scholarly journals Association between Apolipoprotein E genotype and the gut microbiome composition in humans and mice

2018 ◽  
Author(s):  
Tam T.T. Tran ◽  
Simone Corsini ◽  
Lee Kellingray ◽  
Claire Hegarty ◽  
Gwénaëlle Le Gall ◽  
...  
Keyword(s):  
Apolipoprotein E ◽  
Gut Microbiome ◽  
Amplicon Sequencing ◽  
Short Chain Fatty Acids ◽  
Faecal Microbiota ◽  
Potential Therapeutic Target ◽  
Microbiome Composition ◽  
The Impact ◽  
Microbiota Diversity ◽  
Apolipoprotein E Genotype

AbstractApolipoprotein E (APOE) genotype is the strongest prevalent genetic risk factor for Alzheimer’s disease. Numerous studies have provided insights into the pathological mechanisms. However, a comprehensive understanding of the impact ofAPOEgenotype on microflora speciation and metabolism is completely lacking. The aim of this study was to investigate the association betweenAPOEgenotype and the gut microbiome composition in human andAPOE-targeted replacement (TR,APOE3andAPOE4) transgenic mice. Faecal microbiota amplicon sequencing from matched individuals with differentAPOEgenotypes revealed no significant differences in overall microbiota diversity (alpha or beta diversity) in group-aggregated humanAPOEgenotypes. However, several bacterial taxa showed significantly different relative abundance betweenAPOEgenotypes. Notably, we detected an association ofPrevotellaceaeandRuminococcaceaeand several butyrate-producing genera abundances withAPOEgenotypes. These findings were confirmed by comparing the gut microbiota ofAPOE-TR mice. Furthermore, metabolomic analysis of faecal water from murine samples detected significant differences in microbe-associated amino acids and short-chain fatty acids betweenAPOEgenotypes. Together, the findings indicate thatAPOEgenotype associated with specific gut microbiome profiles in both humans and inAPOE-TR mice. This suggests that the gut microbiome is worth further investigation as a potential therapeutic target to mitigate the deleterious impact of theAPOE4allele on cognitive decline and the prevention and treatment of AD.

Associations between gut microbiome, short chain fatty acids and blood pressure across ethnic groups: the HELIUS study

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
B Verhaar ◽  
D Collard ◽  
A Prodan ◽  
J.H.M Levels ◽  
A.H Zwinderman ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Fatty Acids ◽  
Ethnic Groups ◽  
Gut Microbiome ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Funding Source ◽  
Microbiome Composition ◽  
Helius Study ◽  
Chain Fatty Acids

Abstract Background Gut microbiome composition is shaped by a combination of host genetic make-up and dietary habits. In addition, large ethnic differences exist in microbiome composition. Several studies in humans and animals have shown that differences in gut microbiota and its metabolites, including short chain fatty acids (SCFA), are associated with blood pressure (BP). We hypothesized that gut microbiome composition and its metabolites may be differently associated with BP across ethnic groups. Purpose To investigate associations of gut microbiome composition and fecal SCFA levels with BP across different ethnic groups. Methods We assessed the association between gut microbiome composition and office BP among 4672 subjects (mean age 49.8±11.7 years, 52%F) of 6 different ethnic groups participating in the HELIUS study. Gut microbiome composition was determined using 16S rRNA sequencing. Associations between microbiome composition and blood pressure were assessed using machine learning prediction models. The resulting best predictors were correlated with BP using Spearman's rank correlations. Fecal SCFA levels were measured with high-performance liquid chromatography in an age- and body mass index (BMI)-matched subgroup of 200 participants with either extreme low or high systolic BP. Differences in abundances of best predictors and fecal SCFA levels between high and low BP groups were assessed with Mann-Whitney U tests. Results Gut microbiome composition explained 4.4% of systolic BP variance. Best predictors for systolic BP included Roseburia spp. (ρ −0.15, p<0.001), Clostridium spp. (ρ −0.14, p<0.001), Romboutsia spp. (ρ −0.10, p<0.001), and Ruminococceae spp. (ρ −0.15, p<0.001) (Figure 1). Explained variance of the microbiome composition was highest in Dutch subjects (4.8%), but very low in African Surinamese, Ghanaian, and Turkish ethnic groups (ranging from 0–0.77%) Hence, we selected only participants with Dutch ethnicity for the matched subgroup. Participants with high BP had lower abundance of Roseburia hominis (p<0.01) and Roseburia spp. (p<0.05) compared to participants with low BP. However, fecal acetate (p<0.05) and propionate (p<0.01) levels were higher in participants with high BP. Conclusions In this cross-sectional study, gut microbiome composition was moderately associated with BP. Associations were strongly divergent between ethnic groups, with strongest associations in Dutch participants. Intriguingly, while Dutch participants with high BP had lower abundances of several SCFA-producing microbes, they had higher fecal SCFA levels. Intervention studies with SCFAs could provide more insight in the effects of these metabolites on BP. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): The Academic Medical Center (AMC) of Amsterdam and the Public Health Service of Amsterdam (GGD Amsterdam) provided core financial support for HELIUS. The HELIUS study is also funded by research grants of the Dutch Heart Foundation (Hartstichting; grant no. 2010T084), the Netherlands Organization for Health Research and Development (ZonMw; grant no. 200500003), the European Integration Fund (EIF; grant no. 2013EIF013) and the European Union (Seventh Framework Programme, FP-7; grant no. 278901).

scholarly journals Gut microbiome signatures of risk and prodromal markers of Parkinson’s disease

2019 ◽  
Author(s):  
Sebastian Heinzel ◽  
Velma T. E. Aho ◽  
Ulrike Suenkel ◽  
Anna-Katharina von Thaler ◽  
Claudia Schulte ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Gut Microbiome ◽  
Physical Inactivity ◽  
Disease Onset ◽  
Rem Sleep Behavior Disorder ◽  
Sleep Behavior ◽  
Microbiome Composition ◽  
Β Diversity ◽  
The Impact

AbstractObjectivesAlterations of the gut microbiome in Parkinson’s disease (PD) have been repeatedly demonstrated. However, little is known about whether such alterations precede disease onset and how they may be related to risk and prodromal markers of PD. We investigated associations of these features with gut microbiome composition.MethodsEstablished risk and prodromal markers of PD as well as factors related to diet/lifestyle, bowel function and medication were studied in relation to bacterial α-/β-diversity, enterotypes, and taxonomic composition in stool samples of 666 elderly TREND study participants.ResultsAmong risk and prodromal markers, physical inactivity, constipation and age showed associations with α- and β-diversity, and for both measures subthreshold parkinsonism and physical inactivity showed interaction effects. Moreover, male sex, possible REM-sleep behavior disorder (RBD), smoking as well as body-mass-index, antidiabetic and urate-lowering medication were associated with β-diversity. Physical inactivity and constipation severity were increased in individuals with the Firmicutes-enriched enterotype. Subthreshold parkinsonism was least frequently observed in individuals with the Prevotella-enriched enterotype. Differentially abundant taxa were linked to constipation, physical inactivity, possible RBD, and subthreshold parkinsonism. Substantia nigra hyperechogenicity, olfactory loss, depression, orthostatic hypotension, urinary/erectile dysfunction, PD family history and the overall prodromal PD probability showed no significant microbiome associations.InterpretationSeveral risk and prodromal markers of PD are associated with changes in gut microbiome composition. However, the impact of the gut microbiome on PD risk and potential microbiome-dependent subtypes in the prodrome of PD need further investigation based on prospective clinical and (multi)omics data in incident PD cases.

scholarly journals Metabolic phenotyping for understanding the gut microbiome and host metabolic interplay

2017 ◽  
Vol 1 (4) ◽  
pp. 325-332 ◽  
Author(s):  
Abigail R. Basson ◽  
Anisha Wijeyesekera
Keyword(s):  
Gut Microbiome ◽  
Skin Diseases ◽  
Compositional Analysis ◽  
Exciting Field ◽  
Inflammatory Skin Diseases ◽  
Metabolic Phenotyping ◽  
Microbiome Composition ◽  
Host Health ◽  
The Impact ◽  
Analytical Approaches

There is growing interest in the role of the gut microbiome in human health and disease. This unique complex ecosystem has been implicated in many health conditions, including intestinal disorders, inflammatory skin diseases and metabolic syndrome. However, there is still much to learn regarding its capacity to affect host health. Many gut microbiome research studies focus on compositional analysis to better understand the causal relationships between microbial communities and disease phenotypes. Yet, microbial diversity and complexity is such that community structure alone does not provide full understanding of microbial function. Metabolic phenotyping is an exciting field in systems biology that provides information on metabolic outputs taking place in the system at a given moment in time. These readouts provide information relating to by-products of endogenous metabolic pathways, exogenous signals arising from diet, drugs and other lifestyle and environmental stimuli, as well as products of microbe–host co-metabolism. Thus, better understanding of the gut microbiome and host metabolic interplay can be gleaned using such analytical approaches. In this review, we describe research findings focussed on gut microbiota–host interactions, for functional insights into the impact of microbiome composition on host health. We evaluate different analytical approaches for capturing metabolic activity and discuss analytical methodological advancements that have made a contribution to the field. This information will aid in developing novel approaches to improve host health in the future, and therapeutic modulation of the microbiome may soon augment conventional clinical strategies.

scholarly journals Gut Microbiome Modulation Based on Probiotic Application for Anti-Obesity: A Review on Efficacy and Validation

2019 ◽  
Vol 7 (10) ◽  
pp. 456 ◽  
Author(s):  
Kaliyan Barathikannan ◽  
Ramachandran Chelliah ◽  
Momna Rubab ◽  
Eric Banan-Mwine Daliri ◽  
Fazle Elahi ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Molecular Mechanisms ◽  
Short Chain Fatty Acids ◽  
Genetic Profile ◽  
Fecal Transplantation ◽  
Intestinal Microbes ◽  
Prevalence Of Obesity ◽  
Future Direction ◽  
The Impact

The growing prevalence of obesity has become an important problem worldwide as obesity has several health risks. Notably, factors such as excessive food consumption, a sedentary way of life, high sugar consumption, a fat-rich diet, and a certain genetic profile may lead to obesity. The present review brings together recent advances regarding the significance of interventions involving intestinal gut bacteria and host metabolic phenotypes. We assess important biological molecular mechanisms underlying the impact of gut microbiota on hosts including bile salt metabolism, short-chain fatty acids, and metabolic endotoxemia. Some previous studies have shown a link between microbiota and obesity, and associated disease reports have been documented. Thus, this review focuses on obesity and gut microbiota interactions and further develops the mechanism of the gut microbiome approach related to human obesity. Specifically, we highlight several alternative diet treatments including dietary changes and supplementation with probiotics. The future direction or comparative significance of fecal transplantation, synbiotics, and metabolomics as an approach to the modulation of intestinal microbes is also discussed.

scholarly journals The Prebiotic Inulin Beneficially Alters the Gut Microbiome and Associated Metabolites in an APOE4 Mouse Model (P08-133-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Lucille Yanckello ◽  
Jared Hoffman ◽  
Ishita Parikh ◽  
Jessie Hoffman ◽  
Stefan Green ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Dietary Intervention ◽  
Disease Risk ◽  
Short Chain Fatty Acids ◽  
Apoe4 Allele ◽  
Funding Sources ◽  
Tryptophan Metabolites ◽  
Host Metabolism ◽  
Microbiota Diversity

Abstract Objectives The APOE4 allele is a genetic risk factor for certain diseases, due in part to alterations in lipid and glucose metabolism. The gut microbiota is also known to impact metabolic and can be beneficially modulated by prebiotics. Prebiotics are fermented into metabolites by the gut microbiota. These metabolites act as gut-brain axis components. However, the interaction of the APOE4 allele, gut microbiota, and prebiotics are unknown. The goal of the study was to use prebiotic diet to restore the gut microbiome of mice with human APOE4 (E4FAD) genes. We hypothesized that the microbial compositions of E4 mice fed inulin, compared to control fed, will correlate to metabolites being produced by the microbiome that confer benefit to host metabolism. Methods At 3 months of age the E4FAD mice were fed for 4 months with either control or inulin diet. We used 16S rRNA sequencing to determine gut microbiota diversity and species variations; non-targeted UPLC-MS/MS and GC-MS analysis was used to determine metabolic profiles of blood. Results The inulin fed mice showed a more beneficial microbial taxa profile than those mice that were control fed. Control mice showed higher levels of dimethylglycine, choline, creatine and the polyamine spermine. Higher levels of spermine, specifically, correlate to higher levels of the Proteobacteria which has been implicated in GI disorders. E4 inulin fed mice showed higher levels of bile acids, short chain fatty acids and metabolites involved in energy, increased levels of tryptophan metabolites and robust increases in sphingomyelins. Specifically in E4 inulin fed mice we saw increases in certain genera of bacteria, all of which have been implicated in being beneficial to the composition of the microbiome and producing one or more of the above mentioned metabolites. Conclusions We believe the disparities of microbial metabolite production between E4 inulin fed mice and E4 control fed mice can be attributed to differences in certain taxa that produce these metabolites, and that higher levels of these taxa are due to the dietary intervention of inulin. Despite the APOE4 allele increasing one's risk for certain diseases, we believe that beneficially modulating the gut microbiota may be one way to enhance host metabolism and decrease disease risk over time. Funding Sources NIH/NIDDK T323048107792, NIH/NIA R01AG054459, NIEHS/NIH P42ES007380. Supporting Tables, Images and/or Graphs

scholarly journals Gut microbial ecology of Xenopus tadpoles across life stages

2020 ◽  
Author(s):  
Thibault Scalvenzi ◽  
Isabelle Clavereau ◽  
Mickaël Bourge ◽  
Nicolas Pollet
Keyword(s):  
Gut Microbiome ◽  
Essential Amino Acids ◽  
Biological Processes ◽  
Nitrogen Recycling ◽  
16S Rdna Gene ◽  
Microbiome Composition ◽  
Metabolic Interactions ◽  
Molecular Components ◽  
The Impact ◽  
Shed Light

AbstractBackgroundThe microorganism world living in amphibians is still largely under-represented and under-studied in the literature. Among anuran amphibians, African clawed frogs of the Xenopus genus stand as well-characterized models with an in-depth knowledge of their developmental biological processes including their metamorphosis. We used different approaches including flow cytometry and 16s rDNA gene metabarcoding to analyze the succession of microbial communities and their activities across different body habitats of Xenopus tropicalis. We used metagenomic and metatranscriptomic sequencing to evaluate the metabolic capacity of the premetamorphic tadpole’s gut microbiome.ResultsWe analyzed the bacterial components of the Xenopus gut microbiota, the adult gut biogeography, the succession of communities during ontogeny, the impact of the alimentation in shaping the tadpole’s gut bacterial communities, the transmission of skin and fecal bacteria to the eggs. We also identified the most active gut bacteria and their metabolic contribution to tadpole physiology including carbohydrate breakdown, nitrogen recycling, essential amino-acids and vitamin biosynthesis.ConclusionsWe present a comprehensive new microbiome dataset of a laboratory amphibian model. Our data provide evidences that studies on the Xenopus tadpole model can shed light on the interactions between a vertebrate host and its microbiome. We interpret our findings in light of bile acids being key molecular components regulating the gut microbiome composition during amphibian development and metamorphosis. Further studies into the metabolic interactions between amphibian tadpoles and their microbiota during early development and metamorphosis should provide useful information on the evolution of host-microbiota interactions in vertebrates.

scholarly journals Metformin Affects Gut Microbiome Composition and Function and Circulating Short-Chain Fatty Acids: A Randomized Trial

Diabetes Care ◽  
2021 ◽  
pp. dc202257
Author(s):  
Noel T. Mueller ◽  
Moira K. Differding ◽  
Mingyu Zhang ◽  
Nisa M. Maruthur ◽  
Stephen P. Juraschek ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Randomized Trial ◽  
Gut Microbiome ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Microbiome Composition ◽  
And Function ◽  
Chain Fatty Acids

scholarly journals Changes in the Gut Microbiome Community of nonhuman primate following radiation injury

2020 ◽  
Author(s):  
Raj Kalkeri ◽  
Kevin Walters ◽  
William Van Der Pol ◽  
Braden C. McFarland ◽  
Nathan Fisher ◽  
...  
Keyword(s):  
Radiation Exposure ◽  
Gut Microbiome ◽  
Radiation Injury ◽  
Lactobacillus Reuteri ◽  
Whole Body ◽  
High Dose ◽  
Microbiome Composition ◽  
Post Irradiation ◽  
High Doses ◽  
The Impact

Abstract Background Composition and maintenance of the microbiome is vital to gut homeostasis. However, there is limited knowledge regarding the impact of high doses of radiation, which can occur as a result of cancer radiation therapy, nuclear accidents or intentional release of a nuclear or radioactive weapon, on the composition of the gut microbiome. Therefore, we sought to analyze alterations to the gut microbiome of nonhuman primates (NHPs) exposed to high doses of radiation. Methods Fecal samples were collected from 19 NHPs (Chinese rhesus macaques, Macaca mulatta) one day prior and one and four days after exposure to 7.4 Gy cobalt-60 gamma-radiation (LD70 − 80/60). The 16S V4 rRNA sequences were extracted from each sample, followed by bioinformatics analysis using the QIIME platform. Results Alpha Diversity (Shannon Diversity Index), revealed no major difference between pre- and post-irradiation, whereas Beta diversity analysis showed significant differences in the microbiome after irradiation (day + 4) compared to baseline (pre-irradiation). The Firmicutes/Bacteriodetes ratio, a factor known to be associated with disruption of metabolic homeostasis, decreased from 1.2 to less than 1 post-radiation exposure. Actinobacillus, Bacteroides, Prevotella (Paraprevotellaceae family) and Veillonella genera were significantly increased by more than 2-fold and Acinetobacter and Aerococcus genus were decreased by more than 10-fold post-irradiation. Fifty-two percent (10/19) of animals exposed to radiation demonstrated diarrhea at day 4 post-irradiation. Comparison of microbiome composition of feces from animals with and without diarrhea at day 4 post-irradiation revealed an increase in Lactobacillus reuteri associated with diarrhea and a decrease of Lentisphaerae and Verrucomicrobioa phyla and Bacteroides in animals exhibiting diarrhea. Conclusion Our findings demonstrate that substantial alterations in the microbiome composition of NHPs occur following radiation injury and provide insight into early changes with high-dose, whole-body radiation exposure. Future studies will help identify microbiome biomarkers of radiation exposure and develop effective therapeutic intervention to mitigate the radiation injury.

scholarly journals Glyphosate and its formulations Roundup Bioflow and RangerPro alter bacterial and fungal community composition in the rat caecum microbiome

2021 ◽  
Author(s):  
Robin Mesnage ◽  
Simona Panzacchi ◽  
Emma Bourne ◽  
Charles A Mein ◽  
Melissa Perry ◽  
...  
Keyword(s):  
Bacterial Diversity ◽  
Gut Microbiome ◽  
Amplicon Sequencing ◽  
Dependent Manner ◽  
Fungal Community Composition ◽  
Potential Health ◽  
Opportunistic Fungi ◽  
Microbiome Composition ◽  
Bacterial Microbiota ◽  
Multigenerational Effects

The potential health consequences of glyphosate-induced gut microbiome alterations have become a matter of intense debate. As part of a multifaceted study investigating toxicity, carcinogenicity and multigenerational effects of glyphosate and its commercial herbicide formulations, we assessed changes in bacterial and fungal populations in the caecum microbiota of rats exposed prenatally until adulthood (13 weeks after weaning) to three doses of glyphosate (0.5, 5, 50 mg/kg body weight/day), or to the formulated herbicide products Roundup Bioflow and RangerPro at the same glyphosate-equivalent doses. Caecum bacterial microbiota were evaluated by 16S rRNA sequencing whilst the fungal population was determined by ITS2 amplicon sequencing. Results showed that both fungal and bacterial diversity were affected by the Roundup formulations in a dose-dependent manner, whilst glyphosate alone significantly altered only bacterial diversity. At taxa level, a reduction in Bacteroidota abundance, marked by alterations in the levels of Alloprevotella, Prevotella and Prevotellaceae UCG-003, was concomitant to increased levels of Firmicutes (e.g., Romboutsia, Dubosiella, Eubacterium brachy group or Christensenellaceae) and Actinobacteria (e.g., Enterorhabdus, Adlercreutzia, or Asaccharobacter). Treponema and Mycoplasma also had their levels reduced by the pesticide treatments. Analysis of fungal composition indicated that the abundance of the rat gut commensal Ascomycota Kazachstania was reduced while the abundance of Gibberella, Penicillium, Claviceps, Cornuvesica, Candida, Trichoderma and Sarocladium were increased by exposure to the Roundup formulations, but not to glyphosate. Altogether, our data suggest that glyphosate and its Roundup RangerPro and Bioflow caused profound changes in caecum microbiome composition by affecting the fitness of major commensals, which in turn reduced competition and allowed opportunistic fungi to grow in the gut, in particular in animals exposed to the herbicide formulations. This further indicates that changes in gut microbiome composition might influence the long-term toxicity, carcinogenicity and multigenerational effects of glyphosate-based herbicides.

scholarly journals Maternal effects on early-life gut microbiome maturation in a wild nonhuman primate

2021 ◽  
Author(s):  
Alice Baniel ◽  
Lauren Petrullo ◽  
Arianne Mercer ◽  
Laurie Reitsema ◽  
Sierra Sams ◽  
...  
Keyword(s):  
Maternal Effects ◽  
Gut Microbiome ◽  
Early Life ◽  
Amplicon Sequencing ◽  
Microbial Colonization ◽  
Fecal Samples ◽  
Microbiome Composition ◽  
16S Rrna Amplicon Sequencing ◽  
Gut Colonization ◽  
First Time

Early-life gut microbial colonization is an important process shaping host physiology, immunity and long-term health outcomes in humans and other animals. However, our understanding of this dynamic process remains poorly investigated in wild animals, where developmental mechanisms can be better understood within ecological and evolutionary relevant contexts. Using 16s rRNA amplicon sequencing on 525 fecal samples from a large cohort of infant and juvenile geladas (Theropithecus gelada), we characterized gut microbiome maturation during the first three years of life and assessed the role of maternal effects in shaping offspring microbiome assembly. Microbial diversity increased rapidly in the first months of life, followed by more gradual changes until weaning. As expected, changes in gut microbiome composition and function with increasing age reflected progressive dietary transitions: in early infancy when infants rely heavily on their mother's milk, microbes that facilitate milk glycans and lactose utilization dominated, while later in development as graminoids are progressively introduced into the diet, microbes that metabolize plant complex polysaccharides became dominant. Furthermore, the microbial community of nursing infants born to first-time (primiparous) mothers was more "milk-oriented" compared to similarly-aged infants born to experienced (multiparous) mothers. Comparisons of matched mother-offspring fecal samples to random dyads did not support vertical transmission as a conduit for these maternal effects, which instead could be explained by slower phenotypic development (and associated slower gut microbiome maturation) in infants born to first-time mothers. Together, our findings highlight the dynamic nature of gut colonization

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