Circadian (14): The Gut Test
The bone’s intrinsic clock is not the only sign from which we can derive a clinical understanding of our circadian rhythm. If you recognise any organ in this way, you will be able to make an educated guess on each of their clocks. In this article, we are going to talk about how to observe this clock in our guts using ASCA antibodies.
ASCA is an old conventional tool that is only starting to become more popular within the gastroenterology specialty doctors in the past decade. Despite first being developed some 40 years ago, the work they expected this tool to do is beyond what it was made for. Most specialists in gastrointestinal medicine are interested in telling apart inflammatory bowel disease (‘my problem’) from irritable bowel syndrome (‘not my problem’); so ASCA never made it to the top of the list, especially when competing with other markers like calprotectin. I was actually there as a witness when fecal calprotectin entered the scene in 2012 when NICE finally recommended this test to distinguish the two diseases. I was working in a team led by Dr Phil Roberts whose guidance has benefited me a lot to this day, but had never understood ASCA properly until recently when I had to do my due preparation before starting my own clinic.
ASCA stands for Anti-Saccharomyces Cerevisiae Antibodies, which is why we abbreviate it. I didn’t spell its full name out to confuse anyone, rather to point to a simple fact: Saccharomyces cerevisiae is Latin for baker’s yeast. Now we can put it in plain English—ASCA means antibodies fighting baker’s yeast. I bet that feels much better.
Most of us will be exposed to this common yeast in our environment. You don’t have to be Italian eating your pasta to have this fungus in your gut. It is present in your bread and brew, but is also normally found on kitchen surfaces that these products have been on. You probably will swallow a bunch as you walk past the bakery simply enjoying the smell of fresh bread, which you thought could do you no harm as long as you don’t eat them. They are even on our fruit peels. Before baker’s yeast was available on the shelves, we used to catch them wild by placing the right ‘bait’ under fruit trees. Let’s just agree that they are pretty hard to avoid.
Despite this, it doesn’t mean that we don’t stand a chance against this organism. For a start, they are too big to cause an issue, meaning they normally pass through the gut to come out from the other end without causing a problem. A bigger advantage to us is that they are not toxic, even if for some reason they did get past our gut lining. This is where we finally relate everything back to the brain vs gut clock.
Under normal physiological circumstances, the melatonin we make at night helps repair the gut whilst we are asleep. The gut cells have receptors to melatonin called MT2, which when activated increases the production of occludin. As the name says, occludin basically seals or ‘occludes’ the gaps between any two gut cells to make the gut lining tamper-proof. This way uninvited guests like baker’s yeast will have to stay outside the gates they are not meant to trespass.
By contrast, under most modern human’s circumstances, even if they are lucky enough to make melatonin in the first place, the gut cells need to be in the same time zone as the pineal gland to be able to express enough MT2 to benefit from the melatonin signal. Without these two in sync, the hours of sleep we spend every night won’t be effective enough for complete gut repair of the tight junctions. Upon waking, the gut enters daytime with problems it hasn’t fixed from the day before. Some gaps between its cells remain unfilled, making the lining open to external invasion. This is essentially what a leaky gut is. It is not that the inside of our body leaks out into the gut, rather the other way around. Your gut residents can now leak into your body.
When baker’s yeast (or part of it) ‘leaks’ into our body past the single-cell layer gut lining, the immediate front it encounters is the immune system. Baker’s yeast still possesses no weapon to cause any damage or injury to our physical body, but the immune system does not recognise it as a registered citizen. This gut-based police produce antibodies as a reaction against the border breach. If it helps, without making any judgement you can think of it as how most countries treat illegal immigrants who came with no intention of malice. As is with the immigration policy, if our bodies overreact to this uninvited comer, a simple matter may snowball into a bigger problem we will struggle to control.
When I read ASCA, I see your gut clock. If you have a gut circadian issue and it is left to get worse, one day your gastroenterologist will be the one reading this result. Their interpretation then won’t be about leaky gut, as it has gone too far beyond a simple leak and therefore deserves its own solemn name: Crohn’s disease.