Raised Cecal Veillonella (Firmicutes)/S 24-7 (Bacteriodetes) May Not Cause Salt-Sensitive Hypertension

摘要

“They” were always there. Or at least, “they” were there since antiquity; since the time that foraging for food in the wild invariably meant consuming “them” laced on the food. In the hollow organs and on the surface, “they” live peacefully, in harmony. “They”: The “Microbiome.” Trillions of “them”! (Sonnenburg et al., 2004 ; B?ckhed et al., 2005 ; Pluznick, 2014 ; Lanza et al., 2015 ; McNally and Brown, 2015 ; Mermel, 2015 ; Woolhouse et al., 2015 ) When the balance gets tipped off, at least in some organs, clinical signs are manifested. For example, Gardnerella , a common constituent of vaginal micro-organisms, colonize and smear the epitheliocyte producing the so-called “clue cells,” and manifest a local secretory phenome, along with odorous volatile substances production, the “whiff,” so commonly detected during presentations of bacterial vaginosis (BV) in the STI clinic (Machado and Cerca, 2015 ). “They” love the lack of oxygen. The greatest fermentor in the human body is the post-esophageal gut; the anaerobic environment is capable of producing an environment where gases may be formed, both in the foregut, through the small intestines, and in the hindgut, with the gradient of bioreactor activity increasing in that order. We are all so accustomed with the “wind.” Though the precise biological significance of these luminal gas productions is not known (Azpiroz, 2005 ), in the surgical ward, especially after abdominal laparotomy, the history of the passed “wind” is a tale of relief, a sure sign that the dreaded risk for the development of ileus has passed (Cosyns et al., 2015 ). In the foregut, especially in the stomach, casual clinical correlation has been demonstrated between the presence of Helicobacter pylori and development of gastric ulcers (Marshall and Warren, 1984 ). Though the organism has been isolated form the stomach, direct evidence that their colonization is the first event in development of gastric ulcers has never been provided (Beasley et al., 2015 ). Furthermore, recent evidence show that Helicobacter has co-evolved in the human stomach for several million years and may actually play symbiotic roles (Blaser, 2012 ; Sitaraman, 2015 ). In fact, urease producing organisms have been recently demonstrated even in the small intestines, where the pH is relatively higher (near the alkaline range), and thus there may be special chemical roles, yet undefined, of urease producing organisms in the alkaline intestinal luminal environment (Shen et al., 2015 ). My reason for this prelude is to generate discussion regarding some recent reports that have attempted to propose causative link between microbiome populations and their cohort changes as mechanistic basis for hypertension, continuing the recent trend of linking microbiome organizations or alterations to chronic diseases. One of this is a recent well-performed study that endeavors to establish a relation between altered cecal populations of microbes in Dahl salt sensitive rats as the basis for their hypertension (Mell et al., 2015 ). I present an alternate viewpoint that the microbiome changes reported in this manuscript may not necessarily be causative. Previous studies have proposed the role of gut microbiota and metabolite sensing by G coupled receptors in kidney (Pluznick et al., 2013 ). Oral administration of Lactobacillus -fermented milk reduce blood pressure in spontaneously-hypertensive rats (SHR) and humans, and it has been suggested that this may be mediated by short peptide sequences from bacterial metabolites (Yamamoto et al., 1994 ; Nakamura et al., 1995 ; Seppo et al., 2003 ; Sekirov et al., 2010 ; Khalesi et al., 2014 ). Other studies have shown that the gut microbes metabolize phospholipid to TMAO, and this may predispose to cardiovascular disease (Wang et al., 2011 ). However, TMAO can be well-metabolized (Barrett and Kwan, 1985 ) and how this suggested metabolite predispose to cardiovascular stress is not well established. In this recent report (Mell et al., 2015 ), 16S rRNA gene sequencing obtained from fecal samples of Dahl salt-sensitive (S) and Dahl salt resistant (R) rats demonstrated that the phylum Bacteriodetes (family S24-7) and Firmicutes (family Vellionellaceae) were higher in the S rats compared with the R rats. Both strains were subjected to the following protocols: (i) maintained on a high-salt diet (ii) antibiotics treatment for ablation of microbiota and (iii) transplanted with S or R rat cecal contents. Blood pressure (BP) monitoring was performed under the pre-described circumstances. Surprisingly, antibiotic ablation of gut microbiota of S rats did not cause significant decrease of blood pressure in comparison to R rats (Mell et al., 2015 ). This may support the inference that colonic microbiota and/or its metabolites may not play fundamental role in blood pressure elevation in S rats. Alternatively, we also do not know whether the microbiota resulted in overgrowth of another intraluminal non-targeted spec