Three-Links in the Inflammatory Circuit of Chronic Health Conditions You Need to Break

Chronic inflammation is fueled by a trio — dysfunctional immunity, defective gut barrier, and dysbiotic microbiome

Tanvi Shinde, PhD
Aug 17, 2020 · 10 min read

hronic inflammation is the central player in the most challenging health conditions of our time. You name it — obesity, diabetes, cancer, rheumatoid arthritis, bowel diseases, heart diseases, asthma, and even mental disorders — sustained inflammation is the critical underlying factor in all of these chronic immune and metabolic conditions that significantly compromises our quality of life.

Inflammation in itself is not a villain as it is our body’s essential survival mechanism to fight-off pathogens and repair injured tissues. So how does this friend to foe make our life miserable and play an important role in these chronic health conditions?

Hippocrates said, “All Disease Begins in the Gut”, so let us take a deep dive into our gut to find the answers to the chronic inflammatory diseases. Our gastrointestinal tract or gut is an ecosystem in itself housing about 70–80% of our body’s immune cells.

That makes it a control room for our immunity. It presents us with immune defense tools to fight off infections and diseases. Our gut not only digests the food we eat but also decides what nutrients will be absorbed and what will enter the circulatory system through its special barrier lining made up of epithelial cells.

The gut ecosystem also hosts about 100 trillion microorganisms that make up our microbiota. The diverse microbiota along with its metabolites they manufacture play an important part in decision making inside this gut’s immunity control room.

In fact, our microbiota is the commander-in-chief of the immune system.

The trio that links the chronic inflammatory circuit

Image by Tanvi Shinde

Chronic diseases such as obesity, diabetes, bowel disorders, chronic lung conditions, cardiovascular diseases, rheumatoid arthritis, aging-related disorders and even neurological disorders all have either direct or in-direct connection with our gut.

The inflammation in these chronic conditions involves a signature recurrent inflammatory circuit made up of three links residing in our gut — dysfunctional immunity, weakened gut barrier integrity, and dysbiosis.

These three components of the inflammatory circuit are highly interlinked and this strong association between these factors is what makes the inflammation chronic and difficult to resolve.

It is, however, not clear yet which of these components starts first and fuel the others (like the chicken or egg analogy) and remains an unsolved scientific mystery. But there is plenty of scientific evidence to support the significant role of all these three components in most chronic conditions.

Let us understand how are each of these three links is involved in chronic inflammation

Immune system

Inability of immune system to stop inflammatory response at the right time

A number of factors including our genetics, the environment we live in, and most importantly, the type of food we eat are known to push our immune system into a dysfunctional mode in case of chronic health conditions.

These factors damage the immune system’s ability to alarm its appropriate army of immune cells, control their behavior, and to stop them after the infection is cleared to let the healing process begin. This sort of uncontrolled behavior of specific immune cells that become exceedingly inflammatory is what leads to sustained damage to tissues and organs causing either low-grade or high-grade chronic inflammation in most lifestyle diseases.

Such chronic inflammation when continued over longer durations jeopardizes our immune system’s ability to use efficient defense tools to fight infections. Either it becomes incapable of producing effective antibodies and T-cells that are required for clearing the pathogens and/or sends a large number of inflammatory cells that cause more damage than protect us, as seen in severe cases of COVID-19 patients.

Such a dysfunctional immune system puts those with chronic illness at a higher risk of mortality by either increasing susceptibility to severe infections or developing comorbidities — obesity and diabetes, diabetes and heart disease, and irritable bowel disease and cancer.

But the dysfunctional immune system and its inability to contain the inflammatory response is only one part of the problem. There are at least two more associates in the inflammatory business that feed the sustenance of immune dysregulations and inflammation in chronic diseases.

Gut epithelial barrier

Weakened barrier integrity/increased permeability allow entry of toxic substances and pathogens

Image by Tanvi Shinde

Our gut is lined by a chain of epithelial cells held together by what is called tight junctions. The epithelial cells along with its tight junctions act as a barrier that tightly controls what gets absorbed in the bloodstream, when in a healthy state — absorbing nutrients and secreting waste.

This system is like border security at the airport preventing illegal substances and prohibited items from entering. In individuals with chronic conditions, this gate-keeping mechanism is broken or leaky allowing partially digested food, toxins, and microbes to penetrate the tissues beneath it.

This usually leads to an inflammatory response from the immune system that gets alarmed with all sorts of unwarranted things entering the tissues and circulatory system, thus, extending the negative effects beyond the gut. In addition to sending the immune system into havoc, such defect in the barrier integrity is also known to accompany microbial dysbiosis in the gut adding more fuel to the fire.

Dysbiotic gut microbiota

Bloom of pathogens and reduction of beneficial microbes results in more inflammation

Our gut harbors about 100 trillion microorganisms which dictate our well-being, our ability to fight off diseases, and even our responsiveness to drugs and treatments. Disturbances in the balance and diversity among the microorganisms residing in our gut are known as microbial dysbiosis. Dysbiotic gut microbiota is one of the prominent signatures of chronic diseases.

Image by enriquelopezgarre from Pixabay

Imagine if all forests were dominated by only a few types of trees. This would mean an unbalanced ecosystem — supporting a reduced variety of birds, animals, and creatures that otherwise thrive on diversification in the ecosystem.

The dysbiotic gut is like this unbalanced forest ecosystem — reduced diversity and unbalanced. In all chronic inflammatory conditions, bloom in members of pathogenic bacteria is observed along with a reduction in numbers and types of beneficial bacteria.

Among the lost populations of gut bacteria in chronically ill patients are some of the famous probiotic bacteria like lactobacilli and bifidobacteria residing in our gut. This means losing out on an array of positive functions that all these lost beneficial bacteria usually play in influencing our well-being.

In addition to training our immune system, specific members of these beneficial bacteria are known to synthesize vitamins, antimicrobials, and even neurochemicals that influence our brain functions.

Some particular bacteria are equipped with machinery to ferment undigested carbohydrates (dietary fiber/prebiotics) from our diet to manufacture anti-inflammatory chemicals like the short-chain fatty acids (SCFAs). Among several SCFAs produced in the gut, butyrate, propionate, and acetate play important positive roles in the gut and at distant organs through their transport via the circulatory system.

While the bacteria are amongst the most studied microbes in our gut, the role of other microbes in health and diseases including that of fungi, archaea, and even viruses are being intensively explored by the scientists.

Image by Tanvi Shinde

Sometimes, it is not the microbes itself, but the metabolites they produce that may be important in health and diseases. Compared to that of healthy people, the disturbances in the microbiota community results in reduced production of vital metabolites like the SCFAs.

SCFAs not only can strengthen barrier integrity, influence the immune system to function effectively to control inflammation, but can also modulate glucose tolerance and insulin sensitivity, and benefit brain functions.

In individuals with chronic neurological disorders, the abnormality in levels of important neurotransmitters like GABA, dopamine, and serotonin (last two famously known as the happy hormones) is confirmed. These brain chemicals generated by a specific group of bacteria in the gut keep your brain healthy and happy.

Such a reduction in important chemicals in chronic inflammation is accompanied by an increase in toxic substances (lipopolysaccharide or LPS) due to the dominance of pathogenic bacteria. Due to defects in the gut barrier in chronic diseases, LPS gets transported into circulating blood, causing systemic inflammation. The imbalance in microbiota and their byproducts feeds the vicious cycle of inflammation.

The microbial dysbiosis in the gut is the third link to the loop that when interlinked with dysregulated immunity and defect in the gut barrier, completes the inflammatory circuit that lights the recurrent inflammation in chronic diseases.

Resolving the chronic inflammatory circuit

Current medical approaches to reduce inflammation in chronic conditions primarily focus on suppressing either the inflammatory response of the immune system or increase anti-inflammatory response, while some treatments target the reduction of disease symptoms.

The design of such approaches fails to address the resolution of the complete inflammatory circuit and its components. I am not saying the current approaches are wrong or useless, but I feel they are incomplete, focussing only on the branches of the problem, not on the root of the problem.

Photo by Daniel Tausis on Unsplash

Okay, imagine your house is on fire (of course, hypothetically) and you run with buckets of water one after the other to save your bedroom and your study because they are your favorite places in the house (and have important documents and cash stored). Do you think this is the best approach? Most will agree that the best approach would be to ring the Fire Services to try and save the whole house. Now, some of you will say, “umm, but at least by the time the fire fighters arrive let me try to save my favorite rooms so less damage is caused”. Now trying to save only your favourite rooms-approach might work if the fire has not spread much and can be contained, much like an acute inflammation. But if it has spread across the house, as incase of chronic inflammatory situation, the heat from the neighbouring rooms will be enough to put your efforts to waste. So I hope we are on same page now that the fire fighters will be more better equipped to put the fire out to save your whole house.

Similarly, if the treatment of chronic diseases is designed to focus only on making the immune system more effective at containing the inflammation, we are ignoring the fact that leaky gut barrier and dysbiotic microbiota are enough to spread the inflammation again and continue the chronic cycle.

So instead, a more pragmatic strategy would be to employ treatments that can modulate each of the links in the chronic circuit simultaneously. The simultaneous resolution of all links would be more effective as this approach addresses the whole inflammation in the circuit and in-process would break the continuity of the inflammation.

So, how do we do this? Who can be that fireman to put off that whole inflammation in our body?

“Let food be thy medicine, and let medicine be thy food” — Hippocrates

Yes, food can be our fireman in fighting the inflammation in chronic conditions. A healthy one of course! Pair it up with your medical treatment and that can do wonders as well. Healthy nutrition should be diverse, naturally sourced. Nutrition that is rich in fruits and vegetables, fermented foods that carry probiotic/beneficial bacteria and healthy fats from fish, meat, eggs, and nuts.

The diet rich in fruits and vegetables will provide you with the dietary fiber/prebiotic to feed your microbiota to help manufacture SCFAs to repair our gut barrier and improve immune functions. Pair those fiber-rich foods with evidence-based probiotic-rich foods/supplements to replenish the lost bacteria in our gut. The combination of probiotics and prebiotic is known as synbiotic, which can provide additional synergistic benefits.

Gut microbiota in individuals with chronic inflammatory diseases is often known to have reduced levels of fiber-digesting bacteria in their gut. So, eating those fruits and vegetables/prebiotic supplements is of no help without the right bugs to ferment the undigested fiber into anti-inflammatory SCFAs in our gut. Similarly, having fermented foods rich in all those good bacteria is not much beneficial if you do not feed them with dietary fiber and help them settle in.

Consuming energy-dense, ultra-processed foods carrying refined carbohydrates and fats, sugary foods can significantly damage the gut microbiota. The ultra-refined foods that are stripped off of their nutrition can cause serious damage to our immune system.

Such a “Westernised Diet” is one of the main risk factors of chronic inflammation in lifestyle diseases the world is struggling with since the last few decades. It is like adding more charcoal to the already heated BBQ grill if you continue eating such high-processed foods. And who knows this over-heated BBQ could have been responsible for initiating that fire in your house in the first place!

To close

Chronic inflammation is a recurrent circuit that is made up of three links — dysfunctional immunity, defective barrier integrity, and dysbiosis in the microbiota. Healthy functional foods + medical treatments that can resolve the whole circuit simultaneously is the best strategy to discontinue the vicious cycle of inflammation in chronic health diseases.


Make informed choices about your Health

Tanvi Shinde, PhD

Written by

. Biomedical Researcher interested in inflammation and microbiome for gut health and beyond . Published Academic author . Gut Health Evangelist . Mom . Reader .



A Medika Life Publication for the Medical Community

Tanvi Shinde, PhD

Written by

. Biomedical Researcher interested in inflammation and microbiome for gut health and beyond . Published Academic author . Gut Health Evangelist . Mom . Reader .



A Medika Life Publication for the Medical Community

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