Gut Microbiome, Functional Food, Atherosclerosis, and Vascular Calcifications—Is There a Missing Link?

The gut microbiome is represented by the genome of all microorganisms (symbiotic, potential pathogens, or pathogens) residing in the intestine. These ecological communities are involved in almost all metabolic diseases and cardiovascular diseases are not excluded. Atherosclerosis, with a continuously increasing incidence in recent years, is the leading cause of coronary heart disease and stroke by plaque rupture and intraplaque hemorrhage. Vascular calcification, a process very much alike with osteogenesis, is considered to be a marker of advanced atherosclerosis. New evidence, suggesting the role of dietary intake influence on the diversity of the gut microbiome in the development of vascular calcifications, is highly debated. Gut microbiota can metabolize choline, phosphatidylcholine, and L-carnitine and produce vasculotoxic metabolites, such as trimethylamine-N-oxide (TMAO), a proatherogenic metabolite. This review article aims to discuss the latest research about how probiotics and the correction of diet is impacting the gut microbiota and its metabolites in the atherosclerotic process and vascular calcification. Further studies could create the premises for interventions in the microbiome as future primary tools in the prevention of atherosclerotic plaque and vascular calcifications.

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Folate and vitamin B-12 deficiencies additively impaired memory function and disturbed the gut microbiota in amyloid-β infused rats

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000624 ◽

2019 ◽

pp. 1-13 ◽

Cited By ~ 2

Author(s):

Sunmin Park ◽

Sunna Kang ◽

Da Sol Kim

Keyword(s):

Insulin Resistance ◽

Gut Microbiota ◽

Insulin Signaling ◽

Gut Microbiome ◽

Metabolic Diseases ◽

Memory Function ◽

Amyloid Β ◽

Impaired Memory ◽

Ca1 Region ◽

Folate And Vitamin B12

Abstract. Folate and vitamin B12(V-B12) deficiencies are associated with metabolic diseases that may impair memory function. We hypothesized that folate and V-B12 may differently alter mild cognitive impairment, glucose metabolism, and inflammation by modulating the gut microbiome in rats with Alzheimer’s disease (AD)-like dementia. The hypothesis was examined in hippocampal amyloid-β infused rats, and its mechanism was explored. Rats that received an amyloid-β(25–35) infusion into the CA1 region of the hippocampus were fed either control(2.5 mg folate plus 25 μg V-B12/kg diet; AD-CON, n = 10), no folate(0 folate plus 25 μg V-B12/kg diet; AD-FA, n = 10), no V-B12(2.5 mg folate plus 0 μg V-B12/kg diet; AD-V-B12, n = 10), or no folate plus no V-B12(0 mg folate plus 0 μg V-B12/kg diet; AD-FAB12, n = 10) in high-fat diets for 8 weeks. AD-FA and AD-VB12 exacerbated bone mineral loss in the lumbar spine and femur whereas AD-FA lowered lean body mass in the hip compared to AD-CON(P < 0.05). Only AD-FAB12 exacerbated memory impairment by 1.3 and 1.4 folds, respectively, as measured by passive avoidance and water maze tests, compared to AD-CON(P < 0.01). Hippocampal insulin signaling and neuroinflammation were attenuated in AD-CON compared to Non-AD-CON. AD-FAB12 impaired the signaling (pAkt→pGSK-3β) and serum TNF-α and IL-1β levels the most among all groups. AD-CON decreased glucose tolerance by increasing insulin resistance compared to Non-AD-CON. AD-VB12 and AD-FAB12 increased insulin resistance by 1.2 and 1.3 folds, respectively, compared to the AD-CON. AD-CON and Non-AD-CON had a separate communities of gut microbiota. The relative counts of Bacteroidia were lower and those of Clostridia were higher in AD-CON than Non-AD-CON. AD-FA, but not V-B12, separated the gut microbiome community compared to AD-CON and AD-VB12(P = 0.009). In conclusion, folate and B-12 deficiencies impaired memory function by impairing hippocampal insulin signaling and gut microbiota in AD rats.

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Novel Interactions Between Circulating microRNAs and Gut Microbiota Composition in Human Obesity.

10.21203/rs.3.rs-66883/v1 ◽

2020 ◽

Author(s):

Taís Silveira Assmann ◽

Amanda Cuevas-Sierra ◽

José Ignacio Riezu-Boj ◽

Fermin Milagro ◽

J Alfredo Martínez

Keyword(s):

Gut Microbiota ◽

Gut Microbiome ◽

Target Genes ◽

Metabolic Diseases ◽

Bacterial Species ◽

Microbiota Composition ◽

Circulating Mirnas ◽

Clinical Trial Registration ◽

Body Adiposity ◽

Gut Microbiota Composition

Abstract Background: Unbalances in microRNAs (miRNA) and gut microbiota patterns have been proposed as putative factors concerning onset and development of obesity and other metabolic diseases. However, the determinants that mediate the interactions between miRNAs and the gut microbiome impacting on obesity are scarcely understood. Thus, the aim of this article was to investigate possible interactions between circulating miRNAs and gut microbiota composition in obesity. Method: The analyzed sample comprised 78 subjects with obesity [cases, body mass index (BMI): 30 – 40 kg/m2] and 25 eutrophic individuals (controls, BMI £ 25 kg/m2). The expression of 96 miRNAs was investigated in plasma of all individuals using miRCURY LNA miRNA Custom PCR Panels (Exiqon). Bacterial DNA sequencing was performed following the Illumina 16S protocol. The FDR (Benjamini-Hochberg test, q-value) correction was used for multiple comparison analyses.Results: A total of 26 circulating miRNAs and 12 bacterial species were found differentially expressed between cases and controls. Interestingly, an interaction among three miRNAs (miR-130b-3p, miR-185-5p, and miR-21-5p) with Bacteroides eggerthi, and BMI levels was evidenced (r2= 0.148, P= 0.004). Those miRNAs that correlated with obesity-associated gut bacteria abundance are known to regulate target genes that participate in metabolism-related pathways, such as fatty acid degradation, carbohydrate digestion and absorption, insulin signaling, and glycerolipid metabolism. Conclusion: This study characterized an interaction between the abundance of 4 bacterial species and 14 circulating miRNAs in relation to body adiposity. Moreover, the current study also suggests that miRNAs may serve as a communication mechanism between the gut microbiome and human hosts. Clinical trial registration: clinicaltrials.gov (reg. no. NCT02737267).

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Sex differences in gut microbiome in high-fat-diet fed rats.

10.21203/rs.3.rs-31327/v1 ◽

2020 ◽

Author(s):

Ying Shi ◽

Fangzhi Yue ◽

Lin Xing ◽

Shanyu Wu ◽

Lin Wei ◽

...

Keyword(s):

Sex Differences ◽

Gut Microbiota ◽

Gut Microbiome ◽

High Fat Diet ◽

Metabolic Diseases ◽

Normal Diet ◽

Female Rats ◽

Male Rats ◽

High Fat ◽

Alcoholic Fatty Liver

Abstract Background Sex differences in obesity and related metabolic diseases are well recognized, however, the mechanism has not been elucidated. Gut microbiota and its metabolites may play a vital role in the development of obesity and metabolic diseases. The aim of the present study was to investigate sex differences in gut microbiota and its metabolites in a high-fat-diet (HFD) obesity rats and identify microbiota genera potentially contributing to such differences in obesity and non-alcoholic fatty liver disease (NAFLD) susceptibility. Results Sprague–Dawley rats were divided into the following groups (seven animals per group): (1) male rats on a normal diet (MND), (2) male rats on HFD (MHFD), (3) female rats on a normal diet (FND), and (4) female rats on HFD (FHFD). HFD induced more body weight gain and fat storage in female rats, however, lower hepatic steatosis in FHFD than in MHFD rats was observed. When considering gut microbiota composition, FHFD rats had lower microbiome diversity than MHFD. A significant increase of Firmicutes phylum and Bilophila genus was detected in MHFD rats, as compared with FHFD, which showed increased relative abundance of Murimonas and Roseburia . Moreover, propionic and lauric acid levels were higher in FHFD than those in MHFD rats. Conclusion HFD induced sex-related alterations in gut microbiome and fatty acids. Furthermore, the genus Bilophila and Roseburia might contribute to sex differences observed in obesity and NAFLD susceptibility.

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Host response to cholestyramine can be mediated by the gut microbiota

10.1101/2020.12.08.416487 ◽

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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Oral Administration ofPorphyromonas gingivalisAlters the Gut Microbiome and Serum Metabolome

mSphere ◽

10.1128/msphere.00460-18 ◽

2018 ◽

Vol 3 (5) ◽

Cited By ~ 27

Author(s):

Tamotsu Kato ◽

Kyoko Yamazaki ◽

Mayuka Nakajima ◽

Yasuhiro Date ◽

Jun Kikuchi ◽

...

Keyword(s):

Gut Microbiota ◽

Periodontal Disease ◽

Oral Administration ◽

Gut Microbiome ◽

Metabolic Diseases ◽

Microbiota Composition ◽

Content Type ◽

Increased Risk ◽

Metabolite Profiles ◽

Gut Microbiota Composition

ABSTRACTPeriodontal disease induced by periodontopathic bacteria likePorphyromonas gingivalisis demonstrated to increase the risk of metabolic, inflammatory, and autoimmune disorders. Although precise mechanisms for this connection have not been elucidated, we have proposed mechanisms by which orally administered periodontopathic bacteria might induce changes in gut microbiota composition, barrier function, and immune system, resulting in an increased risk of diseases characterized by low-grade systemic inflammation. Accumulating evidence suggests a profound effect of altered gut metabolite profiles on overall host health. Therefore, it is possible thatP. gingivaliscan affect these metabolites. To test this, C57BL/6 mice were administered withP. gingivalisW83 orally twice a week for 5 weeks and compared with sham-inoculated mice. The gut microbial communities were analyzed by pyrosequencing the 16S rRNA genes. Inferred metagenomic analysis was used to determine the relative abundance of KEGG pathways encoded in the gut microbiota. Serum metabolites were analyzed using nuclear magnetic resonance (NMR)-based metabolomics coupled with multivariate statistical analyses. Oral administration ofP. gingivalisinduced a change in gut microbiota composition. The distributions of metabolic pathways differed between the two groups, including those related to amino acid metabolism and, in particular, the genes for phenylalanine, tyrosine, and tryptophan biosynthesis. Also, alanine, glutamine, histidine, tyrosine, and phenylalanine were significantly increased in the serum ofP. gingivalis-administered mice. In addition to altering immune modulation and gut barrier function, oral administration ofP. gingivalisaffects the host’s metabolic profile. This supports our hypothesis regarding a gut-mediated systemic pathology resulting from periodontal disease.IMPORTANCEIncreasing evidence suggest that alterations of the gut microbiome underlie metabolic disease pathology by modulating gut metabolite profiles. We have shown that orally administeredPorphyromonas gingivalis, a representative periodontopathic bacterium, alters the gut microbiome; that may be a novel mechanism by which periodontitis increases the risk of various diseases. Given the association between periodontal disease and metabolic diseases, it is possible thatP. gingivaliscan affect the metabolites. Metabolite profiling analysis demonstrated that several amino acids related to a risk of developing diabetes and obesity were elevated inP. gingivalis-administered mice. Our results revealed that the increased risk of various diseases byP. gingivalismight be mediated at least in part by alteration of metabolic profiles. The findings should add new insights into potential links between periodontal disease and systemic disease for investigators in periodontal disease and also for investigators in the field of other diseases, such as metabolic diseases.

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Gut microbiome-Mediterranean diet interactions in improving host health

F1000Research ◽

10.12688/f1000research.18992.1 ◽

2019 ◽

Vol 8 ◽

pp. 699 ◽

Cited By ~ 4

Author(s):

Ravinder Nagpal ◽

Carol A. Shively ◽

Thomas C. Register ◽

Suzanne Craft ◽

Hariom Yadav

Keyword(s):

Gut Microbiota ◽

Health Effects ◽

Mediterranean Diet ◽

Gut Microbiome ◽

Unsaturated Fatty Acids ◽

Metabolic Diseases ◽

Human Subjects ◽

Wide Range ◽

Host Health ◽

The Mediterranean

The gut microbiota plays a fundamental role in host health and disease. Host diet is one of the most significant modulators of the gut microbial community and its metabolic activities. Evidence demonstrates that dietary patterns such as the ‘Western diet’ and perturbations in gut microbiome (dysbiosis) have strong associations with a wide range of human diseases, including obesity, metabolic syndrome, type-2 diabetes and cardiovascular diseases. However, consumption of Mediterranean-style diets is considered healthy and associated with the prevention of cardiovascular and metabolic diseases, colorectal cancers and many other diseases. Such beneficial effects of the Mediterranean diet might be attributed to high proportion of fibers, mono- and poly-unsaturated fatty acids, antioxidants and polyphenols. Concurrent literature has demonstrated beneficial modulation of the gut microbiome following a Mediterranean-style diet in humans as well as in experimental animal models such as rodents. We recently demonstrated similar positive changes in the gut microbiome of non-human primates consuming a Mediterranean-style diet for long term (30 months). Therefore, it is rational to speculate that this positive modulation of the gut microbiome diversity, composition and function is one of the main factors intermediating the health effects of Mediterranean diet on the host. The present perspective discusses the evidences that the Mediterranean diet induces gut microbiome modulation in rodents, non-human primates and human subjects, and discusses the potential role of gut microbiota and microbial metabolites as one of the fundamental catalysts intermediating various beneficial health effects of Mediterranean diet on the host.

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Metagenomic Study Revealed the Potential Role of the Gut Microbiome in Gout

10.1101/2019.12.21.19014142 ◽

2019 ◽

Author(s):

Yongliang Chu ◽

Yufen Huang ◽

Qingchun Huang ◽

Xuefeng Xie ◽

Peng Wang ◽

...

Keyword(s):

Gut Microbiota ◽

Gut Microbiome ◽

Lipid A ◽

Metabolic Diseases ◽

Healthy Controls ◽

Positive Performance ◽

Metagenomic Study ◽

Anti Inflammatory ◽

Mannose Metabolism

ABSTRACTEmerging evidence has indicated an association between the gut microbiome and arthritis diseases including gout. This metagenomic study aims to investigate the possible role of gut microbiota in the development of gout. The results exhibit gout patients have higher abundance of Prevotella, Fusobacterium spp. and Bacteroides spp., whereas healthy controls have higher abundance of Enterobacteriaceae spp., butyrate-producing species, including Roseburia spp., Butyrivibrio spp. and Coprococcus spp. and anti-inflammatory Faecalibacterium prausnitzii. Functional analysis shows gut microbiome of gout patients have higher potential for fructose, mannose metabolism and lipid A biosynthesis, but lower potential for urate degradation and SCFAs production. Enterobacteriaceae spp. may contribute to urate degradation and provide immunostimulatory effect in healthy controls. A disease classifier based on gut microbiota shows positive performance in the discovery and validation cohorts (93.03% and 89.13% accuracy, respectively). The effect of uric-acid-lowering and anti-inflammatory drugs on the gut microbiome is mild. Integrative analyses of four additional diseases (obesity, type 2 diabetes, ankylosing spondylitis and rheumatoid arthritis) indicates gout seems to be more similar to autoimmune diseases than metabolic diseases. This work demonstrates an altered gut microbiota might influence the development of gout and provides new insights into the diagnosis and treatment of the disease.

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Vitamin D Through Balancing Gut Microbiota to Improve Non-alcoholic Steatohepatitis (Nash): A Study Protocol for a Randomized Clinical Trial

10.21203/rs.3.rs-868710/v1 ◽

2021 ◽

Author(s):

Yilan Zeng ◽

Dongxia Luo ◽

Li Wang ◽

Mei Luo ◽

Chuangjie Mao ◽

...

Keyword(s):

Clinical Trial ◽

Vitamin D ◽

Gut Microbiota ◽

Fatty Liver ◽

Gut Microbiome ◽

Metabolic Diseases ◽

Topological Analysis ◽

High Dose ◽

Alcoholic Fatty Liver ◽

Alcoholic Steatohepatitis

Abstract BackgroundVitamin D deficiency (VDD) is overwhelmingly prevalent worldwide in association with metabolic syndrome (MetS), type-2 diabetes (T2D), and non-alcoholic fatty liver diseases (NAFLD). Whether vitamin D supplement or treatment can improve these metabolic diseases is controversial, due in part to absence of large-scale trials. On the other hand, unbalanced gut microbiome, dysbiosis, plays key roles in these metabolic diseases. Moreover, whether sunlight exposure or vitamin D can determine the gut microbiome is elusive. The present study aims to investigate whether intramuscular administration of high dose of vitamin D2 can improve non-alcoholic steatohepatitis (NASH) through balancing of gut microbiome. Methods/designIn a randomized, open-labeled, and parallel-group trial, NASH subjects will be enrolled and randomly allocated to receive ergocalciferol (VD2) treatment or not, n=80 for each group. The NASH patients, diagnosed according to the guideline for NAFLD treatment of China, will be given an initial dose of VD2 at 600,000IU by intramuscular injection followed by additional three administration every other 30 days with total of four injections in 120 days. Anthropometry, liver functions, the metabolic panel will be measured. Fatty liver index will be determined by topological analysis of ultrasound data. Serum 25-hydroxyvitamin D (25(OH)D) and fecal microbiome will be measured. Discussion: This study will determine the efficacy of high dose of VD2 to relieve NASH symptoms and on gut microbiota. Trial registrationChinese Clinical Trial Registry, ChiCTR1800017879, registered on Aguste 20th, 2018.

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Gut microbiota modulation induced by Zika virus infection in immunocompetent mice

Scientific Reports ◽

10.1038/s41598-020-80893-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Rafael Corrêa ◽

Igor de Oliveira Santos ◽

Heloísa Antoniella Braz-de-Melo ◽

Lívia Pimentel de Sant’Ana ◽

Raquel das Neves Almeida ◽

...

Keyword(s):

Gut Microbiota ◽

Gut Microbiome ◽

Zika Virus ◽

Hypervariable Region ◽

Microbiota Composition ◽

Colon Tissue ◽

Zikv Infection ◽

Immunological Responses ◽

Immunocompetent Mice ◽

Gut Microbiota Composition

AbstractGut microbiota composition can modulate neuroendocrine function, inflammation, and cellular and immunological responses against different pathogens, including viruses. Zika virus (ZIKV) can infect adult immunocompetent individuals and trigger brain damage and antiviral responses. However, it is not known whether ZIKV infection could impact the gut microbiome from adult immunocompetent mice. Here, we investigated modifications induced by ZIKV infection in the gut microbiome of immunocompetent C57BL/6J mice. Adult C57BL/6J mice were infected with ZIKV and the gut microbiota composition was analyzed by next-generation sequencing of the V4 hypervariable region present in the bacterial 16S rDNA gene. Our data showed that ZIKV infection triggered a significant decrease in the bacteria belonging to Actinobacteria and Firmicutes phyla, and increased Deferribacteres and Spirochaetes phyla components compared to uninfected mice. Interestingly, ZIKV infection triggered a significant increase in the abundance of bacteria from the Spirochaetaceae family in the gut microbiota. Lastly, we demonstrated that modulation of microbiota induced by ZIKV infection may lead to intestinal epithelium damage and intense leukocyte recruitment to the intestinal mucosa. Taken together, our data demonstrate that ZIKV infection can impact the gut microbiota composition and colon tissue homeostasis in adult immunocompetent mice.

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The gut microbiome of laboratory mice: considerations and best practices for translational research

Mammalian Genome ◽

10.1007/s00335-021-09863-7 ◽

2021 ◽

Author(s):

Aaron C. Ericsson ◽

Craig L. Franklin

Keyword(s):

Human Physiology ◽

Best Practices ◽

Gut Microbiota ◽

Translational Research ◽

Mouse Models ◽

Gut Microbiome ◽

Predictive Power ◽

Environmental Influences ◽

Pharmacological Intervention ◽

Laboratory Mice

AbstractJust as the gut microbiota (GM) is now recognized as an integral mediator of environmental influences on human physiology, susceptibility to disease, and response to pharmacological intervention, so too does the GM of laboratory mice affect the phenotype of research using mouse models. Multiple experimental factors have been shown to affect the composition of the GM in research mice, as well as the model phenotype, suggesting that the GM represents a major component in experimental reproducibility. Moreover, several recent studies suggest that manipulation of the GM of laboratory mice can substantially improve the predictive power or translatability of data generated in mouse models to the human conditions under investigation. This review provides readers with information related to these various factors and practices, and recommendations regarding methods by which issues with poor reproducibility or translatability can be transformed into discoveries.

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