Oral microbial signatures associated with age and frailty in Canadian adults.

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.

Association Between Gut Microbiome and Frailty in the Older Adult Population in Korea.

Frailty is a common geriatric syndrome associated with the risk of adverse health outcomes. Recently, 2 key pathophysiological characteristics of frailty, altered energy metabolism and dysregulated immunity, have been reported to be associated with gut microbiome dysbiosis, indicating that the gut microbiome plays a role in frailty. However, few studies have directly examined the relationship between the gut microbiome and frailty. Here, we investigated the association of frailty measures with the gut microbiome using 16S rRNA gene sequencing data obtained from the fecal samples of 176 Korean older adults. Overall frailty was scored using the Korean Frailty Index (FI). Grip strength and Geriatric Depression Scale (GDS) scores were used as physical and mental frailty measures, respectively. In contrast to age, metabolic, and inflammatory biomarkers, the frailty measures were associated with interindividual variations in microbial composition (false discovery rate [FDR] < 0.2). Both FI and GDS scores were negatively associated with microbial diversity (FDR < 0.2). Frailty measures showed distinct associations with specific microbial taxa and metabolic functions. Particularly, the Bacteroides enterotype was found only in subjects categorized in the frail group. Moreover, we observed that the abundance of beneficial taxa, such as Prevotella copri and Coprococcus eutactus, was reduced in frailer individuals, whereas that of detrimental taxa, such as Bacteroides fragilis and Clostridium hathewayi, was increased (FDR < 0.2). Our findings suggest that the gut microbiome can be used an indicator of an increased risk of frailty or a target for improving health in frail older adults.

Interactions Between the Aging Gut Microbiome and Common Geriatric Giants: Polypharmacy, Frailty, and Dementia.

The gut microbiome has pervasive bidirectional relationships with pharmacotherapy, chronic disease, and physical and cognitive function. We conducted a narrative review of the current literature to examine the relationships between the gut microbiome, medication use, sarcopenia and frailty, and cognitive impairment. Data from in vitro experiments, in vivo experiments in invertebrates and complex organisms, and humans indicate associations between the gut microbiome and geriatric syndromes. Better understanding of the direct and indirect roles of the microbiome may inform future prevention and management of geriatric syndromes.

Gut Microbial Ecosystem in Parkinson Disease: New Clinicobiological Insights from Multi-Omics.

OBJECTIVE: Gut microbiome alterations in Parkinson disease (PD) have been reported repeatedly, but their functional relevance remains unclear. Fecal metabolomics, which provide a functional readout of microbial activity, have scarcely been investigated. We investigated fecal microbiome and metabolome alterations in PD, and their clinical relevance. METHODS: Two hundred subjects (104 patients, 96 controls) underwent extensive clinical phenotyping. Stool samples were analyzed using 16S rRNA gene sequencing. Fecal metabolomics were performed using two platforms, nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography-mass spectrometry. RESULTS: Fecal microbiome and metabolome composition in PD was significantly different from controls, with the largest effect size seen in NMR-based metabolome. Microbiome and NMR-based metabolome compositional differences remained significant after comprehensive confounder analyses. Differentially abundant fecal metabolite features and predicted functional changes in PD versus controls included bioactive molecules with putative neuroprotective effects (eg, short chain fatty acids [SCFAs], ubiquinones, and salicylate) and other compounds increasingly implicated in neurodegeneration (eg, ceramides, sphingosine, and trimethylamine N-oxide). In the PD group, cognitive impairment, low body mass index (BMI), frailty, constipation, and low physical activity were associated with fecal metabolome compositional differences. Notably, low SCFAs in PD were significantly associated with poorer cognition and low BMI. Lower butyrate levels correlated with worse postural instability-gait disorder scores. INTERPRETATION: Gut microbial function is altered in PD, characterized by differentially abundant metabolic features that provide important biological insights into gut-brain pathophysiology. Their clinical relevance further supports a role for microbial metabolites as potential targets for the development of new biomarkers and therapies in PD. ANN NEUROL 2021;89:546-559.

Aging, Frailty, and the Microbiome-How Dysbiosis Influences Human Aging and Disease.

The human gut microbiome is a collection of bacteria, protozoa, fungi, and viruses that coexist in our bodies and are essential in protective, metabolic, and physiologic functions of human health. Gut dysbiosis has traditionally been linked to increased risk of infection, but imbalances within the intestinal microbial community structure that correlate with untoward inflammatory responses are increasingly recognized as being involved in disease processes that affect many organ systems in the body. Furthermore, it is becoming more apparent that the connection between gut dysbiosis and age-related diseases may lie in how the gut microbiome communicates with both the intestinal mucosa and the systemic immune system, given that these networks have a common interconnection to frailty. We therefore discuss recent advances in our understanding of the important role the microbiome plays in aging and how this knowledge opens the door for potential novel therapeutics aimed at shaping a less dysbiotic microbiome to prevent or treat age-related diseases.

Biomarkers of Physical Frailty and Sarcopenia: Coming up to the Place?

Physical frailty and sarcopenia (PF&S) recapitulates all the hallmarks of aging and has become a focus in geroscience. Factors spanning muscle-specific processes (e.g., mitochondrial dysfunction in skeletal myocytes) to systemic changes (e.g., inflammation and amino acid dysmetabolism) have been pinpointed as possible contributors to PF&S pathophysiology. However, the search for PF&S biomarkers allowing the early identification and tracking of the condition over time is ongoing. This is mainly due to the phenotypic heterogeneity of PF&S, its unclear pathophysiology, and the frequent superimposition of other age-related conditions. Hence, presently, the identification of PF&S relies upon clinical, functional, and imaging parameters. The adoption of multi-marker approaches (combined with multivariate modeling) has shown great potential for addressing the complexity of PF&S pathophysiology and identifying candidate biological markers. Well-designed longitudinal studies are necessary for the incorporation of reliable biomarkers into clinical practice and for unveiling novel targets that are amenable to interventions.

Effects of Probiotics and Prebiotics on Frailty and Ageing: A Narrative Review.

Globally, the population over the age of 60 is growing fast, but people age in different ways. Frailty, shown by the accumulation of age-related deficits, is a state of increased vulnerability to adverse outcomes among people of the same chronological age. Ageing results in a decline in diversity and homeostasis of microbiomes, and gut flora changes are related to health deficit accumulation and adverse health outcomes. In older people, health deficits including inappropriate intake, sarcopenia, physical inactivity, polypharmacy, and social vulnerability are factors associated with gut dysbiosis. The use of probiotics and prebiotics is a cost-effective and widely available intervention. Intake of probiotics and prebiotics may improve the homeostasis of gut microflora and prevent frailty and unhealthy aging. However, health effects vary among probiotics and prebiotics and among individual populations. This narrative review summarizes recent evidence about the relationship between prebiotic and probiotic consumption with health outcomes in older people.

The intestinal microbiome and its relevance for functionality in older persons.

PURPOSE OF REVIEW: This article summarizes the advances of research on the role of the intestinal microbiota in influencing sarcopenia, frailty, and cognitive dysfunction in older individuals, and thus its relevance for healthy active ageing. RECENT FINDINGS: Age-related alterations of intestinal microbiota composition may negatively influence muscle protein synthesis and function by promoting chronic systemic inflammation, insulin resistance, oxidative stress, and reducing nutrient bioavailability. However, this 'gut-muscle axis' hypothesis is not supported by human data to date. Some observational studies have instead demonstrated that, in older individuals, frailty and Alzheimer-type dementia are associated with fecal microbiota dysbiosis, that is, reduced biodiversity and overexpression of pathobionts. The main possible mechanisms of the 'gut-brain axis' in cognitive function modulation include effects on neurotransmission, neuroinflammation, and amyloid deposition. Conversely, longevity in good health may be associated with the maintenance of a fecal microbiota composition similar to that of healthy young adults. However, the role of gut microbiota as an independent modulator of frailty and cognition still remains uncertain, being influenced by several physiological factors, including diet and exercise. SUMMARY: The intestinal microbiome composition represents a possible determinant of functional performance in older people, and a promising target for antiaging therapeutic interventions.

The Gut Microbiota and Healthy Aging: A Mini-Review.

The gut microbiota shows a wide inter-individual variation, but its within-individual variation is relatively stable over time. A functional core microbiome, provided by abundant bacterial taxa, seems to be common to various human hosts regardless of their gender, geographic location, and age. With advancing chronological age, the gut microbiota becomes more diverse and variable. However, when measures of biological age are used with adjustment for chronological age, overall richness decreases, while a certain group of bacteria associated with frailty increases. This highlights the importance of considering biological or functional measures of aging. Studies using model organisms indicate that age-related gut dysbiosis may contribute to unhealthy aging and reduced longevity. The gut microbiome depends on the host nutrient signaling pathways for its beneficial effects on host health and lifespan, and gut dysbiosis disrupting the interdependence may diminish the beneficial effects or even have reverse effects. Gut dysbiosis can trigger the innate immune response and chronic low-grade inflammation, leading to many age-related degenerative pathologies and unhealthy aging. The gut microbiota communicates with the host through various biomolecules, nutrient signaling-independent pathways, and epigenetic mechanisms. Disturbance of these communications by age-related gut dysbiosis can affect the host health and lifespan. This may explain the impact of the gut microbiome on health and aging.

Composition of salivary microbiota in elderly subjects.

Frailty is gaining attention worldwide with the aging of society. Despite the potential lethality and multiple signs and symptoms in affected individuals, preclinical detection of early manifestations leading to frailty syndrome have not been established. We speculated that the composition of the oral microbiota is associated with general frailty, as well as a relationship between gut microbiota and general health condition. In the present study, we investigated the salivary microbiota composition in samples from healthy and frail elderly individuals using 16S rRNA sequencing analysis for characterization. We found a significant difference in diversity between elderly individuals living in a nursing home (EN) and healthy control (HC) subjects, as well as in the microbiota composition at the phyla level. A supervised orthogonal partial least squared discriminant analysis (OPLS-DA) revealed a significant difference in clear classification trend between the EN and HC groups, with all observations falling within the Hotellings T2 (0.95) ellipse, with model fitness parameters of R 2(cum) = 0.937 and Q 2(cum) = 0.888, respectively. In addition, the score plots by unsupervised principal component analysis (PCA) showed a clear classification trend in both groups. Our findings suggest that general frailty is associated with oral microbiota composition and formation.

The nursing home elder microbiome stability and associations with age, frailty, nutrition and physical location.

PURPOSE: The microbiome from nursing home (NH) residents is marked by a loss in diversity that is associated with increased frailty. Our objective was to explore the associations of NH environment, frailty, nutritional status and residents' age to microbiome composition and potential metabolic function. METHODOLOGY: We conducted a prospective longitudinal cohort study of 23 residents, 65 years or older, from one NH that had four floors: two separate medical intensive floors and two floors with active elders. Residents were assessed using the mini nutritional assessment tool and clinical frailty scale. Bacterial composition and metabolic potential of residents' stool samples was determined by metagenomic sequencing. We performed traditional unsupervised correspondence analysis and linear mixed effect modelling regression to assess the bacteria and functional pathways significantly affected by these covariates.Results/Key findings. NH resident microbiomes demonstrated temporal stability (PERMANOVA P=0.001) and differing dysbiotic associations with increasing age, frailty and malnutrition scores. As residents aged, the abundance of microbiota-encoded genes and pathways related to essential amino acid, nitrogenous base and vitamin B production declined. With increasing frailty, residents had lower abundances of butyrate-producing organisms, which are associated with increased health and higher abundances of known dysbiotic species. As residents became malnourished, butyrate-producing organisms declined and dysbiotic bacterial species increased. Finally, the microbiome of residents living in proximity shared similar species and, as demonstrated for Escherichia coli, similar strains. CONCLUSION: These findings support the conclusion that a signature 'NH' microbiota may exist that is affected by the residents' age, frailty, nutritional status and physical location.