PA Hospital clinician Professor (Prof) Gerald Holtmann is leading the charge in revolutionising gastroenterology, hepatology, and gastrointestinal (GI) endoscopy research and recently secured with his team, a major government grant to continue his work.
His expertise extends beyond patient care, as he spearheads groundbreaking research in liver disease, endoscopy, and luminal gastroenterology, focusing on conditions affecting the GI tract.
“The multidisciplinary research we conduct can be labelled as Neurogastroenterology,” he said.
“This concerns chronic or relapsing abdominal symptoms in patients, resulting in disordered gut function. Emerging evidence suggests that its severity is a consequence of disturbed interaction and communication between the brain and GI tract.”
The announcement of National Health and Medical Research Council funding actually came about due to work that began several years ago when Prof Holtmann and his team recognised that studies concerning the GI microbiome held potential in changing patient treatment pathways and overall outcomes. This work resulted in the successful formation of a microbiome biobank.
“We were inspired by similar research conducted across the globe.
“Beyond simply focusing on the microbes commonly found in the stool, our approach also encompassed investigation and assessment of microbes colonising the GI tract, looking specifically at the small intestine.”
This topical focus on intestinal microbes was of particular interest owing to the relative surface area of the small intestine.
“If we were to flatten out all the surface structures of the small intestine, the resultant surface area would equal that of a cricket field,” Prof Holtmann remarked.
“You can imagine the repercussions should this surface be colonised by bacteria.
“The immune system and cells are in constant interaction with the microbes in the gut. Certain microbes stimulate and suppress immune function while others produce specific metabolites that supports mucosal integrity. Some microbes could even influence brain function,” he added.
“This has implications for the whole body.”
The PA Hospital is credited with being the anchor point for such research, beginning with the formation of the Centre of Research Excellence in Digestive Health. The culmination of a decade’s worth of knowledge have generated novel interventions that has allowed researchers and clinicians like Prof Holtmann and his team to establish available drugs for different implications and leave a positive impact on patient outcomes.
“Our recent government grant (NHMRC Grant) has afforded us the opportunity to further our collection of biologic material in our biobank. Such an expansion informs the teams understanding of specific patient cohorts and drives our research into the modulation of microbes in the small intestine,” he said.
“These can be cultured to find the link between specific symptom types and allows us to test the microbe’s response to specific therapeutic options.”
Prof Holtmann elaborated further, citing two examples where such studies were proven crucial.
Firstly, the medication Simethicone was shown in previous clinical trial to have effects relational to symptom improvement. In fact, this vitally available treatment was found to inhibit specific microbes that contributes towards the colonisation of the gut.
“We were actively trying to prove that non-antibiotic interventions can achieve similar outcomes in patients without the risk of developing a resistance to antibiotics,” he said.
Primary sclerosing cholangitis (PSC), a rare GI disease characterised by inflammation and scarring of the bile ducts, along with other functional GI disorders are highly prevalent. There are currently no proven effective therapy options and usually requires drastic interventions like transplants. However, with the availability of the biobank, prospective randomised trials where specific microbe samples were collected and tested.
“We linked the small intestine microbiome and its responsiveness to antibiotics with a patient’s risk profile.”
For the first time, benchmarked against strict criteria and compared with others, Prof Holtmann and colleagues were voted within the top 150 gastro departments in a regular ranking conducted by the American publication, Newsweek.
“This is good news to hear. I think the whole team is excited that we are now on the list. It really motivates all of us to continue to strive for continued effort and progress,” he said.
“You can appreciate that typically American gastro units feature more prominently in this American journal. To come out in front of thousands of gastroenterology departments across the United States is a great result,.”
Prof. Holtmann expressed his gratitude to the support he received for research from funders, including the PA Foundation who contributed in part to the establishment of the biobank.
“We started to gain completely new insights into many disease mechanisms at the PA Hospital. The work that we do would not have been possible without the support of the Foundation,” he said.
“This is a very exciting time for novel solutions. The public needs to know that we (researchers and clinicians) are at the forefront of breakthrough.”
