“You are what you eat” The gut microbiota and cardiometabolic disease

Written by Gaston L. Cluzel1, Noel M. Caplice2 1PhD Student , APC Microbiome Ireland | 2Professor Cardiovascular Sciences, Cardiologist, PI APC Microbiome Ireland - University College Cork, Cork University Hospital

Cardiovascular disease (CVD) is the leading cause of mortality worldwide, accounting for a third of total annual death. The combination of obesity related disorders and cardiometabolic disease has now reached epidemic proportions, threatening to overwhelm healthcare services in the developed industrialised world. Current strategies for fighting symptomatic cardiometabolic disease rely heavily on labour intensive surgical procedures or drugs with limited efficacy and potentially hazardous secondary effects. Therefore, new thinking and treatment approaches are urgently required to fight CVD in the midst of the current metabolic syndrome pandemic.

The human gut is inhabited by a rich community of trillions of microorganisms known as the gut microbiota. The presence of these bacteria, yeasts, viruses and protozoa inside the human body is a consequence of millions of years of co-evolution, during which microorganisms have adapted to take advantage of the sheltering environment that is our gut. The gut microbiota as a “super-organism/ organ” has developed strategies so as to be immune-tolerated by our body. The host (our body) enjoys the fruits of these commensal microorganisms since they offer a protection against pathogenic gastrointestinal infections, improve digestion and provide key macro and micronutrients essential for health. However, the gut microbiota must be tightly controlled by our body since changes within this microbial community may initiate health disorders.

Recent research has identified a strong link between the gut microbiota and cardiovascular health, shedding light on a novel and promising field of potential intervention for CVD patients. Indeed, the gut microbiota not only plays a critical role in regulating physiological processes such as digestion, metabolism and immune response but can be considered as a hidden but essential metabolic organ. For instance, alteration in the gut microbiota, a phenomenon known as “dysbiosis”, has been associated with health disorders such as gastrointestinal disease, metabolic syndrome and systemic inflammation - all of which can contribute to progression of CVD. Therefore, manipulating the gut microbiota could constitute a reliable strategy for fighting cardiometabolic disorders.

The gut microbiota lies at the interface between our diet and our intestine which is the largest human immune interface (6 metres long) with the external environment. It is directly exposed to our daily dietary habits and can change its composition within days of exposure to a poor diet. Moreover the proximity of the gut microbiota to the gut lining means signaling between this organ and the human body is continuous with potential for good and bad outcomes. Certain diets promote a healthy microbiota that in turn benefits our gut health and by extension the general health of the host. For instance, the “Mediterranean” diet - rich in plant-based ingredients, nuts and fibre - is associated with a thriving microbiota rich in beneficial bacterial species. This type of diet has also been shown to promote weight loss and reduces the cardiovascular effects of obesity and metabolic syndrome. On the other hand, a “Westernised” diet rich in fats, sugars and processed ingredients leads to dysbiosis with a microbiota depleted of beneficial bacterial species and is typically associated with obesity and cardiometabolic related disorders. Beyond diet, certain food components appear to be particularly efficient in shaping the gut microbiota and promoting health. Dietary fibre and certain prebiotics are not digested by the body but instead are fermented by the gut microbiota, promoting the growth of beneficial bacterial species. Initiating their beneficial effect on the microbiota prebiotics also improve host health and may be a modifier of CVD risk. Indeed, clinical studies have found that prebiotics can promote weight loss, improve lipid profiles, reduce low grade inflammation, and improve insulin sensitivity, all of which are risk factors for CVD. Moreover, reports from preclinical studies suggest that prebiotics may tackle some of the root mechanisms of CVD by preventing cellular and metabolic events that precede full blown CVD. It is also possible to intervene on the microbiota directly using bacteria or yeast preparations, enriched for chosen beneficial species, to colonise our guts. Probiotics are described as live microorganisms that can provide health benefits when consumed in adequate amounts. Probiotics can also be combined with prebiotics in an attempt to obtain a greater effect than individual components; this is called a synbiotic treatment. Probiotics and synbiotics exhibit numerous health benefits and have been shown to reduce some CVD risk factors in clinical studies. Finally, it is also possible to colonise patient’s microbiota with the microorganisms of a healthy donor. This technique is called faecal microbiota transplantation (FMT) and its success could reside in the transfer of beneficial microbiota properties from donor to patient. FMT has been most successful in treating gastrointestinal disease driven by clostridium difficle. While this technique is still experimental in other diseases, early studies have shown promising results in reducing inflammation and improving metabolic health, paving the way to clinical trials in the near future.

Although microbiota-targeted strategies show promising results in preventing CVD and other disorders, there is still a vast chasm in our knowledge deficit within this emerging field of research. The gut microbiota is an incredibly diverse environment composed of trillions of organisms with vast numbers of different species interacting at a protein, carbohydrate, complex sugar, amino acid, fatty acid and hormonal level. This complexity makes mechanistic interpretation of microbe-host interactions very difficult to decipher short of reductionist methods on one hand or machine learning tools on the other. Moreover, each human being has a unique microbial signature that evolves constantly throughout our life having been hardwired as early as neonatal life with respect to training of the host’s immune system. Therefore, the major challenge of this field does not reside in the capacity of gut microbes to prevent CVD but rather in our ability to harness their power reliably at the scale of human populations.

In response to this challenge, current biomedical research

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