scholarly journals THE INFLUENCE OF LIFE-EXTENDING MUTATION AND DIETARY INTERVENTION ON GUT MICROBIOTA

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S834-S834
Author(s):  
Michal Masternak ◽  
Denise S Wiesenborn ◽  
Augusto Schneider ◽  
Till Strowig ◽  
Karl –Herbert Schafer ◽  
...  

Abstract The gastrointestinal microbiota represents a large and complex ecological system of different microorganisms. Recently, there is an increasing interest in the impact of microbiota on development of different age-related diseases. We tested the changes of gut microbiota during development in long-living Ames dwarf (df/df) mice and we compared the effects of this life-extending mutation with the impact of calorie restriction (CR). Importantly, the analysis of microbiome showed significant differences in the ratio of Bacteroidetes and Firmicutes when comparing df/df and normal (N) mice (p<0.001). The LefSe analysis showed distinct microbiome distribution between CR and ad libitum (AL) feeding regimen in N animals (p<0.004), yet there was lack of similar changes in response to CR in df/df mice. In summary, our study showed significant genotype impact on gut microbiota and we showed that life-extending CR regimen provide divergent effects on gut microbiota in N when comparing with df/df mice.

mSystems ◽  
2019 ◽  
Vol 4 (6) ◽  
Author(s):  
Liying Zhang ◽  
Xinhe Xue ◽  
Rui Zhai ◽  
Xin Yang ◽  
Hui Li ◽  
...  

ABSTRACT Calorie restriction (CR) is accompanied by self-imposed daily restriction of food intake and an extended fasting period between meals. The impact of restricting feeding to the dark or light phase on the effects of CR remains elusive. Here, light-fed CR mice showed physiological changes, such as muscle loss, concomitant with changes in the gut microbiota structure and composition. After switching to ad libitum access to food, light-fed mice had a period of food-craving behavior and short-lived physiological changes, while dark-fed mice displayed lasting changes in fat accumulation, glucose metabolism, intestinal barrier function, and systemic inflammatory markers. Moreover, the gut microbiota was modulated by when the food was consumed, and the most abundant Lactobacillus operational taxonomic unit (OTU) promoted by CR was enhanced in dark-fed mice. After switching to ad libitum feeding, the gut microbiota of dark-fed mice returned to the state resembling that of mice fed normal chow ad libitum, but that of light-fed mice was still significantly different from the other two groups. Together, these data indicate that for CR, restricting food consumption to the active phase brought better metabolic phenotype associated with potentially beneficial structural shifts in the gut microbiota. IMPORTANCE Aberrant feeding patterns whereby people eat more frequently throughout the day and with a bias toward late-night eating are prevalent in society today. However, whether restriction of food to daytime in comparison to nighttime, coupled with restricted calorie intake, can influence gut microbiota, metabolism, and overall health requires further investigation. We surveyed the effects of the shift in feeding time on gut microbiota and metabolic phenotype in calorie-restricted mice and found that avoiding eating during the rest period may generate more beneficial effects in mice. This work strengthens the evidence for using “when to eat” as an intervention to improve health during calorie restriction.


2020 ◽  
Author(s):  
Abbi R. Hernandez ◽  
Quinten P. Federico ◽  
Sara N. Burke

AbstractDeclining health and cognition are hallmarks of advanced age that reduce both the quality and length of the lifespan. While caloric restriction has been highlighted as a dietary intervention capable of improving the healthspan by restoring metabolic function in late life, time-restricted feeding and changes in dietary macronutrient composition may be more feasible alternatives with similar health outcomes. To investigate the potential of these two interventions, a pilot cohort of fully mature adult rats were placed on a time-restricted feeding regimen of a ketogenic or micronutrient and calorically matched control diet from 8 to 21 months of age. A third group of rats was permitted to eat standard chow ad libitum. At 22 months, all rats were then placed on time-restricted feeding and tested on a biconditional association task. While the data presented here are preliminary (small sample size of 3-4/diet group), additional animals are currently undergoing the feeding regimen, and will be added into the behavioral studies at a later date. For the current data, regardless of dietary composition, time-restricted-fed rats performed significantly better than ad libitum-fed rats. This observation could not be accounted for by differences in motivation, procedural or sensorimotor impairments, indicating that mid-life dietary interventions capable of preventing metabolic impairments may also serve to prevent age-related cognitive decline.


2019 ◽  
Vol 75 (7) ◽  
pp. e1-e8 ◽  
Author(s):  
Denise S Wiesenborn ◽  
Eric J C Gálvez ◽  
Lina Spinel ◽  
Berta Victoria ◽  
Brittany Allen ◽  
...  

Abstract The gut microbiome (GM) represents a large and very complex ecosystem of different microorganisms. There is an extensive interest in the potential role of the GM in different diseases including cancer, diabetes, cardiovascular diseases, and aging. The GM changes over the lifespan and is strongly associated with various age-related diseases. Ames dwarf (df/df) mice are characterized by an extended life- and healthspan, and although these mice are protected from many age-related diseases, their microbiome has not been studied. To determine the role of microbiota on longevity animal models, we investigated the changes in the GM of df/df and normal control (N) mice, by comparing parents before mating and littermate mice at three distinct time points during early life. Furthermore, we studied the effects of a 6-month calorie restriction (CR), the most powerful intervention extending the lifespan. Our data revealed significant changes of the GM composition during early life development, and we detected differences in the abundance of some bacteria between df/df and N mice, already in early life. Overall, the variability of the microbiota by genotype, time-point, and breeding pair showed significant differences. In addition, CR caused significant changes in microbiome according to gastrointestinal (GI) location (distal colon, ileum, and cecum), genotype, and diet. However, the overall impact of the genotype was more prominent than that of the CR. In conclusion, our findings suggest that the gut microbiota plays an important role during postnatal development in long-living df/df mice and CR dietary regimen can significantly modulate the GM.


2021 ◽  
Vol 22 (4) ◽  
pp. 1665
Author(s):  
Guglielmina Chimienti ◽  
Anna Picca ◽  
Flavio Fracasso ◽  
Francesco Russo ◽  
Antonella Orlando ◽  
...  

Calorie restriction (CR) is the most efficacious treatment to delay the onset of age-related changes such as mitochondrial dysfunction. However, the sensitivity of mitochondrial markers to CR and the age-related boundaries of CR efficacy are not fully elucidated. We used liver samples from ad libitum-fed (AL) rats divided in: 18-month-old (AL-18), 28-month-old (AL-28), and 32-month-old (AL-32) groups, and from CR-treated (CR) 28-month-old (CR-28) and 32-month-old (CR-32) counterparts to assay the effect of CR on several mitochondrial markers. The age-related decreases in citrate synthase activity, in TFAM, MFN2, and DRP1 protein amounts and in the mtDNA content in the AL-28 group were prevented in CR-28 counterparts. Accordingly, CR reduced oxidative mtDNA damage assessed through the incidence of oxidized purines at specific mtDNA regions in CR-28 animals. These findings support the anti-aging effect of CR up to 28 months. Conversely, the protein amounts of LonP1, Cyt c, OGG1, and APE1 and the 4.8 Kb mtDNA deletion content were not affected in CR-28 rats. The absence of significant differences between the AL-32 values and the CR-32 counterparts suggests an age-related boundary of CR efficacy at this age. However, this only partially curtails the CR benefits in counteracting the generalized aging decline and the related mitochondrial involvement.


Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Liang Xie ◽  
Rikeish R Muralitharan ◽  
Evany Dinakis ◽  
Michael E Nakai ◽  
Hamdi Jama ◽  
...  

High fibre (HF) diet protects against hypertension via the production of acidic metabolites, e.g. short-chain fatty acids, by the gut microbiota. While these metabolites have a direct role in blood pressure (BP) regulation, their acidic nature may activate proton-sensing receptors, which have anti-inflammatory functions. G-protein coupled receptor 65 (GPR65) is a proton-sensing receptor activated around pH 6.5 and is critical for gut homeostasis. We hypothesized that GPR65 is involved in the cardiovascular protection by dietary fibre. We first measured cecal pH of C57BL/6 (WT) mice after a 7-day dietary intervention with either HF or low fibre (LF) diets (n=6/group). HF diet lowered cecal pH to a level where GPR65 is highly activated, compared to the LF diet (6.5±0.1 vs 7.6±0.1, P<0.001). The impact of pH and GPR65 on T cell production of IFNγ, a pro-inflammatory cytokine, in vitro was measured by flow cytometry. Acidic pH inhibited the production of IFNγ by CD8+ T cells (pH 6.5 vs pH 7.5, P<0.001). Cells lacking GPR65 had higher IFNγ at both pH (P<0.001). To determine if GPR65 is involved in BP regulation by dietary fibre, WT and GPR65 knockout ( Gpr65 -/- ) mice were implanted with minipumps containing angiotensin II (Ang II, 0.5mg/kg/day, 28 days, n=8-9/group) and fed with HF diet. BP, cardiorenal function and immune cell infiltration were measured. Gpr65 -/- mice had higher BP compared to WT mice after 2 weeks (mean arterial pressure ± SEM; WT 79.8±2.4 vs Gpr65 -/- 95.8±1.6mmHg, P<0.001) and 4 weeks of Ang II infusion (WT 92.3±2.4 vs Gpr65 -/- 99.5±1.3, P=0.062). Gpr65 -/- mice developed cardiac (P=0.035) and renal (P=0.025) hypertrophy, and impaired renal natriuretic (P=0.054) and diuretic (P=0.056) function compared to WT mice. This was accompanied by higher macrophage (P=0.009) and γδ T cell (P=0.014) infiltration in the kidneys. In conclusion, our data suggest that pH-sensing by GPR65 contributes to the protection against hypertension by dietary fibre via inflammatory mechanisms. This is a novel mechanism that contributes to BP regulation via the gut microbiota.


Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3082
Author(s):  
M. Victoria Moreno-Arribas ◽  
Begoña Bartolomé ◽  
José L. Peñalvo ◽  
Patricia Pérez-Matute ◽  
Maria José Motilva

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.


2021 ◽  
Author(s):  
Sabine Hazan ◽  
Sheldon Jordan

Abstract Background: Reports have been surfacing surrounding CNS-associated symptoms in individuals affected by coronavirus disease 19 (COVID-19). Tourette syndrome is a neuropsychiatric disorder with usual onset in childhood. Gut microbiota can affect central physiology and function via the microbiota-gut-brain axis. The authors of this case report describe Tourette’s-like symptoms in a patient resulting from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection disrupting gut microbiota. Case Presentation: This case involves a 16-year-old female that developed acute onset Tourette’s-like symptoms along with neuropsychiatric symptoms after exposure to and infection from SARS-CoV-2. The patient had negative nasopharyngeal (NP) real-time reverse transcription-PCR (RT-PCR) tests for SARS-CoV-2 on five occasions from August of 2020 through June of 2021. The patient’s symptoms continued to worsen over the next six months until next-generation sequencing (NGS) revealed SARS-CoV-2 in her stool. Her treatment was adjusted as NGS revealed SARS-CoV-2 in her stool. Repair of the gastrointestinal microbiota, treatment with nutraceutical and pharmaceutical agents, as well as alterations in her surroundings resulted in dramatic improvement in the microbiome and a significant reduction of symptoms.Discussion: The use of (RT-PCR) testing to determine the presence or absence of SARS-CoV-2 may be inadequate and inaccurate for individuals that have been exposed to the virus. In addition, the impact of SARS-CoV-2 infection of the GI tract may cause significant havoc in the gut microbiota. Additional testing, eradication of infectious agents, as well as restoration of the gut microbiome are needed to effectively manage and treat this condition. The patient’s symptoms worsened over the next six months until next-generation sequencing (NGS) revealed SARS-CoV-2 in her stool and her treatment was adjusted. Treatment with nutraceuticals and alterations in her surroundings was followed by a more normal microbiome and a dramatic reduction in symptoms.


2017 ◽  
Author(s):  
Milton Thomas ◽  
Megan Webb ◽  
Sudeep Ghimire ◽  
Amanda Blair ◽  
Kenneth Olson ◽  
...  

AbstractIn North America, antibiotic feed additives such as monensin and tylosin are added to the finishing diets of feedlot cattle to counter the ill-effects of feeding diets with rapidly digestible carbohydrates. While these feed additives have been proven to improve feed efficiency, and reduce liver abscess incidence, how these products impact the gastrointestinal microbiota is not completely understood. Furthermore, there are concerns that antibiotic feed additives may expand the antibiotic resistome of feedlot cattle by enriching antimicrobial resistance genes in pathogenic and nonpathogenic bacteria in the gut microbiota. In this study, we analyzed the impact of providing antibiotic feed additives to feedlot cattle using metagenome sequencing of treated and untreated animals. Our results indicate that use of antibiotic feed additives does not produce discernable changes at the phylum level however treated cattle had reduced the abundance of gram-positive bacteria at the genus level. The abundance of Ruminococcus, Erysipelotrichaceae and Lachanospira in the gut of treated steers was reduced. This may impact the ability of these animals to exclude pathogens from the gut. However, our results did not show any correlation between the presence of antimicrobial resistance genes in the gut microbiota and the administration of antibiotic feed additives.


2020 ◽  
Author(s):  
Lina Maria Martinez-Lopez ◽  
Amy Pepper ◽  
Rachel Pilla ◽  
Andrew Woodward ◽  
Jan Suchodolski ◽  
...  

Abstract Background Dietary content and environmental factors can shape the gut microbiota, and consequently, the way the gut microbiota metabolises fats, carbohydrates and proteins, affecting overall health of the host. We evaluated the impact of 3 diets (high protein, high fibre and hypoallergenic [hydrolysed protein]) diets on the gut microbiota of healthy dogs in a cross-over sequential study. Results We showed that diet can have a large effect on the gut microbiome in dogs, regardless of the order of feeding. High-protein (all meat) diets were characterised by an increase in bacteria belonging to the Fusobacteria and Bacteroidetes phyla, whereas a high-fibre commercial diet correlated with increases in Firmicutes and Actinobacteria phyla. However, the individual dog’s baseline microbiota had the most impact on the magnitude and nature of the changes in response to dietary intervention. Conclusion Our results suggest that the dog faecal microbiome is driven by protein and fibre composition, and targeted modification of these patterns could be useful in the modulation of the gut microbiota in different diseases.


2021 ◽  
Vol 28 (4) ◽  
pp. 5-13
Author(s):  
Marcello Mikhael Kadharusman ◽  
Radiana Dhewayani Antarianto ◽  
Novi Silvia Hardiany

Calorie restriction (CR) prolongs lifespan in various species and also minimises pathologies caused by aging. One of the characteristics seen in age-related pathologies is stem cell exhaustion. Here, we review the various impacts of CR on mammalian health mediated through stem cell potency in various tissues. This study comprised of a literature search through NCBI, Science Direct, Google Scholar and PubMed, focusing on the impact of CR on pluripotency. In the skeletal muscle, CR acts as an anti-inflammatory agent and increases the presence of satellite cells endogenously to improve regeneration, thus causing a metabolic shift to oxidation to meet oxygen demand. In the intestinal epithelium, CR suppresses the mechanistic target of rapamycin complex 1 (mTORC1) signalling in Paneth cells to shift the stem cell equilibrium towards self-renewal at the cost of differentiation. In haematopoiesis, CR prevents deterioration or maintains the function of haematopoietic stem cells (HSCs) depending on the genetic variation of the mice. In skin and hair follicles, CR increases the thickness of the epidermis and hair growth and improves hair retention through stem cells. CR mediates the proliferation and self-renewal of stem cells in various tissues, thus increasing its regenerative ability.


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