CARDIOVASCULAR DISEASE AND GUT HEALTH

Three of the first four main causes of death globally in 2015 published by WHO [1] were subsets of cardiovascular disease. Ischaemic heart disease and stroke are the world’s biggest killers, accounting for a combined 15 million deaths in 2015. These diseases have remained the leading causes of death globally in the last 15 years.

          High levels of LDL (Low Density Lipoprotein) in the blood have been associated with higher risk for cardiovascular disease, something that can be considered common knowledge, at least said in its simpler (albeit misleading) form: cholesterol causes heart disease. This initiated a still rolling avalanche of low-fat labels on everything, from crisps to children's milk, and made us produce terrifyingly dangerous products such as trans-fats in an effort to avoid a heart attack or stroke. Just as most medical issues, the connection between cholesterol and cardiovascular disease is not as straightforward, and swapping your 3% milk for a 0.5% one may not be the best way to keep yourself healthy. Here I explore how the gut itself may affect the issue of cholesterol. 

What is LDL and HDL?

          Hydrophobic cholesterol is not dissolvable in the aqueous environment of our blood, but needs to be transported to and from the cells of our body. It therefore needs a protein carrier: a lipoprotein. There are two types of cholesterol lipoproteins, low and high density. 

          High density lipoprotein, HDL is often referred to as the "good cholesterol". This is because it carries cholesterol from our body or blood back towards our liver, essentially removing circulating cholesterol and thus lowering the chances for plaque formation. 

          Low density lipoprotein, LDL is the one referred to as "bad cholesterol". This protein carrier transports cholesterol from the liver, where it is produced, to all cells of the body. Cholesterol is an essential component of the plasma membrane which lowers its fluidity, and therefore is needed by every cell. It is said to be low-density because as the cholesterol gets removed from it to be given to cells, it has a lower cholesterol density than the other lipid carrier protein. It remains longer in the bloodstream and can therefore contribute to plaque buildup in blood vessels. 

How these lipoproteins are connected to gut health and ultimately cardiovascular disease however, requires a bit more explanation. 

Get to know your gut

          The human body body is home to about 100 trillion bacterial cells [2]. For reference, that means we have about 3 bacterial cells for each of our own human cells [3]. These staggering numbers live in our gut in the highest concentrations [4]. For this reason, the highest concentration of immune cells in our body is also in the gut [5]. In order for the microbiota and immune cells not to mix with one another, the gut epithelial cells secrete mucin: a physical mucous barrier composed of different defensive compounds. Continuous secretion of this barrier is essential to keep the immune system from attacking the gut bacteria.

          This layer may become compromised due to overactivity of immune cells causing it to break down, or when it isn't produced properly by the gut cells. 

          The epithelial cells of the gut feed on short-chain-fatty-acids produced by "good gut bacteria" which in turn feed on fermentable fibres [6][7]. Lack of fermentable fibres in the diet can lead to starvation of these epithelial cells, which compromises the mucin layer and allows the immune system to come into contact with gut bacteria. 

From bacteria to cholesterol

          When the immune system attacks the gut fauna, it kills bacterial cells, releasing endotoxins into the blood [8]. Endotoxins are especially dangerous. They are recognised as foreign invaders by our immune system, and when their numbers increase in the blood, the immune cascade can be so strong that it may cause sepsis and death. 

The body has devised a system to keep endotoxin numbers for becoming dangerously high. LDLs can act as endotoxin "sponges", allowing them to bind to docking sites on the lipoproteins [9]. The problem is, that the endotoxins bind on the same sites on the lipoprotein that it uses to get back to the liver and out of the circulation, in a way "locking out" the LDL which is now left to stay in the bloodstream. These endotoxin-studded lipoproteins can still be attacked by immune cells, which want to kill what they think are bacteria. Not being alive, LDLs cannot be killed, so this structure of immune cells and endotoxin-studded LDL starts to clump, potentially forming plaques. 

          Travelling plaques can get stuck in the heart: causing heart attacks, or in the brain: causing strokes, leading us back to the main causes of death published by WHO. 

So practically, what does this mean?

These discoveries highlight the importance of a healthy gut on our cardiovascular health. So what makes a healthy gut in the terms of its mucin layer?

Promotion of short-chain-fatty-acid synthesising gut bacteria through feeding them with fermentable fibres is essential. Fermentable fibres are found in fruits and vegetables, especially in sauerkraut, mushrooms and barely. 

At the same time, it is important to also make sure that your "bad" gut bacteria, those that feed on sugar are not promoted and overfed, which can lead to them occupying the space needed for the "good bacteria": lowering sugar consumption, especially in its processed form. This not only keeps in check the amount of "bad" gut bacteria, but also lowers the chances for the recently-discovered bacterial-level insulin resistance, which can lead to gut cell starvation and compromise of the mucin layer. 

[1] http://www.who.int/mediacentre/factsheets/fs310/en/

[2] American Academy of Microbiology FAQ: Human Microbiome January 2014

[3] Judah L. Rosner for Microbe Magazine, Feb 2014. Ten Times More Microbial Cells than Body Cells in Humans?

[4] Quigley, EM (2013). "Gut bacteria in health and disease". Gastroenterol Hepatol (N Y). 9 (9): 560–9. PMC 3983973 . PMID 24729765.

[5] http://gut.bmj.com/content/gutjnl/30/12/1679.full.pdf

[6] Commensal bacteria-dependent indole production enhances epithelial barrier function in the colon.

[7] Den Besten, Gijs et al. “The Role of Short-Chain Fatty Acids in the Interplay between Diet, Gut Microbiota, and Host Energy Metabolism.” Journal of Lipid Research 54.9 (2013): 2325–2340. PMC. Web. 4 Dec. 2017.

[8] Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites.Wikoff WR, Anfora AT, Liu J, Schultz PG, Lesley SA, Peters EC, Siuzdak GProc Natl Acad Sci U S A. 2009 Mar 10; 106(10):3698-703.

[9] Low density lipoproteins inhibit endotoxin activation of monocytes. Weinstock C1, Ullrich H, Hohe R, Berg A, Baumstark MW, Frey I, Northoff H, Flegel WA.