gastroenterologist

As food passes through the digestive tract, muscles flex to keep things moving smoothly. Loss of motility can result in acid reflux, inability to transfer food out of the stomach, or constipation.

Dysmotility disorders are often diagnosed with a catheter carrying pressure transducers that detect GI tract contractions. MIT researchers have created a novel gadget inspired by an old Incan technology, the quipu — a collection of knotted ropes used to transfer information — that might offer a cheaper and easier-to-manufacture alternative to existing diagnostics for GI dysmotility.

The MIT researchers and their collaborators at Brigham and Women’s Hospital demonstrated in animal tests that their simple device, a silicone tube filled with liquid metal and knotted many times, produces measurements similar to those produced by the state-of-the-art diagnostic technique known as high-resolution manometry.

“We’re able to make a measurement that would normally require devices that cost thousands of dollars and an instrument that is much more complicated,” says Giovanni Traverso, the Karl van Tassel Career Development Assistant Professor of Mechanical Engineering at MIT, a gastroenterologist at Brigham and Women’s Hospital, and the study’s senior author.

The study’s principal authors are MIT research scientists Kewang Nan and Sahab Babaee, and it was published today in Nature Biomedical Engineering.

Dysmotility Diagnosis

Contractions of the gastrointestinal system are essential for transporting food through the tract, and disruptions of these contractions at any point might result in health concerns. The gold-standard manometry test can be performed to determine if the GI tract muscles are correctly functioning to create those waves.

“High-resolution manometry can detect the pressure and speed of the contractile waves, but those devices are very expensive, in the tens of thousands of dollars, and they require maintenance and sterilising between patients,” Traverso explains.

Traverso (who grew up in Peru) and Nan believed that the Incan technique of quipu may be used to influence the development of a simpler diagnosis. Before writing, the Inca and other ancient Andean cultures employed quipu devices, which are made of colourful threads twisted in various ways, to record information and deliver messages.

“Our objective was to create a device that was equivalent to existing commercially available catheter-based pressure transducers while also lowering the cost and making it easier to build and deploy,” Nan explains.

The researchers started with a basic silicone catheter, which they filled with gallium-indium eutectic, a liquid metal that is harmless in minute amounts, and sealed at both ends. This tube can respond to pressure changes in an unknotted condition, but it is not sensitive enough to detect pressure changes in the gastrointestinal system.

When the researchers added knots at regular intervals throughout the tube, the catheter became considerably more sensitive to pressure fluctuations and could detect pressures up to roughly 200 millimetres of mercury, which is about the greatest pressure encountered in the human digestive system.

The greater sensitivity is due to the knots elongating the cross-section of the tube, making it easier to compress, as demonstrated by the researchers using computer simulations. Furthermore, when the tube is knotted, three or four parts of the tube are stacked on top of one another, increasing its sensitivity to pressure fluctuations.

The researchers also discovered that pressure sensitivity varies depending on the type of knot and how firmly it is tied. The researchers utilised knots spaced approximately 1 centimetre apart to match the spacing of pressure transducers in a manometer for use in the digestive tract, but they might be positioned closer together for other uses, the researchers said.

The researchers utilised the quipu-inspired sensor to monitor pressure in the oesophagus while food was ingested in animal models. They also assessed the rectoanal inhibitory reflex (RAIR). The novel devices produced pressure measures that were comparable to the gold-standard manometry approach in both experiments.

Less complicated option

The researchers also demonstrated that the gadgets can resist high temperatures and can be sterilised using an autoclave, a typical medical equipment used to sterilise things using heat and pressure. This offers them a competitive edge over conventional manometry catheters, which cannot be autoclaved and must be chemically cleaned. Furthermore, because the devices are so cheap to build, they might be thrown after each use if autoclaves aren’t accessible.

“They’re incredibly quick and super cheap to create,” Nan explains. “Another reason for making GI manometers inexpensive and disposable is to encourage decentralised diagnosis. Being inexpensive increases accessibility by lowering costs, and being disposable further aids public acceptability by removing maintenance costs and minimising difficulty during usage.”

The quipu-inspired sensors might be beneficial in locations where current manometry equipment is unavailable, as well as in more industrialised areas as a less-expensive, easier-to-use alternative to manometry.

“I believe that this type of diagnosis might be widely employed in both developing and developed world settings,” Traverso adds. “The next stage is to find possible partners to assist us in manufacturing them, and then test them in patients.”

Walter Chan, director of the Center for Gastrointestinal Motility at Brigham and Women’s Hospital; Johannes Kuosmanen, an MIT technical associate; Vivian Feig, a postdoc at MIT and Brigham and Women’s; Yiyue Luo, an MIT graduate student; Shriya Srinivasan, a postdoc at MIT and Brigham and Women’s; Christina Patterson, an MIT undergraduate; and Ahmad Mujtaba Jebran

The MIT Department of Mechanical Engineering financed the study.

There is no clear evidence that modern life’s stress or a steady diet of fast food causes stomach and small intestine ulcers, but they are still common in our society: one out of every ten Americans will experience the burning, gnawing abdominal pain of a peptic (or gastric) ulcer at some point in their lives.

Peptic ulcers are holes or cracks in the protective lining of the duodenum (the upper section of the small intestine) or the stomach, which are in touch with stomach acids and enzymes. Duodenal ulcers occur more frequently than stomach ulcers.

Esophageal ulcers are very uncommon, forming in the oesophagus (or swallowing tube) as a result of pharmaceutical exposure, such as some antibiotics or anti-inflammatories, or alcohol addiction.

Until the mid-1980s, conventional thinking held that ulcers were caused by stress, a hereditary proclivity for increased stomach acid output, and bad living practises (including overindulging in rich and fatty foods, alcohol, caffeine, and tobacco). It was thought that such impacts lead to the accumulation of stomach acids, which destroy the protective lining of the stomach, duodenum, or oesophagus.

While increased stomach acid output undoubtedly contributes to the formation of ulcers, a relatively new viewpoint contends that bacterial infection is the major cause of peptic ulcers. Indeed, studies undertaken since the mid-1980s have revealed that the bacterium Helicobacter pylori (H. pylori) is present in more than 90% of duodenal ulcers and around 80% of stomach ulcers. However, new data show that such numbers are dropping.

Other variables appear to contribute to ulcer development, particularly in people infected with H. pylori:

• Overuse of over-the-counter painkillers (such as aspirin, ibuprofen, and naproxen)
• Heavy alcohol use
• Psychological stress
• Smoking

Other research indicates that stomach ulcers are more common in elderly persons. This might be due to:

• Arthritic is common among the elderly, and relieving arthritis pain may include taking aspirin or ibuprofen on a regular basis.
• The pylorus (the valve between the stomach and the duodenum) relaxes with age, allowing excess bile (a chemical generated in the liver to promote digestion) to leak into the stomach and erode the stomach lining.

People with type A blood are also more prone to develop malignant stomach ulcers for unknown reasons.

Duodenal ulcers are more common in patients with type O blood, presumably because they lack the material on the surface of blood cells that protects the duodenal lining.

DIAGNOSTICS

If your doctor suspects you have a peptic ulcer, they will most likely begin with a physical exam and certain tests:

• They’ll feel your stomach and ask whether you’ve had any soreness, pain, or bloating. They may use a stethoscope to listen for any noises coming from your stomach.
• The next step will be to conduct tests to search for H. pylori bacteria. For these, your doctor may collect blood, stool, or breath samples from you.
• In certain situations, especially if you’re older and your symptoms include weight loss or loss of appetite, they may use a long, flexible tube called an endoscope to examine your neck and stomach for indications of an ulcer. (You will be given sleeping medication.) A tiny sample of tissue from an ulcer can also be taken with an endoscope and examined in a laboratory.
• Before taking X-rays of your stomach, they may ask you to consume a milky liquid called barium. This drink covers your digestive tract, making issues like ulcers more visible.

TREATMENT

If you have a peptic ulcer, your doctor will propose a treatment strategy based on the source of the problem:

• The most frequent treatment is a combination of antibiotics to kill the H. pylori bacteria and medicines to reduce stomach acid. Proton pump inhibitors (such as Aciphex or Nexium) and antibiotics are common examples. PPIs will be prescribed to you for several weeks.
• You must stop taking over-the-counter pain relievers if they are the cause of your ulcer.
• They may also provide a protectant, which encapsulates ulcers to protect them from stomach acid.

Lifestyle changes can help, too. You might need to:

• Quit smoking.
• Drink less alcohol or caffeine.
• Stay away from foods that make your symptoms worse.

After treatment, your doctor may want to keep a close eye on you, depending on:

• The size of your ulcer and where it was
• How well the treatment worked
• If you had any other problems

If left untreated, an ulcer can lead to significant complications such as gastrointestinal haemorrhage. Untreated ulcers can potentially cause a hole in your stomach, which may require surgery to repair.

Complex interplay: the gut-immune-brain axis

The early development of the gut, the brain and the immune system are closely interrelated. Researchers refer to this as the gut-immune-brain axis. Bacteria in the gut cooperate with the immune system, which in turn monitors gut microbes and develops appropriate responses to them. In addition, the gut is in contact with the brain via the vagus nerve as well as via the immune system. “We investigated the role this axis plays in the brain development of extreme preterm infants,” says the first author of the study, David Seki. “The microorganisms of the gut microbiome — which is a vital collection of hundreds of species of bacteria, fungi, viruses and other microbes — are in equilibrium in healthy people. However, especially in premature babies, whose immune system and microbiome have not been able to develop fully, shifts are quite likely to occur. These shifts may result in negative effects on the brain,” explains the microbiologist and immunologist.

Patterns in the microbiome provide clues to brain damage

“In fact, we have been able to identify certain patterns in the microbiome and immune response that are clearly linked to the progression and severity of brain injury,” adds David Berry, microbiologist and head of the research group at the Centre for Microbiology and Environmental Systems Science (CMESS) at the University of Vienna as well as Operational Director of the Joint Microbiome Facility of the Medical University of Vienna and University of Vienna. “Crucially, such patterns often show up prior to changes in the brain. This suggests a critical time window during which brain damage of extremely premature infants may be prevented from worsening or even avoided.”

Comprehensive study of the development of extremely premature infants

Starting points for the development of appropriate therapies are provided by the biomarkers that the interdisciplinary team was able to identify. “Our data show that excessive growth of the bacterium Klebsiella and the associated elevated ??-T-cell levels can apparently exacerbate brain damage,” explains Lukas Wisgrill, Neonatologist from the Division of Neonatology, Pediatric Intensive Care Medicine and Neuropediatrics at the Department of Pediatric and Adolescent Medicine at the Medical University of Vienna. “We were able to track down these patterns because, for a very specific group of newborns, for the first time we explored in detail how the gut microbiome, the immune system and the brain develop and how they interact in this process,” he adds. The study monitored a total of 60 premature infants, born before 28 weeks gestation and weighing less than 1 kilogram, for several weeks or even months. Using state-of-the-art methods — the team examined the microbiome using 16S rRNA gene sequencing, among other methods — the researchers analysed blood and stool samples, brain wave recordings (e.g. aEEG) and MRI images of the infants’ brains.

Research continues with two studies

The study, which is an inter-university clusterproject under the joint leadership by Angelika Berger (Medical University of Vienna) and David Berry (University of Vienna), is the starting point for a research project that will investigate the microbiome and its significance for the neurological development of prematurely born children even more thoroughly. In addition, the researchers will continue to follow the children of the initial study. “How the children’s motoric and cognitive skills develop only becomes apparent over several years,” explains Angelika Berger. “We aim to understand how this very early development of the gut-immune-brain axis plays out in the long term. ” The most important cooperation partners for the project are already on board: “The children’s parents have supported us in the study with great interest and openness,” says David Seki. “Ultimately, this is the only reason we were able to gain these important insights. We are very grateful for that.”

Source: University of Vienna