Ten years of Aora Health

Dr. Drewes opened the key-note session by showing how complex pancreatic digestion is, from the vagal reflex to secretin, cholecystokinin and enzyme activation in the duodenum, and why so much can go wrong. His central message: pancreatic exocrine insufficiency is far more common than clinicians think, and most of it occurs in people without a primary pancreatic disease.

• PEI is often overlooked after surgery. He cited rates of up to 100% after Billroth II and bariatric surgery, and an estimated 25–50% even after laparoscopic gallbladder removal.
• Many other conditions carry PEI, including critical illness, heart failure, kidney disease, IBD and diabetes. He described this as perhaps the biggest awareness gap in gastroenterology.
• There is no perfect test. Fecal elastase is the most practical option, but it and the breath test both have pitfalls, so diagnosis often relies on clinical judgement and the response to treatment.
• Adherence matters. Older studies suggest only about half of patients take their enzymes, although a recent cohort of more than 2,000 patients found about 70% did. His rule: “when in doubt, prescribe it out”, then follow the patient.

Dr. Domínguez-Muñoz explained why diabetes and ageing are two of the hottest topics in PEI. The exocrine and endocrine pancreas work as one organ, and both diabetes and ageing are linked to pancreatic atrophy and reduced secretion of enzymes and bicarbonate. With the diabetic and elderly populations growing worldwide, the number of people potentially affected is huge.

• Pancreatic secretion is often reduced in type 1 and type 2 diabetes and in older adults, but low secretion is not the same as clinically relevant PEI.
• In his view, only patients with symptoms of maldigestion and/or nutritional deficiencies should be screened. Factors such as long-standing diabetes with microvascular complications or poor glycaemic control make PEI more likely.
• Fecal elastase is sensitive but not specific (94% and 69% in his group's meta-analysis). A normal result practically rules PEI out, but in low-prevalence groups most low results are false positives. When the diagnosis is unclear, the response to a trial of enzyme therapy can support it.
• When PEI is confirmed, treatment is mandatory: nutritional support plus PERT, typically 40,000–50,000 lipase units with main meals and half with snacks.

Dr. Singh reviewed the physiology of fat digestion, including the often-forgotten roles of intraluminal pH, bile salts and gastric lipase. He then walked through five real cases from his own clinic, with the audience weighing in on each answer.

• Check the diagnosis first. Disorders of gut-brain interaction are far more prevalent than chronic pancreatitis, and a low fecal elastase can mislead.
• Gastric lipase can compensate for a failing pancreas for a long time, so some patients with PEI on paper may not need PERT.
• Underdosing and overdosing both happen. US and European recommendations converge on 40,000–50,000 lipase units per meal (half for snacks). In non-CF studies, raising the dose often did not improve fat absorption further.
• Look for confounders such as short gut, bacterial overgrowth, motility disorders, diet, alcohol and cost-related non-adherence. In one patient with short gut and an intact pancreas, stopping PERT and using a structured-lipid medical food was followed by a 25 lb weight gain over two months.

Moderated by Dr. Löhr, the round table took questions from the audience, sent by QR code and from the floor, on everyday PERT practice and on what is coming next for PEI.

• Asked whether long-term pancreatic enzyme therapy suppresses the pancreas's own secretion or causes dependence, Dr. Drewes answered no. Dr. Domínguez-Muñoz cited an earlier study by his group, using direct pancreatic function testing, that found no effect.
• PEI and diabetes both predispose to SIBO. Dr. Domínguez-Muñoz considers it when the response to PERT is poor, often treating empirically when the picture fits and using a breath test when unsure.
• Dr. Singh sees symptom improvement as the most practical marker of response. Dr. Domínguez-Muñoz partly disagreed: in a European registry of more than 1,000 PEI patients, low protein was the most frequent nutritional problem, and he stressed sarcopenia and body measurements.
• The panel debated how much the extent of surgery matters. Dr. Singh noted most patients after distal pancreatectomy do not develop PEI symptoms, while Dr. Drewes argued that abdominal surgery itself can cause PEI. Dr. Domínguez-Muñoz said pregnancy is not a contraindication to PERT and that no study has shown a risk.
• Looking ahead: a better diagnostic test (an NIH-funded study of a malabsorption blood test is about to begin in the US), finding out whether patients with non-pancreatic conditions benefit from PERT, and alternatives to porcine enzymes given current shortages. There are still no head-to-head trials of porcine and microbial enzymes.

Dr. Prados and Dr. Faghih, moderated by Dr. Ana López (Aora Health), discussed disorders of gut-brain interaction (DGBI), for which around 40% of adults worldwide meet the criteria. They worked through a clinical case: a 38-year-old woman with bloating, distension and constipation.

• The move from “functional disorders” to DGBI reflects a biological model of motility, visceral hypersensitivity and sensory pathways, and tells patients their symptoms are real. There is still no validated biomarker.
• For the case, both favoured a positive diagnosis rather than endless testing, while looking for triggers such as stress or a previous infection. Dr. Faghih noted DGBI is more common than early chronic pancreatitis; alarm features would prompt further work-up.
• Bloating and visible distension are different, and the amount of gas does not match how bloated patients feel. In some patients abdomino-phrenic dyssynergia drives distension; in a randomised trial, biofeedback significantly reduced it.
• Dr. Prados called the gut microbiome a key player that is not yet ready for routine clinical use. Dr. Faghih noted that human studies show association rather than causality.
• Symptoms, diet and the nervous system should be treated together. Both saw multidisciplinary care with nutrition and psychology support as essential, but hard to access and fund. Better biomarkers and education for doctors and patients are the main needs ahead.

Dr. Rosendahl reviewed the evidence for non-porcine (fungal and microbial) enzymes. The European guideline recommends pancreatin as first-line treatment because that is where the clinical evidence lies, and non-porcine products cannot be recommended until trials are done.

• Non-porcine enzymes have much higher enzymatic activity and are acid stable. This could allow digestion to begin in the stomach and fewer lipase units, although how it translates clinically, including dosing, is still open.
• A small, old dog study and a dynamic digestion model (TIM) suggested results similar to pancreatin. The few small human studies slightly favoured porcine products, though he judged the differences unlikely to be clinically relevant.
• Possible advantages include a broad enzyme spectrum, independence from animal breeding and perhaps a lower environmental impact. Limitations include degradation by proteases and inactivation by bile salts.
• New clinical trials are needed, including one in Leipzig after gastrectomy. He also raised the possibility that combining porcine and non-porcine products might reduce pill burden in some patients.

Dr. Drewes returned to present the design of a new randomised non-inferiority trial comparing Enzymax Forte with pancreatin in patients with chronic pancreatitis and PEI. The trial was just getting under way, with the first patients due to be enrolled the following week, so no results are available yet.

• Rationale: microbial enzymes may offer higher activity, a broader pH range and greater stability. There is also demand for non-porcine options (for religious, dietary and zoonotic-risk reasons) and a worldwide enzyme shortage. He described the existing data as unpublished pilot data.
• Design: 110 patients with confirmed PEI, randomised to pancreatin or Enzymax Forte for 12 weeks. The primary endpoint is the validated PEI-Q questionnaire, with formal validation for India done within the trial. Secondary endpoints cover stool, symptoms, quality of life, pain and sarcopenia.
• The trial runs at centres in Hyderabad, India, where enrolment is expected to take about four months, and is monitored from Denmark. A protocol paper has been submitted, so the analysis is fixed in advance.
• A nested physiological sub-study measuring the coefficient of fat absorption is being considered.

Dr. Villamiel introduced CIAL, the Institute of Food Science Research run jointly by CSIC and the Autonomous University of Madrid. She then presented the newly started joint research line with Aora: encapsulating iron in pectins to address iron-deficiency anaemia.

• CIAL has 17 research groups and six specialised services, including a gastrointestinal digestion simulator she described as unique in Spain.
• Iron supplements face low solubility and bioavailability. Encapsulation can protect iron from oxidation, limit direct contact with the gut lining, improve taste and allow targeted release.
• Published studies point to low-methoxyl pectins, often obtained from agri-food by-products, as promising carriers thanks to their gelling properties and mucoadhesion.
• Next steps are scaling up from the lab, controlling release and confirming results in vivo, supported by an industrial doctorate with the Community of Madrid.