Dr Charlie Andrews talks to Dr James Kinross, PhD, FRCS

Dr. Kinross is a senior lecturer in surgery at Imperial College in London. He is also a practicing colorectal surgeon in the NHS with a clinical interest in the prevention and treatment of colon cancer. He leads a team of amazing researchers working to better define how the microbiome causes cancer and other chronic diseases of the gut. He is increasingly interested in how the gut microbiome develops in newborn babies and the implications on our long-term health. He is the author of the well know book DARK MATTER.

Here are the key learnings for primary care on the microbiome from the attached transcript of the Ingest podcast with James Kinross:

1. What the Microbiome Is and Why It Matters

• Definition: The microbiome is the collection of all microscopic organisms (bacteria, viruses, fungi, etc.) and the environment they inhabit within a specific niche in the body, such as the gut, skin, or lungs.
• Symbiosis: The microbiome has a symbiotic relationship with the host, evolved over millennia. It is not static but dynamic and changes throughout life.
• Personalization: Each person’s microbiome is unique, impacting how individuals respond to treatments and develop diseases[1].

2. Microbiome Development and Early Life

• Early Colonization: The microbiome starts developing in utero, influenced by the mother’s microbiome, and is further shaped by birth route, breastfeeding, and early environmental exposures.
• Critical Window: Early life is a critical period for microbiome development. Disruption, especially through antibiotic use, can have long-term effects on immune system development and disease risk[1].
• Antibiotics Impact: Repeated or broad-spectrum antibiotic use in early life can lead to persistent changes in the microbiome, increasing the risk of immune-mediated diseases (e.g., allergies, asthma, eczema), obesity, and other non-communicable diseases[1].

3. Microbiome and the Immune System

• Immune Regulation: The microbiome plays a crucial role in shaping both the innate and adaptive immune systems. It influences how the body recognizes and responds to threats.
• Disease Risk: Early disruption of the microbiome can increase susceptibility to autoimmune diseases, allergies, and chronic conditions later in life.
• Gene-Environment-Microbiome Interaction: Disease risk is not just about genes and environment but also involves the microbiome (GEM interaction), which is highly personalized and dynamic[1].

4. Probiotics, Prebiotics, and Diet

• Probiotics: There is evidence supporting the use of probiotics, especially multi-strain, high-dose formulations, during and after antibiotic courses. However, probiotics must be taken consistently for weeks to have an effect.
• Prebiotics and Diet: Feeding the microbiome with a high-fiber, plant-based diet is crucial for maintaining a healthy gut ecosystem. Processed foods and sugary drinks should be minimized, especially during illness or antibiotic treatment[1].
• Practical Advice: Clinicians should recommend probiotics and dietary changes as part of a holistic approach to gut health, but the evidence for specific strains is still evolving[1].

5. Microbiome Testing

• Direct-to-Consumer Testing: Online microbiome tests are not currently recommended due to lack of stand...

• (00:00:00) - Ingest: The microbiome
• (00:01:06) - Dark Matter
• (00:03:45) - What exactly is the microbiome?
• (00:06:11) - What is the microbiome?
• (00:08:49) - The role of the microbiome in health
• (00:09:54) - Antimicrobial agents in the gut
• (00:13:20) - Probiotics and antibiotics
• (00:15:37) - How the microbiome affects the immune system
• (00:24:05) - The role of the microbiome in health
• (00:27:04) - Will we measure the microbiome 100%?
• (00:31:02) - Primary care: The microbiome challenge
• (00:32:22) - Probiotics and the future of gut health
• (00:36:02) - The microbiome of the human gut

The episode features Dr. David Bartlett, a retired GP and neuroendocrine cancer patient, offering a dual perspective as both clinician and patient.

Key Learnings from this episode.

Patient Experience and Diagnostic Challenges

• Dr. Bartlett’s symptoms began with severe, intermittent abdominal pain, starting in 2001, but he did not seek medical help for several years due to a combination of stoicism, not wanting to trouble others, and a belief in the commonality of benign causes.
• Over 15 years, he experienced repeated misdiagnoses, primarily being labeled as having irritable bowel syndrome (IBS) despite atypical features (severe pain, minimal bowel habit change, and no systemic symptoms).
• Multiple opinions and investigations (including ultrasounds and CT scans) failed to identify the underlying cause, with a key scan being misread by local radiologists.
• The correct diagnosis of a small bowel neuroendocrine tumour was only made after a tertiary centre re-examined previous scans, highlighting the importance of specialist review and persistence in unexplained cases.

Clinical Red Flags and Symptomatology

• Dr. Bartlett’s case underscores that neuroendocrine tumors can present with isolated, severe abdominal pain without classic red flags (vomiting, weight loss, significant bowel changes)[1].
• He retrospectively identified subtle signs of carcinoid syndrome (flushing, one episode of profound diarrhoea, and skin changes), which are present in only about 10% of small bowel neuroendocrine tumour cases.
• The lack of awareness about neuroendocrine tumors, even among experienced clinicians, contributed to the diagnostic delay[1].

Lessons for Primary Care and Clinicians

• The story illustrates the risk of anchoring on common diagnoses (like IBS) and the need to reconsider the diagnosis when symptoms are severe, persistent, or atypical.
• It highlights the value of listening to the patient’s narrative, especially when symptoms do not fit classic patterns, and the importance of considering rare conditions in the differential diagnosis.
• The episode emphasises the need for ongoing education about neuroendocrine tumours and the importance of keeping rare but serious conditions on the diagnostic radar in primary care.

Management Insights

• Standard treatment for small bowel neuroendocrine tumours often includes monthly somatostatin analog injections (e.g., lanreotide).
• Surgical intervention may be considered, but it carries specific risks such as carcinoid crisis, requiring specialised perioperative management.
• The decision for surgery is individualised, weighing potential symptomatic improvement against procedural risks.

Systemic and Human Factors

• Dr. Bartlett’s experience reflects how personal traits (stoicism, reluctance to seek help) and systemic issues (misinterpretation of scans, diagnostic inertia) can delay diagnosis.
• The narrative also demonstrates the importance of patient advocacy, persistence, and the value of second (or third) opinions, especially in complex or unresolved cases.

Educational Value

• The episode serves as a reminder for clinicians to maintain a broad differential, revisit diagnoses when the clinical picture changes, and to be aware of their own cognitive biases.
• It also advocates for the inclusion of patient voices in medical education to better understand the lived experience and challenges of rare diseases like neuroendocrine cancer.

Summary Table: Key Learnings

• (00:00:10) - Ingest
• (00:02:07) - David Bartlett on neuroendocrine cancer
• (00:05:32) - Irritable bowel syndrome, 15 years after first bout
• (00:12:09) - Carcinoid syndrome in small bowel neuroendocrine tumors
• (00:16:10) - Neuroendocrine tumour, surgery and recovery
• (00:20:43) - Somaostatin analogues for neuroendocrine cancer
• (00:25:43) - The role of the multidisciplinary team in bowel cancer care
• (00:28:21) - The battle with depression in your 50s
• (00:30:00) - General Practice and the Art of Medicine
• (00:33:13) - General Practice: The challenge of slowing down
• (00:35:35) - Neuroendocrine Cancer UK support group
• (00:39:28) - David's story of cancer
• (00:40:38) - David's Neuroendocrine Cancer Episode 1

Dr Charlie Andrews talks to Dr John Leeds. John Leeds is a Consultant Pancreaticobiliary Physician and Endoscopist based at the Freeman Hospital in Newcastle and an Honorary Clinical Senior Lecturer based in the Population Health Sciences Institute at Newcastle University. He is involved in research in pancreaticobiliary disorders including benign and malignant conditions as well as outcomes from therapeutic/advanced endoscopy.

John is a member of the British Society of Gastroenterology and Pancreatic Society of Great Britain and Ireland. He serves on the endoscopy and Pancreas committees for BSG and is the website lead for PSGBI.

He is also a founder member of the BSG Pancreas Clinical Research Group which is coordinating research for the society.

Key Learnings from this episode:

1. Challenges in Early Detection of Pancreatic Cancer • Pancreatic cancer is often diagnosed at an advanced stage due to the deep location of the pancreas and the lack of early symptoms. • Tumors in the body and tail of the pancreas can grow significantly before causing symptoms, often invading major arteries or veins, making them inoperable. • Tumors in the head of the pancreas may present earlier due to bile duct obstruction, leading to jaundice, but even these are often detected late.
2. Early Symptoms and Red Flags • Early symptoms are vague or absent, making early diagnosis difficult. • Possible early indicators include: • Weight loss (often a sign of advanced disease). • New-onset diabetes, particularly in individuals with a normal BMI or without typical risk factors for type 2 diabetes. • Jaundice, which is a significant red flag and often indicates a serious underlying condition. • Classic signs like painless jaundice and Courvoisier’s sign (palpable gallbladder) are important but not always present.
3. Limitations of Current Screening Methods • There is no reliable biomarker or screening test for pancreatic cancer: • CA19-9 is not suitable as a screening tool due to its lack of specificity (elevated in other conditions). • Imaging techniques like CT scans or MRIs are used but have limitations, including incidental findings that may lead to unnecessary anxiety (“scanxiety”) and over-investigation. • Screening is currently limited to high-risk groups, such as those with familial pancreatic cancer syndromes or hereditary pancreatitis.
4. High-Risk Groups for Screening • Familial pancreatic cancer accounts for less than 10% of cases. Criteria for screening include: • Multiple family members with pancreatic cancer, especially diagnosed under age 50–60. • Genetic syndromes like BRCA mutations, familial adenomatous polyposis (FAP), and Peutz-Jeghers syndrome. • Hereditary pancreatitis patients have an increased risk but are harder to screen due to pre-existing pancreatic abnormalities.
5. Emerging Research and Future Directions • Studies are exploring potential biomarkers, such as microbiome signatures in the pancreas, which might help identify high-risk individuals in the future. • Trials like the EuroPAC study focus on surveillance protocols for high-risk individuals using imaging techniques like MRI or endoscopic ultrasound. • Research into new-onset diabetes as a potential marker for pancreatic cancer is ongoing but currently has a low yield due to the high prevalence of type 2 diabetes unrelated to malignancy.
6. Considerations for Screening and Surveillance • Screening should be carefully targeted to avoid over-diagnosis and unnecessary investigations. • The psychological impact of screening (e.g., anxiety from incidental findings) must be considered. • Smoking cessation is emphasized as smoking is a significant risk factor for pancreatic cancer.
7. Advances in Treatment Approaches • PET-CT scans are increasingly used to detect systemic disease that might not be evident on standard CT scans. • Neoadjuvant treatments (therapy before surgery) are being...

• (00:00:00) - Ingest
• (00:00:53) - Pancreatic Cancer
• (00:04:03) - New diabetes and pancreatic cancer
• (00:08:01) - Pancreatic Cancer: Screening
• (00:15:42) - Determining breast cancer early is hard
• (00:16:03) - Pulmonary neuroendocrine tumors of the pancreas
• (00:22:26) - Pancreatic cancer 20, Management
• (00:29:00) - Pancreatic cancer, management principles
• (00:33:48) - Primary Care Take Home: Pancreas, pain
• (00:40:29) - Primary Care: Pancreas Cancer Episode 2