Confocal Laser Endomicroscopy (CLE) - Expert Interview with Dr. Kai Wiemer

Dr. Kai Wiemer is a board-certified specialist in internal medicine and gastroenterology and heads Medical Clinic II—the Department of Gastroenterology—at the Knappschaft Clinic in Kamen, Westphalia. With his many years of experience in the diagnosis and treatment of diseases of the gastrointestinal tract as well as liver and pancreatic diseases, he has established himself as a highly regarded specialist. He has in-depth knowledge of endoscopy, the treatment of chronic inflammatory bowel diseases, and colorectal cancer screening.

Dr. Wiemer completed his medical training at Goethe University in Frankfurt am Main, where he acquired a broad range of expertise. Over the course of his career, he has specialized in interventional endoscopy, endosonography, and nutritional medicine. Of particular note are his skills in performing ERCP (endoscopic retrograde cholangiopancreatography) and cholangioscopy, which—thanks to his precise and successful procedures—have made him a recognized expert in this field.

In addition to his clinical work, Dr. Wiemer has also placed a strong emphasis on medical research and continuing education. He has led several research projects and published scientific papers that have contributed to the advancement of gastroenterological treatment approaches. Furthermore, he is actively involved in the training and continuing education of medical staff and consistently promotes continuing education initiatives in gastroenterology.

As a co-author of the S1 guideline on functional dyspepsia (“irritable stomach”) published by the German Society for Neurogastroenterology and Motility (Deutsche Gesellschaft für Neurogastroenterologie und Motilität e.V.), Dr. Wiemer has played a key role in the further development of guidelines in this specialty. In his daily work, he takes a holistic approach that prioritizes individualized patient care and close collaboration with his team to ensure optimal patient care. His dedication and passion for gastroenterology have established him as a recognized expert in his field.

In an interview with Dr. Wiemer, the editorial team of the Leading Medicine Guide learned more about confocal laser endomicroscopy, an innovative imaging technique featuring high-resolution real-time microscopy.

Confocal laser endomicroscopy is an innovative technique that is becoming increasingly important in gastroenterology. It enables high-resolution, microscopic examination of tissue in real time during an endoscopy. This technique is used in particular for the diagnosis and monitoring of diseases of the gastrointestinal tract. This includes the early detection of cancer, the examination of chronic inflammatory bowel diseases such as Crohn’s disease and ulcerative colitis, as well as the assessment of precancerous lesions and polyps. By enabling the visualization of tissue changes at the cellular level, CLE contributes to more precise diagnosis and more personalized treatment planning.

Confocal laser endomicroscopy is an advanced imaging technique that distinguishes itself from other methods for diagnosing gastrointestinal diseases primarily through its exceptional level of detail. 

“Confocal laser endomicroscopy, or CLE for short, enables microscopically precise tissue diagnosis in real time during an endoscopic examination for the first time. Unlike traditional methods, in which a biopsy is first taken and the tissue is then examined in the laboratory, CLE allows for the direct observation of reactions in the intestinal mucosa—for example, in response to a provocation test with specific nutrients. This makes it possible to visualize changes immediately without having to take samples. One particular area of application is the diagnosis of so-called “leaky gut” syndrome—that is, a compromised intestinal barrier—which has often been considered controversial until now. “With CLE, this permeability can now be objectively and immediately detected,” explains Dr. Wiemer at the beginning of our conversation, adding:

“In practice, this means that patients are admitted as inpatients for the test, since delayed reactions can also occur during allergy provocation tests. The examination is performed as part of a gastroscopy under sedation—so the patient is asleep during the procedure. Digested food is introduced into the duodenum, the first section of the small intestine. At the same time, CLE technology is used: a special laser scanner is advanced through the endoscope to the mucosa. With magnification of up to 1,000 times, the reaction of the intestinal mucosa can be observed in real time. Prior to the procedure, a fluorescent contrast agent—known as fluorescein—is administered intravenously. This agent has long been used in ophthalmology as well. The goal is to determine whether, in the case of a compromised intestinal barrier, the contrast agent leaks from the blood vessels into the surrounding tissue—a clear sign of a barrier dysfunction. First, the presence of a primary intestinal barrier dysfunction is assessed. If the barrier is intact, a possible secondary dysfunction can then be induced and visualized by administering certain foods—for example, in the context of a leaky gut. All of this happens in real time and enables highly precise diagnostics directly on the patient.”

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Leaky gut, also known as “permeable intestine,” describes a condition in which the intestinal wall is damaged and no longer properly fulfills its function as a barrier. Normally, the intestinal mucosa prevents harmful substances from entering the bloodstream. With leaky gut, however, the tight junctions between the cells of the intestinal wall are loose, allowing toxins, undigested food particles, and pathogens to enter the body. This can trigger inflammation and an overreaction of the immune system, which has been linked to various health problems such as digestive issues, skin conditions, and chronic inflammation.

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There is a standard protocol that covers the five most common food allergens: egg white, soy, milk, yeast, peanuts, and wheat. This protocol is used in both clinical practice and research studies. 

“During the test, we check whether the patient reacts to any of these food allergens, which causes fluorescein to leak from the blood vessels into the interstitial space. This reaction becomes visible and enables a precise diagnosis. After the test, the results can be discussed with the patient, and nutritional counseling by qualified staff is offered as needed. A real-world example: We recently tested a patient who had been struggling with irritable bowel syndrome symptoms for years without an exact cause being identified. Using CLE technology, we were able to clearly determine that she reacted to wheat, even though gluten intolerance had already been ruled out. This brought her great relief, as she now finally had a clear cause for her symptoms. “It wasn’t the gluten that triggered the reaction, but possibly a sensitivity to certain proteins in wheat, such as amylase-trypsin inhibitors (ATI), which can also be found in other gluten-containing grains,” explains Dr. Wiemer.

There is no clear answer to the question of whether the number of people who have allergic reactions to these foods has increased. There is certainly greater health awareness and a growing willingness to investigate food intolerances more closely. New diagnostic methods—including both serological tests and imaging techniques such as CLE—offer better diagnostic capabilities today than they did 20 or 30 years ago. Even conditions such as irritable bowel syndrome, which were often treated in the past solely through a process of elimination, can now be investigated using more precise methods. “In patients whose neurological tests are normal and who do not have a classic IgE-mediated allergy, CLE can help identify an intestinal barrier disorder (leaky gut) that may be responsible for their symptoms. A major advantage of this method is that the examination can be performed during a gastroscopy lasting about 20 minutes. Such changes are not visible during a normal endoscopy. CLE technology makes it possible to observe the reactions of the intestinal mucosa in real time and capture them in images, enabling precise and reliable diagnosis,” explains Dr. Wiemer.

CLE represents a precise diagnostic option that can be used for a wide range of patients. In certain cases, however, conventional endoscopy is sufficient—for example, when it comes to ruling out or confirming celiac disease. 

“In conventional endoscopy, the endoscope is inserted into the stomach, and if celiac disease is suspected, tissue samples are taken from the small intestine for subsequent examination in the laboratory. During a CLE examination, which is designed for a more detailed analysis, the patient lies on the examination table, similar to a standard gastroscopy. The endoscope is inserted into the descending portion of the small intestine, the duodenum. There, a laser probe is advanced through the endoscope to examine the mucosa in this region. First, the examination determines whether the intestinal barrier is intact or whether there are already signs of a leaky gut, i.e., a compromised intestinal barrier. In some cases, this barrier may already be compromised without food provocation, which requires further testing to determine the exact cause. In such cases, allergy testing may also be necessary,” says Dr. Wiemer, adding:

“However, if the intestinal barrier is intact, the examination continues with various provocation agents. These are also introduced into the small intestine via the endoscope. The mucosa’s reaction to these substances is then observed. A positive test is indicated, for example, by the leakage of fluorescein—a contrast agent—from the blood vessels into the tissue. Cell death often occurs in the intestinal mucosa as well, a process known as ‘cell shedding.’ During this process, small cell fragments detach and become visible with the fluorescein. These reactions are typical signs of a compromised intestinal barrier and confirm a positive test result. After the examination, the patient may be referred to a nutrition counseling session, where they receive comprehensive advice and support to adjust their diet based on the results. This is an important part of the treatment plan, as proper nutrition plays a central role in treating leaky gut and other intestinal problems.”

The nutritional counseling the patient receives following the CLE test does not involve strict rules, but rather recommendations designed to help support their gut health and alleviate their symptoms. 

“Of course, it’s not possible to monitor every patient around the clock, and we know from experience—for example, when caring for patients with celiac disease or those with chronic inflammatory bowel diseases—that to err is human. Anyone can have a moment of weakness and eat something that doesn’t quite align with the recommendations. The key advantage, however, is that the patient then at least knows exactly where their symptoms are coming from. For example, if they react to wheat and then treat themselves to a roll, they’ll understand why they’re experiencing symptoms, and that can be a huge relief. They no longer have to wonder what caused their discomfort. The situation becomes problematic when people turn to advertisements in search of simple solutions to relieve the symptoms of irritable bowel syndrome. These ads promote products containing probiotics in the form of yogurt drinks or capsules, which may provide some relief, but they are not miracle cures. Especially in the case of a specific intolerance, such as wheat intolerance, simply consuming such a product is not enough. It’s a complex issue, and relying solely on dietary supplements will not address the root cause of the problem,” explains Dr. Wiemer.

Another issue that frequently comes up is the difficulty consumers face in selecting the right foods at supermarkets, especially when they are dealing with specific intolerances or allergies. 

The multitude of ingredients and the often obscure terms on labels can be confusing. The industry should recognize its responsibility and label ingredients more clearly, especially in processed products such as baked goods or instant soups, which often contain additives that are difficult for consumers to understand. It would be a step forward if manufacturers were to name these ingredients more clearly. A simpler solution could also be to opt for fresh, unprocessed foods whenever possible, which is always a good choice anyway.

Dr. Wiemer comments on this: “When it comes to gut health, there is a clear link between diet and the microbiome. A varied, seasonal, and fresh diet helps keep the microbiome in balance. However, anyone who severely restricts their diet or relies too heavily on dietary supplements risks a reduced diversity of bacteria in the gut. One example was a young man who followed a very restrictive diet and took a variety of dietary supplements. His microbiome was severely limited in some areas. The recommendation to eat as varied and seasonal a diet as possible has a positive effect on the microbiome and helps keep it in balance. Patients who come to us with symptoms similar to those of leaky gut often realize that they have unnecessarily restricted their diets. If they react to the challenge tests, they at least know that they don’t have to avoid every food, but that their symptoms might stem from other factors. This realization can be a huge relief and help patients regain control over their diet,” he emphasizes:

“For a healthy gut microbiome, it’s especially important to eat fiber-rich foods, particularly from plant-based sources. A balanced diet rich in fresh vegetables, fruits, and whole grains is crucial. Even though it’s normal for the gut to have to work harder to digest fiber-rich plant-based foods, you shouldn’t be discouraged if you experience mild discomfort after eating raw foods—this usually goes away on its own. A widespread myth claims that you shouldn’t eat green salad in the evening because it’s hard to digest. I consider this notion outdated. As with many other old traditions—such as the belief that one shouldn’t go into the water after eating—these are rumors with no scientific basis.”

CLE offers significant advantages over conventional imaging methods, particularly when distinguishing between active inflammation and scar tissue.

“Laser endomicroscopy in gastroenterological endoscopy has existed in its current form since the early 2000s, and I am very pleased that we can bring this method more into the spotlight. It is particularly important that patients know this examination is available to them. It is by no means a private service, but is open to all patients. This is a point that should be emphasized time and again, precisely because this condition—such as irritable bowel syndrome—affects many people. It would be unfortunate if we were to offer this treatment method as a form of two-tiered healthcare, as that would not be in the spirit of equitable healthcare.”

Knappschaft Kliniken Kamen offers specialized gastroenterological care with a focus on modern, minimally invasive procedures. The goal of the clinic in Kamen is to replace surgical interventions with innovative treatment methods. Furthermore, the integration of new technologies into medical care is being promoted.

“It is particularly important to me to emphasize that our focus is not exclusively on CLE. This method represents only a small part of our work. Our main activity lies in gastroenterology, with a special emphasis on interventional endoscopy. These are procedures that can replace surgical interventions in many cases. Our goal is to avoid major surgical procedures for our patients by utilizing modern endoscopic techniques. This endoscopy goes far beyond traditional gastro- and colonoscopy, which nearly every gastroenterologist offers in an outpatient setting. What particularly sets us apart is “third-space” endoscopy—that is, modern resection techniques, such as the removal of tumors within the thin layer of connective tissue beneath the mucosa of the gastrointestinal tract. Furthermore, we use endosonographic techniques, for example, to puncture adjacent organs to obtain tissue samples and place stents. This type of “surgery-replacing” endoscopy is the mainstay of our clinic. We also offer a 24/7 endoscopy on-call service, which means we are available around the clock, all year round, for emergencies. This also includes ERCP on-call service, which only a few centers in the region are able to provide. “This service is a core offering for us, and we’re proud to be able to provide it in this form,” says Dr. Wiemer, who, at the end of our conversation, offers a glimpse into the future:

“We would like to have greater visibility, especially in the region, even though we are well-connected and strategically located—right at the Kamener Kreuz, a major transportation hub connecting north, south, east, and west. We offer a full range of outpatient and inpatient gastroenterology services, including neurogastroenterology, interventional endoscopy, and nutritional medicine—all within a highly specialized and efficient unit supported by a great team. In terms of medical progress, we also see great potential for the future in artificial intelligence (AI). We have already integrated AI technologies into endoscopy, particularly in colorectal cancer screening. Furthermore, as part of the Knappschaftsverbund, we are affiliated with a major university AI center. We are currently in discussions about potential joint research projects, both in the field of CLE and in endoscopy in general. This AI center is one of the leading ones in Germany, and the collaboration could bring decisive progress to our work and to medical care.”

Dr. Wiemer—thank you very much for this insightful conversation!