Changes in Microbial Community Composition Related to Sex and Colon Cancer by Nrf2 Knockout

The frequency of azoxymethane/dextran sulfate sodium (AOM/DSS)-induced carcinogenesis in male mice is higher than that in female mice. Previous studies have reported that 17β-estradiol inhibits tumorigenesis in males by modulating nuclear factor-erythroid 2-related factor 2 (Nrf2). This study aimed to investigate the changes in mouse gut microbiome composition based on sex, AOM/DSS-induced colorectal cancer (CRC), and Nrf2 genotype. The gut microbiome composition was determined by 16S rRNA gene sequencing fecal samples obtained at week 16 post-AOM administration. In terms of sex differences, our results showed that the wild-type (WT) male control mice had higher alpha diversity (i.e. Chao1, Shannon, and Simpson) than the WT female control mice. The linear discriminant analysis effect size (LEfSe) results revealed that the abundances of Akkermansia muciniphila and Lactobacillus murinus were higher in WT male control mice than in WT female controls. In terms of colon tumorigenesis, the alpha diversity of the male CRC group was lower than that of the male controls in both WT and Nrf2 KO, but did not show such changes in females. Furthermore, the abundance of A. muciniphila was higher in male CRC groups than in male controls in both WT and Nrf2 KO. The abundance of Bacteroides vulgatus was higher in WT CRC groups than in WT controls in both males and females. However, the abundance of L. murinus was lower in WT female CRC and Nrf2 KO male CRC groups than in its controls. The abundance of A. muciniphila was not altered by Nrf2 KO. In contrast, the abundances of L. murinus and B. vulgatus were changed differently by Nrf2 KO depending on sex and CRC. Interestingly, L. murinus showed negative correlation with tumor numbers in the whole colon. In addition, B. vulgatus showed positive correlation with inflammatory markers (i.e. myeloperoxidase and IL-1β levels), tumor numbers, and high-grade adenoma, especially, developed mucosal and submucosal invasive adenocarcinoma at the distal part of the colon. In conclusion, Nrf2 differentially alters the gut microbiota composition depending on sex and CRC induction.

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Gut Microbiome Analysis As A Non-Invasive Tool for the Early Diagnosis of Cholangiocarcinoma

10.21203/rs.3.rs-147842/v1 ◽

2021 ◽

Author(s):

Jialiang Li ◽

Xueyan Li ◽

Sina Zhang ◽

Chen Jin ◽

Zixia Lin ◽

...

Keyword(s):

Gut Microbiota ◽

Gut Microbiome ◽

Microbial Community Composition ◽

Intestinal Flora ◽

Alpha Diversity ◽

16S Rrna Gene Sequencing ◽

Intestinal Microbiome ◽

Rrna Gene ◽

Non Invasive ◽

Hepatobiliary Cancer

Abstract BACKGROUNDThe liver-microbiome axis is implicated in the pathogenesis of hepatobiliary cancer, and the role of the gut microbiota in cholangiocarcinoma (CCA) remains unclear.METHODWe conducted a case-control study on the intestinal flora of 33 CCA patients and 47 cholelithiasis individuals. We performed 16S rRNA gene sequencing to identify disease-related gut microbiota and assess the potential of the intestinal microbiome as a non-invasive biomarker for CCA.RESULTWe found that gut microbiome of CCA patients had a significantly higher alpha diversity (Shannon and Observed species indices, p = 0.006 and p = 0.02, respectively) and an overall different microbial community composition (p = 0.032). The genus Muribaculaceae_unclassified was most strongly associated with CCA (p < 0.001). We put forward a disease predictive model including twelve intestinal microbiome genera distinguished CCA patients from CF patients with an area under curve (AUC) of approximately 0.93 (95%CI, 0.85–0.987). The forecasting performance of this model was better than CA19-9. Moreover, genera Ezakiella and Garciella were only observed among intrahepatic cholangiocarcinoma patients. Further, we assessed predicted functional modules alternations CCA patients and uncovered a microbiota pattern specific to CCA.CONCLUSIONOur findings provide evidence of the intestinal microbiome as a non-invasive biomarker for CCA.

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Abstract 18: Gut Microbiome Modifies the Protective Effects of a Mediterranean Dietary Pattern Against Diabetes Mellitus in US Hispanics/ Latinos: The Hispanic Community Health Study/ Study of Latinos (HCHS/SOL)

Circulation ◽

10.1161/circ.141.suppl_1.18 ◽

2020 ◽

Vol 141 (Suppl_1) ◽

Cited By ~ 1

Author(s):

Dong Wang ◽

Qibin Qi ◽

Zheng Wang ◽

Mykhaylo Usyk ◽

Daniela Sotres-Alvarez ◽

...

Keyword(s):

Diabetes Mellitus ◽

Relative Abundance ◽

Gut Microbiome ◽

16S Rrna Gene Sequencing ◽

Health Study ◽

Rrna Gene ◽

Inverse Association ◽

Protective Effects ◽

Acid Fermentation ◽

Microbiome Composition

Introduction: Little is known about whether the effect of a healthy diet on diabetes mellitus (DM) is modified by the gut microbiome in human. Hypothesis: We hypothesize that the gut microbiome modifies the inverse association between the Mediterranean diet (MedDiet) and risk of DM. Methods: This study included 543 DM cases, 805 with impaired glucose tolerance (IGT) and 394 with normal glucose regulation (NGR) in adults 23-83yrs old from the HCHS/SOL. Fecal samples were profiled using 16s rRNA gene sequencing. We applied QIIME 2 to cluster sequences into OTUs and assign taxonomies, and PICRUSt to predict metagenomic gene functions. Adherence to the MedDiet was evaluated by a MedDiet index using the average of two 24-hr dietary recalls. We applied MaAsLin2 to quantify associations between the MedDiet index and microbial features with adjustment for confounding factors listed in the caption of Fig. 1. Results: MedDiet was associated with phylogenetically diverse, rare, and abundant gut microbes (Fig. 1a). For example, a higher MedDiet index was associated with a higher relative abundance of Faecalibacterium Prausnitzii [FDR-adjusted p (q) =0.002], but a lower relative abundance of Collinsella aerofaciens ( q =0.009). We found that several microbial functions related to plant-derived polysaccharide degradation such as fructuronate reductase ( q =0.02), and short-chain fatty acid fermentation such as butyryl-CoA dehydrogenase ( q =0.002) were enriched in participants with higher MedDiet index. We found that the inverse association between MedDiet and risk of DM was more pronounced in participants with greater abundance of Prevotella copri , but weaker in participants whose gut microbial communities were dominated by Bacteroides ( P interaction =0.02 for IGT/DM vs NGR, Fig. 1b). Conclusions: Adherence to the MedDiet is associated with diverse gut microorganisms and microbial functions. The inverse association between MedDiet and risk of DM might be modified by gut microbiome composition. 1

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Changes in the Intestinal Microbiome during a Multispecies Probiotic Intervention in Compensated Cirrhosis

Nutrients ◽

10.3390/nu12061874 ◽

2020 ◽

Vol 12 (6) ◽

pp. 1874 ◽

Cited By ~ 1

Author(s):

Angela Horvath ◽

Marija Durdevic ◽

Bettina Leber ◽

Katharina di Vora ◽

Florian Rainer ◽

...

Keyword(s):

Gut Microbiome ◽

Controlled Trial ◽

16S Rrna Gene Sequencing ◽

Intestinal Microbiome ◽

Rrna Gene ◽

Microbiome Composition ◽

Beneficial Effects ◽

Compensated Cirrhosis ◽

Gut Barrier Function ◽

Probiotic Treatment

Probiotics have been used in trials to therapeutically modulate the gut microbiome and have shown beneficial effects in cirrhosis. However, their effect on the microbiome of cirrhosis patients is not fully understood yet. Here, we tested the effects of a multispecies probiotic on microbiome composition in compensated cirrhosis. The gut microbiome composition of 58 patients with compensated cirrhosis from a randomized controlled trial who received a daily dose of multispecies probiotics or placebo for six months was analysed by 16S rRNA gene sequencing. Microbiome composition of patients who received probiotics was enriched with probiotic strains and the abundance of Faecalibacterium prausnitzii, Syntrophococcus sucromutans, Bacteroides vulgatus, Alistipes shahii and a Prevotella species was increased in the probiotic group compared to the placebo group. Patients who had microbiome changes in response to probiotic treatment also showed a significant increase in neopterin and a significant decrease in faecal zonulin levels after intervention, which was not observed in placebo-treated patients or patients with unchanged microbiome compositions. In conclusion, multispecies probiotics may enrich the microbiome of compensated cirrhotic patients with probiotic bacteria during a six-month intervention and beneficially change the residential microbiome and gut barrier function.

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Gut microbiome profiling of a rural and urban South African cohort reveals biomarkers of a population in lifestyle transition

BMC Microbiology ◽

10.1186/s12866-020-02017-w ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

O. H. Oduaran ◽

F. B. Tamburini ◽

V. Sahibdeen ◽

R. Brewster ◽

F. X. Gómez-Olivé ◽

...

Keyword(s):

South African ◽

Gut Microbiome ◽

Geographical Location ◽

16S Rrna Gene Sequencing ◽

Overweight And Obesity ◽

Future Research ◽

Epidemiological Transition ◽

Rrna Gene ◽

Microbiome Composition ◽

Targeted Interventions

Abstract Background Comparisons of traditional hunter-gatherers and pre-agricultural communities in Africa with urban and suburban Western North American and European cohorts have clearly shown that diet, lifestyle and environment are associated with gut microbiome composition. Yet, little is known about the gut microbiome composition of most communities in the very diverse African continent. South Africa comprises a richly diverse ethnolinguistic population that is experiencing an ongoing epidemiological transition and concurrent spike in the prevalence of obesity, largely attributed to a shift towards more Westernized diets and increasingly inactive lifestyle practices. To characterize the microbiome of African adults living in more mainstream lifestyle settings and investigate associations between the microbiome and obesity, we conducted a pilot study, designed collaboratively with community leaders, in two South African cohorts representative of urban and transitioning rural populations. As the rate of overweight and obesity is particularly high in women, we collected single time-point stool samples from 170 HIV-negative women (51 at Soweto; 119 at Bushbuckridge), performed 16S rRNA gene sequencing on these samples and compared the data to concurrently collected anthropometric data. Results We found the overall gut microbiome of our cohorts to be reflective of their ongoing epidemiological transition. Specifically, we find that geographical location was more important for sample clustering than lean/obese status and observed a relatively higher abundance of the Melainabacteria, Vampirovibrio, a predatory bacterium, in Bushbuckridge. Also, Prevotella, despite its generally high prevalence in the cohorts, showed an association with obesity. In comparisons with benchmarked datasets representative of non-Western populations, relatively higher abundance values were observed in our dataset for Barnesiella (log2fold change (FC) = 4.5), Alistipes (log2FC = 3.9), Bacteroides (log2FC = 4.2), Parabacteroides (log2FC = 3.1) and Treponema (log2FC = 1.6), with the exception of Prevotella (log2FC = − 4.7). Conclusions Altogether, this work identifies putative microbial features associated with host health in a historically understudied community undergoing an epidemiological transition. Furthermore, we note the crucial role of community engagement to the success of a study in an African setting, the importance of more population-specific studies to inform targeted interventions as well as present a basic foundation for future research.

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Alterations of gut microbiome in autoimmune hepatitis

Gut ◽

10.1136/gutjnl-2018-317836 ◽

2019 ◽

Vol 69 (3) ◽

pp. 569-577 ◽

Cited By ~ 27

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.

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Microbe-Metabolite Associations Linked to the Rebounding Murine Gut Microbiome Postcolonization with Vancomycin-Resistant Enterococcus faecium

mSystems ◽

10.1128/msystems.00452-20 ◽

2020 ◽

Vol 5 (4) ◽

Author(s):

Andre Mu ◽

Glen P. Carter ◽

Lucy Li ◽

Nicole S. Isles ◽

Alison F. Vrbanac ◽

...

Keyword(s):

Gut Microbiome ◽

Enterococcus Faecium ◽

Molecular Mechanisms ◽

Microbial Community Composition ◽

16S Rrna Gene Sequencing ◽

Rrna Gene ◽

Content Type ◽

Functional Roles ◽

Specific Pathogen ◽

Vancomycin Resistant

ABSTRACT Vancomycin-resistant Enterococcus faecium (VREfm) is an emerging antibiotic-resistant pathogen. Strain-level investigations are beginning to reveal the molecular mechanisms used by VREfm to colonize regions of the human bowel. However, the role of commensal bacteria during VREfm colonization, in particular following antibiotic treatment, remains largely unknown. We employed amplicon 16S rRNA gene sequencing and metabolomics in a murine model system to try and investigate functional roles of the gut microbiome during VREfm colonization. First-order taxonomic shifts between Bacteroidetes and Tenericutes within the gut microbial community composition were detected both in response to pretreatment using ceftriaxone and to subsequent VREfm challenge. Using neural networking approaches to find cooccurrence profiles of bacteria and metabolites, we detected key metabolome features associated with butyric acid during and after VREfm colonization. These metabolite features were associated with Bacteroides, indicative of a transition toward a preantibiotic naive microbiome. This study shows the impacts of antibiotics on the gut ecosystem and the progression of the microbiome in response to colonization with VREfm. Our results offer insights toward identifying potential nonantibiotic alternatives to eliminate VREfm through metabolic reengineering to preferentially select for Bacteroides. IMPORTANCE This study demonstrates the importance and power of linking bacterial composition profiling with metabolomics to find the interactions between commensal gut bacteria and a specific pathogen. Knowledge from this research will inform gut microbiome engineering strategies, with the aim of translating observations from animal models to human-relevant therapeutic applications.

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Dietary sphinganine is selectively assimilated by members of the gut microbiome

10.1101/2020.06.08.140665 ◽

2020 ◽

Author(s):

Min-Ting Lee ◽

Henry H. Le ◽

Elizabeth L. Johnson

Keyword(s):

Gut Microbiome ◽

16S Rrna Gene Sequencing ◽

Dietary Lipids ◽

Rrna Gene ◽

Bioactive Components ◽

Microbiome Composition ◽

Metabolic Products ◽

Comparative Metabolomics ◽

Rrna Gene Sequencing ◽

Gut Microbial Community

AbstractFunctions of the gut microbiome have a growing number of implications for host metabolic health, with diet being one of the most significant influences on microbiome composition. Compelling links between diet and the gut microbiome suggest key roles for various macronutrients, including lipids, yet how individual classes of dietary lipids interact with the microbiome remain largely unknown. A class of lipids known as sphingolipids are bioactive components of most foods and are produced by prominent gut microbes. This makes sphingolipids intriguing candidates for shaping diet-microbiome interactions. Here, we use a click-chemistry based approach to track the incorporation of bioorthogonal dietary omega-alkynyl sphinganine (sphinganine alkyne – SAA) into the gut microbial community (Click). Identification of microbe and SAA-specific metabolic products was achieved by fluorescence-based sorting of SAA containing microbes (Sort), 16S rRNA gene sequencing to identify the sphingolipid-interacting microbes (Seq), and comparative metabolomics to identify products of SAA assimilation by the microbiome (Spec). Together this approach, Click-Sort-Seq-Spec (ClickSSS), revealed that SAA-assimilation was nearly exclusively performed by gut Bacteroides, indicating that sphingolipid-producing bacteria play a major role in processing dietary sphinganine. Comparative metabolomics of cecal microbiota from SAA-treated mice showed conversion of SAA to a suite of dihydroceramides, consistent with metabolic activity via Bacteroides and Bifidobacterium. Additionally, other sphingolipid-interacting microbes were identified with a focus on an uncharacterized ability of Bacteroides and Bifidobacterium to metabolize dietary sphingolipids. Therefore, ClickSSS provides a platform to study the flux of virtually any alkyne-labeled metabolite in diet-microbiome interactions.

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APOE Genetics Influence Murine Gut Microbiome

10.21203/rs.3.rs-746611/v1 ◽

2021 ◽

Author(s):

Diana J. Zajac ◽

Stefan J. Green ◽

Lance A. Johnson ◽

Steven Estus

Keyword(s):

Gut Microbiome ◽

Beta Diversity ◽

Univariate Analysis ◽

Microbial Community Composition ◽

Alpha Diversity ◽

Amplicon Sequencing ◽

Linear Discriminant ◽

Fecal Microbiome ◽

Female Mice ◽

The Impact

Abstract Background: Apolipoprotein E (APOE) alleles impact pathogenesis and risk for multiple human diseases, making them primary targets for disease treatment and prevention. Previously, we and others reported an association between APOE alleles and the gut microbiome. Here, we tested whether these results are confirmed by using mice that were maintained under ideal conditions for microbiome analyses. Methods: To model human APOE alleles, this study used APOE targeted replacement (TR) mice on a C57Bl/6 background. To minimize genetic drift, APOE3 mice were crossed to APOE2 or APOE4 mice prior to the study, and the resulting heterozygous progeny crossed further to generate the study mice. To maximize environmental homogeneity, mice with mixed genotypes were housed together and used bedding from the cages was mixed and added back as a portion of new bedding. Fecal samples were obtained from mice at three-, five- and seven-months of age, and microbiota analyzed by 16S ribosomal RNA gene amplicon sequencing. APOE2/E2 and APOE2/E3 mice were categorized as APOE2, APOE3/E4 and APOE4/E4 mice were categorized as APOE4, and APOE3/E3 mice were categorized as APOE3. Linear discriminant analysis of Effect Size (LefSe) identified taxa associated with APOE status, depicted as cladograms to show phylogenetic relatedness. The influence of APOE status was tested onalpha-diversity (Shannon H index) and beta-diversity (principal coordinate analyses and PERMANOVA). Individual taxa associated with APOE status were identified by classical univariate analysis. Whether findings in the APOE mice were replicated in humans was evaluated by using published microbiome genome wide association data. Results: Cladograms revealed robust differences with APOE in male mice and limited differences in female mice. The richness and evenness (alpha-diversity) and microbial community composition (beta-diversity) of the fecal microbiome was robustly associated with APOE status in male but not female mice. Classical univariate analysis revealed individual taxa that were significantly increased or decreased with APOE, illustrating a stepwise APOE2-APOE3-APOE4 pattern of association. The Clostridia class, Clostridiales order, Ruminococacceae family and related genera increased with APOE2 status. The Erysipelotrichia phylogenetic branch increased with APOE4 status, a finding that extended to humans.Conclusions: In this study wherein mice were maintained in an ideal fashion for microbiome studies, gut microbiome profiles were strongly and significantly associated with APOE status in male APOE-TR mice. Erysipelotrichia in particular appears to increase with APOE4 in both mice and humans. Further evaluation of these findings in humans, as well as studies evaluating the impact of the APOE-associated microbiota on disease-relevant phenotypes, will be necessary to determine if alterations in the gut microbiome represents a novel mechanism whereby APOE alleles impact disease.

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Dietary sphinganine is selectively assimilated by members of the mammalian gut microbiome

The Journal of Lipid Research ◽

10.1194/jlr.ra120000950 ◽

2020 ◽

pp. jlr.RA120000950 ◽

Cited By ~ 1

Author(s):

Min-Ting Lee ◽

Henry H Le ◽

Elizabeth L Johnson

Keyword(s):

Gut Microbiome ◽

16S Rrna Gene Sequencing ◽

Dietary Lipids ◽

Rrna Gene ◽

Microbiome Composition ◽

Bioorthogonal Labeling ◽

Comparative Metabolomics ◽

Metabolic Activities ◽

Rrna Gene Sequencing ◽

Gut Microbial Community

Functions of the gut microbiome have a growing number of implications for host metabolic health, with diet being one of the most significant influences on microbiome composition. Compelling links between diet and the gut microbiome suggest key roles for various macronutrients, including lipids, yet how individual classes of dietary lipids interact with the microbiome remains largely unknown. Sphingolipids are bioactive components of most foods and are also produced by prominent gut microbes. This makes sphingolipids intriguing candidates for shaping diet–microbiome interactions. Here, we used a click chemistry–based approach to track the incorporation of bioorthogonal dietary omega-alkynyl sphinganine (sphinganine alkyne [SAA]) into the murine gut microbial community (Bioorthogonal labeling). We identified microbial and SAA-specific metabolic products through fluorescence-based sorting of SAA-containing microbes (Sort), 16S rRNA gene sequencing to identify the sphingolipid-interacting microbes (Seq), and comparative metabolomics to identify products of SAA assimilation by the microbiome (Spec). Together, this approach, termed Bioorthogonal labeling-Sort-Seq-Spec (BOSSS), revealed that SAA assimilation is nearly exclusively performed by gut Bacteroides, indicating that sphingolipid-producing bacteria play a major role in processing dietary sphinganine. Comparative metabolomics of cecal microbiota from SAA-treated mice revealed conversion of SAA to a suite of dihydroceramides, consistent with metabolic activities of Bacteroides and Bifidobacterium. Additionally, other sphingolipid-interacting microbes were identified with a focus on an uncharacterized ability of Bacteroides and Bifidobacterium to metabolize dietary sphingolipids. We conclude that BOSSS provides a platform to study the flux of virtually any alkyne-labeled metabolite in diet–microbiome interactions.

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

Current Developments in Nutrition ◽

10.1093/cdn/nzaa045_026 ◽

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.

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