Longitudinal development of the gut microbiota in healthy and diarrheic piglets induced by age‐related dietary changes

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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Gut Microbiota Is Involved in Alcohol-Induced Osteoporosis in Young and Old Rats Through Immune Regulation

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.636231 ◽

2021 ◽

Vol 11 ◽

Author(s):

Ming Cheng ◽

Bo Tan ◽

Xiaojing Wu ◽

Feng Liao ◽

Fei Wang ◽

...

Keyword(s):

Alcohol Consumption ◽

Gut Microbiota ◽

Bone Metabolism ◽

Alcohol Metabolism ◽

Excessive Alcohol Consumption ◽

Young Rats ◽

Age Related ◽

Different Ages ◽

Old Rats

Long-term and excessive alcohol consumption are risk factors for osteoporosis. Excessive drinking can reduce bone density and also cause imbalance of gut microbiota. And gut microbiota can affect bone metabolism through various mechanisms, and the regulation of gut microbiota is closely related to age. However, the effects of gut microbiota on alcohol-induced osteoporosis at different ages are unclear. In this study, young and old rats were used to induce osteoporosis by long-term alcohol consumption, and alcohol metabolism, bone morphology, bone absorption and immune activity of rats were analyzed to determine the effects of alcohol on rats of different ages. In addition, changes of gut microbiota in rats were analyzed to explore the role of gut microbiota in alcohol-induced osteoporosis in rats of different ages. The results showed the ability of alcohol metabolism was only associated with age, but not with alcohol consumption. Long-term alcohol consumption resulted in the changes of bone metabolism regulating hormones, bone loss, activation of receptor activator of NF-κB ligand (RANKL) signaling and inflammatory response. And osteoporosis was more severe in old rats than young rats, suggesting that alcohol-induced osteoporosis is age-related. In addition, long-term drinking also affected the composition of gut microbiota in rats, with a significant increase in the proportion of pro-inflammatory microorganisms. Overall, this study found that long-term alcohol consumption induced osteoporosis and affected the composition of gut microbiota. And alcohol can activate T lymphocytes directly or indirectly by regulating the changes of gut microbiota to produce cytokines, and further activate osteoclasts. In addition, the osteoporosis was more severe in the old rats than young rats, which may be due to the higher diversity and stronger regulation ability of gut microbiota in young rats compared with old rats.

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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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Relationship between Wine Consumption, Diet and Microbiome Modulation in Alzheimer’s Disease

Nutrients ◽

10.3390/nu12103082 ◽

2020 ◽

Vol 12 (10) ◽

pp. 3082

Author(s):

M. Victoria Moreno-Arribas ◽

Begoña Bartolomé ◽

José L. Peñalvo ◽

Patricia Pérez-Matute ◽

Maria José Motilva

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Gut Microbiota ◽

Neurodegenerative Disorder ◽

Current Knowledge ◽

Intestinal Microbiome ◽

Dietary Polyphenols ◽

Age Related ◽

Wine Polyphenols ◽

The Impact

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder leading to the most common form of dementia in elderly people. Modifiable dietary and lifestyle factors could either accelerate or ameliorate the aging process and the risk of developing AD and other age-related morbidities. Emerging evidence also reports a potential link between oral and gut microbiota alterations and AD. Dietary polyphenols, in particular wine polyphenols, are a major diver of oral and gut microbiota composition and function. Consequently, wine polyphenols health effects, mediated as a function of the individual’s oral and gut microbiome are considered one of the recent greatest challenges in the field of neurodegenerative diseases as a promising strategy to prevent or slow down AD progression. This review highlights current knowledge on the link of oral and intestinal microbiome and the interaction between wine polyphenols and microbiota in the context of AD. Furthermore, the extent to which mechanisms bacteria and polyphenols and its microbial metabolites exert their action on communication pathways between the brain and the microbiota, as well as the impact of the molecular mediators to these interactions on AD patients, are described.

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Age-related changes in intestinal permeability and gut microbiota after ischemic stroke

Journal of Neuroimmunology ◽

10.1016/j.jneuroim.2014.08.260 ◽

2014 ◽

Vol 275 (1-2) ◽

pp. 97

Author(s):

Joshua Crapser ◽

Rodney Ritzel ◽

Sarah Doran ◽

Edward Koellhoffer ◽

Anita Patel ◽

...

Keyword(s):

Ischemic Stroke ◽

Gut Microbiota ◽

Intestinal Permeability ◽

Age Related ◽

Age Related Changes

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A Cross-Sectional Study of Compositional and Functional Profiles of Gut Microbiota in Sardinian Centenarians

mSystems ◽

10.1128/msystems.00325-19 ◽

2019 ◽

Vol 4 (4) ◽

Cited By ~ 10

Author(s):

Lu Wu ◽

Tiansheng Zeng ◽

Angelo Zinellu ◽

Salvatore Rubino ◽

David J. Kelvin ◽

...

Keyword(s):

Gut Microbiota ◽

Healthy Aging ◽

High Capacity ◽

Functional Independence ◽

Metagenomic Sequencing ◽

Bifidobacterium Adolescentis ◽

Content Type ◽

Age Related ◽

Genes Encoding ◽

Functional Profiles

ABSTRACT Sardinia, Italy, has a high prevalence of residents who live more than 100 years. The reasons for longevity in this isolated region are currently unknown. Gut microbiota may hold a clue. To explore the role gut microbiota may play in healthy aging and longevity, we used metagenomic sequencing to determine the compositional and functional differences in gut microbiota associated with populations of different ages in Sardinia. Our data revealed that the gut microbiota of both young and elderly Sardinians shared similar taxonomic and functional profiles. A different pattern was found in centenarians. Within the centenarian group, the gut microbiota was correlated with the functional independence measurement of the host. Centenarians had a higher diversity of core microbiota species and microbial genes than those in the young and elderly. We found that the gut microbiota in Sardinian centenarians displayed a rearranged taxonomic pattern compared with those of the young and elderly, featured by depletion of Faecalibacterium prausnitzii and Eubacterium rectale and enriched for Methanobrevibacter smithii and Bifidobacterium adolescentis. Moreover, functional analysis revealed that the microbiota in centenarians had high capacity for central metabolism, especially glycolysis and fermentation to short-chain fatty acids (SCFAs), although the gut microbiota in centenarians was low in genes encoding enzymes involved in degradation of carbohydrates, including fibers and galactose. IMPORTANCE The gut microbiota has been proposed as a promising determinant for human health. Centenarians as a model for extreme aging may help us understand the correlation of gut microbiota with healthy aging and longevity. Here we confirmed that centenarians had microbiota elements usually associated with benefits to health. Our finding of a high capacity of glycolysis and related SCFA production represented a healthy microbiome and environment that is regarded as beneficial for host gut epithelium. The low abundance of genes encoding components of pathways involved in carbohydrate degradation was also found in the gut microbiota of Sardinian centenarians and is often associated with poor gut health. Overall, our study here represents an expansion of previous research investigating the age-related changes in gut microbiota. Furthermore, our study provides a new prospective for potential targets for gut microbiota intervention directed at limiting gut inflammation and pathology and enhancing a healthy gut barrier.

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2461 Increasing butyrate levels by microbial manipulation or drug administration to delay Parkinson’s disease progression

Journal of Clinical and Translational Science ◽

10.1017/cts.2018.86 ◽

2018 ◽

Vol 2 (S1) ◽

pp. 15-15

Author(s):

Stephanie M. Garcia ◽

Wenbo Zhou ◽

Curt R. Freed

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Cognitive Function ◽

Gut Microbiota ◽

Disease Progression ◽

Sodium Butyrate ◽

Motor Deficit ◽

Behavioral Deficits ◽

Age Related ◽

Sodium Phenylbutyrate

OBJECTIVES/SPECIFIC AIMS: Determine if synthetic or endogenously produced butyrate can delay Parkinson’s disease (PD) progression, attenuate PD associated GI dysfunction, and impact the gut-microbiota in mice expressing human mutant aSyn. METHODS/STUDY POPULATION: Two transgenic mouse models expressing human mutant alpha-synuclein (aSyn) will be used. Transgenic mice expressing aSyn A53T display GI dysfunction before motor deficit onset and will be used to investigate treatment impact on PD associated GI dysfunction. Mice expressing aSyn Y39C more accurately recapitulate age-related neuropathology and behavioral deficits and will be used to assess treatment impact on PD-associated neuropathology, motor, and cognitive function. Mice will receive a synthetic sodium butyrate, sodium phenylbutyrate, or a synbiotic treatment regimen for 3 months. Disease progression will be assessed by aSyn brain and gut neuropathology, brain and gut inflammatory status, behavioral deficits, and gastrointestinal function. In addition, fecal and gut-microbiota composition and neuroprotective gene expression in the brain will be investigated. RESULTS/ANTICIPATED RESULTS: Our preliminary data shows that both sodium butyrate and sodium phenylbutyrate delay disease progression in aSyn Y39C mice. Butyrate-treated mice have reduced aSyn oligomerization, reduced Lewy body formation, and improved motor and cognitive function compared to placebo-treated mice. 16S rRNA sequencing did not reveal fecal-microbiota shifts between treatment groups or with age progression. Further analysis assessing expression levels for genes with anti-oxidant and protein degradation roles will be performed to determine if sodium butyrate and sodium phenylbutyrate similarly impact cellular mechanisms to delay neurodegeneration. Our future experiments will focus on comparing sodium butyrate and synbiotic treatment outcomes in aSyn A53T mice. DISCUSSION/SIGNIFICANCE OF IMPACT: Our lab developed a Tg mouse model that more accurately recapitulate age-related symptoms, pathology, and mechanisms observed in PD patients compared with animal models onset by neurotoxins. Our use of an age-dependent model of a severe form of Parkinsonism, DLB, will better predict clinical outcomes in PD populations. We will be the first to assess if elevating select microbial product production enhances neuroprotective brain activity in a PD model. Results obtained will further characterize gut-brain axis communication mechanisms. These proposed experiments will be the first to determine if elevating microbial products improves GI deficits associated with PD and may lead to insight on the gut-brain axis role in PD. Overall, this proposal will be the first to investigate a novel, highly accessible treatment with the potential to delay PD progression and target motor, cognitive, and GI deficits associated with PD. Due to the current FDA approval of probiotics and prebiotics that enhance butyrate production, results obtained may be quickly translated for clinical use.

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Role of the Gut Microbiota in Age-Related Chronic Inflammation

Endocrine Metabolic & Immune Disorders - Drug Targets ◽

10.2174/187153012803832620 ◽

2012 ◽

Vol 12 (4) ◽

pp. 361-367 ◽

Cited By ~ 36

Author(s):

Tayyab Rehman

Keyword(s):

Gut Microbiota ◽

Chronic Inflammation ◽

Age Related

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Positive Effects of Exercise Intervention without Weight Loss and Dietary Changes in NAFLD-Related Clinical Parameters: A Systematic Review and Meta-Analysis

Nutrients ◽

10.3390/nu13093135 ◽

2021 ◽

Vol 13 (9) ◽

pp. 3135

Author(s):

Ambrin Farizah Babu ◽

Susanne Csader ◽

Johnson Lok ◽

Carlos Gómez-Gallego ◽

Kati Hanhineva ◽

...

Keyword(s):

Weight Loss ◽

Resistance Training ◽

Gut Microbiota ◽

Aerobic Exercise ◽

Density Lipoprotein ◽

Lipoprotein Cholesterol ◽

Clinical Parameters ◽

Significant Weight Loss ◽

Alcoholic Fatty Liver ◽

Dietary Changes

One of the focuses of non-alcoholic fatty liver disease (NAFLD) treatment is exercise. Randomized controlled trials investigating the effects of exercise without dietary changes on NAFLD-related clinical parameters (liver parameters, lipid metabolism, glucose metabolism, gut microbiota, and metabolites) were screened using the PubMed, Scopus, Web of Science, and Cochrane databases on 13 February 2020. Meta-analyses were performed on 10 studies with 316 individuals who had NAFLD across three exercise regimens: aerobic exercise, resistance training, and a combination of both. No studies investigating the role of gut microbiota and exercise in NAFLD were found. A quality assessment via the (RoB)2 tool was conducted and potential publication bias, statistical outliers, and influential cases were identified. Overall, exercise without significant weight loss significantly reduced the intrahepatic lipid (IHL) content (SMD: −0.76, 95% CI: −1.04, −0.48) and concentrations of alanine aminotransaminase (ALT) (SMD: −0.52, 95% CI: −0.90, −0.14), aspartate aminotransaminase (AST) (SMD: −0.68, 95% CI: −1.21, −0.15), low-density lipoprotein cholesterol (SMD: −0.34, 95% CI: −0.66, −0.02), and triglycerides (TG) (SMD: −0.59, 95% CI: −1.16, −0.02). The concentrations of high-density lipoprotein cholesterol, total cholesterol (TC), fasting glucose, fasting insulin, and glycated hemoglobin were non-significantly altered. Aerobic exercise alone significantly reduced IHL, ALT, and AST; resistance training alone significantly reduced TC and TG; a combination of both exercise types significantly reduced IHL. To conclude, exercise overall likely had a beneficial effect on alleviating NAFLD without significant weight loss. The study was registered at PROSPERO: CRD42020221168 and funded by the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement no. 813781.

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The Roles of the Gut Microbiota and Chronic Low-Grade Inflammation in Older Adults With Frailty

Frontiers in Cellular and Infection Microbiology ◽

10.3389/fcimb.2021.675414 ◽

2021 ◽

Vol 11 ◽

Author(s):

YuShuang Xu ◽

XiangJie Liu ◽

XiaoXia Liu ◽

Di Chen ◽

MengMeng Wang ◽

...

Keyword(s):

Older Adults ◽

Gut Microbiota ◽

Chronic Inflammation ◽

Healthy Aging ◽

Low Grade ◽

Age Related ◽

Composition Structure ◽

Low Grade Inflammation

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.

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