Elsevier

Journal of Cardiac Failure

Volume 21, Issue 12, December 2015, Pages 973-980
Journal of Cardiac Failure

Review Article
Intersections Between Microbiome and Heart Failure: Revisiting the Gut Hypothesis

https://doi.org/10.1016/j.cardfail.2015.09.017Get rights and content

Highlights

  • In the setting of HF, substantial hemodynamic changes such as hypoperfusion and congestion in the intestines can alter gut morphology, permeability, function, and possibly the growth and composition of gut microbiota.

  • Cardiorenal alterations via metabolites derived from gut microbiota can potentially mediate or modulate HF pathophysiology.

  • Trimethylamine N-oxide (TMAO) has emerged as a key mediator that provides a mechanistic link between gut microbiota and multiple cardiovascular diseases, including HF.

  • Potential intervention strategies may target this microbiota-driven pathology, including dietary modification, prebiotics/probiotics, and selective binders of microbial enzymes or molecules.

Abstract

Microbes play an important role in human health and disease. In the setting of heart failure (HF), substantial hemodynamic changes, such as hypoperfusion and congestion in the intestines, can alter gut morphology, permeability, function, and possibly the growth and composition of gut microbiota. These changes can disrupt the barrier function of the intestines and exacerbate systemic inflammation via microbial or endotoxin translocation into systemic circulation. Furthermore, cardiorenal alterations via metabolites derived from gut microbiota can potentially mediate or modulate HF pathophysiology. Recently, trimethylamine N-oxide (TMAO) has emerged as a key mediator that provides a mechanistic link between gut microbiota and multiple cardiovascular diseases, including HF. Potential intervention strategies which may target this microbiota-driven pathology include dietary modification, prebiotics/probiotics, and selective binders of microbial enzymes or molecules, but further investigations into their safety and efficacy are warranted.

Section snippets

Gut Microbiota in Health and Disease

There are ∼1014 bacterial organisms belonging to >2,000 species within our bodies, the vast majority being in the gut.1 These are commensal microorganisms that colonize in the human gut and play a crucial role in protection from environmental exposure, digestion, and absorption of nutrients.2, 3, 4 The phylogenetic composition of the bacterial communities evolves toward an adult-like configuration during the 1st few years of life. The shaping of gut microbiota is largely influenced by lifestyle

Alteration of Gut and Gut Microbiota in Heart Failure

The gut is a blood-demanding organ, and villi (and microvilli) are prone to functional ischemia due to reduced blood flow.12 The arteries form dense capillary networks close to the top of the villi. This anatomic arrangement allows countercurrent exchange of oxygen from the arteries to the veins along their course within the villus. This results in a descending gradient of tissue oxygen concentration from the base to the tip of the villus. This gradient is inversely related to blood flow12;

Potential Intervention Strategies

Therapeutic tools available to modulate the microbiota-driven pathogenesis of HF remain limited. However, based on evidence that mechanistically links gut microbiota and HF, potential intervention strategies include targeting the composition of the microbiota or the biochemical pathways (Table 1). The composition of the microbiota can be modulated by diet,61 antibiotics, prebiotics/probiotics, and fecal transplantation. The biochemical pathways involved in microbiota-driven pathology can be

Conclusion

Millions of years of coevolution between humans and microorganisms have led to a mutualistic relationship, in which diverse ecosystems of gut microbiota contribute to the maintenance of our metabolic homeostasis. The interaction of heart and gut, or heart-intestine axis, has emerged as a novel concept to provide new insights into the intricate mechanisms of HF. However, at the present time the role of gut microbiota–targeted interventions remains uncertain in the absence of solid well conducted

Disclosures

None.

References (71)

  • E.A. Deitch

    Bacterial translocation or lymphatic drainage of toxic products from the gut: what is important in human beings?

    Surgery

    (2002)
  • J. Niebauer et al.

    Endotoxin and immune activation in chronic heart failure: a prospective cohort study

    Lancet

    (1999)
  • P. Evenepoel et al.

    Uremic toxins originating from colonic microbial metabolism

    Kidney Int Suppl

    (2009)
  • K. Yang et al.

    Indoxyl sulfate induces oxidative stress and hypertrophy in cardiomyocytes by inhibiting the AMPK/UCP2 signaling pathway

    Toxicol Lett

    (2015)
  • B.J. Bennett et al.

    Trimethylamine-N-oxide, a metabolite associated with atherosclerosis, exhibits complex genetic and dietary regulation

    Cell Metab

    (2013)
  • J.D. Bell et al.

    Nuclear magnetic resonance studies of blood plasma and urine from subjects with chronic renal failure: identification of trimethylamine-N-oxide

    Biochim Biophys Acta

    (1991)
  • W.H. Tang et al.

    Prognostic value of elevated levels of intestinal microbe-generated metabolite trimethylamine-N-oxide in patients with heart failure: refining the gut hypothesis

    J Am Coll Cardiol

    (2014)
  • W.H. Tang et al.

    Intestinal microbiota–dependent phosphatidylcholine metabolites, diastolic dysfunction, and adverse clinical outcomes in chronic systolic heart failure

    J Card Fail

    (2015)
  • M. Ufnal et al.

    Trimethylamine-N-oxide: a carnitine-derived metabolite that prolongs the hypertensive effect of angiotensin II in rats

    Can J Cardiol

    (2014)
  • G.N. Kalambokis et al.

    Rifaximin improves systemic hemodynamics and renal function in patients with alcohol-related cirrhosis and ascites

    Clin Gastroenterol Hepatol

    (2012)
  • A.C. Costanza et al.

    Probiotic therapy with Saccharomyces boulardii for heart failure patients: a randomized, double-blind, placebo-controlled pilot trial

    Int J Cardiol

    (2015)
  • F. Backhed et al.

    Host-bacterial mutualism in the human intestine

    Science

    (2005)
  • J.K. Nicholson et al.

    Gut microorganisms, mammalian metabolism and personalized health care

    Nat Rev Microbiol

    (2005)
  • M. Li et al.

    Symbiotic gut microbes modulate human metabolic phenotypes

    Proc Natl Acad Sci U S A

    (2008)
  • T. Yatsunenko et al.

    Human gut microbiome viewed across age and geography

    Nature

    (2012)
  • S.R. Gill et al.

    Metagenomic analysis of the human distal gut microbiome

    Science

    (2006)
  • P.J. Turnbaugh et al.

    An obesity-associated gut microbiome with increased capacity for energy harvest

    Nature

    (2006)
  • L. Wen et al.

    Innate immunity and intestinal microbiota in the development of type 1 diabetes

    Nature

    (2008)
  • F. Backhed et al.

    The gut microbiota as an environmental factor that regulates fat storage

    Proc Natl Acad Sci U S A

    (2004)
  • M.E. Dumas et al.

    Metabolic profiling reveals a contribution of gut microbiota to fatty liver phenotype in insulin-resistant mice

    Proc Natl Acad Sci U S A

    (2006)
  • B. Mell et al.

    Evidence for a link between gut microbiota and hypertension in the Dahl rat model

    Physiol Genomics

    (2015)
  • A. Krack et al.

    Studies on intragastric PCO2 at rest and during exercise as a marker of intestinal perfusion in patients with chronic heart failure

    Eur J Heart Fail

    (2004)
  • J.K. Hsiao et al.

    Magnetic resonance imaging detects intestinal barrier dysfunction in a rat model of acute mesenteric ischemia/reperfusion injury

    Invest Radiol

    (2009)
  • N. Hashimoto et al.

    Effect of acute portal hypertension on gut mucosa

    Hepatogastroenterology

    (2002)
  • J. Alverdy et al.

    The impact of stress and nutrition on bacterial-host interactions at the intestinal epithelial surface

    Curr Opin Clin Nutr Metab Care

    (2005)
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    See page 979 for disclosure information.

    Funding: National Institutes of Health and Office of Dietary Supplements (R01HL103931, P20HL113452, 1R01DK106000). Dr Nagatomo is the recipient of the Postdoctoral Fellowship award from the Myocarditis Foundation (MYF1401MF).

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