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      Gut Bacteria and Hydrogen Sulfide: The New Old Players in Circulatory System Homeostasis

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          Abstract

          Accumulating evidence suggests that gut bacteria play a role in homeostasis of the circulatory system in mammals. First, gut bacteria may affect the nervous control of the circulatory system via the sensory fibres of the enteric nervous system. Second, gut bacteria-derived metabolites may cross the gut-blood barrier and target blood vessels, the heart and other organs involved in the regulation of the circulatory system. A number of studies have shown that hydrogen sulfide (H 2S) is an important biological mediator in the circulatory system. Thus far, research has focused on the effects of H 2S enzymatically produced by cardiovascular tissues. However, some recent evidence indicates that H 2S released in the colon may also contribute to the control of arterial blood pressure. Incidentally, sulfate-reducing bacteria are ubiquitous in mammalian colon, and H 2S is just one among a number of molecules produced by the gut flora. Other gut bacteria-derived compounds that may affect the circulatory system include methane, nitric oxide, carbon monoxide, trimethylamine or indole. In this paper, we review studies that imply a role of gut microbiota and their metabolites, such as H 2S, in circulatory system homeostasis.

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          Composition and energy harvesting capacity of the gut microbiota: relationship to diet, obesity and time in mouse models.

          Increased efficiency of energy harvest, due to alterations in the gut microbiota (increased Firmicutes and decreased Bacteroidetes), has been implicated in obesity in mice and humans. However, a causal relationship is unproven and contributory variables include diet, genetics and age. Therefore, we explored the effect of a high-fat (HF) diet and genetically determined obesity (ob/ob) for changes in microbiota and energy harvesting capacity over time. Seven-week-old male ob/ob mice were fed a low-fat diet and wild-type mice were fed either a low-fat diet or a HF-diet for 8 weeks (n=8/group). They were assessed at 7, 11 and 15 weeks of age for: fat and lean body mass (by NMR); faecal and caecal short-chain fatty acids (SCFA, by gas chromatography); faecal energy content (by bomb calorimetry) and microbial composition (by metagenomic pyrosequencing). A progressive increase in Firmicutes was confirmed in both HF-fed and ob/ob mice reaching statistical significance in the former, but this phylum was unchanged over time in the lean controls. Reductions in Bacteroidetes were also found in ob/ob mice. However, changes in the microbiota were dissociated from markers of energy harvest. Thus, although the faecal energy in the ob/ob mice was significantly decreased at 7 weeks, and caecal SCFA increased, these did not persist and faecal acetate diminished over time in both ob/ob and HF-fed mice, but not in lean controls. Furthermore, the proportion of the major phyla did not correlate with energy harvest markers. The relationship between the microbial composition and energy harvesting capacity is more complex than previously considered. While compositional changes in the faecal microbiota were confirmed, this was primarily a feature of high-fat feeding rather than genetically induced obesity. In addition, changes in the proportions of the major phyla were unrelated to markers of energy harvest which changed over time. The possibility of microbial adaptation to diet and time should be considered in future studies.
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            Biogenic methane formation in marine and freshwater environments: CO2 reduction vs. acetate fermentation—Isotope evidence

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              Serum indoxyl sulfate is associated with vascular disease and mortality in chronic kidney disease patients.

              As a major component of uremic syndrome, cardiovascular disease is largely responsible for the high mortality observed in chronic kidney disease (CKD). Preclinical studies have evidenced an association between serum levels of indoxyl sulfate (IS, a protein-bound uremic toxin) and vascular alterations. The aim of this study is to investigate the association between serum IS, vascular calcification, vascular stiffness, and mortality in a cohort of CKD patients. One-hundred and thirty-nine patients (mean +/- SD age: 67 +/- 12; 60% male) at different stages of CKD (8% at stage 2, 26.5% at stage 3, 26.5% at stage 4, 7% at stage 5, and 32% at stage 5D) were enrolled. Baseline IS levels presented an inverse relationship with renal function and a direct relationship with aortic calcification and pulse wave velocity. During the follow-up period (605 +/- 217 d), 25 patients died, mostly because of cardiovascular events (n = 18). In crude survival analyses, the highest IS tertile was a powerful predictor of overall and cardiovascular mortality (P = 0.001 and 0.012, respectively). The predictive power of IS for death was maintained after adjustment for age, gender, diabetes, albumin, hemoglobin, phosphate, and aortic calcification. The study presented here indicates that IS may have a significant role in the vascular disease and higher mortality observed in CKD patients.
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                Author and article information

                Contributors
                Role: Academic Editor
                Role: Academic Editor
                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                17 November 2016
                November 2016
                : 21
                : 11
                : 1558
                Affiliations
                [1 ]Department of Experimental Physiology and Pathophysiology, Laboratory of Centre for Preclinical Research, Medical University of Warsaw, Warsaw 02 091, Poland; lennytomasova@ 123456gmail.com (L.T.); piotr.konopelski@ 123456wp.pl (P.K.)
                [2 ]Institute of Clinical and Translational Research, Biomedical Research Center, Slovak Academy of Sciences, Bratislava 845 05, Slovakia
                Author notes
                [* ]Correspondence: mufnal@ 123456wum.edu.pl ; Tel./Fax: +48-22-116-6195
                Article
                molecules-21-01558
                10.3390/molecules21111558
                6273628
                27869680
                05c8f97f-634c-494a-9857-5182a3365f35
                © 2016 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 05 October 2016
                : 14 November 2016
                Categories
                Review

                microbiota,gut bacteria,hydrogen sulfide,sulfur,tmao,indole,cardiovascular diseases,hypertension

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