Bowel Research UK is a Charitable Incorporated Organisation (CIO) registered in England and Wales (1186061) www.bowelresearchuk.org email: trustfundraising@bowelresearchuk.org Funding Partner Update 2025 With your help, we’re investing in breakthrough research to end bowel cancer and bowel disease Bowel Research UK is funding cutting ‑ edge medical research projects into bowel cancer and serious bowel conditions. Our mission is to save lives and improve quality of life through research that makes a real difference. Your award to our charity has been vital to this mission. By supporting new PhD places and early ‑ career research, your contributions are helping to progress the next generation of experts who will continue to change the field of bowel medicine for years to come. Your grants not only fund the studies themselves but are also helping to leverage further funding. Our ‘proof ‑ of ‑ concept’ grants make it possible for teams to attract next-stage funding and move up towards larger scale studies and development. We make sure that every donation to Bowel Research UK works hard to make the maximum impact. Our Scientific Advisory Committee and Grants Committee, composed of clinicians and academic experts, choose high ‑ risk/high ‑ reward projects in under-funded areas of medical research, ensuring that the work you help to fund is most likely to make a significant improvement to patient care. Bowel Research UK depends on donations and awards from our funding partners to keep our research programmes going. On behalf of all the researchers, patients and families whose lives will be improved by this work, thank you. We are enormously grateful to the Trusts, Foundations and individual donors who make our work possible. We present the following updates on our recent research project which your awards have supported. Let’s end bowel cancer and bowel disease. Bowel Research UK is a Charitable Incorporated Organisation (CIO) registered in England and Wales (1186061) www.bowelresearchuk.org email: trustfundraising@bowelresearchuk.org Research Highlight: How colorectal stem cells and fibroblasts affect cancer growth The Team Professor Simon Bukzaki and PhD student Yi Zhou at the University of Oxford The Research This study is investigating how specific colon cells drive cancer growth and how to stop it. The team is focusing on interactions between epithelial colorectal stem cells (CSCs) and fibroblasts (specialized cells that produce proteins which support tissues in the body). Normally, CSCs divide in a controlled way to maintain healthy tissue, but in cancer they become unregulated and resistant to treatment. Fibroblasts, which send signals to epithelial cells, are linked to faster, harder-to-treat tumours. By studying how these two cell types communicate, the project aims to uncover mechanisms that fuel cancer progression and identify new treatment targets. Using advanced molecular techniques, the team identified specific cell types and proteins involved in these interactions, uncovering potential new drug targets for colon cancer treatment. What’s Next The team plans to develop tools to track and analyse distinct cell types within the colon and to test whether modifying fibroblasts can reduce their harmful influence on bowel tissue. They also plan to explore whether the cancer-promoting effects of fibroblasts continue after being separated from cancer cells and investigate how genetic mutations in cancer cells shape their interactions with fibroblasts. Why It Matters This research could improve our understanding of how colon cancer develops and spreads, revealing new ways to treat it. By targeting the interaction between cancer cells and fibroblasts, the team hopes to develop therapies tailored to individual patients, leading to better outcomes. PhD Student Yi Zhou is investigating the role of certain colorectal cells in bowel cancer growth Bowel Research UK is a Charitable Incorporated Organisation (CIO) registered in England and Wales (1186061) www.bowelresearchuk.org email: trustfundraising@bowelresearchuk.org Research Highlight: How acidic tumour microenvironments affect cancer development The Team Professor Pawel Swietach and the Swietach Group at the University of Oxford The Research This study investigates how colorectal cancer cells adapt to the acidic environments created by their own metabolism. The team is uncovering how certain adaptations enable cancer cells to survive and whether this can be exploited for treatment. Using live colorectal cancer cell samples, researchers identified acid- resistant cells and discovered new enzyme activities linked to their survival. They also found that high acidity can suppress cancer cells’ responses to oxygen deprivation, suggesting acidity plays a larger role in cancer development than previously thought. The research will now explore the broader role of the AKR enzyme, which appears central to cancer cells’ survival under acidic conditions. The team aims to determine whether blocking AKR activity can halt tumour growth. Following this project’s success, they are applying to the Medical Research Council for funding to identify drugs that could form future therapies. Why It Matters Understanding how bowel cancer cells survive in harsh environments opens the door to treatments that disarm their defences while minimising harm to patients. This research could lead to new therapies that weaken tumour survival mechanisms. It may also enhance the effectiveness of treatments such as immunotherapy, which often performs poorly on acidic tumours. Because similar adaptations occur in many solid cancers, these findings could benefit patients beyond those with colorectal cancer. Prof. Swietach is investigating tumour microenvironments affect cancer development “We are excited about the prospects of specifically targeting adapted cancer cells while sparing healthy tissue. This could make cancer treatment more effective with fewer side effects.” - Prof. Pawel Swietach Prof. Pawel Swietach Bowel Research UK is a Charitable Incorporated Organisation (CIO) registered in England and Wales (1186061) www.bowelresearchuk.org email: trustfundraising@bowelresearchuk.org Research Highlight: The DAMASCUS Study – Understanding Diverticulitis Around the World The Team Mr. Dale Vimalachandran at the University of Liverpool The Research Acute diverticulitis, an inflammation of small pouches which can form in the bowel, is affecting more people than ever before. However, the best way to manage this disease remains uncertain. The DAMASCUS Study united clinicians and hospitals from 48 countries in the largest global collaboration ever on acute diverticulitis. The study found major global differences in how diverticulitis is treated. More than 90% of patients with mild disease were given antibiotics even when not recommended. Hospital admission rates varied widely, with some countries managing most patients as outpatients while others admitted nearly all. In lower-income countries, patients were more likely to have emergency surgery without scans, and many who underwent surgery needed a permanent stoma. Death rates were higher in poorer regions, showing that treatment and outcomes differ greatly around the world. Why It Matters Because of the success of the DAMASCUS Study, further research is now underway to analyse longer-term outcomes, helping to understand how early management decisions affect ongoing recovery. The DAMASCUS study evidenced that treatment for diverticulitis differs greatly across the world. Overuse of antibiotics and unnecessary hospital admissions add strain to health systems and carry risks of antibiotic resistance, while surgical practices vary between countries. By exposing these differences, DAMASCUS is helping to improve global care and inspire new research, paving the way for safer and more consistent treatment for patients everywhere. “This project would not have been possible without Bowel Research UK. Their investment in an area of bowel disease that has received little attention has created a long- term legacy that will benefit generations of patients.” - Mr Dale Vimalachandran Lead Investigator – Mr Dale Vimalachandran Bowel Research UK is a Charitable Incorporated Organisation (CIO) registered in England and Wales (1186061) www.bowelresearchuk.org email: trustfundraising@bowelresearchuk.org Research Highlight: Developing New Treatments for Children with Hirschsprung’s Disease The Team Dr Rachel Harwood at the University of Liverpool The Research Each year in the UK, around 170 babies are diagnosed with Hirschsprung’s disease (HSCR). This is a rare condition where nerve cells fail to develop in part of a baby’s bowel, leading to dangerous blockages soon after birth. Currently, the only treatment is surgery to remove a section of bowel. Sadly, many of these children continue to suffer from constipation and infections, and some require a permanent stoma. In 2024, many of our supporters awarded funding towards our Hirschsprung’s appeal. This helped Bowel Research UK to facilitate a new research project into this rare and debilitating disease. Dr Harwood’s team has discovered that, even in the part of the bowel without normal nerves, nerve stem cells are present. These stem cells could, in theory, grow into healthy nerve cells. In the lab, they can grow these into small clusters called neurospheres. The researchers want to understand why these cells do not develop properly inside the body and whether certain medicines can help them grow into the right kinds of nerves. By studying bowel tissue from children with HSCR and comparing it to normal bowel tissue, the team will test how these cells respond to different growth signals— some of which are controlled by drugs already used for other conditions. Why It Matters This work could point towards a completely new way for babies with Hirschsprung’s disease to be treated. Instead of major surgery, future treatments might utilise a child’s own stem cells to repair their bowel. This could help patients avoid lifelong complications and improve their quality of life. These findings could also help us understand how nerves in the gut develop, paving the way for new therapies for different bowel and nerve conditions. Dr Rachel Harwood is researching potential new treatments for Hirschsprung’s Disease Bowel Research UK is a Charitable Incorporated Organisation (CIO) registered in England and Wales (1186061) www.bowelresearchuk.org email: trustfundraising@bowelresearchuk.org The Microbiome Research Project: Our Specialised Grant Round Funds Four New Studies In 2024 Bowel Research UK launched its first grants round dedicated to a specific area of research: the gut microbiome and its impact on human health. The gut microbiome – the community of microscopic organisms in our digestive tract – is increasingly recognised as a powerful influence on health, and yet very little research exists to explore its potential in detecting and preventing disease. We received an encouraging response from partners excited to support our microbiome research. Thanks to this support we were able to give the go-ahead to four research teams with grants totalling over £330,000. The successful grant recipients are summarised here: The Gut Microbiome & Responses to Bowel Cancer Treatment Mr Ahsan Javed, University of Liverpool Understanding how the gut microbiome affects how bowel cancer patients respond to treatment. This work could lead to microbiome-based biomarkers or adjunct therapies to improve patient outcomes. How Bacteria Feed on Dead Cells and Contribute to Gut Wall Damage Dr C.J. Anderson, University of Edinburgh Mapping how gut bacteria consume dead cells in the gut wall and how this may lead to damage or disease. This may provide novel targets for therapy to protect gut wall integrity and prevent progression of bowel disease. Faecal Microbiota Transplant (FMT) Delivered by Capsule for Inflammatory Bowel Disease Dr James Alexander, Imperial College London & St Mark’s Hospital, London Investigating whether encapsulated FMT can help people with IBD to manage symptoms. If successful, this could provide a less invasive, more effective therapy for IBD patients. Analysing the Composition and Processing of FMT and Its Effectiveness Dr Richard Horniblow, University of Birmingham A study into how the material in Faecal Microbiota Transplants changes as it is processed into a medicinal form, and how that impacts its effectiveness. Understanding the mechanism of action of FMT will help standardise and improve treatments. Bowel Research UK is a Charitable Incorporated Organisation (CIO) registered in England and Wales (1186061) www.bowelresearchuk.org email: trustfundraising@bowelresearchuk.org Our Plans for 2026 Funding More Research into Bowel Cancer and Bowel Disease Bowel Research UK’s 2026-2028 strategy is focused on growing our portfolio, making more vital research possible than ever before. We will continue to support areas of research which are less studied or under-represented, responding to the most urgent gaps in current medical research, and ensuring that the learning gained from our work is poised to make the most meaningful difference. Focused Funding Rounds Following the success of the 2024 Microbiome Research Project, in 2026 we will be promoting our other specialised funding priority areas. Funding awarded to each priority area will be restricted to research into that subject. These will include: Bowel Cancer Research Early-Career and PhD studies ‘Hard to Fund’ Research and more. Working for Patient Inclusion We remain committed to involving patients, carers, and the public in the research process, ensuring that their perspectives shape our research agenda. This approach is crucial to improving our research outcomes and ensuring their relevance to real-world treatment and care. Bowel Research UK is a Charitable Incorporated Organisation (CIO) registered in England and Wales (1186061) www.bowelresearchuk.org email: trustfundraising@bowelresearchuk.org We’ve made amazing progress, but there’s still so much more to do Bowel cancer is the UK’s 4 th most common cancer, and the 2 nd most common cause of cancer death. Meanwhile, 500,000 people are living with inflammatory bowel disease, and over 1,000,000 live with other bowel conditions which impact their daily life. We invite you to join us again in our mission to end bowel disease. Each year, we receive more high-quality research proposals than we can fund. A donation to Bowel Research UK will help us to provide staffing, laboratory equipment and resources to sustain a vital research project at one of our funded sites across the UK. We are always happy to discuss the potential for your award to support specific areas of research, or studies in a chosen region of the UK. Thank you once again for your support. If you have any questions about this research or any of our other projects across the UK, please get in touch. Email: trustfundraising@bowelresearchuk.org Phone: 020 3540 8694 Web: www.bowelresearchuk.org DPhil student Matthew Dean is working on new potential treatments for bowel cancer alongside Prof. Pawel Swietach