of metformin on gut microbiota. To fully understand the mechanism of action of metformin in treating diseases other than diabetes, it is especially important to investigate the impact of long-term metformin treatment on the gut microbiome in non-diabetic status. In this study, we treated healthy mice with metformin for 30 days, and observed 46 significantly changed gut microbes by using the 16S rRNA-based microbiome profiling technique. We found that microbes from the Verrucomicrobiaceae and Prevotellaceae classes were enriched, while those from Lachnospiraceae and Rhodobacteraceae were depleted. We further compared the altered microbiome profile with the profiles under various disease conditions using our recently developed comparative microbiome tool known as MicroPattern. Interestingly, the treatment of diabetes patients with metformin positively correlates with colon cancer and type 1 diabetes, indicating a confounding effect on the gut microbiome in patients with diabetes. However, the treatment of healthy mice with metformin exhibits a negative correlation with multiple inflammatory diseases, indicating a protective anti-inflammatory role of metformin in non-diabetes status. This result underscores the potential effect of metformin on gut microbiome homeostasis, which may contribute to the treatment of non-diabetic diseases.
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Project description:Exposure to early life stress (ELS) is associated with a greater risk of chronic disease development including depression and cardiovascular disease. Altered gut microbiota has been linked to both depression and cardiovascular disease in mice and humans. Rodent models of early life neglect are used to characterize the mechanistic links between early life stress (ELS) and the risk of disease later in life. However, little is understood about ELS exposure and the gut microbiota in the young mice and the influence of the maternal inheritance of the gut microbiota. We used a mouse model of ELS, maternal separation with early weaning (MSEW), and normally reared mice to determine whether the neonate microbiota is altered, and if so, are the differences attributable to changes in dam microbiota that are then transmitted to their offspring. Individual amplicon sequence variants (ASVs) displayed differential abundance in the microbiota of MSEW compared with normally reared pups at postnatal day (PD) 28. Additionally, ELS exposure reduced the alpha diversity and altered microbial community composition at PD28. The composition, levels of alpha diversity, and abundance of individual ASVs in the microbiota of dams were similar from MSEW or normally reared cohorts. Thus, the observed shifts in the abundance of individual bacterial ASVs in the neonates and young pups are likely driven by endogenous effects of MSEW in the offspring host and are not due to inherited differences from the dam. This knowledge suggests that exposure to ELS has a direct effect on microbial factors on the risk of chronic disease development.
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Project description:The microbiota-gut-brain axis has attracted significant attention with respect to studying the mechanisms of brain aging; however, the specific connection between gut microbiota and aging remains unclear. The abnormal expression and mutation of proteins belonging to the P4-ATPase family, including Atp11b, results in a variety of neurological diseases. The results of our analysis demonstrate that there was a shift in the abundance of certain gut microbiota in Atp11b-knockout (KO) mice. Specifically, there was an increase in pro-inflammatory bacteria that accelerate aging and a decrease in probiotics that delay aging. Consequently, an enhanced oxidative stress response was observed, which was characterized by a reduction in the superoxide dismutase (SOD) activity and an increase in malondialdehyde (MDA) and reactive oxygen species (ROS) levels. In addition, our data demonstrate that there was a decrease in the number of cells in the dentate gyrus (DG) region of the hippocampus, and aggravation of aging-related pathological features such as senescence β-galactosidase (SA-β-Gal), p-HistoneH2AX (Ser139), and p16INK4. Moreover, KO mice show typical aging-associated behavior, such as memory impairment and slow pain perception. Taken together, we demonstrate a possible mechanism of aging induced by gut microbiota in Atp11b-KO mice, which provides a novel perspective for the treatment of aging through the microbiota-gut-brain axis.
| S-EPMC9221138 | biostudies-literature
Project description:Calorie restriction has been regarded as the only experimental regimen that can effectively lengthen lifespan in various animal models, but the actual mechanism remains controversial. The gut microbiota has been shown to have a pivotal role in host health, and its structure is mostly shaped by diet. Here we show that life-long calorie restriction on both high-fat or low-fat diet, but not voluntary exercise, significantly changes the overall structure of the gut microbiota of C57BL/6 J mice. Calorie restriction enriches phylotypes positively correlated with lifespan, for example, the genus Lactobacillus on low-fat diet, and reduces phylotypes negatively correlated with lifespan. These calorie restriction-induced changes in the gut microbiota are concomitant with significantly reduced serum levels of lipopolysaccharide-binding protein, suggesting that animals under calorie restriction can establish a structurally balanced architecture of gut microbiota that may exert a health benefit to the host via reduction of antigen load from the gut.
| S-EPMC3717500 | biostudies-literature
Project description:BackgroundHuman gut microbiota are important for human health and have been regarded as a "forgotten organ", whose variation is closely linked with various factors, such as host genetics, diet, pathological conditions and external environment. The diversity of human gut microbiota has been correlated with aging, which was characterized by different abundance of bacteria in various age groups. In the literature, most of the previous studies of age-related gut microbiota changes focused on individual species in the gut community with supervised methods. Here, we aimed to examine the underlying aging progression of the human gut microbial community from an unsupervised perspective.ResultsWe obtained raw 16S rRNA sequencing data of subjects ranging from newborns to centenarians from a previous study, and summarized the data into a relative abundance matrix of genera in all the samples. Without using the age information of samples, we applied an unsupervised algorithm to recapitulate the underlying aging progression of microbial community from hosts in different age groups and identify genera associated to this progression. Literature review of these identified genera indicated that for individuals with advanced ages, some beneficial genera are lost while some genera related with inflammation and cancer increase.ConclusionsThe multivariate unsupervised analysis here revealed the existence of a continuous aging progression of human gut microbiota along with the host aging process. The identified genera associated to this aging process are meaningful for designing probiotics to maintain the gut microbiota to resemble a young age, which hopefully will lead to positive impact on human health, especially for individuals in advanced age groups.
| S-EPMC6819604 | biostudies-literature
Project description:Wushen (WS) is a mixed food containing 55 natural products that is beneficial to human health. This study aimed to reveal the preventive effect of WS on aging via a combined analysis of gut microbiome and metabolome. Senescence-accelerated mouse prone 8 (SAMP8) mice were used as aging model and senescence-accelerated mouse resistant 1 (SAMR1) mice as control. The mice were fed four diet types; control diet (for SAMR1 mice), standard diet (for SAMP8 mice, as SD group), WS diet, and fecal microbiota transplantation (FMT; transplanted from aging-WS mice). Our results showed that the weight, food intake, neurological function, and general physical conditions significantly improved in WS-fed mice compared to those fed with SD. The CA1 hippocampal region in WS-fed aged mice showed fewer shriveled neurons and increased neuronal layers compared to that of the SD group. WS-fed mice showed a decrease in malondialdehyde and an increase in superoxide dismutase levels in the brain; additionally, IL-6 and TNF-α levels significantly decreased, whereas IL-2 levels and the proportion of lymphocytes, CD3+CD8+ T, and CD4+IFNγ+T cells increased in WS-fed mice. After fed with WS, the abundance of Ruminococcus and Butyrivibrio markedly increased, whereas Lachnoclostridium and Ruminiclostridium significantly decreased in the aging mice. In addition, 887 differentially expressed metabolites were identified in fecal samples, among these, Butyrivibrio was positively correlated with D-glucuronic acid and Ruminococcus was positively associated with 5-acetamidovalerate. These findings provide mechanistic insight into the impact of WS on aging, and WS may be a valuable diet for preventing aging.
| S-EPMC8312451 | biostudies-literature
Project description:BackgroundThe gut microbiota in healthy older individuals typically show a decrease in beneficial bacteria like Bifidobacterium and Lactobacillus, alongside an increase in pro-inflammatory microbes such as Enterobacteriaceae and Clostridia. These changes contrast with younger and middle-aged individuals and appear to correlate with cognitive status. Although there is extensive research on gut microbiota and cognitive functions in cognitively impaired elderly individuals, its impact on cognitively healthy elderly populations has not been extensively studied.MethodA comprehensive literature search was conducted across PubMed, EBSCO, Web of Science, and Scopus databases to identify studies exploring the relationship between gut microbiota composition and cognitive functioning in healthy older adults. During the literature screening process, each record was initially assessed by its title, abstract, and keywords to exclude articles that did not align with the scope of this review. Three authors independently screened and retrieved the records. The inclusion criteria included: (1) publication in peer-reviewed journals; (2) studies involving neurologically, cognitively, and medically healthy populations; (3) participants identified as older adults, defined for this review as individuals aged 45 years and older due to the limited number of records; (4) analysis of gut microbiota; and (5) assessment of cognitive function. Subsequently, full texts were analyzed to determine eligibility. The exclusion criteria encompassed: (1) incorrect publication type; (2) inappropriate sample population; (3) unsuitable study design; (4) absence of one or more inclusion criteria; and (5) studies based on animal research. A risk of bias assessment was performed for each included study using the Joanna Briggs Institute (JBI) checklist, ensuring all selected studies met established quality standards.ResultsA total of 6 eligible research articles from a possible 1752 published until March 2024 were identified and included. We categorized the included studies into two groups based on their focus: the taxonomic composition of gut microbiota and the alpha diversity, which is the variety of organisms within a sample. Additionally, two methods were identified for assessing cognition: neuropsychological tests and physiological measurements, notably electroencephalography (EEG). The studies show varying results regarding the abundance of specific bacterial taxa and their cognitive associations. Notably, the relationship between certain bacteria and cognition may vary when analyzed at different taxonomic levels, such as phylum versus family.ConclusionsChanges in gut microbiota composition in the elderly, even without a cognitive impairment diagnosis, could potentially serve as early biological markers for Alzheimer's disease or other dementias before mild cognitive impairment appears.
| S-EPMC10974508 | biostudies-literature