EDITOR’S CORNER
Alfred A. Bove, MD, PhD
Editor-in-Chief, CardioSource WorldNews
Inflammation Revisited –
The Microbiome
W
e like to think that, at some point in time,
we come to a revelation that provides
insight into health and disease processes,
and then develop strategies to either support the
process if it improves health or create methods to
stop or slow the process if it is detrimental to health.
An important example of this process is the evolution
of our understanding of atherosclerosis itself; namely,
as a lengthy process involving lipid deposition in the
vascular wall, plaque formation, narrowing of arteries that supply vital organs and, ultimately, occlusion
of the blood supply to an organ or tissue with subsequent ischemic injury.
We have developed drugs to retard the atherosclerotic process, lifestyle changes that contribute to
a reduction of atherosclerosis, and have better ways
to manage comorbidities that seem to contribute
to the process. Yet our success in eliminating these
disorders is limited. In spite of our therapies to reduce
the atherosclerotic burden, we still see a significant
amount of pathology.
The observations raise the question of whether
there is another process that we are not accounting
for that contributes to the burden of disease. Based on
data accumulated over the last decade, research tells
us we are missing the important role that inflammation plays in chronic tissue injury.
The connection between inflammation and atherosclerotic disease is complex. It involves inflammatory
networks that link the atherosclerotic process to the
autonomic nervous system, bone marrow, spleen, and
other organs. We have come to understand the atherosclerotic process as one involving a number of inflammatory cells that secrete pro-inflammatory cytokines
that in turn aggravate the cell injury caused by the
inflammatory process, producing a systemic inflammatory milieu that favors atherothrombotic events.
However, for clinicians, the challenge has been
translating this inflammatory hypothesis of atherosclerosis into something of clinical value. The early
logical choice was corticosteroids but this approach
was abandoned amidst concern for impaired wall
healing resulting in cardiac rupture. Selective and
nonselective nonsteroidal anti-inflammatory drugs
(NSAIDs) have been analyzed, but with the exception of aspirin, all of these agents increase the risk
for acute myocardial infarction, especially in those
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patients known to have ischemic heart disease. With
current therapies for atherosclerosis unable to target
these cellular inflammatory mechanisms, the situation is ripe for exploitation with new methods to
reduce atherosclerosis risk.
Bacteria and the Microbiota
An important concept that has evolved from our
understanding of the cellular milieu that exists in
the body is the knowledge that a variety of bacteria
dwell in our tissues; some may provide benefit to
stable organ function, while others may aggravate the
inflammatory process to cause chronic disease. These
are classified as microbiota.
chronic diseases are likely to involve drugs that alter
the gut microbiota to improve organ and tissue function. Dysfunction of gut microbiota has been shown
to induce metabolic endotoxemia, provoking an inflammatory response that, in turn, can cause insulin
resistance, metabolic syndrome, obesity, diabetes,
inflammatory bowel disease, and altered immunity.
Figuring out those interventions that favor growth
of favorable microbiota can lead us to new therapies
allowing us to approach these disorders in an entirely
new way.
Some foods may be atherogenic because of unfavorable effects of microbiota on food metabolism.
For example, meat and eggs seem to stimulate the
In spite of our therapies to reduce the
atherosclerotic burden, we still see a
significant amount of pathology.
Gut microbiota include more than 1,000 bacterial
species in an adult. The microbiota can be protective
against allergic reactions, inflammation, and cardiac
pathological states while adverse changes in the microbiota result in chronic pathological conditions that
include the cardiovascular system. Future targets for
therapy of chronic cardiac disease will include therapies that enhance favorable microbiota and suppress
unfavorable species.
Bacterial colonies that exist in the colon in particular can confer immunity or alter bacterial flora
to improve organ function. One example: the use of
lactobacilli as therapy for Clostridium difficile infection. In this case, the microbiota replace pathogenic
bacteria with friendly bacteria that help to control the
C. difficile colonization. Other studies suggest that gut
microbiota can exert beneficial effects on metabolic
diseases. A new pathway for research in this area is
to evaluate the effects of antibiotics on gut bacteria
that can influence metabolic function.
Future therapies for patients with acute and
production of adverse microbiota. The production
of trimethylamine and its metabolite TMA-N-oxide
(TMAO) are thought to accelerate the atherosclerotic proc