This article has been fact-checked by Dr Luke O’Neill, professor of biochemistry in the School of Biochemistry and Immunology at Trinity College Dublin.

What is Inflammation?

Inflammation is our bodies complex biological response to injury and infection, which activates our immune system to produce an array of small protein molecules called pro-inflammatory cytokines. This is a normal, healthy and adaptive function to help us navigate our environments safely. But when this response persists we end up with chronic inflammation throughout the body and as you will see, this is not so good.

Chronic inflammation is the persistent over-reactivity of our immune system and this is a problem which underpins much of modern disease.

Why Might Our Immune System Overreact?

Our environment has a major influence on our gut health, which in turn has a major influence on our immune health. Beginning in utero and continuing through the first few years of life, the environment appears to have a particularly powerful impact, this is because the world of bacteria that will be with us the rest of our lives (our microbiota, also known as our enteric nervous system or our body’s second brain) develops to a large extent by age 2 or 3. The greatest density of immune cells in our entire body is found in our small intestine, so our immune system develops in tandem with our gut bacteria. Accordingly, the importance of early life on the development of the immune system cannot be overemphasised.

It has been well documented that exposure to dirt, germs and bugs aids in the development of the immune system, and if we have robust exposure to such things, we’ll be less inflamed and have a healthier immune system as adults. Today, many children are lathered with antibacterial soaps, hardly ever touch dirt, are given antibiotics and, compared to how humans lived for millions of years, exist in a germ-free bubble. As a result, the immune system is poorly trained, overreactive and often attacks the wrong target - like the body’s healthy tissue. This mainly applies to allergic inflammation – as seen in asthma for instance, but there’s evidence to suggest it might also apply to other inflammatory diseases.

Other Causes of Inflammation?

Okay, so even though we all come with some degree of predetermined gut and immune health as a result of our early development. There are of course other factors that can contribute to making that baseline better or worse, namely our lifestyle choices. Life stress, poor quality diet, poor quality sleep, physical inactivity, exposure to household/cosmetic chemical ingredients, alcohol consumption and habits like smoking are all factors which influence inflammation in the body.

I cannot stress enough how important it is to keep levels of inflammatory biomarkers in the body as low as possible for our overall physical and mental wellbeing, and we can do this by taking advantage of the factors that we can control. I have referenced The Blue Zone Study many times in many articles, it is a global study of health and longevity, and the results concluded that a low level of inflammatory cytokines was the single most important biomarker predicting survival in centenarians (a person who has reached the age of 100 years) and supercentenarians.

Low basal (or background) inflammation = a longer, healthier life.

How to Lower Inflammation?

Committed healthy lifestyle choices like yoga, meditation and breathwork have been scientifically proven to lower inflammation by mitigating for life stress and physical inactivity. The act of giving up smoking, allocating eight hours for sleep and consuming reasonable amounts of alcohol are all self-explanatory. So, let’s tackle the more complex factor influencing inflammation, the gut - and diet is a huge contributor here, as the Western diet (high fat/sugar) promotes continuous low grade inflammation.

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Our digestive tract is arguably the leading source of inflammation in the body.

As if that wasn’t quite enough, if our gut becomes chronically inflamed we cannot properly absorb the nutrients from our food.

Longterm chronic inflammation causes more serious problems with the functioning of the immune system and this dysregulation can result in a wide number of autoimmune conditions.

To get a handle on gut health and in turn inflammation, may I refer you to someone far more qualified than me in this area. Dr Michael Ruscio is a leader in the field and his book ‘Healthy Gut, Healthy You’, seen below, quite literally changed the quality of my life - everything from my skin to my mindset improved significantly after reading and implementing the guidelines in this book. It empowered me with science-based knowledge and clearly defined solutions after many years of failed quick-fixes and attempts to decipher this often muddied area of research. If you suspect that you may be suffering from longterm inflammation of your digestive tract, I cannot recommend this book highly enough.

Another (indirectly related) bible for gut health and lowered inflammation is Matthew Walker’s ‘Why We Sleep’, and this is another read I cannot recommend highly enough.

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Does Chronic Inflammation Cause Depression?

According to the World Health Organisation, there are more than 250 million people of all ages suffering from major depressive disorder worldwide. A diagnosis incorporating a broad range of symptoms since the DSM definition was amended in the 1980s subsuming a greater number of people into a standardised treatment protocol - namely pharmaceuticals, like antidepressants or SSRI’s (selective serotonin reuptake inhibitors). And while pharmaceuticals most certainly have their place in treatment, they are not without side effects and are often over-prescribed considering the fact that we have a growing understanding of what underlies these mental health issues.

Chronic systemic inflammation being a major contributing factor.

Depression is, of course, a complex disorder affected by many components, ranging from genetics to nutrition to environmental stress. However, coming back to that mind/body or brain/gut connection, first discussed in the vagus nerve article. Can an inflamed gut lead to an inflamed mind? This mechanism by which our immune system can directly affect our mood, our behaviours and our brains is certainly a rich avenue for discussion.

Inflammation has been shown to have a negative effect on the brain and there is certainly a link between anxiety, depression and inflammation. Studies have shown people suffering from depression have 50% more inflammatory biomarkers in their blood than the average person. In fact, these biomarkers can now predict the risk for major depression. But this correlation is not a clear indication of causation - did the inflammation cause the depression, or did the depression cause the inflammation?

Thanks to science (and some very unfortunate experimental volunteers who were injected with pro-inflammatory cytokines and endotoxins) we have the answer to that and yes, the relationship between inflammation and depression is actually causal. An inflamed gut can cause an inflamed mind. Pro-inflammatory cytokines can cross the blood-brain barrier directly linking the immune system to the brain, and once these molecules are in the brain they affect the function of neurotransmitters regulating mood, anxiety, pleasure, reward and motivation.

An Interesting Fact…

In the case of serotonin - our happiness neurotransmitter - pro-inflammatory cytokines in the brain increase its metabolism, reducing the amount of serotonin left in the synapse where it can exert all of its effects on mood and anxiety.

Higher inflammation = lower serotonin = less positive mood/higher anxiety.

But even more cruel than that, inflammation further lowers serotonin levels by depriving the brain of its precursor molecule tryptophan (5-HTP), the building block the brain uses to make serotonin. An inflamed body actually diverts 5-HTP into a competing metabolic pathway which then converts 5-HTP into a chemical compound called kynurenine instead of serotonin. Kynurenine is metabolised by the body into quinolinic acid (which, interestingly is a biosynthetic precursor to nicotine). Quinolinic acid is neurotoxic and further associated with depression.

Inflammation not only lowers serotonin levels, but it also turns the building blocks of serotonin into neurotoxic chemicals associated with depression! A double whammy.

Based on this research, mitigating chronic inflammation is a very good idea across the board for longevity and wellbeing. It is possible that as the science continues to emerge, mitigating chronic inflammation may become a chief aim of the treatment process for depression alongside existing therapies - incorporating a more multi-pronged lifestyle intervention - and monitoring inflammatory biomarkers may become a direct measure of therapeutic success.

References

Eisenberger, N. I., Berkman, E. T., Inagaki, T. K., Rameson, L. T., Mashal, N. M., Irwin, M. R. (2016) “Inflammation-Induced Anhedonia: Endotoxin Reduces Ventral Striatum Responses to Reward.” Biological Psychiatry, U.S. National Library of Medicine. Retrieved from pubmed.ncbi.nlm.nih.gov/20719303/.

Kiecolt-Glaser, J. K., et al. (2015) “Inflammation: Depression Fans the Flames and Feasts on the Heat.” American Journal of Psychiatry, vol. 172, no. 11, pp. 1075–1091.

Knight, H. (2015) “How Chronic Inflammation Can Lead to Cancer.” MIT News. Retrieved from news.mit.edu/2015/how-chronic-inflammation-can-lead-to-cancer-0807.

Moieni, Mona, et al. (2015) “Sex Differences in Depressive and Socioemotional Responses to an Inflammatory Challenge: Implications for Sex Differences in Depression.” Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology. Nature Publishing Group, retrieved from www.ncbi.nlm.nih.gov/pmc/articles/PMC4915253/.

Owens, M., et al. (2014). “First Biological Marker for Major Depression Could Enable Better Diagnosis, Treatment.” ScienceDaily. Retrieved from www.sciencedaily.com/releases/2014/02/140217161108.htm.

Ruscio, M. (2018). Healthy Gut, Healthy You. Ruscio Institute LLC: USA.

Inflammation Explained.