Altered Gut Microbiome Composition and Tryptic Activity of the 5xFAD Alzheimer’s Mouse Model

2017 ◽  
Vol 56 (2) ◽  
pp. 775-788 ◽  
Author(s):  
Carolin Brandscheid ◽  
Florian Schuck ◽  
Sven Reinhardt ◽  
Karl-Herbert Schäfer ◽  
Claus U. Pietrzik ◽  
...  
Keyword(s):  
Mouse Model ◽  
Gut Microbiome ◽  
Microbiome Composition ◽  
Tryptic Activity

scholarly journals TMOD-19. ELUCIDATING THE RESISTANCE TO IMMUNOTHERAPY IN BRAIN TUMORS USING A HUMANIZED MICROBIOME MOUSE MODEL

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi266-vi266
Author(s):  
Kory Dees ◽  
Hyunmin Koo ◽  
Joseph Hakim ◽  
J Fraser Humphreys ◽  
David Crossman ◽  
...  
Keyword(s):  
Mouse Model ◽  
Tumor Growth ◽  
Mouse Models ◽  
Gut Microbiome ◽  
Standard Of Care ◽  
Similar Efficacy ◽  
Healthy Human ◽  
Human Donor ◽  
Microbiome Composition ◽  
Gut Microbe

Abstract Although the immunotherapy anti-PD-1 works well in glioblastoma (GBM) pre-clinical mouse models, the therapy has not demonstrated a similar efficacy in patient clinical trials. Recent studies have linked the gut microbe composition to tumor growth and response to immunotherapy in some cancers. To date, all GBM pre-clinical studies have been done in mouse models using mouse gut microbiomes. There are significant differences between mouse and human microbial gut compositions, with up to 85% of gut bacteria found in laboratory mice not found in humans. Because it is known that the gut microbe composition can impact the immune system, we hypothesize that the non-responsiveness of GBM patients to immunotherapy may be due to the composition of the gut microbiome. Therefore, we have generated a humanized microbiome mouse model in which mice have been colonized by human donor microbes in their GI tract (two different healthy human donors (HuM1 and HuM2)). In preliminary results, we have found that HuM1 mice are resistant to anti-PD-1, while HuM2 mice are responders to anti-PD-1 in the GL261 syngeneic intracranial model. These mice are genetically identical and only differ in gut microbiome composition. Furthermore, we found that HuM2 mice exhibited a significant increase in cytotoxic CD8+T-cells producing IFN-γ and significant increased CD8+/Treg ratio in the spleen following anti-PD-1 treatment, which was not observed in the HuM1 mice. When testing the efficacy of standard of care temozolomide (TMZ) in our humanized mice, we found that TMZ significantly prolonged survival of both HuM1 and HuM2 mice with intracranial tumors. However, HuM2 mice exhibited superior efficacy (p< 0.001; 57% survival), compared to HuM1 mice (p< 0.01; 0% survival). We are extending these studies to analyze additional humanized microbiome lines as well as GBM patient donor lines to more accurately understand individual responses to tumor growth and responsiveness to therapies.

scholarly journals Gut Microbiome Alterations Precede Cerebral Amyloidosis and Microglial Pathology in a Mouse Model of Alzheimer’s Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-15 ◽  
Author(s):  
Yijing Chen ◽  
Lihua Fang ◽  
Shuo Chen ◽  
Haokui Zhou ◽  
Yingying Fan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Neurodegenerative Disorder ◽  
Wild Type ◽  
Microbiome Composition ◽  
Cerebral Amyloidosis ◽  
Model Of Alzheimer’S Disease

Emerging evidence suggests that the gut microbiome actively regulates cognitive functions and that gut microbiome imbalance is associated with Alzheimer’s disease (AD), the most prevalent neurodegenerative disorder. However, the changes in gut microbiome composition in AD and their association with disease pathology, especially in the early stages, are unclear. Here, we compared the profiles of gut microbiota between APP/PS1 transgenic mice (an AD mouse model) and their wild-type littermates at different ages by amplicon-based sequencing of 16S ribosomal RNA genes. Microbiota composition started diverging between the APP/PS1 and wild-type mice at young ages (i.e., 1–3 months), before obvious amyloid deposition and plaque-localized microglial activation in the cerebral cortex in APP/PS1 mice. At later ages (i.e., 6 and 9 months), there were distinct changes in the abundance of inflammation-related bacterial taxa including Escherichia-Shigella, Desulfovibrio, Akkermansia, and Blautia in APP/PS1 mice. These findings suggest that gut microbiota alterations precede the development of key pathological features of AD, including amyloidosis and plaque-localized neuroinflammation. Thus, the investigation of gut microbiota might provide new avenues for developing diagnostic biomarkers and therapeutic targets for AD.

scholarly journals Taxonomic signatures of cause-specific mortality risk in human gut microbiome

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Aaro Salosensaari ◽  
Ville Laitinen ◽  
Aki S. Havulinna ◽  
Guillaume Meric ◽  
Susan Cheng ◽  
...  
Keyword(s):  
Mortality Risk ◽  
Gut Microbiome ◽  
Human Gut ◽  
Cross Sectional ◽  
Microbiome Composition ◽  
Human Gut Microbiome ◽  
Non Invasive ◽  
Sequencing Technologies

AbstractThe collection of fecal material and developments in sequencing technologies have enabled standardised and non-invasive gut microbiome profiling. Microbiome composition from several large cohorts have been cross-sectionally linked to various lifestyle factors and diseases. In spite of these advances, prospective associations between microbiome composition and health have remained uncharacterised due to the lack of sufficiently large and representative population cohorts with comprehensive follow-up data. Here, we analyse the long-term association between gut microbiome variation and mortality in a well-phenotyped and representative population cohort from Finland (n = 7211). We report robust taxonomic and functional microbiome signatures related to the Enterobacteriaceae family that are associated with mortality risk during a 15-year follow-up. Our results extend previous cross-sectional studies, and help to establish the basis for examining long-term associations between human gut microbiome composition, incident outcomes, and general health status.

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&lt;0.001), Clostridium spp. (ρ −0.14, p&lt;0.001), Romboutsia spp. (ρ −0.10, p&lt;0.001), and Ruminococceae spp. (ρ −0.15, p&lt;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&lt;0.01) and Roseburia spp. (p&lt;0.05) compared to participants with low BP. However, fecal acetate (p&lt;0.05) and propionate (p&lt;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 Infant gut microbiome composition is associated with non-social fear behavior in a pilot study

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Alexander L. Carlson ◽  
Kai Xia ◽  
M. Andrea Azcarate-Peril ◽  
Samuel P. Rosin ◽  
Jason P. Fine ◽  
...  
Keyword(s):  
Pilot Study ◽  
Gut Microbiome ◽  
Brain Structures ◽  
Experimental Manipulation ◽  
Human Infant ◽  
Microbiome Composition ◽  
Social Fear ◽  
Infant Gut Microbiome ◽  
First Year Of Life ◽  
Fear Behavior

AbstractExperimental manipulation of gut microbes in animal models alters fear behavior and relevant neurocircuitry. In humans, the first year of life is a key period for brain development, the emergence of fearfulness, and the establishment of the gut microbiome. Variation in the infant gut microbiome has previously been linked to cognitive development, but its relationship with fear behavior and neurocircuitry is unknown. In this pilot study of 34 infants, we find that 1-year gut microbiome composition (Weighted Unifrac; lower abundance of Bacteroides, increased abundance of Veillonella, Dialister, and Clostridiales) is significantly associated with increased fear behavior during a non-social fear paradigm. Infants with increased richness and reduced evenness of the 1-month microbiome also display increased non-social fear. This study indicates associations of the human infant gut microbiome with fear behavior and possible relationships with fear-related brain structures on the basis of a small cohort. As such, it represents an important step in understanding the role of the gut microbiome in the development of human fear behaviors, but requires further validation with a larger number of participants.

scholarly journals Fecal Metaproteomics Reveals Reduced Gut Inflammation and Changed Microbial Metabolism Following Lifestyle-Induced Weight Loss

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 726
Author(s):  
Ronald Biemann ◽  
Enrico Buß ◽  
Dirk Benndorf ◽  
Theresa Lehmann ◽  
Kay Schallert ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Weight Loss ◽  
Gut Microbiome ◽  
Taxonomic Composition ◽  
Low Grade ◽  
Gut Inflammation ◽  
Functional Changes ◽  
Microbiome Composition ◽  
Before And After ◽  
Human Proteins

Gut microbiota-mediated inflammation promotes obesity-associated low-grade inflammation, which represents a hallmark of metabolic syndrome. To investigate if lifestyle-induced weight loss (WL) may modulate the gut microbiome composition and its interaction with the host on a functional level, we analyzed the fecal metaproteome of 33 individuals with metabolic syndrome in a longitudinal study before and after lifestyle-induced WL in a well-defined cohort. The 6-month WL intervention resulted in reduced BMI (−13.7%), improved insulin sensitivity (HOMA-IR, −46.1%), and reduced levels of circulating hsCRP (−39.9%), indicating metabolic syndrome reversal. The metaprotein spectra revealed a decrease of human proteins associated with gut inflammation. Taxonomic analysis revealed only minor changes in the bacterial composition with an increase of the families Desulfovibrionaceae, Leptospiraceae, Syntrophomonadaceae, Thermotogaceae and Verrucomicrobiaceae. Yet we detected an increased abundance of microbial metaprotein spectra that suggest an enhanced hydrolysis of complex carbohydrates. Hence, lifestyle-induced WL was associated with reduced gut inflammation and functional changes of human and microbial enzymes for carbohydrate hydrolysis while the taxonomic composition of the gut microbiome remained almost stable. The metaproteomics workflow has proven to be a suitable method for monitoring inflammatory changes in the fecal metaproteome.

scholarly journals The phyllosphere microbiome of host trees contributes more than leaf phytochemicals to variation in the Agrilus planipennis Fairmaire gut microbiome structure

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Judith Mogouong ◽  
Philippe Constant ◽  
Pierre Legendre ◽  
Claude Guertin
Keyword(s):  
Microbial Community ◽  
Gut Microbiome ◽  
Strong Predictor ◽  
Emerald Ash Borer ◽  
Agrilus Planipennis ◽  
Food Sources ◽  
Microbiome Composition ◽  
Living Organisms ◽  
Insect Gut ◽  
Gut Microbial Community

AbstractThe microbiome composition of living organisms is closely linked to essential functions determining the fitness of the host for thriving and adapting to a particular ecosystem. Although multiple factors, including the developmental stage, the diet, and host-microbe coevolution have been reported to drive compositional changes in the microbiome structures, very few attempts have been made to disentangle their various contributions in a global approach. Here, we focus on the emerald ash borer (EAB), an herbivorous pest and a real threat to North American ash tree species, to explore the responses of the adult EAB gut microbiome to ash leaf properties, and to identify potential predictors of EAB microbial variations. The relative contributions of specific host plant properties, namely bacterial and fungal communities on leaves, phytochemical composition, and the geographical coordinates of the sampling sites, to the EAB gut microbial community was examined by canonical analyses. The composition of the phyllosphere microbiome appeared to be a strong predictor of the microbial community structure in EAB guts, explaining 53 and 48% of the variation in fungi and bacteria, respectively. This study suggests a potential covariation of the microorganisms associated with food sources and the insect gut microbiome.

scholarly journals Interaction between Host MicroRNAs and the Gut Microbiota in Colorectal Cancer

mSystems ◽  
2018 ◽  
Vol 3 (3) ◽  
Author(s):  
Ce Yuan ◽  
Michael B. Burns ◽  
Subbaya Subramanian ◽  
Ran Blekhman
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Gut Microbiota ◽  
Mirna Expression ◽  
Gut Microbiome ◽  
Noncoding Rna ◽  
Microbial Community Composition ◽  
Host Cells ◽  
Microbiome Composition ◽  
Small Noncoding Rna

ABSTRACT Although variation in gut microbiome composition has been linked with colorectal cancer (CRC), the factors that mediate the interactions between CRC tumors and the microbiome are poorly understood. MicroRNAs (miRNAs) are known to regulate CRC progression and are associated with patient survival outcomes. In addition, recent studies suggested that host miRNAs can also regulate bacterial growth and influence the composition of the gut microbiome. Here, we investigated the association between miRNA expression and microbiome composition in human CRC tumor and normal tissues. We identified 76 miRNAs as differentially expressed (DE) in tissue from CRC tumors and normal tissue, including the known oncogenic miRNAs miR-182, miR-503, and mir-17~92 cluster. These DE miRNAs were correlated with the relative abundances of several bacterial taxa, including Firmicutes , Bacteroidetes , and Proteobacteria . Bacteria correlated with DE miRNAs were enriched with distinct predicted metabolic categories. Additionally, we found that miRNAs that correlated with CRC-associated bacteria are predicted to regulate targets that are relevant for host-microbiome interactions and highlight a possible role for miRNA-driven glycan production in the recruitment of pathogenic microbial taxa. Our work characterized a global relationship between microbial community composition and miRNA expression in human CRC tissues. IMPORTANCE Recent studies have found an association between colorectal cancer (CRC) and the gut microbiota. One potential mechanism by which the microbiota can influence host physiology is through affecting gene expression in host cells. MicroRNAs (miRNAs) are small noncoding RNA molecules that can regulate gene expression and have important roles in cancer development. Here, we investigated the link between the gut microbiota and the expression of miRNA in CRC. We found that dozens of miRNAs are differentially regulated in CRC tumors and adjacent normal colon and that these miRNAs are correlated with the abundance of microbes in the tumor microenvironment. Moreover, we found that microbes that have been previously associated with CRC are correlated with miRNAs that regulate genes related to interactions with microbes. Notably, these miRNAs likely regulate glycan production, which is important for the recruitment of pathogenic microbial taxa to the tumor. This work provides a first systems-level map of the association between microbes and host miRNAs in the context of CRC and provides targets for further experimental validation and potential interventions.

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