scholarly journals Genetic determinants of gut microbiota composition and bile acid profiles in mice

2019 ◽  
Author(s):  
Julia H. Kemis ◽  
Vanessa Linke ◽  
Kelsey L. Barrett ◽  
Frederick J. Boehm ◽  
Lindsay L. Traeger ◽  
...  
Keyword(s):  
Bile Acid ◽  
Gut Microbiota ◽  
Fecal Microbiota ◽  
Microbiota Composition ◽  
Host Genetics ◽  
Host Genetic ◽  
Insight Into ◽  
Gut Microbiota Composition ◽  
Validation Experiments

AbstractThe microbial communities that inhabit the distal gut of humans and other mammals exhibit large inter-individual variation. While host genetics is a known factor that influences gut microbiota composition, the mechanisms underlying this variation remain largely unknown. Bile acids (BAs) are hormones that are produced by the host and chemically modified by gut bacteria. BAs serve as environmental cues and nutrients to microbes, but they can also have antibacterial effects. We hypothesized that host genetic variation in BA metabolism and homeostasis influence gut microbiota composition. To address this, we used the Diversity Outbred (DO) stock, a population of genetically distinct mice derived from eight founder strains. We characterized the fecal microbiota composition and plasma and cecal BA profiles from 400 DO mice maintained on a high-fat high-sucrose diet for ∼22 weeks. Using quantitative trait locus (QTL) analysis, we identified several genomic regions associated with variations in both bacterial and BA profiles. Notably, we found overlapping QTL forTuricibacter sp.and plasma cholic acid, which mapped to a locus containing the gene for the ileal bile acid transporter,Slc10a2. Mediation analysis and subsequent follow-up validation experiments suggest that differences inSlc10a2gene expression associated with the different strains influences levels of both traits and revealed novel interactions betweenTuricibacterand BAs. This work illustrates how systems genetics can be utilized to generate testable hypotheses and provide insight into host-microbe interactions.Author summaryInter-individual variation in the composition of the intestinal microbiota can in part be attributed to host genetics. However, the specific genes and genetic variants underlying differences in the microbiota remain largely unknown. To address this, we profiled the fecal microbiota composition of 400 genetically distinct mice, for which genotypic data is available. We identified many loci of the mouse genome associated with changes in abundance of bacterial taxa. One of these loci is also associated with changes in the abundance of plasma bile acids—metabolites generated by the host that influence both microbiota composition and host physiology. Follow up validation experiments provide mechanistic insights linking host genetic differences, with changes in ileum gene expression, bile acid-bacteria interactions and bile acid homeostasis. Together, this work demonstrates how genetic approaches can be used to generate testable hypothesis to yield novel insight into how host genetics shape gut microbiota composition.

Yeast β-glucan reduces obesity-associated Bilophila abundance and modulates bile acid metabolism in healthy and high-fat diet mouse models

2021 ◽  
Author(s):  
Sik Yu So ◽  
Qinglong Wu ◽  
Kin Sum Leung ◽  
Zuzanna Maria Kundi ◽  
Tor C Savidge ◽  
...  
Keyword(s):  
Bile Acid ◽  
Gut Microbiota ◽  
High Fat Diet ◽  
Metabolic Health ◽  
Metabolic Phenotype ◽  
Bile Acid Metabolism ◽  
Microbiota Composition ◽  
High Fat ◽  
Mrna Accumulation ◽  
Gut Microbiota Composition

Emerging evidence links dietary fiber with altered gut microbiota composition and bile acid signaling in maintaining metabolic health. Yeast β-glucan (Y-BG) is a dietary supplement known for its immunomodulatory effect, yet its impact on the gut microbiota and bile acid composition remains unclear. This study investigated whether dietary forms of Y-BG modulate these gut-derived signals. We performed 4-week dietary supplementation in healthy mice to evaluate effects of different fiber composition (soluble vs particulate Y-BG) and dose (0.1 vs. 2%). We found that 2% particulate Y-BG induced robust gut microbiota community shifts with elevated liver Cyp7a1 mRNA abundance and bile acid synthesis. These diet-induced responses were notably different when compared to the prebiotic inulin, and included a marked reduction in fecal Bilophila abundance which we demonstrated as translatable to obesity in population-scale American Gut and TwinsUK clinical cohorts. This prompted us to test whether 2% Y-BG maintained metabolic health in mice fed 60% HFD over 13 weeks. Y-BG consistently altered the gut microbiota composition and reduced Bilophila abundance, with trends observed in improvement of metabolic phenotype. Notably, Y-BG improved insulin sensitization and this was associated with enhanced ileal Glpr1r mRNA accumulation and reduced Bilophila abundance. Collectively, our results demonstrate that Y-BG modulates gut microbiota community composition and bile acid signaling, but the dietary regime needs to be optimized to facilitate clinical improvement in metabolic phenotype in an aggressive high-fat diet animal model.

scholarly journals Genetic determinants of gut microbiota composition and bile acid profiles in mice

PLoS Genetics ◽  
2019 ◽  
Vol 15 (8) ◽  
pp. e1008073 ◽  
Author(s):  
Julia H. Kemis ◽  
Vanessa Linke ◽  
Kelsey L. Barrett ◽  
Frederick J. Boehm ◽  
Lindsay L. Traeger ◽  
...  
Keyword(s):  
Bile Acid ◽  
Gut Microbiota ◽  
Microbiota Composition ◽  
Genetic Determinants ◽  
Bile Acid Profiles ◽  
Gut Microbiota Composition

scholarly journals Fecal Microbiota Transplantation Controls Murine Chronic Intestinal Inflammation by Modulating Immune Cell Functions and Gut Microbiota Composition

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 517 ◽  
Author(s):  
Claudia Burrello ◽  
Maria Rita Giuffrè ◽  
Angeli Dominique Macandog ◽  
Angelica Diaz-Basabe ◽  
Fulvia Milena Cribiù ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Gut Microbiota ◽  
Immune Cells ◽  
Intestinal Inflammation ◽  
Fecal Microbiota Transplantation ◽  
Experimental Colitis ◽  
Fecal Microbiota ◽  
Microbiota Composition ◽  
Chronic Intestinal Inflammation ◽  
Gut Microbiota Composition

Different gastrointestinal disorders, including inflammatory bowel diseases (IBD), have been linked to alterations of the gut microbiota composition, namely dysbiosis. Fecal microbiota transplantation (FMT) is considered an encouraging therapeutic approach for ulcerative colitis patients, mostly as a consequence of normobiosis restoration. We recently showed that therapeutic effects of FMT during acute experimental colitis are linked to functional modulation of the mucosal immune system and of the gut microbiota composition. Here we analysed the effects of therapeutic FMT administration during chronic experimental colitis, a condition more similar to that of IBD patients, on immune-mediated mucosal inflammatory pathways. Mucus and feces from normobiotic donors were orally administered to mice with established chronic Dextran Sodium Sulphate (DSS)-induced colitis. Immunophenotypes and functions of infiltrating colonic immune cells were evaluated by cytofluorimetric analysis. Compositional differences in the intestinal microbiome were analyzed by 16S rRNA sequencing. Therapeutic FMT in mice undergoing chronic intestinal inflammation was capable to decrease colonic inflammation by modulating the expression of pro-inflammatory genes, antimicrobial peptides, and mucins. Innate and adaptive mucosal immune cells manifested a reduced pro-inflammatory profile in FMT-treated mice. Finally, restoration of a normobiotic core ecology contributed to the resolution of inflammation. Thus, FMT is capable of controlling chronic intestinal experimental colitis by inducing a concerted activation of anti-inflammatory immune pathways, mechanistically supporting the positive results of FMT treatment reported in ulcerative colitis patients.

scholarly journals Comparative Analysis of Fecal Microbiota Composition Between Rheumatoid Arthritis and Osteoarthritis Patients

Genes ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 748 ◽  
Author(s):  
Jin-Young Lee ◽  
Mohamed Mannaa ◽  
Yunkyung Kim ◽  
Jehun Kim ◽  
Geun-Tae Kim ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Bacterial Species ◽  
Amplicon Sequencing ◽  
Fecal Microbiota ◽  
Rrna Gene ◽  
Microbiota Composition ◽  
Stool Samples ◽  
Gut Microbiota Composition

The aim of this study was to investigate differences between the gut microbiota composition in patients with rheumatoid arthritis (RA) and those with osteoarthritis (OA). Stool samples from nine RA patients and nine OA patients were collected, and DNA was extracted. The gut microbiome was assessed using 16S rRNA gene amplicon sequencing. The structures and differences in the gut microbiome between RA and OA were analyzed. The analysis of diversity revealed no differences in the complexity of samples. The RA group had a lower Bacteroidetes: Firmicutes ratio than did the OA group. Lactobacilli and Prevotella, particularly Prevotella copri, were more abundant in the RA than in the OA group, although these differences were not statistically significant. The relative abundance of Bacteroides and Bifidobacterium was lower in the RA group. At the species level, the abundance of certain bacterial species was significantly lower in the RA group, such as Fusicatenibacter saccharivorans, Dialister invisus, Clostridium leptum, Ruthenibacterium lactatiformans, Anaerotruncus colihominis, Bacteroides faecichinchillae, Harryflintia acetispora, Bacteroides acidifaciens, and Christensenella minuta. The microbial properties of the gut differed between RA and OA patients, and the RA dysbiosis revealed results similar to those of other autoimmune diseases, suggesting that a specific gut microbiota pattern is related to autoimmunity.

scholarly journals Gut Microbiota Composition and Metabolomic Profiles of Wild and Captive Chinese Monals (Lophophorus lhuysii) 

2020 ◽  
Author(s):  
Dandan Jiang ◽  
Xin He ◽  
Marc Valitutto ◽  
Li Chen ◽  
Qin Xu ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
High Performance ◽  
Bird Species ◽  
Alpha Diversity ◽  
Integrated Approach ◽  
Fecal Microbiota ◽  
Rrna Gene ◽  
Microbiota Composition ◽  
Metabolomic Profile ◽  
Gut Microbiota Composition

Abstract Background：The Chinese monal (Lophophorus lhuysii) is an endangered bird species, with a wild population restricted to the mountains of southwest China, and only one known captive population in the world. We investigated the fecal microbiota and metabolome of wild and captive Chinese monals to explore differences and similarities in nutritional status and digestive characteristics. An integrated approach combining 16S ribosomal RNA (16S rRNA) gene sequencing and ultra-high performance liquid chromatography (UHPLC) based metabolomics were used to examine the fecal microbiota composition and the metabolomic profile of Chinese monals. Results: The results showed that the alpha diversity of gut microbes in the wild group were significantly higher than that in the captive group and the core bacterial taxa in the two groups showed remarkable differences at phylum, class, order, and family levels. Metabolomic profiling also revealed differences, mainly related to galactose, starch and sucrose metabolism, fatty acid, bile acid biosynthesis and bile secretion. Furthermore, strong correlations of metabolite types and bacterial genus were detected. Conclusions: There were remarkable differences in the gut microbiota composition and metabolomic profile between wild and captive Chinese monals. This study has established a baseline for a normal gut microbiota and metabolomic profile for wild Chinese monals, thus allowing us to evaluate if differences seen in captive organisms have an impact on their overall health and reproduction.

scholarly journals Leveraging host-genetics and gut microbiota to determine immunocompetence in pigs

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Yuliaxis Ramayo-Caldas ◽  
Laura M. Zingaretti ◽  
David Pérez-Pascual ◽  
Pamela A. Alexandre ◽  
Antonio Reverter ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Association Studies ◽  
Host Genome ◽  
Phenotypic Variance ◽  
Microbiota Composition ◽  
Microbial Composition ◽  
Phagocytic Capacity ◽  
Host Genetics ◽  
Gut Microbiota Composition ◽  
Variance Explained

Abstract Background The gut microbiota influences host performance playing a relevant role in homeostasis and function of the immune system. The aim of the present work was to identify microbial signatures linked to immunity traits and to characterize the contribution of host-genome and gut microbiota to the immunocompetence in healthy pigs. Results To achieve this goal, we undertook a combination of network, mixed model and microbial-wide association studies (MWAS) for 21 immunity traits and the relative abundance of gut bacterial communities in 389 pigs genotyped for 70K SNPs. The heritability (h2; proportion of phenotypic variance explained by the host genetics) and microbiability (m2; proportion of variance explained by the microbial composition) showed similar values for most of the analyzed immunity traits, except for both IgM and IgG in plasma that was dominated by the host genetics, and the haptoglobin in serum which was the trait with larger m2 (0.275) compared to h2 (0.138). Results from the MWAS suggested a polymicrobial nature of the immunocompetence in pigs and revealed associations between pigs gut microbiota composition and 15 of the analyzed traits. The lymphocytes phagocytic capacity (quantified as mean fluorescence) and the total number of monocytes in blood were the traits associated with the largest number of taxa (6 taxa). Among the associations identified by MWAS, 30% were confirmed by an information theory network approach. The strongest confirmed associations were between Fibrobacter and phagocytic capacity of lymphocytes (r = 0.37), followed by correlations between Streptococcus and the percentage of phagocytic lymphocytes (r = -0.34) and between Megasphaera and serum concentration of haptoglobin (r = 0.26). In the interaction network, Streptococcus and percentage of phagocytic lymphocytes were the keystone bacterial and immune-trait, respectively. Conclusions Overall, our findings reveal an important connection between gut microbiota composition and immunity traits in pigs, and highlight the need to consider both sources of information, host genome and microbial levels, to accurately characterize immunocompetence in pigs.

scholarly journals Metformin induces weight loss associated with gut microbiota alteration in non-diabetic obese women: a randomized double-blind clinical trial

2019 ◽  
Vol 180 (3) ◽  
pp. 165-176 ◽  
Author(s):  
Hanieh-Sadat Ejtahed ◽  
Raul Y Tito ◽  
Seyed-Davar Siadat ◽  
Shirin Hasani-Ranjbar ◽  
Zahra Hoseini-Tavassol ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Gut Microbiota ◽  
Amplicon Sequencing ◽  
Fecal Microbiota ◽  
Pharmacological Therapy ◽  
Microbiota Composition ◽  
Obese Women ◽  
Double Blind ◽  
Baseline Values ◽  
Gut Microbiota Composition

Objective The increasing prevalence of obesity over the past few decades constitutes a global health challenge. Pharmacological therapy is recommended to accompany life-style modification for obesity management. Here, we perform a clinical trial to investigate the effects of metformin on anthropometric indices and gut microbiota composition in non-diabetic, treatment-naive obese women with a low-calorie diet (LCD). Design Randomized double-blind parallel-group clinical trial Methods Forty-six obese women were randomly assigned to the metformin (500 mg/tab) or placebo groups using computer-generated random numbers. Subjects in both groups took two tablets per day for 2 months. Anthropometric measurements and collection of blood and fecal samples were done at the baseline and at the end of the trial. Gut microbiota composition was assessed using 16S rRNA amplicon sequencing. Results Twenty-four and twenty-two subjects were included in the metformin + LCD and placebo + LCD groups, respectively; at the end of trial, 20 and 16 subjects were analyzed. The metformin + LCD and placebo + LCD caused a 4.5 and 2.6% decrease in BMI from the baseline values, respectively (P < 0.01). Insulin concentration decreased in the metformin + LCD group (P = 0.046). The overall fecal microbiota composition and diversity were unaffected in the metformin + LCD group. However, a significant specific increase in Escherichia/Shigella abundance was observed after metformin + LCD intervention (P = 0.026). Fecal acetate concentration, but not producers, was significantly higher in the placebo + LCD group, adjusted for baseline values and BMI (P = 0.002). Conclusions Despite the weight reduction after metformin intake, the overall fecal microbiota composition remained largely unchanged in obese women, with exception of changes in specific proteobacterial groups.

Dysbiosis of Fecal Microbiota in Allergic Rhinitis Patients

2020 ◽  
Vol 34 (5) ◽  
pp. 650-660 ◽  
Author(s):  
Xiang Liu ◽  
Jing Tao ◽  
Jing Li ◽  
Xiaolin Cao ◽  
Yong Li ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
Statistical Analysis ◽  
Gut Microbiota ◽  
Study Groups ◽  
Fecal Microbiota ◽  
Rrna Gene ◽  
Microbiota Composition ◽  
Linear Discriminant ◽  
Α Diversity ◽  
Gut Microbiota Composition

Background The gut microbiota plays an important role in shaping the immune system and may be closely connected to the development of allergic diseases. Objective This study aimed to determine the gut microbiota composition in Chinese allergic rhinitis (AR) patients as compared with healthy controls (HCs). Methods We collected stool samples from 93 AR patients and 72 age- and sex-matched HCs. Gut microbiota composition was analyzed using QIIME targeting the 16S rRNA gene. Functional pathways were predicted using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States. Statistical analysis was performed using the R program, linear discriminant analysis effect size (LefSe), analysis of QIIME, and statistical analysis of metagenomic profiles, among other tests. Results Compared with HCs, AR patients had significantly lower gut-microbiota α-diversity ( P < .001). The gut microbiota composition significantly differed between the 2 study groups. At the phylum level, the relative abundance of Bacteroidetes was higher while those of Actinobacteria and Proteobacteria were lower in the AR group than in the HC group ( P < .001, q < 0.001). At the genus level, Escherichia-Shigella, Prevotella, and Parabacteroides ( P < .001, q < 0.001) had significantly higher relative abundances in the AR group than in the HC group. LefSe analysis indicated that Escherichia-Shigella, Lachnoclostridium, Parabacteroides, and Dialister were potential biomarkers for AR. In addition, predictive metagenome functional analysis showed that pyruvate, porphyrin, chlorophyll, purine metabolism, and peptidoglycan biosynthesis significantly differed between the AR and HC groups. Conclusion A comparison of the gut microbiota of AR patients and HCs suggested that dysbiosis of the fecal microbiota is involved in the development of AR. The present results may reveal key differences and identify targets for preventive or therapeutic intervention.

scholarly journals Susceptibility to Campylobacter Infection Is Associated with the Species Composition of the Human Fecal Microbiota

mBio ◽  
2014 ◽  
Vol 5 (5) ◽  
Author(s):  
Johan Dicksved ◽  
Patrik Ellström ◽  
Lars Engstrand ◽  
Hilpi Rautelin
Keyword(s):  
Gut Microbiota ◽  
Mouse Models ◽  
Fecal Microbiota ◽  
Microbiota Composition ◽  
Content Type ◽  
Culture Positive ◽  
Abattoir Workers ◽  
Gut Microbiota Composition

ABSTRACTThe gut microbiota is essential for human health, but very little is known about how the composition of this ecosystem can influence and respond to bacterial infections. Here we address this by prospectively studying the gut microbiota composition before, during, and after naturalCampylobacterinfection in exposed poultry abattoir workers. The gut microbiota composition was analyzed with 16S amplicon sequencing of fecal samples from poultry abattoir workers during the peak season ofCampylobacterinfection in Sweden. The gut microbiota compositions were compared between individuals who became culture positive forCampylobacterand those who remained negative. Individuals who becameCampylobacterpositive had a significantly higher abundance ofBacteroides(P= 0.007) andEscherichia(P= 0.002) species than those who remained culture negative. Furthermore, this group had a significantly higher abundance ofPhascolarctobacterium(P= 0.017) andStreptococcus(P= 0.034) sequences than theCampylobacter-negative group, which had an overrepresentation ofClostridiales(P= 0.017), unclassifiedLachnospiraceae(P= 0.008), andAnaerovorax(P= 0.015) sequences. Intraindividual comparisons of the fecal microbiota compositions yielded small differences over time inCampylobacter-negative participants, but significant long-term changes were found in theCampylobacter-positive group (P< 0.005). The results suggest that the abundance of specific genera in the microbiota reduces resistance toCampylobactercolonization in humans and thatCampylobacterinfection can have long-term effects on the composition of the human fecal microbiota.IMPORTANCEStudies using mouse models have made important contributions to our understanding of the role of the gut microbiota in resistance to bacterial enteropathogen colonization. The relative abundances ofEscherichia coliandBacteroidesspecies have been pointed out as important determinants of susceptibility to Gram-negative pathogens in general andCampylobacterinfection in particular. In this study, we assessed the role of the human gut microbiota in resistance toCampylobactercolonization by studying abattoir workers that are heavily exposed to these bacteria. Individuals with a certain composition of the gut microbiota became culture positive forCampylobacter. As their microbiotas were characterized by high abundances ofBacteroidesspp. andE. coli, well in line with the findings with mouse models, these bacterial species likely play an important role in colonization resistance also in humans.

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