Effect of rice bran fermented with Saccharomyces cerevisiae and Lactobacillus plantarum on gut microbiome of mice fed high-sucrose diet

2019 ◽  
Vol 10 (7) ◽  
pp. 811-821
Author(s):  
J. Shibayama ◽  
M. Goto ◽  
T. Kuda ◽  
M. Fukunaga ◽  
H. Takahashi ◽  
...  
Keyword(s):  
Bile Acid ◽  
Rice Bran ◽  
Gut Microbiome ◽  
Control Diet ◽  
Alpha Diversity ◽  
Blood Lipid ◽  
Operational Taxonomic Unit ◽  
Rrna Gene ◽  
High Sucrose

To clarify the effect of rice bran (RB) and fermented RB (FRB) in a high-sucrose and low-dietary fibre diet on the gut microbiome, the in vitro bile acid-lowering capacity and caecal microbiota of ICR mice fed with 20% RB or FRB diets for two weeks were determined. The caecal microbiome was analysed by 16S rRNA gene amplicon sequencing. The in vitro bile acid-lowering capacity was high for FRB. In mouse experiments, triacylglycerol and total cholesterol were generally lower with FRB, although the faecal frequency was highest in mice fed with RB. The Shannon-Wiener and Simpson’s indices for alpha-diversity in the microbiome of mice fed with RB and FRB, were higher than mice fed the control diet. At the phylum level in the caecal microbiome, Firmicutes and Bacteroidetes were high with FRB and RB, respectively. At the operational taxonomic unit level, some bacterial groups related to diabetes and gut toxicity, such as Lachnospiraceae and Enterorhabdus mucosicola, were high for RB but not for FRB diets. These results suggest that FRB, rather than RB, intake improve the intestinal environment and blood lipid condition.

scholarly journals Gut microbiome composition in the Hispanic Community Health Study/Study of Latinos is shaped by geographic relocation, environmental factors, and obesity

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Robert C. Kaplan ◽  
Zheng Wang ◽  
Mykhaylo Usyk ◽  
Daniela Sotres-Alvarez ◽  
Martha L. Daviglus ◽  
...  
Keyword(s):  
Community Health ◽  
Gut Microbiome ◽  
Alpha Diversity ◽  
Amplicon Sequencing ◽  
Shannon Index ◽  
Health Study ◽  
Rrna Gene ◽  
Cross Sectional ◽  
Hispanic Community ◽  
The Usa

Abstract Background Hispanics living in the USA may have unrecognized potential birthplace and lifestyle influences on the gut microbiome. We report a cross-sectional analysis of 1674 participants from four centers of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), aged 18 to 74 years old at recruitment. Results Amplicon sequencing of 16S rRNA gene V4 and fungal ITS1 fragments from self-collected stool samples indicate that the host microbiome is determined by sociodemographic and migration-related variables. Those who relocate from Latin America to the USA at an early age have reductions in Prevotella to Bacteroides ratios that persist across the life course. Shannon index of alpha diversity in fungi and bacteria is low in those who relocate to the USA in early life. In contrast, those who relocate to the USA during adulthood, over 45 years old, have high bacterial and fungal diversity and high Prevotella to Bacteroides ratios, compared to USA-born and childhood arrivals. Low bacterial diversity is associated in turn with obesity. Contrasting with prior studies, our study of the Latino population shows increasing Prevotella to Bacteroides ratio with greater obesity. Taxa within Acidaminococcus, Megasphaera, Ruminococcaceae, Coriobacteriaceae, Clostridiales, Christensenellaceae, YS2 (Cyanobacteria), and Victivallaceae are significantly associated with both obesity and earlier exposure to the USA, while Oscillospira and Anaerotruncus show paradoxical associations with both obesity and late-life introduction to the USA. Conclusions Our analysis of the gut microbiome of Latinos demonstrates unique features that might be responsible for health disparities affecting Hispanics living in the USA.

scholarly journals Biliary Microbiota and Bile Acid Composition in Cholelithiasis

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Vyacheslav A. Petrov ◽  
María A. Fernández-Peralbo ◽  
Rico Derks ◽  
Elena M. Knyazeva ◽  
Nikolay V. Merzlikin ◽  
...  
Keyword(s):  
Bile Acid ◽  
Acid Composition ◽  
Acid Concentration ◽  
Gallstone Disease ◽  
Alpha Diversity ◽  
Taurocholic Acid ◽  
Rrna Gene ◽  
Microbial Composition ◽  
Opisthorchis Felineus ◽  
Taxonomic Profile

Background. A functional interplay between BAs and microbial composition in gut is a well-documented phenomenon. In bile, this phenomenon is far less studied, and with this report, we describe the interactions between the BAs and microbiota in this complex biological matrix. Methodology. Thirty-seven gallstone disease patients of which twenty-one with Opisthorchis felineus infection were enrolled in the study. The bile samples were obtained during laparoscopic cholecystectomy for gallstone disease operative treatment. Common bile acid composition was measured by LC-MS/MS. Gallbladder microbiota were previously analyzed with 16S rRNA gene sequencing on Illumina MiSeq platform. The associations between bile acid composition and microbiota were analyzed. Results. Bile acid signature and Opisthorchis felineus infection status exert influence on beta-diversity of bile microbial community. Direct correlations were found between taurocholic acid, taurochenodeoxycholic acid concentrations, and alpha-diversity of bile microbiota. Taurocholic acid and taurochenodeoxycholic acid both show positive associations with the presence of Chitinophagaceae family, Microbacterium and Lutibacterium genera, and Prevotella intermedia. Also, direct associations were identified for taurocholic acid concentration and the presence of Actinomycetales and Bacteroidales orders, Lautropia genus, Jeotgalicoccus psychrophilus, and Haemophilus parainfluenzae as well as for taurochenodeoxycholic acid and Acetobacteraceae family and Sphingomonas genus. There were no differences in bile acid concentrations between O. felineus-infected and noninfected patients. Conclusions/Significance. Associations between diversity, taxonomic profile of bile microbiota, and bile acid levels were evidenced in patients with cholelithiasis. Increase of taurochenodeoxycholic acid and taurocholic acid concentration correlates with bile microbiota alpha-diversity and appearance of opportunistic pathogens.

scholarly journals In Vitro Fecal Fermentation Patterns of Arabinoxylan from Rice Bran on Gut Microbiota in Normal Weight and Overweight/Obese Subjects

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1560-1560
Author(s):  
Inah Gu ◽  
Wing Shun Lam ◽  
Daya Marasini ◽  
Cindi Brownmiller ◽  
Brett Savary ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Rice Bran ◽  
Block Design ◽  
16S Rrna Gene Sequencing ◽  
Short Chain Fatty Acids ◽  
Normal Weight ◽  
Rrna Gene ◽  
Gut Health ◽  
The Impact

Abstract Objectives Arabinoxylan is a non-starch polysaccharide and rich in wheat, rice and many other cereal grains. Diets high in fiber help promoting gut health in obesity. The objective of this study was to investigate the impact of arabinoxylan from rice bran on the gut microbiota and short chain fatty acids (SCFA) in normal weight (NW) and overweight/obese (OO) subjects through in vitro fecal fermentation. Methods Arabinoxylan was extracted from rice bran fiber. For in vitro fecal fermentation, each fecal sample from NW (n = 6, 3 males and 3 females) and OO (n = 7, 3 males and 4 females) was diluted into anaerobic medium with three treatments: control (no substrates), fructooligosaccharides (FOS, a well-known prebiotic), and arabinoxylan. Samples were incubated at 37˚C and aliquots were taken at 0, 4, 8, 12 and 24 h. SCFA content from samples at all timepoints was analyzed using HPLC. Samples at 0 and 24 h were used for gut microbiota analysis through 16S rRNA gene sequencing. Statistical analyses were performed for the randomized complete block design, where the weight classes are confounded with blocks (subjects). Friedman test was used to determine the difference at 5% level of significance. Results As a result, arabinoxylan treatment significantly increased total SCFA concentration in both NW and OO subjects than control (P < 0.05), comparable to FOS treatment. Between weight classes under arabinoxylan treatment, OO group showed a significantly higher total SCFA content than NW group (P < 0.05). Arabinoxylan changed gut microbial population at the genus level, stimulating Bifidobacterium, Collinsella and Blautia and decreasing Clostridium XIVa and b, Dorea and Oscillibacter (P < 0.05). In addition, different microbiome population was shown in weight classes with three treatments, showing higher Bacteroides in NW and higher Prevotella in OO. Conclusions These results showed that arabinoxylan from rice bran modified gut microbiota in both weight classes, increasing total SCFA content. This study suggests that arabinoxylan from rice bran may have a potential impact on microbial gut health in obesity with prebiotic activities. Funding Sources University of Arkansas.

Alterations of gut microbiome in autoimmune hepatitis

Gut ◽  
2019 ◽  
Vol 69 (3) ◽  
pp. 569-577 ◽  
Author(s):  
Yiran Wei ◽  
Yanmei Li ◽  
Li Yan ◽  
Chunyan Sun ◽  
Qi Miao ◽  
...  
Keyword(s):  
Autoimmune Hepatitis ◽  
Gut Microbiome ◽  
Alpha Diversity ◽  
Disease Status ◽  
16S Rrna Gene Sequencing ◽  
Rrna Gene ◽  
Healthy Controls ◽  
Microbial Composition ◽  
Cross Sectional ◽  
Treatment Naïve

ObjectiveThe significance of the liver-microbiome axis has been increasingly recognised as a major modulator of autoimmunity. The aim of this study was to take advantage of a large well-defined corticosteroids treatment-naïve group of patients with autoimmune hepatitis (AIH) to rigorously characterise gut dysbiosis compared with healthy controls.DesignWe performed a cross-sectional study of individuals with AIH (n=91) and matched healthy controls (n=98) by 16S rRNA gene sequencing. An independent cohort of 28 patients and 34 controls was analysed to validate the results. All the patients were collected before corticosteroids therapy.ResultsThe gut microbiome of steroid treatment-naïve AIH was characterised with lower alpha-diversity (Shannon and observed operational taxonomic units, both p<0.01) and distinct overall microbial composition compared with healthy controls (p=0.002). Depletion of obligate anaerobes and expansion of potential pathobionts including Veillonella were associated with disease status. Of note, Veillonella dispar, the most strongly disease-associated taxa (p=8.85E–8), positively correlated with serum level of aspartate aminotransferase and liver inflammation. Furthermore, the combination of four patients with AIH-associated genera distinguished AIH from controls with an area under curves of approximately 0.8 in both exploration and validation cohorts. In addition, multiple predicted functional modules were altered in the AIH gut microbiome, including lipopolysaccharide biosynthesis as well as metabolism of amino acids that can be processed by bacteria to produce immunomodulatory metabolites.ConclusionOur study establishes compositional and functional alterations of gut microbiome in AIH and suggests the potential for using gut microbiota as non-invasive biomarkers to assess disease activity.

scholarly journals Impacts of Aging and Blackcurrant Supplementation on the Gut Microbiome Profile of Female Mice (P20-031-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Sang Gil Lee ◽  
Cao Lei ◽  
Melissa Melough ◽  
Junichi Sakaki ◽  
Kendra Maas ◽  
...  
Keyword(s):  
Relative Abundance ◽  
Gut Microbiome ◽  
Health Benefits ◽  
Alpha Diversity ◽  
Young Female ◽  
Rrna Gene ◽  
Fecal Samples ◽  
Female Mice ◽  
Aged Mice ◽  
Young Mice

Abstract Objectives Blackcurrant, an anthocyanin-rich berry, has multiple health benefits. The purpose of this study was to examine the impacts of blackcurrant supplementation and aging on gut bacterial communities in female mice. Methods Three-month and 18-month old female mice were provided standard chow diets with or without anthocyanin-rich blackcurrant extract (BC) (1% w/w) for four months. Upon study completion, fecal samples were collected directly from the animals’ colons. Microbiome DNA was extracted from the fecal samples and the V3-V4 regions of their 16S rRNA gene were amplified and sequenced using Results Taxonomic analysis showed a significantly decrease in alpha diversity in aged female mice, compared to young counterparts. BC consumption did not alter the alpha diversity in either young or aged mice compared to control diets. For beta diversity, we observed the clustering was associated with age but not diet. The phylogenic abundance analysis showed that the relative abundance of several phyla, including Firmicutes, Bacteroidetes, Cyanobacteria, Proteobacteria, and Tenericutes was higher in aged compared to young mice. Among them, the abundance of Firmicutes was downregulated by BC in the young but not the aged mice. The abundance of Bacteroidetes was increased by BC in both the young and the aged groups. Noticeably, Verrucomicrobia was the only phylum whose relative abundance was upregulated in the aged female mice compared to the young mice. Meanwhile, its relative abundance in the aged group was suppressed by BC. Interestingly, Desulfovibrio, which is the most representative sulfate-reducing genus, was detectable only in young female mice, and BC increased its relative abundance. Conclusions Our results characterized the gut microbiome compositions in young and aged female mice, and indicated that the gut microbiome of young and aged female mice responded differently to four month BC administration. Through additional research, the microbial alterations observed in this study should be further investigated to inform our understanding of the effect of BC on the gut microbiome, the possible health benefits related to these changes, and the differing effects of BC supplementation across populations. Funding Sources This study was supported by the USDA NIFA Seed Grant (#2016-67018-24492) and the University of Connecticut Foundation Esperance Funds to Dr. Ock K. Chun. We thank the National Institute on Aging for providing aged mice for the project and Just the Berries Ltd. for providing the blackcurrant extract.

scholarly journals A contribution to the larval amphibian microbiome: characterization of bacterial microbiome of Ichthyophis bannanicus (Order: Gymnophiona) and comparison with the other two amphibian orders

2021 ◽  
Author(s):  
Amrapali Rajput ◽  
Shipeng Zhou ◽  
Madhava Meegaskumbura
Keyword(s):  
Gut Microbiome ◽  
Alpha Diversity ◽  
The Other ◽  
Rrna Gene ◽  
Scaling Analysis ◽  
Skin Microbiome ◽  
Sequencing Platform ◽  
Bacterial Phyla ◽  
Faecal Samples ◽  
Skin Samples

It is known that animal-associated microbiomes form indispensable relationships with hosts and are responsible for many functions important for host-survival. Next-gen driven approaches documenting the remarkable diversity of microbiomes have burgeoned, with amphibians too, benefiting from such treatments. The microbiome of Gymnophiona (caecilians), one of the three amphibian orders, constituting of 3% of amphibians, however, remains almost unknown. The present study aims to address this knowledge gap through analysis of the microbiome of Ichthyophis bannanicus. As these caecilian larvae are aquatic and hence exposed to a greater propensity for bacterial microbiomic interchange, we hypothesize that bacterial phyla would overlap between gut and skin. Further, from the host-specificity patterns observed in other vertebrate taxa, we hypothesize that Gymnophiona have different dominant gut bacterial microbiomes at a higher taxonomic level when compared to the larvae of the other two amphibian orders (Anura and Caudata). We used 16S rRNA gene amplicon sequencing based on Illumina Nova sequencing platform to characterize and compare the gut (represented by faecal samples) and skin microbiome of I. bannanicus larvae (N = 13), a species distributed across South-East-Asia and the only caecilian species occurring in China. We compared our gut microbiome results with published anuran and caudate larval microbiomes. For I. bannanicus, a total of 4,053 operational taxonomic units (OTU) across 13 samples were detected. Alpha-diversity indices were significant between gut and skin samples. Non-metric multidimensional scaling analysis suggest that gut and skin samples each contained a distinct microbiome at OTU level. We record significant differences between the bacterial phyla of gut and skin samples in larvae of I. bannanicus. The study provides an overview of gut and skin bacterial microbiomes of a caecilian, while highlighting the major differences between larval microbiomes of the three amphibian orders. We find a partial overlap of gut bacterial microbiomes at phylum level for the three orders; however, the relative abundance of the dominant phyla is distinct. The skin and gut microbiomes are distinct with little overlap of species, highlighting that gut-skin axis is weak. This in turn suggests that many of the microbial species on skin and gut are functionally specialized to those locations. We also show that the skin microbiome is more diverse than the gut microbiome at species level; however, a reason for this could be a portion of the gut microbiome not being represented in faecal samples. These first microbiome information from a caecilian lay the foundation for comparative studies of the three amphibian orders.

scholarly journals 83 Lifelong dynamics of the swine gut microbiome: from birth to market

2019 ◽  
Vol 97 (Supplement_2) ◽  
pp. 48-48
Author(s):  
Xiaofan Wang ◽  
Tsung Cheng Tsai ◽  
Charles V Maxwell ◽  
Jiangchao Zhao
Keyword(s):  
Growth Performance ◽  
Gut Microbiome ◽  
Community Dynamics ◽  
Alpha Diversity ◽  
Illumina Miseq ◽  
Shannon Index ◽  
Growth Stages ◽  
Rrna Gene ◽  
16 S Rrna

Abstract Despite the recent advances in the swine gut microbiomes during different growth stages, a comprehensive longitudinal study of the lifelong dynamics of the swine gut microbiome is lacking. To fill this gap of knowledge, we selected seventeen piglets (PIC29*380) that were born on the same date from three sows. We collected a total of 274 rectal swabs during lactation (d 0, 11, 20), nursery (d 27, 33, 41, 50, 61), growing (d 76, 90, 104, 116), and finishing (d 130, 146, 159, and 174) stages. Samples were extracted using the Powersoil DNA isolation kit (Qiagen, Hilden, Germany) and sequenced with an Illumina Miseq sequencer targeting the V4 region of the 16 S rRNA gene. Sequences were analyzed with the Deblur algorithm in the QIIME2 package. In general, alpha diversity including community richness (e.g., number of observed features, Chao1) and diversity (e.g., Shannon Index) showed an overall trend of increasing from lactation to the finishing stage (P < 0.01). Gradual and significant changes in community structures were also observed along the four growth stages (ANOSIM, R = 0.66; P < 0.01). Non-parametric permutational multivariate analysis of variance shows that main factors driving the lifelong community dynamics included age and diet. Seventeen phylum members were discovered in the lifelong pig gut microbiome with Firmicutes and Bacteroidetes being the most abundant phyla. LEfSe analysis revealed 63 bacterial features that are stage specific. By using a regressing tree based Random Forest model we identified five bacterial features that are associated with swine growth performance including features 26 (Turicibacteraceae Turicibacter), 27 (Clostridium butyricum), 18 (Clostridiaceae), 19 (Clostridium perfringens) and 4 (Clostridiaceae). Characterization of the lifelong dynamics of 17 healthy pigs from birth to market provides a foundation for gut microbiome studies focusing on swine development, health and growth performance.

scholarly journals Supplementation of Geranylgeraniol and Tocotrienols to High-Fat Diet Shifts the Gut Microbiome Composition and Function in Type 2 Diabetic Mice

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 393-393
Author(s):  
Moamen Elmassry ◽  
Eunhee Chung ◽  
Abdul Hamood ◽  
Chwan-Li Shen
Keyword(s):  
Relative Abundance ◽  
Gut Microbiome ◽  
High Fat Diet ◽  
Alpha Diversity ◽  
Control Group ◽  
Rrna Gene ◽  
High Fat ◽  
Microbiome Composition ◽  
And Function

Abstract Objectives In recent years, characterization of gut microbiota composition and function were linked to the progression of type 2 diabetes mellitus. Recent evidence showed that Geranylgeraniol, an isoprenoid found in fruits, vegetables, and grains, improves glucose homeostasis. Similarly, Tocotrienols, a subfamily of vitamin E, also contains anti-diabetic properties. In this study, we examined the combined effect of geranylgeraniol and tocotrienols on the composition and function of gut microbiome in obese male mice. Methods Forty male C57BL/6J mice were assigned to 4 groups in a factorial design as follows: high-fat diet (HFD) (control group), HFD + geranylgeraniol [400 mg/kg diet] (GG group), HFD + tocotrienols [400 mg/kg diet] (TT group), and HFD + geranylgeraniol + tocotrienols (G + T group) for 14 weeks. 16S rRNA gene sequencing was done from cecal samples and microbiome and data analysis was performed with QIIME2 and PICRUSt2. Results Across all groups, the most abundant phyla were Verrucomicrobia, Firmicutes, Bacteroidetes, and Actinobacteria. There was no difference in alpha diversity among different groups. Different treatments influenced the relative abundance of certain bacteria. In the Bacteroidetes phylum, the relative abundance of family S24–7 increased in the TT group only. In the Firmicutes phylum, the relative abundance of family Lachnospiraceae was reduced upon the supplementation of geranylgeraniol or tocotrienols; individually or in combination. In Verrucomicrobia phylum, Akkermansia muciniphila relative abundance was reduced in the TT group but increased in the G + T group. The results of functional profiling of the gut microbiome revealed that geranylgeraniol supplementation caused an increase in the proportion of biosynthetic pathways related to purine, pyrimidine, and inosine-5’-phosphate and hexitol fermentation, and a decrease in the proportion of pathways involved in the biosynthesis of isoleucine, valine, histidine, arginine, and chorismate. The G + T group increased pathways related to thiamine diphosphate biosynthesis, and decreased others involved into sulfur oxidation and methylerythritol phosphate. Conclusions The influence of geranylgeraniol and tocotrienols supplementation on gut microbiome composition and function, suggests a prebiotic potential for the potential of geranylgeraniol and tocotrienols. Funding Sources American River Nutrition, LLC, Hadley, MA.

scholarly journals Broiler chicken body weights, feed intakes, plasma lipid and small-intestinal bile acid concentrations in response to feeding of chitosan and pectin

1997 ◽  
Vol 78 (2) ◽  
pp. 283-291 ◽  
Author(s):  
A. Razdan ◽  
D. Pettersson ◽  
J. Pettersson
Keyword(s):  
Small Intestine ◽  
Bile Acid ◽  
Broiler Chicken ◽  
Plasma Cholesterol ◽  
Control Diet ◽  
Plasma Lipid ◽  
Cholesterol Ratio ◽  
Body Weights

One-day-old broiler chickens were fed on a control diet based on maize and maize starch or diets containing 30g/kg of 89 % deacetylated chitin (chitosan) or low-methoxyl (34 % degree of esterification) pectin. Feeding of the chitosan diet to chickens significantly reduced body weights and feed intakes compared with animals fed on control or pectin diets on days 5 and 11 of the experiment. On day 12, significant reductions in total plasma cholesterol and HDL-cholesterol concentrations were observed among birds fed on the chitosan but not the pectin diet in relation to control-fed animals. A concomitant increase in the plasma HDL-cholesterol:total cholesterol ratio was observed among chitosan-fed chickens. The generally reduced concentrations of primary and total bile acids in the duodenum of birds fed on the fibre-containing diets on day 13 may have been an indication of a delay in the production and/or secretion of bile. Viscosity of the three broiler-chicken diets was measured after suspension in water, acidification and finally neutralization of the suspensions, in an attempt to simulate the effect of changes in pH and dilution of diets occurring in the gizzard and small intestine of chickens. Viscosity of the chitosan diet was significantly elevated after acidification and significantly reduced at neutralization in comparison with the control and pectin-containingdiets suggesting that the hypolipidaemic influence of chitosan observed in the present study may be due to interruption of enterohepatic bile acid circulation rather than increased viscosity in the small intestine of chickens. The low viscosity of the pectin dietin vitrotogether with the absence of a hypocholesterolaemic effect of this diet when fedin vivoprecludes any conclusion regarding the hypocholesterolaemic mechanism of pectin observed in earlier studies.

scholarly journals Host response to cholestyramine can be mediated by the gut microbiota

2020 ◽  
Author(s):  
Nolan K. Newman ◽  
Philip M. Monnier ◽  
Richard R. Rodrigues ◽  
Manoj Gurung ◽  
Stephany Vasquez-Perez ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Metabolic Diseases ◽  
Control Diet ◽  
Alpha Diversity ◽  
Mammalian Host ◽  
Beneficial Effects ◽  
Glucose Levels ◽  
Diet Induced Obesity ◽  
Expression Of Genes

AbstractThe gut microbiome has been implicated as a major factor contributing to metabolic diseases as well as being contributors to the response to drugs used for the treatment of such diseases. In this study, using a diet-induced obesity mouse model, we tested the effect of cholestyramine, a bile acid sequestrant, on the murine gut microbiome and mammalian metabolism. We also explored the hypothesis that some beneficial effects of this drug on systemic metabolism can be attributed to alterations in gut microbiota. First, we demonstrated that cholestyramine can decrease glucose and epidydimal fat levels. Next, while investigating gut microbiota we found increased alpha diversity of the gut microbiome of cholestyramine-treated mice, with fourteen taxa showing restoration of abundance to levels resembling those in mice fed with a control diet. Analyzing expression of genes known to be regulated by cholestyramine (including Cyp7a1), we confirmed the expected effect of this drug in the liver and ileum. Finally, using a transkingdom network analysis we inferred Acetatifactor muris and Muribaculum intestinale as potential mediators/modifiers of cholestyramine effects on the mammalian host. In addition, A. muris correlated positively with glucagon (Gcg) expression in the ileum and negatively correlated with small heterodimer partner (Shp) expression in the liver. Interestingly, A. muris also correlated negatively with glucose levels, further indicating the potential probiotic role for A. muris. In conclusion, our results indicate the gut microbiome has a role in the beneficial effects of cholestyramine and suggest specific microbes as targets of future investigations.

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