Comparative approaches in animal gut microbiome research have revealed patterns of phylosymbiosis, dietary and physiological convergences, and environment-host interactions. However, most large-scale comparative studies, especially those that are highly cited, have focused on mammals, and efforts to integrate comparative approaches with existing ecological frameworks are lacking. While mammals serve as useful model organisms, developing generalised principles of how animal gut microbiomes are shaped and how these microbiomes interact bidirectionally with host ecology and evolution requires a more complete sampling of the animal kingdom. Here, we provide an overview of what past comparative studies have taught us about the gut microbiome, and how community ecology theory may help resolve certain contradictions in comparative gut microbiome research. We explore whether certain hypotheses are supported across clades, and how the disproportionate focus on mammals has introduced potential bias into gut microbiome theory. We then introduce a methodological solution by which public gut microbiome data of understudied hosts can be compiled and analysed in a comparative context. Our aggregation and analysis of 179 studies shows that generating data sets with rich host diversity is possible with public data and that key gut microbes associated with mammals are widespread across the animal kingdom. We also show the effects that sample size and taxonomic rank have on comparative gut microbiome studies and that results of multivariate analyses can vary significantly with these two parameters. While challenges remain in developing a universal model of the animal gut microbiome, we show that existing ecological frameworks can help bring us one step closer to integrating the gut microbiome into animal ecology and evolution.

To evaluate the association between dairy products consumption and the probability of frailty transitions in community-dwelling older adults.

Longitudinal study.

We included 863 community-dwelling participants ≥65 years from the Chianti region in Italy.

Habitual dietary intake of dairy products (i.e., milk, yogurt, and cheese) was assessed in daily servings using a validated food frequency questionnaire (FFQ) at baseline, 3-, 6-, and 9-years of follow-up. Frailty status at each visit was defined using the Fried criteria, and the probability of transitions between different frailty status and death was assessed through multistate models. The associations between dairy product intakes and frailty transitions during the 9-year period were expressed as hazard ratios (HRs) derived from proportional intensity models.

The mean age at baseline was 74 ± 7 years and 46% of the participants were male. There were no statistically significant associations between the consumption of total, fermented, or non-fermented dairy products and the probabilities of transition from robust or from pre-frail to any of the other frailty conditions or to death. Conversely, a direct association between the consumption of fermented dairy products and the probability of transition from frail to pre-frail was observed in a model adjusted for age, sex, and energy intake (HRper serving/day = 1.90, 95%CI 1.12-3.22). This association was primarily related to yogurt consumption (HRper serving/day = 4.07, 95%CI 1.38-12.02), as the association with cheese consumption was not significant (HRper serving/day = 1.57, 95%CI 0.91-2.71). In the fully adjusted model, only the association between yogurt consumption and frail to pre-frail transition remained statistically significant (HRper serving/day = 3.68, 95%CI 1.10-12.31).

Dairy products, such as milk, yogurt, and cheese, are unlikely to play a predominant role in frailty development in an Italian community-dwelling older population. However, it is advisable to maintain a moderate consumption of dairy products, especially fermented ones, as part of a well-balanced diet to promote healthy aging.

Population aging has become a primary global public health issue, and the prevention of age-associated diseases and prolonging healthy life expectancies are of particular importance. Gut microbiota has emerged as a novel target in various host physiological disorders including aging. Comprehensive understanding on changes of gut microbiota during aging, in particular gut microbiota characteristics of centenarians, can provide us possibility to achieving healthy aging or intervene pathological aging through gut microbiota-directed strategies.

This review aims to summarize the characteristics of the gut microbiota associated with aging, explore potential biomarkers of aging and address microbiota-associated mechanisms of host aging focusing on intestinal barrier and immune status. By summarizing the existing effective dietary strategies in aging interventions, the probability of developing a diet targeting the gut microbiota in future is provided.

This review is focused on three key notions: Firstly, gut microbiota has become a new target for regulating health status and lifespan, and its changes are closely related to age. Thus, we summarized aging-associated gut microbiota features at the levels of key genus/species and important metabolites through comparing the microbiota differences among centenarians, elderly people and younger people. Secondly, exploring microbiota biomarkers related to aging and discussing future possibility using dietary regime/components targeted to aging-related microbiota biomarkers promote human healthy lifespan. Thirdly, dietary intervention can effectively improve the imbalance of gut microbiota related to aging, such as probiotics, prebiotics, and postbiotics, but their effects vary among.

Recent evidence suggests that sarcopenia and subsequent changes in muscle mass and functional outcomes are linked to disruption to the gastrointestinal microbiota composition and/or function via the microbiota-gut-muscle axis. Despite growing interest, few studies have systemically analysed (1) the relationship between the gut microbiota, muscle mass and physical performance and (2) the effects of gut-modulating dietary interventions on these outcomes within older individuals with or without sarcopenia.

Four electronic databases (PubMed, MEDLINE, Embase and Scopus) were searched for articles published from the year 2004 until July 2023. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were followed. Revised Cochrane Risk of Bias (RoB 2.0) and Joanna Briggs Institute (JBI) critical appraisal checklist were utilised to evaluate the risk of bias within intervention and observational studies, respectively.

A total of 20 studies (14 observational and 6 interventional) involving 4071 older participants (mean age 69.9 years, 51.6% female) were included. There was significant heterogeneity regarding interventions and outcome measures used in these studies. Correlations between microbiota diversity and composition and sarcopenia-related functional outcomes were observed. Interventional studies targeting the gut microbiota resulted in improved muscle strength, body composition or physical function in some, but not all, studies.

Despite limitations in the studies reviewed, the findings provide further evidence that the development of sarcopenia is likely influenced by an altered gut microbial environment and that interventions targeting the microbiome could hold therapeutic potential for the treatment or management of sarcopenia.

Frailty is a complex aging-related syndrome characterized by a cumulative loss of physiological reserve and increased vulnerability to adverse clinical outcomes, including falls, disability, incapacity and death. While an increasing number of studies suggest that the gut microbiota may play a key role in the pathophysiology of frailty, direct evaluation of the association between gut microbiome alterations and frailty in older adults remains limited.

To gain insight into gut dysbiosis in frail older adults.

Seven electronic databases (China National Knowledge Infrastructure, VIP, SinoMed, Wanfang, PubMed, Web of Science and EMBASE) were searched for articles published before October 31, 2023 to identify observational studies that compared the microbiomes of older adults with and without frailty. The diversity and composition of the gut microbiota were the main outcomes used to analyze the associations of changes in the gut microbiota with frailty in older adults. The quality of the included studies was assessed via the Newcastle-Ottawa Scale and the Agency for Healthcare Research and Quality.

Eleven observational studies with 912 older adults were included in this review. Consistent results revealed a significant difference in the gut microbiota composition between frail and non-frail older adults, with a significant decrease in α diversity and a significant increase in β diversity in frail older adults. The pooled results revealed that at the phylum level, four microbiota (Actinobacteria, Proteobacteria, Verrucomicrobia and Synergistetes) were significantly enriched, and two microbiota (Firmicutes and Fusobacteria) were significantly depleted in frail older adults. At the family level, the results consistently revealed that the abundances of 6 families, most of which belong to the Actinobacteria or Proteobacteria phylum, were greater in frail than in non-frail older adults. At the genus or species level, consistent results from more than two studies revealed that the abundances of the genera Prevotella, Faecalibacterium, and Roseburia were significantly lower in frail older adults; individual studies revealed that the abundances of some genera or species (e.g., Megamonas, Blautia, and Megasphaera) were significantly lower, whereas those of other genera or species (e.g., Bifidobacterium, Oscillospira, Ruminococcus and Pyramidobacter) were significantly greater in frail older adults.

This systematic review suggests that changes in the gut microbiota are associated with frailty in older adults, which is commonly reflected by a reduction in beneficial species and an increase in pathogenic species. However, further studies are needed to confirm these findings.

Altered gut microbiota (GM) potentially contribute to development or worsening of sarcopenia through a gut-muscle axis. This systematic review aims to compare GM between persons with sarcopenia or low sarcopenia-defining parameters (muscle mass, strength, and physical performance) to those with preserved muscle status, as well as to clarify possible associations between sarcopenia (-defining parameters) and relative abundance (RA) of GM-taxa or GM-(α- or β) diversity indices, in order to clarify whether there is robust evidence of the existence of a GM signature for sarcopenia. This systematic review was conducted according to the PRISMA-reporting guideline and pre-registered on PROSPERO (CRD42021259597). PubMed, Web of Science, Embase, ClinicalTrials.gov, and Cochrane library were searched until 20 July 2023. Included studies reported on GM and sarcopenia or its defining parameters. Observational studies were included with populations of mean age ≥50 years. Thirty-two studies totalling 10 781 persons (58.56% ♀) were included. Thirteen studies defined sarcopenia as a construct. Nineteen studies reported at least one sarcopenia-defining parameter (muscle mass, strength or physical performance). Studies found different GM-taxa at multiple levels to be significantly associated with sarcopenia (n = 4/6), muscle mass (n = 13/14), strength (n = 7/9), and physical performance (n = 3/3); however, directions of associations were heterogeneous and also conflicting for specific GM-taxa. Regarding β-diversity, studies found GM of persons with sarcopenia, low muscle mass, or low strength to cluster differently compared with persons with preserved muscle status. α-diversity was low in persons with sarcopenia or low muscle mass as compared with those with preserved muscle status, indicating low richness and diversity. In line with this, α-diversity was significantly and positively associated with muscle mass (n = 3/4) and muscle strength (n = 2/3). All reported results were significant (P < 0.05). Persons with sarcopenia and low muscle parameters have less rich and diverse GM and can be separated from persons with preserved muscle mass and function based on GM-composition. Sarcopenia and low muscle parameters are also associated with different GM-taxa at multiple levels, but results were heterogeneous and no causal conclusions could be made due to the cross-sectional design of the studies. This emphasizes the need for uniformly designed cross-sectional and longitudinal trials with appropriate GM confounder control in large samples of persons with sarcopenia and clearly defined core outcome sets in order to further explore changes in GM-taxa and to determine a sarcopenia-specific GM-signature.

This study investigates the relationship between frailty severity and gut microbiome characteristics in adults in Kazakhstan. We analyzed 158 participants across four frailty severity (mild to very severe) using metagenomic sequencing of stool samples. Frailty was significantly correlated with age, weight, and functional measures like walking speed and grip strength. Microbial diversity decreased significantly with increasing frailty. Beta diversity analysis revealed distinct clustering patterns based at phylum level. Taxonomically, we observed a significant inverse correlation between Firmicutes abundance and frailty. Classes like Clostridia and Erysipelotrichia decreased with frailty, while Bacteroidia and Actinobacteria increased. At the family level, Oscillospiraceae showed a positive correlation with frailty. Functionally, we identified significant correlations between frailty measures and specific metabolic pathways. The frailty index negatively correlated with pathways involved in cobalamin, arginine and molybdenum cofactor biosynthesis and positively correlated with folate biosynthesis. Physical performance measures strongly correlated with pathways related to nucleotide biosynthesis, and one-carbon metabolism. We propose these identified features may constitute a "frailty-associated metabolic signature" in the gut microbiome. This signature suggests multiple interconnected mechanisms through which the microbiome may influence frailty development, including modulation of inflammation, alterations in energy metabolism, and potential impacts on muscle function through microbial metabolites.

Frailty, a multidimensional indicator of suboptimal aging, reflects cumulative declines across multiple physiological systems. Although age-related changes have been reported in gut microbiota, their role in healthy aging remains unclear. In this study, we calculated frailty index (FI) from 33 health-related items to reflect the overall health status of 1,821 older adults (62-96 years, 55% female) and conducted multi-omics analysis using gut metagenomic sequencing data and plasma metabolomic data. We identified 18 microbial species and 17 metabolites shifted along with frailty severity, with stronger links observed in females. The associations of nine species, including various Clostridium species and Faecalibacterium prausnitzii, with FI were reproducible in two external populations. Plasma glycerol levels, white blood cell count and kidney function partially mediated these associations. A composite microbial score derived from FI significantly predicted 2-year mortality (adjusted hazard ratio across extreme quartiles, 2.86; 95% confidence interval, 1.38-5.93), highlighting the potential of microbiota-based strategies for risk stratification in older adults.

The gut microbiome plays a crucial role in host health throughout the lifespan by influencing brain function during aging. The microbial diversity of the human gut microbiome decreases during the aging process and, as a consequence, several mechanisms increase, such as oxidative stress, mitochondrial dysfunction, inflammatory response, and microbial gut dysbiosis. Moreover, evidence indicates that aging and neurodegeneration are closely related; consequently, the gut microbiome may serve as a novel marker of lifespan in the elderly. In this narrative study, we investigated how the changes in the composition of the gut microbiome that occur in aging influence to various neuropathological disorders, such as mild cognitive impairment (MCI), dementia, Alzheimer's disease (AD), and Parkinson's disease (PD); and which are the possible mechanisms that govern the relationship between the gut microbiome and cognitive impairment. In addition, several studies suggest that the gut microbiome may be a potential novel target to improve hallmarks of brain aging and to promote healthy cognition; therefore, current and future therapeutic interventions have been also reviewed.

This study aimed to assess the association between the oral microbiome, age, and frailty. Data and saliva samples were obtained from male and female participants aged 35-70 years (n = 1357). Saliva samples were analysed by 16S rRNA gene sequencing and differences in microbial diversity and community compositions were examined in relation to chronological age and the frailty index (FI). Most alpha diversity measures (Richness, Shannon Diversity, Faith's Phylogenetic Diversity) showed an inverse association with frailty, whereas a positive association was observed with age and Shannon Diversity and Evenness. A further sex-stratified analysis revealed differences in measures of microbial diversity and composition. Multiple genera were detected as significantly differentially abundant with increasing frailty and age by at least two methods. With age, the relative abundance of Veillonella was reduced in both males and females, whereas increases in Corynebacterium appeared specific to males and Aggregatibacter, Fusobacterium, Neisseria, Stomatobaculum, and Porphyromonas specific to females. Beta diversity was significantly associated with multiple mental health components of the FI. This study shows age and frailty are differentially associated with measures of microbial diversity and composition, suggesting the oral microbiome may be a useful indicator of increased risk of frailty or a potential target for improving health in ageing adults.

Frailty, a complex geriatric syndrome, significantly impedes the goal of achieving 'healthy aging'. Increasing evidence suggests a connection between gut microbiota, systemic inflammation, and disease. However, it remains to be determined whether interventions targeting the intestinal flora can effectively ameliorate frailty. Our research involved fecal microbiota transplantation (FMT) experiments on germ-free (GF) mice, dividing these mice into three groups: a group receiving transplants from healthy elderly individuals (HF group), a group of frailty patients (FF group), and the FF group supplemented with Lactobacillus plantarum BFS1243 (FFL group). Our findings indicated a significant shift in the gut microbiota of the FF group, in contrast to the HF group, characterized by decreased Akkermansia and increased Enterocloster, Parabacteroides, and Eisenbergiella. Concurrently, there was a reduction in amino acids and SCFAs, with BFS1243 partially mitigating these changes. The FF group exhibited an upregulation of inflammatory markers, including PGE2, CRP, and TNF-α, and a downregulation of irisin, all of which were moderated by BFS1243 treatment. Furthermore, BFS1243 improved intestinal barrier integrity and physical endurance in the FF mice. Correlation analysis revealed a negative association between SCFA-producing species and metabolites like lysine and butyric acid with pro-inflammatory factors. In conclusion, our study conclusively demonstrated that alterations in the gut microbiota of elderly individuals can lead to physical frailty, likely due to detrimental effects on the intestinal barrier and a pro-inflammatory state. These findings underscore the potential of gut microbiome modulation as a clinical strategy for treating frailty.

A mounting body of evidence suggests a strong connection between gut microbiota and the risk of frailty. However, the question of causality remains unanswered. In this study, we employed a Mendelian randomization (MR) approach to assess potential causal relationships between gut microbiota and the risk of frailty.

Summary statistics for the gut microbiome were obtained from a genome wide association study (GWAS) meta-analysis of the MiBioGen consortium (N = 18,340). Summary statistics for frailty were obtained from a GWAS meta-analysis, including the UK Biobank and TwinGene (N = 175,226). Our primary analysis utilized the inverse variance weighted (IVW) method. To enhance the robustness of our results, we also applied weighted median methods, MR Egger regression, and MR pleiotropy residual sum and outlier test. Finally, we conducted reverse MR analysis to investigate the potential for reverse causality.

IVW method identified 7 bacterial taxa nominally associated with the risk of FI. Class Bacteroidia (p = 0.033) and genus Eubacterium ruminantium group (p = 0.028) were protective against FI. In addition, class Betaproteobacteria (p = 0.042), genus Allisonella (p = 0.012), genus Bifidobacterium (p = 0.013), genus Clostridium innocuum group (p = 0.036) and genus Eubacterium coprostanoligenes group (p = 0.003) were associated with a higher risk of FI. No pleiotropy or heterogeneity were found.

The MR analysis indicates a causal relationship between specific gut microbiota and FI, offering new insights into the mechanisms underlying FI mediated by gut microbiota.

Diets rich in live microbes can bring various health benefits. However, the association between dietary live microbe intake and frailty has not been studied.

The study utilized data from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. A total of 11,529 participants were included. Sanders et al. classified the level of live microbes in foods into low (<104 CFU/g), medium (104-107 CFU/g), or high (>107 CFU/g). With the methodology of Sanders et al. and dietary questionnaire data, participants were divided into three groups: (1) low dietary live microbe intake group (only low-level foods), (2) medium dietary live microbe intake group (medium but not high-level foods), and (3) high dietary live microbe intake group (any high-level foods). Additionally, foods with medium and high live microbe content were aggravated as MedHi. Frailty index ≥0.25 is defined as frailty. The weighted logistic regression analysis was conducted to examine the relationship between the intake of dietary live microbe and frailty. The restricted cubic splines (RCS) were employed to detect the nonlinear relationships.

In the fully adjusted model, participants with high dietary intake of live microbe had a significantly lower risk of frailty than those with low dietary intake of live microbe (OR = 0.67, 95% CI: 0.56, 0.79). For every 100 grams of MedHi food consumed, the risk of frailty decreased by 11% (OR = 0.89, 95% CI: 0.85, 0.92) after adjusting all covariates. The RCS indicated the existence of non-linear relationships. For those who consumed less than 100 grams of MedHi, increasing MedHi intake may significantly reduce the risk of frailty, but after exceeding 100 grams, the curve gradually levels off.

Our results suggested that increasing dietary live microbe intake was associated with a lower risk of frailty. However, more research is needed to verify this.

Mental disorders are complex disorders influenced by multiple genetic, environmental, and biological factors. Specific microbiota imbalances seem to affect mental health status. However, the mechanisms by which microbiota disturbances impact the presence of depression, stress, anxiety, and eating disorders remain poorly understood. Currently, there are no robust biomarkers identified. We proposed a novel pyramid-layer design to accurately identify microbial/metabolomic signatures underlying mental disorders in the TwinsUK registry. Monozygotic and dizygotic twins discordant for mental disorders were screened, in a pairwise manner, for differentially abundant bacterial genera and circulating metabolites. In addition, multivariate analyses were performed, accounting for individual-level confounders. Our pyramid-layer study design allowed us to overcome the limitations of cross-sectional study designs with significant confounder effects and resulted in an association of the abundance of genus Parabacteroides with the diagnosis of mental disorders. Future research should explore the potential role of Parabacteroides as a mediator of mental health status. Our results indicate the potential role of the microbiome as a modifier in mental disorders that might contribute to the development of novel methodologies to assess personal risk and intervention strategies.

Frailty syndrome denotes a decreased capacity of the body to maintain the homeostasis and stress of the internal environment, which simultaneously increases the risk of adverse health outcomes in older adults, including disability, hospitalization, falls, and death. To promote healthy aging, we should find strategies to cope with frailty. However, the pathogenesis of frailty syndrome is not yet clear. Recent studies have shown that the diversity, composition, and metabolites of gut microbiota significantly changed in older adults with frailty. In addition, several frailty symptoms were alleviated by adjusting gut microbiota with prebiotics, probiotics, and symbiosis. Therefore, we attempt to explore the pathogenesis of frailty syndrome in older people from gut microbiota and summarize the existing interventions for frailty syndrome targeting gut microbiota, with the aim of providing timely and necessary interventions and assistance for older adults with frailty.

The gut microbiota has emerged as a new intervention target for sarcopenia. Prior studies in humans have focused on the association between gut microbiota and skeletal muscle quantity, while the evidence on muscle function and quality is lacking. This study aimed to identify gut microbiota genera associated with skeletal muscle function, quantity, and quality in a general population of Japanese adults.

This cross-sectional study included 164 participants aged 35-80 years, women and men recruited from urban areas of Japan. Fecal samples were collected and analyzed using 16S rRNA gene amplicon sequencing. Skeletal muscle function was measured using handgrip strength and leg extension power (LEP), while skeletal muscle mass was estimated using bioelectrical impedance analysis. Phase angle was used as a measure of skeletal muscle quality. Multivariate linear regression analysis stratified by age group was used to examine the association between the dominant genera of the gut microbiota and skeletal muscle variables.

A significant association was found between Bacteroides and Prevotella 9 with LEP only in the ≥60 years group. When both Bacteroides and Prevotella 9 were included in the same regression model, only Bacteroides remained consistently and significantly associated with LEP. No significant associations were observed between skeletal muscle mass, handgrip strength, and phase angle and major gut microbiota genera.

In this study, we observed a significant positive association between Bacteroides and leg muscle function in older adults. Further studies are required to elucidate the underlying mechanisms linking Bacteroides to lower-extremity muscle function. Geriatr Gerontol Int 2024; 24: 53-60.

The composition of the human gut microbiome has been observed to change over the course of an individual's life. From birth, it is shaped by mode of delivery, diet, environmental exposures, geographic location, exposures to medications, and by aging itself. Here, we present a narrative review of the gut microbiome across the lifespan with a focus on its impacts on aging and age-related diseases in humans. We will describe how it is shaped, and features of the gut microbiome that have been associated with diseases at different phases of life and how this can adversely affect healthy aging. Across the lifespan, and especially in old age, a diverse microbiome that includes organisms suspected to produce anti-inflammatory metabolites such as short-chain fatty acids, has been reported to be associated with healthy aging. These findings have been remarkably consistent across geographic regions of the world suggesting that they could be universal features of healthy aging across all cultures and genetic backgrounds. Exactly how these features of the microbiome affect biologic processes associated with aging thus promoting healthy aging will be crucial to targeting the gut microbiome for interventions that will support health and longevity.

The role of the microbiome in asthma is highlighted, considering its influence on immune responses and its connection to alterations in asthmatic patients. In this context, we review the variables influencing asthma phenotypes from a microbiome perspective and provide insights into the microbiome's role in asthma pathogenesis. Previous cohort studies in patients with asthma have shown that the presence of genera such as Bifidobacterium, Lactobacillus, Faecalibacterium, and Bacteroides in the gut microbiome has been associated with protection against the disease. While, the presence of other genera such as Haemophilus, Streptococcus, Staphylococcus, and Moraxella in the respiratory microbiome has been implicated in asthma pathogenesis, indicating a potential link between microbial dysbiosis and the development of asthma. Furthermore, respiratory infections have been demonstrated to impact the composition of the upper respiratory tract microbiota, increasing susceptibility to bacterial diseases and potentially triggering asthma exacerbations. By understanding the interplay between the microbiome and asthma, valuable insights into disease mechanisms can be gained, potentially leading to the development of novel therapeutic approaches.

Observational studies have shown that the gut microbiome is associated with frailty. However, whether these associations underlie causal effects remains unknown. Thus, this study aimed to assess the genetic correlation and causal relationships between the genetically predicted gut microbiome and frailty using linkage disequilibrium score regression (LDSC) and Mendelian Randomization (MR). Summary statistics for the gut microbiome were obtained from a genome-wide association study (GWAS) meta-analysis of the MiBioGen consortium (N = 18,340). Summary statistics for frailty were obtained from a GWAS meta-analysis, including the UK Biobank and TwinGene (N = 175,226). We used LDSC and MR analyses to estimate the genetic correlation and causality between the genetically predicted gut microbiome and frailty. Our findings indicate a suggestive genetic correlation between Christensenellaceae R-7 and frailty. Moreover, we found evidence for suggestive causal effects of twelve genus-level gut microbes on frailty using at least two MR methods. There was no evidence of horizontal pleiotropy or heterogeneity in the MR analysis. This study provides suggestive evidence for a potential genetic correlation and causal association between several genetically predicted gut microbes and frailty. More population-based observational studies and animal experiments are required to clarify this association and the underlying mechanisms.

As the proportion of older people in the world's population steadily increases, there is an urgent need to identify ways to support healthy aging. The gut microbiome has been proposed to be involved in aging-related diseases and has become an attractive target for improving health in older people. Herein, we cover the relationship between the gut microbiome and chronological age in adults, and then, we discuss the gut microbiome features associated with frailty, as a hallmark of unhealthy aging in older people. Furthermore, we describe the effects of microbiome-targeted interventions, such as dietary patterns and consumption of probiotics, prebiotics, and synbiotics, on modulating the gut microbiome composition and further promoting healthy aging. Further studies are needed to explore the underlying mechanisms of gut microbiome-induced aging complications and to develop personalized microbiome-based strategies for reducing the severity of frailty or preventing the onset of frailty in older adults.

Exposure to nitrogen dioxide might potentially change the makeup and operation of gut microbes. Nitrogen dioxide data was procured from the IEU Open GWAS (N = 456 380). Subsequently, a two-sample Mendelian randomization study was executed, utilizing summary statistics of gut microbiota sourced from the most expansive available genome-wide association study meta-analysis, conducted by the MiBioGen consortium (N = 13 266). The causal relationship between nitrogen dioxide and gut microbiota was determined using inverse variance weighted, maximum likelihood, MR-Egger, Weighted Median, Weighted Model, Mendelian randomization pleiotropy residual sum and outlier, and constrained maximum likelihood and model averaging and Bayesian information criterion. The level of heterogeneity of instrumental variables was quantified by utilizing Cochran's Q statistic. The colocalization analysis was used to examine whether nitrogen dioxide and the identified gut microbiota shared casual variants. Inverse variance weighted estimate suggested that nitrogen dioxide was causally associated with Akkermansia (β = -1.088, 95% CI: -1.909 to -0.267, P = 0.009). In addition, nitrogen dioxide presented a potential association with Bacteroides (β = -0.938, 95% CI: -1.592 to -0.284, P = 0.005), Barnesiella (β = -0.797, 95% CI: -1.538 to -0.055, P = 0.035), Coprococcus 3 (β = 1.108, 95% CI: 0.048-2.167, P = 0.040), Eubacterium hallii group (E. hallii) (β = 0.776, 95% CI: 0.090-1.463, P = 0.027), Holdemania (β = -1.354, 95% CI: -2.336 to -0.372, P = 0.007), Howardella (β = 1.698, 95% CI: 0.257-3.139, P = 0.021), Olsenella (β = 1.599, 95% CI: 0.151-3.048, P = 0.030) and Sellimonas (β = -1.647, 95% CI: -3.209 to -0.086, P = 0.039). No significant heterogeneity of instrumental variables or horizontal pleiotropy was found. The associations of nitrogen dioxide with Akkermansia (PH4 = 0.836) and E. hallii (PH4 = 0.816) were supported by colocalization analysis. This two-sample Mendelian randomization study found that increased exposure to nitrogen dioxide had the potential to impact the human gut microbiota.

Recent studies have shown that gut microorganisms can modulate host lifespan and activities, including sleep quality and motor performance. However, the role of gut microbial genetic variation in regulating host phenotypes remains unclear. In this study, we investigated the links between gut microbial genetic variation and host phenotypes using Saccharomyces cerevisiae and Drosophila melanogaster as research models. Our result suggested a novel role for peroxisome-related genes in yeast in regulating host lifespan and activities by modulating gut oxidative stress. Specifically, we found that deficiency in catalase A (CTA1) in yeast reduced both the sleep duration and lifespan of fruit flies significantly. Furthermore, our research also expanded our understanding of the relationship between sleep and longevity. Using a large sample size and excluding individual genetic background differences, we found that lifespan is associated with sleep duration, but not sleep fragmentation or motor performance. Overall, our study provides novel insights into the role of gut microbial genetic variation in regulating host phenotypes and offers potential new avenues for improving health and longevity.

Geroscience posits that cardiovascular disease (CVD) and other chronic diseases result from progressive erosion of the effectiveness of homeostatic mechanisms that oppose age-related accumulation of molecular damage. This hypothetical common root to chronic diseases explains why patients with CVD are often affected by multimorbidity and frailty and why older age negatively affects CVD prognosis and treatment response. Gerotherapeutics enhance resilience mechanisms that counter age-related molecular damage to prevent chronic diseases, frailty, and disability, thereby extending healthspan. Here, we describe the main resilience mechanisms of mammalian aging, with a focus on how they can affect CVD pathophysiology. We next present novel gerotherapeutic approaches, some of which are already used in management of CVD, and explore their potential to transform care and management of CVD. The geroscience paradigm is gaining traction broadly in medical specialties, with potential to mitigate premature aging, reduce health care disparities, and improve population healthspan.

Nutrients, including protein, calcium, and fat may be associated with risk of frailty, yet specific contributions from whole dairy foods rich in these nutrients remain understudied.

To determine associations between dairy intake (milk, yogurt, cheese, total (milk + yogurt + cheese), low-fat and high-fat dairy, and servings per week) and frailty onset and frailty phenotype components.

Prospective cohort study. All dairy intake exposures (servings per week) were assessed via a food frequency questionnaire.

Participants (aged 33 to 86 years) from the Framingham Offspring Study who were not frail at baseline (1998-2001) completed a food frequency questionnaire and had 1 or 2 follow-up frailty assessments (2005-2008 and 2011-2014) were included.

Frailty was defined as the presence of ≥3 Fried frailty phenotype components: unintentional weight-loss, exhaustion, slowness (gait speed), weakness (grip strength), and low physical activity. Individuals with zero to two components were considered nonfrail.

Repeated measures logistic regression estimated odds ratios and 95% CIs for frailty onset. Logistic (exhaustion and weight loss) and linear regression (gait speed, grip strength, and physical activity) estimated the association between baseline dairy intake and each frailty component at follow-up, adjusting for baseline values for age, sex, energy intake (residual analysis), current smoking, and multivitamin use. Models were further adjusted for health status in a secondary analysis.

Mean baseline age ± SD was 61 ± 9 years (range = 33 to 87 years), and 54% were women. Of 2,550 nonfrail individuals at baseline, 8.8% (2005-2008) and 13.5% (2011-2014) became frail. Higher yogurt intake was associated with decreased odds of frailty (odds ratio 0.96, 95% CI 0.93 to 0.99; P = 0.02). Each additional serving of yogurt (β ± SE) .004 ± .001; P < 0.01) and low-fat dairy (β ± SE) .001 ± .0006; P = 0.04) was associated with significantly faster follow-up gait speed. Dietary intakes of high-fat dairy were associated with increased odds of frailty (odds ratio 1.02, 95% CI 1.00 to 1.04; P = 0.05), but the P value was of borderline significance. No associations were observed for other dairy foods. After adjusting for health status, the associations of high-fat dairy and yogurt with frailty became nonsignificant, although the magnitudes of the associations did not change. The association between yogurt and gait speed decreased in magnitude after adjusting for health status (β ± SE) .002 ± .001; P = 0.01).

Dietary intakes of yogurt were modestly associated with reduced frailty onset and dietary intakes of high-fat dairy had a borderline association with increased odds of frailty, but other dairy food intakes showed no association in this study of healthy adults. Some dairy food intakes were modestly associated with follow-up gait speed. However, effect sizes were small, and the clinical importance of these associations remains undetermined.

The gut microbiota is involved in several aspects of host health and disease, but its role is far from fully understood. This review aims to unveil the role of our microbial community in relation to frailty and clinical outcomes.

Ageing, that is the continuous process of physiological changes that begin in early adulthood, is mainly driven by interactions between biotic and environmental factors, also involving the gut microbiota. Indeed, our gut microbial counterpart undergoes considerable compositional and functional changes across the lifespan, and ageing-related processes may be responsible for - and due to - its alterations during elderhood. In particular, a dysbiotic gut microbiota in the elderly population has been associated with the development and progression of several age-related disorders.

Here, we first provide an overview of the lifespan trajectory of the gut microbiota in both health and disease. Then, we specifically focus on the relationship between gut microbiota and frailty syndrome, that is one of the major age-related burdens. Finally, examples of microbiome-based precision interventions, mainly dietary, prebiotic and probiotic ones, are discussed as tools to ameliorate the symptoms of frailty and its overlapping conditions (e.g. sarcopenia), with the ultimate goal of actually contributing to healthy ageing and hopefully promoting longevity.

The role of the gut microbiota in human health and disease has garnered heightened attention over the past decade. A thorough understanding of microbial variation over the life course and possible ways to influence and optimize the microbial pattern is essential to capitalize on the microbiota's potential to influence human health. Here, we review our current understanding of the concept of plasticity of the human gut microbiota throughout the life course. Characterization of the plasticity of the microbiota has emerged through recent research and suggests that the plasticity in the microbiota signature is largest at birth when the microbial colonization of the gut is initiated and mode of birth imprints its mark, then decreases postnatally continuously and becomes less malleable and largely stabilized with advancing age. This continuing loss of plasticity has important implication for the impact of the exposome on the microbiota and health throughout the life course and the identification of susceptible 'windows of opportunity' and methods for interventions.

With the increasing number of aged population and growing burden of healthy aging demands, a rational standard for evaluation aging is in urgent need. The advancement of medical testing technology and the prospering of artificial intelligence make it possible to evaluate the biological status of aging from a more comprehensive view. In this review, we introduced common aging biomarkers and concluded several famous aging clocks. Aging biomarkers reflect changes in the organism at a molecular or cellular level over time while aging clocks tend to be more of a generalization of the overall state of the organism. We expect to construct a framework for aging evaluation measurement from both micro and macro perspectives. Especially, population-specific aging clocks and multi-omics aging clocks may better fit the demands to evaluate aging in a comprehensive and multidimensional manner and make a detailed classification to represent different aging rates at tissue/organ levels. This framework will promisingly provide a crucial basis for disease diagnosis and intervention assessment in geroscience.

The gut microbiome is a modifier of disease risk because it interacts with nutrition, metabolism, immunity and infection. Aging-related health loss has been correlated with transition to different microbiome states. Microbiome summary indices including alpha diversity are apparently useful to describe these states but belie taxonomic differences that determine biological importance. We analyzed 21,000 fecal microbiomes from seven data repositories, across five continents spanning participant ages 18-107 years, revealing that microbiome diversity and uniqueness correlate with aging, but not healthy aging. Among summary statistics tested, only Kendall uniqueness accurately reflects loss of the core microbiome and the abundance and ranking of disease-associated and health-associated taxa. Increased abundance of these disease-associated taxa and depletion of a coabundant subset of health-associated taxa are a generic feature of aging. These alterations are stronger correlates of unhealthy aging than most microbiome summary statistics and thus help identify better targets for therapeutic modulation of the microbiome.

The gut microbiome is a contributory factor in ageing-related health loss and in several non-communicable diseases in all age groups. Some age-linked and disease-linked compositional and functional changes overlap, while others are distinct. In this Review, we explore targeted studies of the gut microbiome of older individuals and general cohort studies across geographically distinct populations. We also address the promise of the targeted restoration of microorganisms associated with healthier ageing.

Maintenance hemodialysis (MHD) patients are at high risk of sarcopenia. Gut microbiota affects host metabolic and may act in the occurrence of sarcopenia importantly. This study aimed to study the characterization of the gut microbiota in MHD patients with sarcopenia, and to further reveal the complex pathophysiology of sarcopenia in MHD patients.

Fecal samples and clinical data were collected from 30 MHD patients with sarcopenia, and 30 age-and-sex-matched MHD patients without sarcopenia in 1 general hospital of Jiangsu Province from December 2020 to March 2021. 16S rRNA sequencing technology was used to analyze the genetic sequence of the gut microbiota for evaluation of the diversity, species composition, and differential microbiota of the two groups.

Compared to MHD patients without sarcopenia, the ACE index of patients with sarcopenia was lower (P = 0.014), and there was a structural difference in the β-diversity between the two groups (P = 0.001). At the genus level, the relative abundance of Tyzzerella_4 in the sarcopenia group was significantly higher than in the non-sarcopenia group (P = 0.039), and the relative abundance of Megamonas (P = 0.004), Coprococcus_2 (P = 0.038), and uncultured_bacterium_f_Muribaculaceae (P = 0.040) decreased significantly.

The diversity and structure of the gut microbiota of MHD patients with sarcopenia were altered. The occurrence of sarcopenia in MHD patients may be influenced by gut microbiota.

Frailty is a major public issue that affects the physical health and quality of life of older adults, especially as the population ages. Chronic low-grade inflammation has been speculated to accelerate the aging process as well as the development of age-related diseases such as frailty. Intestinal homeostasis plays a crucial role in healthy aging. The interaction between the microbiome and the host regulates the inflammatory response. Emerging evidence indicates that in older adults with frailty, the diversity and composition structure of gut microbiota are altered. Age-associated changes in gut microbiota composition and in their metabolites contribute to increased gut permeability and imbalances in immune function. In this review, we aim to: identify gut microbiota changes in the aging and frail populations; summarize the role of chronic low-grade inflammation in the development of frailty; and outline how gut microbiota may be related to the pathogenesis of frailty, more specifically, in the regulation of gut-derived chronic inflammation. Although additional research is needed, the regulation of gut microbiota may represent a safe, easy, and inexpensive intervention to counteract the chronic inflammation leading to frailty.