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.

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Abstract TP108: Dendritic Cells Mediate the Detrimental Effects of Age-related Gut Dysbiosis After Stroke

Stroke ◽

10.1161/str.51.suppl_1.tp108 ◽

2020 ◽

Vol 51 (Suppl_1) ◽

Author(s):

Pedram Honarpisheh ◽

John d'Aigle ◽

Alexis S. Mobley ◽

William W. Won ◽

J Jesus Bautista Garrido ◽

...

Keyword(s):

Dendritic Cells ◽

Gut Microbiota ◽

Low Grade ◽

Middle Aged ◽

Stroke Outcomes ◽

Mhc Ii ◽

Gut Dysbiosis ◽

Age Related ◽

Specific Manner ◽

Migratory Phenotype

Aging is a non-modifiable risk factor for stroke. Aging is accompanied by chronic low-grade inflammation and gut dysbiosis (a pathological imbalance of microbial organisms in the gut). Age-related gut dysbiosis exacerbates stroke outcomes and can be reversed by manipulation of the gut microbiota (GM) via fecal microbiota transplants (FMTs) from young animals, or “rejuvenation.” But, the mechanisms that mediate these effects are poorly understood. Dendritic cells (DCs) are potent antigen presenting cells and uniquely equipped to mediate the effects of dysbiosis. DCs constantly sample their environment to regulate the inflammatory response to antigens and tissue injury. In this study we investigated the role of intestinal DCs in mediating the detrimental effects of dysbiosis on stroke outcomes. We hypothesize that age-related dysbiosis exacerbates stroke outcomes by inducing an inflammatory and migratory phenotype in intestinal DCs. We studied four cohorts of C57Bl6 mice consisting of (1) naïve young (4mo), (2) naïve aged (22-26mo), (3) middle-aged (14mo) with FMT from aged donors, and (4) naïve young with 60-min middle cerebral artery occlusion (MCAO). Phenotyping of DCs by flow cytometry was performed. Results: In our MCAO cohort, we found a significant increase in activated DCs in the gut (1.4% vs. 7.6%, p = 0.051) but a decrease in frequency of activated DCs in the brain (8.4% vs. 3.9%, p = 0.042). In our FMT cohort, frequency of intestinal DCs was altered in a subset-specific manner after FMT from aged donors. Specifically, our data showed that the MHC-II expression by DC subsets with a migratory phenotype (CD11b + DCs) and resident DCs (CD103 + DCs) were significantly increased when middle-aged mice received FMT from aged donors (p < 0.05). In our naïve cohorts, we found a significant decrease of MHC-II surface expression in brain DCs (p = 0.044) and a significant increase in splenic DCs (p = 0.049) with aging. Conclusion: Our findings show that frequency and maturity state of DCs significantly differ with aging in a tissue- specific manner and can be influenced by manipulation of the gut microbiota. Our data also support the notion that intestinal DCs are involved in mediating the detrimental effects of age-related gut dysbiosis on stroke outcomes.

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Endokrinológiai tényezők és metabolikus folyamatok szerepe az élettartam szabályozásában

Orvosi Hetilap ◽

10.1556/650.2021.32200 ◽

2021 ◽

Vol 162 (33) ◽

pp. 1318-1327

Author(s):

Tamás Halmos ◽

Ilona Suba

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Life Expectancy ◽

Significant Risk ◽

Low Grade ◽

Aging Effects ◽

Protective Function ◽

Beneficial Effects ◽

Age Related

Összefoglaló. Az emberek a lehető leghosszabb ideig akarnak élni, jó egészségben. Ha kiküszöbölnénk a kedvezőtlen külső körülményeket, a várható élettartam meghaladhatná a 100 évet. A 20. és 21. században a jóléti társadalmakban a várható élettartam jelentősen megnőtt, így Magyarországon is. Az áttekintett irodalom alapján megvizsgáltuk, hogy a genetika és az öröklődés mellett milyen endokrinológiai és metabolikus tényezők játszanak szerepet az élet meghosszabbításában. Megvizsgáltunk minden endogén tényezőt, amely pozitívan vagy negatívan befolyásolhatja az életkorral összefüggő betegségeket (Alzheimer-kór, szív- és érrendszeri betegségek, rák) és az élettartamot. Kiemeltük a hyperinsulinaemia, az inzulinrezisztencia, a metabolikus szindróma öregedést gyorsító hatását, az inzulinszerű növekedési hormon-1 ellentmondásos szerepét, valamint az élet meghosszabbításában részt vevő, újabban felfedezett peptideket, mint a klotho és a humanin. Ismertettük a mitochondriumok szerepét az élettartam meghatározásában, bemutattuk a mitohormesis folyamatát és annak stresszvédő funkcióját. Bemutattuk a rapamicin célszervét, az mTOR-t, amelynek gátlása meghosszabbítja az élettartamot, valamint a szirtuinokat. Kitértünk az autophagia folyamatára, és ismertettük a szenolitikumok szerepét az öregedésben. Az időskori autoimmunitás csökkenése hozzájárul az élettartam rövidüléséhez, utaltunk a thymus koordináló szerepére. Kiemeltük a bélmikrobiom fontos szerepét az élettartam szabályozásában. Hivatkoztunk a „centenáriusok” megfigyeléséből nyert humánadatokra. Megvizsgáltuk, milyen beavatkozási lehetőségek állnak rendelkezésre az egészségben tölthető élettartam meghosszabbításához. Az életmódbeli lehetőségek közül kiemeltük a kalóriabevitel-csökkentés és a testmozgás jótékony szerepét. Megvizsgáltuk egyes gyógyszerek feltételezett hatásait. Ezek közé tartozik a metformin, az akarbóz, a rezveratrol. E gyógyszerek mindegyikének hatása hasonló a kalóriamegszorításéhoz. Nincs olyan „csodaszer”, amely igazoltan meghosszabbítja az élettartamot emberben. Egyes géneknek és génmutációknak jótékony hatásuk van, de ezt környezeti tényezők, betegségek, balesetek és más külső ártalmak módosíthatják. Kiemeljük az elhízás, az alacsony fokozatú gyulladás és az inzulinrezisztencia öregedésre gyakorolt gyorsító hatását. A metabolikus szindróma elterjedtsége miatt ez jelentős népegészségügyi kockázatot jelent. Az inzulin, a növekedési hormon és az inzulinszerű növekedési faktorok hatásainak értékelése továbbra is ellentmondásos. Az egészséges, szellemileg és fizikailag aktív életmód, a kalóriacsökkentés mindenképpen előnyös. Az életet meghosszabbító szerek értékelése még vitatott. Orv Hetil. 2021; 162(33): 1318–1327. Summary. People want to live as long as possible in good health. If we eliminate the unfavorable external conditions, the life expectancy could exceed 100 years. In the 20th and 21th centuries, life expectancy in welfare societies increased significantly, including in Hungary. Based on the reviewed literature, we examined what endocrinological and metabolic factors play a role in prolonging life in addition to genetics and inheritance. We examined all endogenous factors that can positively or negatively affect age-related diseases (Alzheimer’s disease, cardiovascular disease, cancer) and longevity. We highlighted the aging effects of hyperinsulinemia, insulin resistance, metabolic syndrome, the controversial role of insulin-like growth factor-1, and more recently discovered peptides involved in prolonging lifespan, such as klotho and humanin. We described the role of mitochondria in determining longevity, we demonstrated the process of mitohormesis and its stress-protective function. We presented the target organ of rapamycin, mTOR, the inhibition of which prolongs lifespan, as well as sirtuins. We covered the process of autophagy and described the role of senolytics in aging. The decrease in autoimmunity in old age contributes to the shortening of life expectancy, we referred to the coordinating role of the thymus. We highlighted the important role of intestinal microbiome in the regulation of longevity. We referred to human data obtained from observations on “centenarians”. We examined what intervention options are available to prolong healthy life expectancy. Among the lifestyle options, we highlighted the beneficial role of calorie reduction and exercise. We examined the putative beneficial effects of some drugs. These include metformin, acarbose, resveratrol. The effect of each of these drugs is similar to calorie restriction. There is no “miracle cure” that has been shown to prolong life-span in humans. Some genes and gene mutations have beneficial effects, but this can be modified by environmental factors, diseases, accidents, and other external harms. We highlight the accelerating effects of obesity, low-grade inflammation, and insulin resistance on aging. Due to the prevalence of metabolic syndrome, this poses a significant risk to public health. The assessment of the effects of insulin, growth hormone, and insulin-like growth factors remains controversial. A healthy, mentally and physically active lifestyle, calorie reduction is definitely beneficial. The evaluation of life-prolonging agents is still controversial. Orv Hetil. 2021; 162(33): 1318–1327.

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Role of Biological Sex in the Cardiovascular-Gut Microbiome Axis

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.759735 ◽

2022 ◽

Vol 8 ◽

Author(s):

Shuangyue Li ◽

Georgios Kararigas

Keyword(s):

Gut Microbiota ◽

Gut Microbiome ◽

Microbial Composition ◽

Biological Sex ◽

Technological Advances ◽

Host Health ◽

Health And Disease ◽

And Function ◽

Insight Into

There has been a recent, unprecedented interest in the role of gut microbiota in host health and disease. Technological advances have dramatically expanded our knowledge of the gut microbiome. Increasing evidence has indicated a strong link between gut microbiota and the development of cardiovascular diseases (CVD). In the present article, we discuss the contribution of gut microbiota in the development and progression of CVD. We further discuss how the gut microbiome may differ between the sexes and how it may be influenced by sex hormones. We put forward that regulation of microbial composition and function by sex might lead to sex-biased disease susceptibility, thereby offering a mechanistic insight into sex differences in CVD. A better understanding of this could identify novel targets, ultimately contributing to the development of innovative preventive, diagnostic and therapeutic strategies for men and women.

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Spring mineral water-borne bacteria reshape gut microbiota profiles and confer health benefits

10.1101/433821 ◽

2018 ◽

Author(s):

YP Chen ◽

LL Tan ◽

DM Chen ◽

Q Xu ◽

JP Song ◽

...

Keyword(s):

Gut Microbiota ◽

Mineral Water ◽

Chromosomal Dna ◽

Local Resident ◽

Mitochondrial Dysfunctions ◽

Sulfate Reducing ◽

Beneficial Effects ◽

Gut Dysbiosis ◽

Live Bacteria ◽

Reducing Bacteria

BackgroundAlthough dietary patterns are recognized to affect health by interfering with gut microbiota homeostasis, whether live or dead bacteria-bearing spring mineral water (MW) would also exert beneficial effects on health upon curing gut dysbiosis remains unknown.ResultsDue to harboring live bacteria, the heated but unboiled MW from Bama, where centenarians are ubiquitously inhabited, reshapes the gut microbiota from a traveler-type to a local resident-type except for Prevotella. While chondroitin sulfate, a component occurring in livestock and poultry meats, increases the richness of sulfatase-secreting bacteria and sulfate-reducing bacteria, Bama MW dampens the overgrowth of those colon-thinning bacteria and hampers the overexpression of multiple genes responsible for anti-inflammation, anti-oxidation, anti-hypoxia, anti-mutagenesis, and anti-tumorigenesis.ConclusionsBama spring MW prevents the early-phase onset of breast cancer by curating gut dysbiosis. MW also compromises chromosomal DNA damage and ameliorate mitochondrial dysfunctions, implying it may extend lifespan.

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Underdevelopment of the gut microbiota and bacteria species as non-invasive markers of prediction in children with autism spectrum disorder

Gut ◽

10.1136/gutjnl-2020-324015 ◽

2021 ◽

pp. gutjnl-2020-324015

Author(s):

Yating Wan ◽

Tao Zuo ◽

Zhilu Xu ◽

Fen Zhang ◽

Hui Zhan ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Gut Microbiota ◽

Gut Microbiome ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Chinese Children ◽

Chronological Age ◽

Microbiome Composition ◽

Children With Asd ◽

Faecal Microbiome

ObjectiveThe gut microbiota has been suggested to play a role in autism spectrum disorder (ASD). We postulate that children with ASD harbour an altered developmental profile of the gut microbiota distinct from that of typically developing (TD) children. Here, we aimed to characterise compositional and functional alterations in gut microbiome in association with age in children with ASD and to identify novel faecal bacterial markers for predicting ASD.DesignWe performed deep metagenomic sequencing in faecal samples of 146 Chinese children (72 ASD and 74 TD children). We compared gut microbial composition and functions between children with ASD and TD children. Candidate bacteria markers were identified and validated by metagenomic analysis. Gut microbiota development in relation to chronological age was assessed using random forest model.ResultsASD and chronological age had the most significant and largest impacts on children’s faecal microbiome while diet showed no correlation. Children with ASD had significant alterations in faecal microbiome composition compared with TD children characterised by increased bacterial richness (p=0.021) and altered microbiome composition (p<0.05). Five bacterial species were identified to distinguish gut microbes in ASD and TD children, with areas under the receiver operating curve (AUC) of 82.6% and 76.2% in the discovery cohort and validation cohort, respectively. Multiple neurotransmitter biosynthesis related pathways in the gut microbiome were depleted in children with ASD compared with TD children (p<0.05). Developing dynamics of growth-associated gut bacteria (age-discriminatory species) seen in TD children were lost in children with ASD across the early-life age spectrum.ConclusionsGut microbiome in Chinese children with ASD was altered in composition, ecological network and functionality compared with TD children. We identified novel bacterial markers for prediction of ASD and demonstrated persistent underdevelopment of the gut microbiota in children with ASD which lagged behind their respective age-matched peers.

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The Gut Microbiome, Aging, and Longevity: A Systematic Review

Nutrients ◽

10.3390/nu12123759 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3759

Author(s):

Varsha D. Badal ◽

Eleonora D. Vaccariello ◽

Emily R. Murray ◽

Kasey E. Yu ◽

Rob Knight ◽

...

Keyword(s):

Systematic Review ◽

Older Adults ◽

Gut Microbiota ◽

Gut Microbiome ◽

Oldest Old ◽

Amino Acid Synthesis ◽

Old Adults ◽

Age Related ◽

Functional Features ◽

Functional Pathways

Aging is determined by complex interactions among genetic and environmental factors. Increasing evidence suggests that the gut microbiome lies at the core of many age-associated changes, including immune system dysregulation and susceptibility to diseases. The gut microbiota undergoes extensive changes across the lifespan, and age-related processes may influence the gut microbiota and its related metabolic alterations. The aim of this systematic review was to summarize the current literature on aging-associated alterations in diversity, composition, and functional features of the gut microbiota. We identified 27 empirical human studies of normal and successful aging suitable for inclusion. Alpha diversity of microbial taxa, functional pathways, and metabolites was higher in older adults, particularly among the oldest-old adults, compared to younger individuals. Beta diversity distances significantly differed across various developmental stages and were different even between oldest-old and younger-old adults. Differences in taxonomic composition and functional potential varied across studies, but Akkermansia was most consistently reported to be relatively more abundant with aging, whereas Faecalibacterium, Bacteroidaceae, and Lachnospiraceae were relatively reduced. Older adults have reduced pathways related to carbohydrate metabolism and amino acid synthesis; however, oldest-old adults exhibited functional differences that distinguished their microbiota from that of young-old adults, such as greater potential for short-chain fatty acid production and increased butyrate derivatives. Although a definitive interpretation is limited by the cross-sectional design of published reports, we integrated findings of microbial composition and downstream functional pathways and metabolites, offering possible explanations regarding age-related processes.

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High Oscillospira abundance indicates constipation and low BMI in the Guangdong Gut Microbiome Project

Scientific Reports ◽

10.1038/s41598-020-66369-z ◽

2020 ◽

Vol 10 (1) ◽

Cited By ~ 3

Author(s):

Yi-ran Chen ◽

Hui-min Zheng ◽

Guo-xia Zhang ◽

Fang-lan Chen ◽

Li-dan Chen ◽

...

Keyword(s):

Blood Pressure ◽

Gut Microbiota ◽

Gut Microbiome ◽

Fasting Blood Glucose ◽

Density Lipoprotein ◽

Sleep Time ◽

Host Health ◽

Low Bmi ◽

Gut Microbial Community ◽

Fold Cross Validation

Abstract Oscillospira is a common yet rarely cultivated gut bacterial genus. Recently human gut microbiota studies have demonstrated its underlying significance for host health. However, little is known about Oscillospira-related host information and the links between Oscillospira and other members of the gut microbial community. To study the ecology of Oscillospira and gain insights into Oscillospira-related host physiological conditions, we analyzed data from the Guangdong Gut Microbiome Project, one of the largest gut microbiota database currently. Data of 6376 participants were analyzed. We studied the prevalence and relative abundance of Oscillospira as well as the profiles of associated microbial communities. We found that Oscillospira is closely related to human health because its abundance was positively correlated with microbial diversity, high density lipoprotein, and sleep time, and was inversely correlated with diastolic blood pressure, systolic blood pressure, fasting blood glucose, triglyceride, uric acid and Bristol stool type. Moreover, random forest analysis with five-fold cross validation showed Oscillospira could be a predictor of low BMI and constipation in the subset. Overall, in this study, we provide a basic understanding of Oscillospira-related microbiota profile and physiological parameters of the host. Our results indicate Oscillospira may play a role in aggravating constipation.

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Gut Microbiome: Profound Implications for Diet and Disease

Nutrients ◽

10.3390/nu11071613 ◽

2019 ◽

Vol 11 (7) ◽

pp. 1613 ◽

Cited By ~ 83

Author(s):

Ronald Hills ◽

Benjamin Pontefract ◽

Hillary Mishcon ◽

Cody Black ◽

Steven Sutton ◽

...

Keyword(s):

Gut Microbiota ◽

Gut Microbiome ◽

Bacterial Species ◽

Intestinal Bacteria ◽

Short Chain Fatty Acids ◽

E Coli ◽

Beneficial Effects ◽

Microbial Profile ◽

Irritable Bowel ◽

Prebiotic Fiber

The gut microbiome plays an important role in human health and influences the development of chronic diseases ranging from metabolic disease to gastrointestinal disorders and colorectal cancer. Of increasing prevalence in Western societies, these conditions carry a high burden of care. Dietary patterns and environmental factors have a profound effect on shaping gut microbiota in real time. Diverse populations of intestinal bacteria mediate their beneficial effects through the fermentation of dietary fiber to produce short-chain fatty acids, endogenous signals with important roles in lipid homeostasis and reducing inflammation. Recent progress shows that an individual’s starting microbial profile is a key determinant in predicting their response to intervention with live probiotics. The gut microbiota is complex and challenging to characterize. Enterotypes have been proposed using metrics such as alpha species diversity, the ratio of Firmicutes to Bacteroidetes phyla, and the relative abundance of beneficial genera (e.g., Bifidobacterium, Akkermansia) versus facultative anaerobes (E. coli), pro-inflammatory Ruminococcus, or nonbacterial microbes. Microbiota composition and relative populations of bacterial species are linked to physiologic health along different axes. We review the role of diet quality, carbohydrate intake, fermentable FODMAPs, and prebiotic fiber in maintaining healthy gut flora. The implications are discussed for various conditions including obesity, diabetes, irritable bowel syndrome, inflammatory bowel disease, depression, and cardiovascular disease.

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Cartilage-gut-microbiome axis: a new paradigm for novel therapeutic opportunities in osteoarthritis

RMD Open ◽

10.1136/rmdopen-2019-001037 ◽

2019 ◽

Vol 5 (2) ◽

pp. e001037 ◽

Cited By ~ 11

Author(s):

Jean-Marie Berthelot ◽

Jérémie Sellam ◽

Yves Maugars ◽

Francis Berenbaum

Keyword(s):

Gut Microbiota ◽

Gut Microbiome ◽

Cartilage Degradation ◽

Low Grade ◽

New Paradigm ◽

Healthy Human ◽

Human Cartilage ◽

Intact Cartilage ◽

Low Grade Inflammation

DNA of gut microbiota can be found in synovium of osteoarthritis and rheumatoid arthritis. This finding could result from the translocation of still alive bacteria from gut to joints through blood, since the diversified dormant microbiota of healthy human blood can be transiently resuscitated in vitro. The recent finding of gut microbiome in human cartilage, which differed between osteoarthritis and controls, suggests that a similar trafficking of dead or alive bacteria from gut microbiota physiologically occurs between gut and epiphysial bone marrow. Subchondral microbiota could enhance cartilage healing and transform components of deep cartilage matrix in metabolites with immunosuppressive properties. The differences of microbiome observed between hip and knee cartilage, either in osteoarthritis or controls, might be the counterpart of subtle differences in chondrocyte metabolism, themselves in line with differences in DNA methylation according to joints. Although bacteria theoretically cannot reach chondrocytes from the surface of intact cartilage, some bacteria enter the vascular channels of the epiphysial growth cartilage in young animals, whereas others can infect chondrocytes in vitro. In osteoarthritis, the early osteochondral plate angiogenesis may further enhance the ability of microbiota to locate close to the deeper layers of cartilage, and this might lead to focal dysbiosis, low-grade inflammation, cartilage degradation, epigenetic changes in chondrocytes and worsening of osteoarthritis. More studies on cartilage across different ethnic groups, weights, and according to age, are needed, to confirm the silent presence of gut microbiota close to human cartilage and better understand its physiologic and pathogenic significance.

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