‘The gut is a sophisticated computer machine,’ says researcher

the immunologist Ruslan MedjitovProfessor of Yale Universityis one of the most respected specialists in the role of inflammation in maintaining the physiological balance of the organism (the so-called homeostasis) and also the inflammatory processes that contribute to the development of most diseases – from cancer to depression; cardiovascular problems intestinal diseases and many more.

One of the discoverers of Toll-Like receptors (molecules found in defense cells responsible for generating signals leading to the production of pro-inflammatory cytokines), Medzhitov is often cited by immunologists as deserving of a Nobel Prize.

In a special issue recently published by the magazine Sciencehe advocated an expanded view of inflammation in health and disease, the subject of a series of three reports that the Stadium published on Saturday (5), Sunday (6) and Wednesday (9). In an interview with the newspaper, Medzhitov said the gut is much more than a food processing tube and has a powerful impact on physiology and behavior.

Immunologist Ruslan Medzhitov, a professor at Yale University, is one of the most respected scholars on the role of inflammation in maintaining physiological balance in the body.

Immunologist Ruslan Medzhitov, a professor at Yale University, is one of the most respected scholars on the role of inflammation in maintaining physiological balance in the body.

Photo: Yale University/Publicity/Estadão

New studies point out that inflammation is associated with almost all human diseases and also with maintaining balance in the body (homeostasis). How can this evidence help improve health care?

Since inflammation is associated with almost all diseases, it is important to find out the cause in different situations. This will enable the development of therapies that prevent unwanted inflammation that perpetuates and amplifies disease processes.

You offer a broader view of the role of inflammation in the body. Could this lead to the creation of better medicines?

Most treatment methods for inflammatory diseases are based on blocking the production of inflammatory signals. The alternative I propose is to block the response of target tissues and organs to inflammatory signals. An analogy: what to do when loud music bothers you? You can lower the volume or put earplugs in your ear and not be disturbed by the sound. Turning down the volume is tantamount to suppressing inflammation, a method that doesn’t always work. Putting earplugs in your ear works to reduce the response to inflammatory signals. This method has not yet been tested, but I think it would be a valuable direction for future research.

How can the excessive use of anti-inflammatories harm the physiological balance of the body?

The abuse of anti-inflammatories can have two negative consequences. First, it can compromise the defense against infections (and certain types of tumours). Second, it can disrupt homeostasis in some cases. An example: recent studies have shown that nonsteroidal anti-inflammatory drugs (such as acetylsalicylic acid and ibuprofen) can reduce the positive effect of exercise and cause ulcers in the intestine, if they are used in high doses and for long periods.

How can inflammatory processes occurring in the gut impact the brain and contribute to the development of depression, neurodegenerative diseases such as Alzheimer’s disease and others?

It’s not yet fully understood, but depression and Alzheimer’s disease are diseases caused or promoted by inflammation. Inflammation causes many forms of depression. It is probably part of the normal physiological response to illness. When we are sick due to an infection, the body’s normal reaction is to lie still in bed, decrease appetite, avoid loud lights and sounds, etc.

We know why some of these reactions occur, but we still don’t understand them all. Depression is the body’s protective response when it is at risk. Probably because it reduces the exploitation of the environment, but it becomes pathological when excessive.

In the case of Alzheimer’s disease, it is different. What is happening has not yet been fully clarified. Whether the neurodegenerative disease is caused by an infection or by gut microbes is not well established. It is very difficult to study Alzheimer’s disease because it takes decades to develop.

The gut is often called the second brain. Is this still correct, in light of new evidence on inflammation signaling between the two organs?

The intestine has its own nervous system (enteric nervous system) which is sometimes called the second brain. It’s fair to think of him that way. The intestine is an underestimated organ. People think he’s just a food processor tube. In fact, it’s a sophisticated computer machine that constantly evaluates what we eat and what needs to be done.

It has a powerful impact on our physiology and behavior. Likewise, it is involved in inflammation directed against microbes and inflammation directed against certain food components. When left unregulated, the former can lead to inflammatory bowel disease and the latter to food allergies.

What are the fundamental gaps in knowledge about inflammation? What question would you like to see answered?

I think the fundamental shortcoming is that we don’t know all the ways inflammation can be induced. This can happen in different ways: when we don’t get enough sleep, when we travel to a foreign country and eat very different foods, when we are in a bad mood, etc. I would like to know what are the common themes here and what are the molecular mechanisms that cause inflammation in these various conditions.?

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