04. Mar 2020

Heidrun Valencak-Hösel

Diverticula: a matter of age or rather the microbiome?

The older we get, the more people find out that their intestines have developed so-called diverticula: While only 10% of people under the age of 50 are affected, every second person over the age of 80 has diverticula in their intestines. Mag. Anita Frauwallner discusses the causes and development of diverticula with Prof. Dr. med. Wolfgang Kruis and what role the targeted and timely use of probiotics could have.

Mag. Anita Frauwallner: During a routine medical check-up, many people are diagnosed with “diverticula” – but only very few understand what these protrusions in the intestines are and what effects they can have on our health and wellbeing. One of your most important fields of study involves these diverticula: Can you explain to our readers what they are?

Prof. Dr. med. Wolfgang Kruis: Let’s take a quick look at the anatomy of the colon before explaining what diverticula are: The intestines are connected to their surroundings through connective tissue (mesenterium). This tissue is responsible for, among others, guiding various inlets and outlets (arteries, veins, lymphatic vessels) and nerve paths to and into the intestinal tube (e.g. to transport nutrients from food throughout the entire organisms or to control bowel movements). An important part of the intestinal wall are the annular and longitudinal muscles. They mix the intestinal contents and transport the food bolus through the entire intestines. Between these individual muscles are little gaps that allow the above-mentioned inlets and outlets into the intestines.

The development of diverticula and diverticular diseases has many causes, many of which occur with age or in correlation with the intestinal flora.

The innermost layer, that basically covers the entire intestinal tube like wallpaper, is the intestinal mucosa. If the pressure increases inside the intestines, the mucosa is squeezed outwards between the gaps in the muscles and connective tissue and form protrusions – this is what we call diverticula. Not only can digestive juices and stool be found in the intestinal lumen, the cavity surrounded by the intestinal tube, but also trillions of intestinal bacteria (a.k.a. microbiome, formerly known as the intestinal flora).
Now, when the intestinal mucosa is pressed outwards, all the contents that are currently in the intestinal lumen can also be found in this protrusion. As long as the diverticula are sealed, nothing really bad can happen. However, if these sacks are damaged or the intestinal barrier becomes permeable, the intestinal contents can enter the abdominal cavity – and this is a big problem: The abdominal cavity is completely sterile. Any contamination, whether through helpful intestinal bacteria, stool or pathogens, leads to inflammation around the diverticula or so-called diverticulitis (note: the ending “-itis” refers to an inflammatory process).

Mag. Anita Frauwallner: In other words, as long as the diverticula are sealed, they can’t cause any problems. It only becomes critical when intestinal bacteria enter the abdominal cavity through, for example, a “Leaky Gut” or when these protrusions burst, contaminate the intestinal cavity and result in inflammation. How often do these diverticula occur, and are these dangerous infections automatically associated with the development of diverticula?
Frau Mag. Frauwallner und Herr Prof. Dr. med. Wolfgang Kuris

Prof. Dr. med. Wolfgang Kruis: Diverticula are most commonly found in countries with a high standard of living. Depending on the age group, diverticula can be found in up to 50% of all people – and that is a tremendous incidence! The likelihood of developing diverticulosis increases with age – but even young people can develop diverticula and its associated problems. However, it is important to understand that not every diverticulum automatically leads to complications, which is why we need to clarify and differentiate between the following definitions: A diverticulosis is the occurrence of diverticula without complaints or signs of inflammation. Out of all the patients that were diagnosed with diverticula, “only” 80% of them had diverticulosis without any complications in the abdomen. Diverticulitis, on the other hand, requires treatment to stop the spread of inflammation as quickly as possible, no matter the severity.

Mag. Anita Frauwallner: You played a big role in one of the largest international studies analysing gene-markers in individuals with diverticulosis, i.e. diverticula without further symptoms. What results did you find? Are there further factors that influence the development of diverticula? And what role does the intestinal flora play?

Prof. Dr. med. Wolfgang Kruis: The study you mentioned analysed 50.000 samples from individuals with diverticulosis throughout Europe – and the results offer a better understanding of the development of diverticula. We already know the genetic signature of many diseases, i.e. all individuals with certain genetic characteristics that increase the risk of developing a certain disease (the mere presence of these genes, however, don’t automatically lead to the development of the disease).
In this scientific study, roughly 40 genetic characteristics were clearly identified in people with diverticulosis: They resemble neither the markers for chronic inflammatory bowel diseases nor those of the irritable colon syndrome. They are, however, similar to the genetic signature of weak connective tissue and diseases that occur in the enteric nervous system: Weak connective tissue, therefore, enables the intestinal mucosa to protrude more easily because of pressure.

There are several causes for the development of diverticula and diverticular diseases, many of which occur with age or in correlation with the intestinal flora: There is a clear correlation between the probability of developing diverticular disease and eating habits. And this is where the microbiome comes into play: Our diet plays a central role in the composition and health of the intestinal flora. Motility disorders have a fundamental impact on the digestive tract. This means that the muscle layers in the intestines are more active, instead of working normally. In patients with diverticular disease, the muscles are thicker because of these disorders, the intestinal tube is constricted, and the intestinal contents move along with more difficulty. As a result, the pressure in the intestines increases and the body tries to squeeze the intestinal contents through the intestinal tube. This increased pressure can be measured clearly in tests: In patients with diverticular disease, the motility is significantly higher than in healthy individuals.

Besides impaired motility, several other factors show a certain connection to the microbiome: Overweight people have a significantly higher risk of developing a diverticular disease – and yet again, this is closely related to an altered intestinal flora. Even the so-called “low-grade inflammation” (i.e. a barely noticeable but nonetheless existing inflammation, comparable to a smouldering fire in the body), as well as an impaired intestinal barrier, are strongly associated with a defective microbiome. The “porous intestine” or “Leaky Gut” (a condition in which important connective proteins between the cells of the intestinal mucosa are severed) also promotes the development of diverticulitis: The bacteria that inhabit the diverticula can now wander through this leaky intestinal barrier into the abdominal cavity and cause inflammation.

The “porous intestine or “Leaky Gut” (a condition in which important connective proteins between the cells of the intestinal mucosa are severed) promotes the development of diverticulitis.

Mag. Anita Frauwallner: In summary, a damaged microbiome can contribute in many ways to the development of diverticulitis. Vice versa, I would assume that positively influencing the intestinal flora with probiotics could be an important new therapeutic option! What does the scientific data say about this, and what do you think are possible starting points for a probiotic therapy as a leading expert?

Prof. Dr. med. Wolfgang Kruis: There is already primary data concerning the microbiome and diverticular disease, with ground-breaking results: We know that people with diverticulosis and diverticulitis show a different intestinal flora to that of healthy people. Even certain complaints in diverticulitis, e.g. severe flatulence, show a special macrobiotic signature: If a certain change occurs in the intestinal flora, it similarly leads to specific symptoms. On the other hand, this offers us the opportunity to reduce complaints with a targeted change of the microbiome.

Probiotics could play a future role in the treatment of diverticular disease.

Yet, there isn’t enough data to make a standard recommendation concerning the treatment of diverticular disease with probiotics. Nevertheless, several primary clinical studies have already shown that the combination of mesalazine (Note: an anti-inflammatory substance) with probiotic bacteria, leads to better results than the drug alone. This was demonstrated in phases with acute complaints, as well as in patients without any noticeable pain at that time. The latter had a more seldom recurrence of symptoms with the combination of anti-inflammatory drugs and probiotics than the comparison groups with just mesalazine or placebos.
Probiotics could play a future role in the treatment of diverticular disease. More research is still necessary but, in my opinion, the following two therapeutic areas are promising for the treatment of diverticular disease: Alleviating symptoms in uncomplicated cases and preventing the recurrence of inflammation. This is where probiotics could really improve the wellbeing of patients by reducing inflammation and improving the intestinal barrier.

Mag. Anita Frauwallner: Thank you for these fascinating insights – we are looking forward to the new scientific results and are pleased that we can make a contribution to this cause!

Prof. Dr. med. Wolfgang KruisA quick introduction

Prof. Dr. med. Wolfgang Kruis was the head physician at the Department of Internal Medicine at the Evangelical Hospital Kalk (Cologne) for a long time and currently focusses on research about inflammatory bowel diseases and diverticular diseases. As the president of the German Society for Probiotic Medicine (DePROM), scientific research into the human microbiome and its impact on the development and treatment of diseases is the bread and butter of his work.

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