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      The influence of the human microbiome and probiotics on cardiovascular health

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          Abstract

          Cardiovascular disease (CVD) is a major cause of death worldwide. Of the many etiological factors, microorganisms constitute one. From the local impact of the gut microbiota on energy metabolism and obesity, to the distal association of periodontal disease with coronary heart disease, microbes have a significant impact on cardiovascular health. In terms of the ability to modulate or influence the microbes, probiotic applications have been considered. These are live microorganisms which when administered in adequate amounts confer a benefit on the host. While a number of reports have established the beneficial abilities of certain probiotic bacterial strains to reduce cholesterol and hypertension, recent research suggests that their use could be more widely applied. This review presents an up-to-date summary of the known associations of the microbiome with CVD, and potential applications of probiotic therapy.

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          Periodontitis: a polymicrobial disruption of host homeostasis.

          Richard Darveau (2010)
          Periodontitis, or gum disease, affects millions of people each year. Although it is associated with a defined microbial composition found on the surface of the tooth and tooth root, the contribution of bacteria to disease progression is poorly understood. Commensal bacteria probably induce a protective response that prevents the host from developing disease. However, several bacterial species found in plaque (the 'red-complex' bacteria: Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola) use various mechanisms to interfere with host defence mechanisms. Furthermore, disease may result from 'community-based' attack on the host. Here, I describe the interaction of the host immune system with the oral bacteria in healthy states and in diseased states.
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            Defining the healthy "core microbiome" of oral microbial communities

            Egija Zaura, Bart JF Keijser, Susan M. Huse … (2009)
            Background Most studies examining the commensal human oral microbiome are focused on disease or are limited in methodology. In order to diagnose and treat diseases at an early and reversible stage an in-depth definition of health is indispensible. The aim of this study therefore was to define the healthy oral microbiome using recent advances in sequencing technology (454 pyrosequencing). Results We sampled and sequenced microbiomes from several intraoral niches (dental surfaces, cheek, hard palate, tongue and saliva) in three healthy individuals. Within an individual oral cavity, we found over 3600 unique sequences, over 500 different OTUs or "species-level" phylotypes (sequences that clustered at 3% genetic difference) and 88 - 104 higher taxa (genus or more inclusive taxon). The predominant taxa belonged to Firmicutes (genus Streptococcus, family Veillonellaceae, genus Granulicatella), Proteobacteria (genus Neisseria, Haemophilus), Actinobacteria (genus Corynebacterium, Rothia, Actinomyces), Bacteroidetes (genus Prevotella, Capnocytophaga, Porphyromonas) and Fusobacteria (genus Fusobacterium). Each individual sample harboured on average 266 "species-level" phylotypes (SD 67; range 123 - 326) with cheek samples being the least diverse and the dental samples from approximal surfaces showing the highest diversity. Principal component analysis discriminated the profiles of the samples originating from shedding surfaces (mucosa of tongue, cheek and palate) from the samples that were obtained from solid surfaces (teeth). There was a large overlap in the higher taxa, "species-level" phylotypes and unique sequences among the three microbiomes: 84% of the higher taxa, 75% of the OTUs and 65% of the unique sequences were present in at least two of the three microbiomes. The three individuals shared 1660 of 6315 unique sequences. These 1660 sequences (the "core microbiome") contributed 66% of the reads. The overlapping OTUs contributed to 94% of the reads, while nearly all reads (99.8%) belonged to the shared higher taxa. Conclusions We obtained the first insight into the diversity and uniqueness of individual oral microbiomes at a resolution of next-generation sequencing. We showed that a major proportion of bacterial sequences of unrelated healthy individuals is identical, supporting the concept of a core microbiome at health.
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              Regulation of host weight gain and lipid metabolism by bacterial bile acid modification in the gut.

              S Joyce, J MacSharry, P G Casey … (2014)
              Alterations in the gastrointestinal microbiota have been implicated in obesity in mice and humans, but the key microbial functions influencing host energy metabolism and adiposity remain to be determined. Despite an increased understanding of the genetic content of the gastrointestinal microbiome, functional analyses of common microbial gene sets are required. We established a controlled expression system for the parallel functional analysis of microbial alleles in the murine gut. Using this approach we show that bacterial bile salt hydrolase (BSH) mediates a microbe-host dialogue that functionally regulates host lipid metabolism and plays a profound role in cholesterol metabolism and weight gain in the host. Expression of cloned BSH enzymes in the gastrointestinal tract of gnotobiotic or conventionally raised mice significantly altered plasma bile acid signatures and regulated transcription of key genes involved in lipid metabolism (Pparγ, Angptl4), cholesterol metabolism (Abcg5/8), gastrointestinal homeostasis (RegIIIγ), and circadian rhythm (Dbp, Per1/2) in the liver or small intestine. High-level expression of BSH in conventionally raised mice resulted in a significant reduction in host weight gain, plasma cholesterol, and liver triglycerides, demonstrating the overall impact of elevated BSH activity on host physiology. In addition, BSH activity in vivo varied according to BSH allele group, indicating that subtle differences in activity can have significant effects on the host. In summary, we demonstrate that bacterial BSH activity significantly impacts the systemic metabolic processes and adiposity in the host and represents a key mechanistic target for the control of obesity and hypercholesterolemia.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Gut Microbes
                Journal ID (iso-abbrev): Gut Microbes
                Journal ID (pmc): KGMI
                Title: Gut Microbes
                Publisher: Taylor & Francis
                ISSN (Print): 1949-0976
                ISSN (Electronic): 1949-0984
                Publication date Collection: 2014
                Publication date (Electronic): 20 December 2014
                Volume: 5
                Issue: 6
                Pages: 719-728
                Affiliations
                [1 ]Canadian Center for Human Microbiome and Probiotic Research; Lawson Health Research Institute ; London, Ontario, Canada
                [2 ]Department of Microbiology and Immunology; Western University ; London, Ontario, Canada
                [3 ]Department of Surgery; Western University ; London, Ontario, Canada
                [4 ]Division of Urology, Department of Surgery; Western University ; London, Ontario, Canada
                Author notes
                [†]

                Joint senior authors.

                [* ]Correspondence to: Gregor Reid; Email: gregor@ 123456uwo.ca
                Article
                Publisher ID: 983775
                DOI: 10.4161/19490976.2014.983775
                PMC ID: 4615746
                PubMed ID: 25529048
                SO-VID: eb81e0aa-a560-4e29-8dd7-e059f74d37f9
                Copyright © © 2014 The Author(s). Published with license by Taylor & Francis Group, LLC© Grace Ettinger, Kyle MacDonald, Gregor Reid, and Jeremy P Burton
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.

                History
                Date received : 14 August 2014
                Date revision received : 13 October 2014
                Date accepted : 29 October 2014
                Page count
                Figures: 1, Tables: 1, References: 120, Pages: 10
                Categories
                Subject: Reviews

                ScienceOpen disciplines: Microbiology & Virology
                Keywords: cardiovascular disease,cardioprotection,dysbiosis,microbiome,probiotics,periodontal disease
                Data availability:
                ScienceOpen disciplines: Microbiology & Virology
                Keywords: cardiovascular disease, cardioprotection, dysbiosis, microbiome, probiotics, periodontal disease

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