“Two Guys Talking $#it” is a podcast where two Gastroenterologists break down complex topics into engaging, educational, and occasionally humorous conversations. From liver health to gut microbiota and everything in between, A/Professor Jonathan Segal and Dr James Haridy deliver insights, share the latest research, and discuss clinical pearls with the odd guest in tow.
Comments, suggestions, questions please contact us on twitter @2guystalkingit or leave a comment below..
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#14: Professor Nick Talley: Dyspepsia, Duodenums and the Trouble With "Functional"
Season 2 · Episode 2
Sunday, August 9, 2026 • Duration 49:04
Professor Nick Talley has spent 35 years building the field of neurogastroenterology, and he'd like us all to stop saying "functional". He is one of the global top medical researchers, a distinguished Australian gastroenterologist, and educator known for his seminal work on neurogastrointestinal disorders and co-authoring classic clinical examination textbooks.
His argument is that the label sends patients and doctors looking in the wrong place. A lot of these people don't have a brain problem, they have a duodenal one, and he makes the case for a term he prefers: neurogastrointestinal disorder. From there he takes us through the pathophysiology his group has spent years building, subtle duodenal eosinophilia that ordinary pathologists aren't counting, an abnormal duodenal microbiome, and food antigens setting off an immune response that eventually becomes self-sustaining.
Then the practical stuff. Why he biopsies the duodenum, why he reaches for antihistamine blockade, why amitriptyline and not nortriptyline, when mirtazapine is the right call, and what he does when everything has failed. Plus when a gastric emptying study actually changes anything, why lactulose breath tests are not helpful, his approach to cyclic vomiting, and a reminder that rumination is not vomiting.
30:02 Gastric emptying, gastroparesis, G-POEM and rumination
33:50 Cyclic vomiting syndrome
36:39 Why amitriptyline and not nortriptyline
37:51 Breath testing: what's useful and what's worthless
40:39 What Nick is excited about in the next five years
44:11 A weird and wonderful therapy for IBS
46:27 A career in academic medicine
50:42 Why pharma abandoned DGBI
52:16 Wrap-up
#13: Jon and James - GLP-1s: From Lizard spit to liver fibrosis
Season 2 · Episode 1
Friday, June 12, 2026 • Duration 41:58
We're back for Season 2, and Jon and James kick things off with one of their favourite topics: Incretin mimetics. The gut is the biggest endocrine organ in the body, and the data in steatotic liver disease is now as good as anything we have in Hepatology for steatotic liver disease.
James and Jon cover the basic pharmacology, how to start and titrate these drugs in practice, what to tell patients about stopping them, the muscle loss question, endoscopy and anaesthesia, and a brief look at where the evidence is going across cardiovascular disease, kidney disease, sleep apnoea, IBD, and cancer. There is a lot going on with these drugs and this episode is the primer.
As always comments, questions, feedback and suggestions please send to:
03:00 What are incretins? The gut as endocrine organ
06:30 Origin story: Gila Monster and the GLP-1 breakthrough 08:30 The drugs: semaglutide, tirzepatide, and what's coming 10:00 How they actually work: satiety, the brain, and fat oxidation
12:00 Who to start: patient selection and caution groups
13:30 Lean MASH and Southeast Asian BMI thresholds
16:00 Exercise, muscle loss, and the resistance training argument
18:30 Side effects: nausea, constipation, lipase, mood
21:00 Endoscopy and anaesthesia: what to do
24:00 Titrating in practice: James's approach
28:00 Stopping the drug: weight regain and the SURMOUNT data
33:00 Personalising treatment: who can stop, who shouldn't 35:00 Eating disorders, body image, and screening
Papers discussed
#12: Season 2 Trailer
Monday, June 8, 2026 • Duration 02:12
We're back. After a longer-than-planned hiatus involving life, work, and the general chaos of being two busy clinicians: Two Guys Talking $#it is returning for Season 2.
The spark? Jon got stopped in a hospital corridor by a non-gastro colleague who'd been listening to the IBS episode with Alex Ford and had shared it with her neighbour. Turns out the show has fans in unexpected places, and that was enough to get us back in front of a microphone.
Season 2 kicks off with one episode a month and a lineup that already has a few things in the works. Same format, same vibe, no Backstreet Boys cover. Glad to have you back.
As always comments, questions, feedback and suggestions please send to: X: @2guystalkingit Email: 2guystalkingit@gmail.com
#11: A/Prof Elliot Tapper - Liver legends, lies and lactulose
Season 1 · Episode 11
Tuesday, July 29, 2025 • Duration 56:57
Today we had the privilege of talking to a true superstar in the world of Hepatology.
Elliot B. Tapper MD is an Associate Professor in the Division of Gastroenterology and Hepatology at the University of Michigan. He is Academic Chief of Hepatology. His primary goal is to empower patients to enjoy a high quality of life. He is an expert in the management of chronic liver disease, performance of clinical trials, and big data for the study of liver disease. He has developed strategies that reduce symptoms and improve quality of life and invented tools that have helped keep patients with cirrhosis at home and away from the hospital. He is the Editor-in-Chief of Hepatology Communications.
In this episode, A/Prof Tapper discusses his journey in hepatology, the impact of social media on medical education, and his innovative research on muscle cramps and pickle juice. He debunks common myths surrounding methotrexate and liver disease, explores the complexities of ammonia levels in hepatic encephalopathy, and shares insights on frailty in liver disease management. The conversation also touches on the evolving perspectives on antibiotic prophylaxis in cirrhosis and the critical importance of diagnostic paracentesis. Elliot emphasizes the positive aspects of hepatology and the exciting developments in the field.
As always comments, questions and feedback please send to: X: @2guystalkingit
08:14 The Power of Social Media in Medical Education
11:10 The Fascination with Pickle Juice and Muscle Cramps
#10: A/Prof Gianluca Ianiro and Dr Benjamin Mullish - The gut microbiome in health and disease
Season 1 · Episode 10
Wednesday, July 9, 2025 • Duration 01:03:20
Today we’re talking bugs, bowels, and breakthroughs with A/Prof Gianluca Ianiro and Dr. Ben Mullish, two microbiome maestros who make poo science strangely fascinating.
A/Prof Gianluca Ianiro is an Associate Professor of Gastroenterology at the Università Cattolica del Sacro Cuore in Rome and a Consultant at the Gastroenterology Unit of the Fondazione Policlinico Universitario Agostino Gemelli IRCCS. His clinical and research interests center on the gut microbiota, with a particular emphasis on fecal microbiota transplantation (FMT) and its applications in gastrointestinal disorders such as Clostridioides difficile infection and irritable bowel syndrome. Recognized as a leading expert in his field, Professor Ianiro has contributed extensively to international consensus guidelines and has been acknowledged for his work with the United European Gastroenterology Rising Star award. He also leads the Microbiome Clinic at Gemelli, translating cutting-edge microbiome research into clinical practice.
Dr. Benjamin Mullish is a Senior Clinical Research Fellow in the Division of Digestive Diseases at Imperial College London and an Honorary Consultant in Hepatology and Gastroenterology at St Mary’s Hospital, part of the Imperial College Healthcare NHS Trust. He is also an IPPRF Research Fellow within the Department of Metabolism, Digestion and Reproduction at Imperial College. His research focuses on the gut microbiome and faecal microbiota transplantation (FMT), particularly in the context of liver disease and gastrointestinal infections.This conversation delves into the complexities of the microbiome, particularly the gut microbiome, and its significant role in health and disease.
We discuss the dynamic nature of the microbiome, the challenges in microbiome research, and the potential for microbiome-based therapeutics. They also explore the roles of prebiotics and probiotics, the future of microbiome diagnostics, and the potential future concept for specialised microbiome clinicians to bridge the gap between research and clinical practice.
#09: A/Professor Emma Halmos & Dr CK Yao - Food is Medicine.. or is it?
Season 1 · Episode 9
Thursday, June 5, 2025 • Duration 56:18
Today we welcome two world-leading dietitians to talk all things diet in IBD and IBS....
A/Prof Emma Halmos is a senior research dietitian at Monash University and the Alfred Hospital. Her scientific achievements have had a major impact in clinical practice nationally and internationally. The most notable was the pivotal feeding study that demonstrated the low FODMAP diet was efficacious in patients with IBS. A/Prof Halmos has been elected onto the D-ECCO (Dietitians of European Crohn’s and Colitis Organisation) committee and is a leading coordinator for the first ECCO guidelines on nutrition in IBD. Her current role at Monash University is leading research on novel dietary therapy to treat IBD and IBS.
Dr CK Yao is a senior research dietitian at Monash University and the Alfred Hospital, and recent NHMRC emerging leader. In 2017, CK completed her PhD investigating dietary manipulation of gut microbial function and the application of gaseous biomarkers in patients with functional and inflammatory bowel disease. Dr Yao currently leads a research programme looking at optimising dietary strategies for patients with ulcerative colitis and those with an ileoanal pouch.We discuss the critical role of diet in managing inflammatory bowel disease (IBD), particularly Crohn's disease and ulcerative colitis.
We explore various dietary patterns, the impact of emulsifiers and ultra-processed foods, and the importance of personalized dietary advice. We talk about the significance of dietitians in guiding patients towards healthier choices. This conversation delves into the complexities of dietary recommendations for various gastrointestinal conditions, particularly focusing on the Mediterranean diet, Crohn's disease, and IBS. We discuss cultural influences on diet, the importance of personalized nutrition, and the emerging trends in dietary therapy. Finally we touch on the new ECCO Diet in IBD guideline that is set to be published soon.
#08: Professor Gideon Hirschfield - The Art and Science of PSC and Autoimmune Hepatitis
Season 1 · Episode 8
Monday, April 28, 2025 • Duration 01:06:21
Summary
Dr Gideon Hirschfield is a leading expert in autoimmune liver diseases, including PSC, PBC, and autoimmune hepatitis. He’s helped shape how these conditions are understood and managed around the world, combining cutting-edge research with a real passion for patient care.
Today he discusses his work with autoimmune liver diseases, particularly primary sclerosing cholangitis (PSC) and autoimmune hepatitis. We discuss some key topics in PSC (including use of Ursodeoxycholic acid, cancer surveillance as well as the PSC/IBD phenotype), and Professor Hirschfield gives us a masterclass in the management of autoimmune hepatitis. He also offers advice for new hepatologists, highlighting the significance of clear diagnoses, individualized patient management, and clinical trials to drive us into the future.
As always comments, questions and feedback please send to: X: @2guystalkingit
06:15 Introduction to Professor Hirschfield and Autoimmune Liver Diseases
07:41 The Role of Ursodeoxycholic Acid in PSC Management
19:06 Understanding the Pathophysiology of PSC
22:43 Cancer Surveillance in PSC Patients
28:39 The Relationship Between PSC and Inflammatory Bowel Disease
32:30 Vancomycin and PSC
36:28 Management Strategies for PSC and IBD Patients including Pouches
#07: Dr Simon Gabe - Rebuilding the gut: Intestinal rehabilitation
Season 1 · Episode 7
Monday, April 7, 2025 • Duration 01:03:27
This is a really special episode with an incredible doctor (Jon says "the best clinician I have ever met").
Today we welcome Dr Simon Gabe, an internationally renowned expert in intestinal rehabilitation. Dr Simon Gabe is a consultant in gastroenterology & intestinal rehabilitation at St Mark’s Hospital and chair of the NHS National Reference Centre for Severe Intestinal Failure at St Mark’s. This is also an Integrated Care centre for intestinal failure and a recognised ESPEN Training Centre. He has a wide clinical experience in dealing with complex nutritional problems, inflammatory bowel disease, fistula management, intestinal failure requiring enteral or parenteral support, home parenteral nutrition and consideration of intestinal transplantation. Dr Gabe is a past President of BAPEN. He co-founded the National Adult Small Intestinal Transplant (NASIT) Forum in the UK and has been an active member of a Clinical Reference Group within NHS England responsible for the development of a clinical network in England for all patients with Intestinal Failure (HIFNET). He currently co-chairs the HPN Clinical Advice and Management Group for NHS England.
As always comments, questions and feedback please send to: X: @2guystalkingit
30:37 Patient Evaluation Process for Intestinal Failure
#06: ECCO Takeaways with Dr Beatriz Gros
Season 1 · Episode 6
Sunday, March 23, 2025 • Duration 01:04:03
Jon and James welcome Dr Beatriz Gros, a leading expert in inflammatory bowel disease (IBD). They discuss key findings from the recent European Crohn's and Colitis Conference in 2025.
Dr. Beatriz Gros (X: @bealoquebea Instagram: @dr.beatrizgros) is a consultant gastroenterologist based in Córdoba, Spain, specializing in inflammatory bowel disease (IBD). She serves as a Consultant Gastroenterologist at Reina Sofía University Hospital in Córdoba and has also worked as a Senior Clinical Fellow at the Western General Hospital in Edinburgh, UK. Dr. Gros has a particular interest in environmental factors associated with the development of IBD and predictors for disease flares, contributing to studies like the PREdiCCt study. She actively engages in medical education through social media platforms such as Instagram and Twitter, and is the creator of the educational website www.ibd-eii.com, which offers summaries of over 140 clinical trials and relevant IBD studies. Dr. Gros’ dedication to advancing IBD research and education has made her a respected figure in the gastroenterology community.
As always comments, questions and feedback please send to:
08:10 Systemic antibody response predicting onset of IBD
13:12 Predicting Disease Onset and Flare Factors
13:45 The PREDICT Study and Its Implications
#05: A/Professor Jason Tye-Din - Coeliac Disease unpacked: Diagnosis, treatment and emerging approaches
Season 1 · Episode 5
Saturday, February 8, 2025 • Duration 57:33
We very excited about the episode today!
We are joined by A/Professor Jason Tye-Din - a leading expert in coeliac disease and immune-mediated gut disorders. He is Coeliac labratory head at the Walter and Eliza Hall Institute of Medical Research, a Mathison Centenary Fellow at the University of Melbourne, and consultant Gastroenterologist at the Royal Melbourne Hospital. His work focuses on the immunology of coeliac disease, novel diagnostic approaches, and developing non-dietary treatments. He is also one of the smartest (and nicest) clinicians that we have had the privilege of working with.
Joining Jason on the podcast today is Dr Cynthia Kanagasundaram. Cynthia is a UK trained Consultant Gastroenterologist with a vast experience in all things gastroenterology. She prides herself on innovation and has developed a novel GUT HUT service which slashed waiting times and improved patient care. She is embarking on a new stage of her career exploring novel diagnostics, techniques and treatments in Coeliac disease in the Tye-Din lab at the WEHI with A/Prof Jason Tye-Din as her supervisor.
Today we delve into the complexities of coeliac disease. We cover the diagnosis, dietary management, refractory celiac disease, models of care and future of coeliac.
The International Celiac Disease Symposium (ICDS 2026) will be held in Melbourne Australia 17-20 November 2026. Details at https://www.icds2026.org
Chapters
00:20 Introduction with Jon and James
04:42 Introduction to A/Prof Tye-Din and Dr Kanagasundaram
06:42 Understanding Coeliac Disease: Diagnosis and Patient Education
09:17 Dietary Considerations: Foods to Avoid and Oats Discussion
12:44 Biopsy Guidelines and Diagnostic Approaches
37:00 MASH data: ESSENCE and Synergy-NASH trials
39:30 Oral formulations: what's available and caveats
40:30 Where bariatric surgery still fits
42:00 Broader indications: IBD, CVD, CKD, cancer
45:00 Global obesity trends and the public health message 47:00 Wrap-up
15:02 The Impact of Emulsifiers and Ultra-Processed Foods
18:07 Practical Dietary Advice for Patients in IBD
21:02 Cultural Considerations in Dietary Recommendations
23:57 Food as Medicine: A Discussion
27:03 Exploring Diverse Dietary Patterns
30:13 Conclusion and Future Directions
32:26 Cultural Influences on Diet and Health
34:40 Dietary Recommendations for active Crohn's Disease
37:22 Understanding Pouch Patients
38:11 Initial Assessment for IBS Patients
44:25 Screening for ARFID
48:03 Emerging Dietary Trends in IBS
51:40 New Guidelines in IBD Nutrition
Papers discussed
Fitzpatrick JA, Gibson PR, Taylor KM, Anderson EJ, Friedman AB, Ardalan ZS, Smith RL, Halmos EP. Clinical Trial: The Effects of Emulsifiers in the Food Supply on Disease Activity in Crohn's Disease: An Exploratory Double-Blinded Randomised Feeding Trial. Aliment Pharmacol Ther. 2025 Apr;61(8):1276-1289. https://pubmed.ncbi.nlm.nih.gov/39967287/
Fitzpatrick JA, Gibson PR, Taylor KM, Halmos EP. Development of Novel High and Low Emulsifier Diets Based upon Emulsifier Distribution in the Australian Food Supply for Intervention Studies in Crohn's Disease. Nutrients. 2024 Jun 18;16(12):1922. . https://pubmed.ncbi.nlm.nih.gov/38931276/
Halmos EP, Gibson PR. Controversies and reality of the FODMAP diet for patients with irritable bowel syndrome. J Gastroenterol Hepatol. 2019 Jul;34(7):1134-1142. https://pubmed.ncbi.nlm.nih.gov/30945376/
Clinical and Immunologic Features of Ultra-Short Celiac Disease. (Link)
A prospective, double-blind, placebo-controlled trial to establish a safe gluten threshold for patients with celiac disease.(Link)
Diagnostic outcomes after gluten challenge in adult patients with unconfirmed coeliac disease already on a gluten-free diet: A 20-year retrospective cohort study.(Link)
AGA Clinical Practice Update on Management of Refractory Celiac Disease: Expert Review. (Link)
Open-Capsule Budesonide for Refractory Celiac Disease. (Link)
Budesonide Induces Favourable Histologic and Symptomatic Recovery in Patients with Non-responsive and Refractory Coeliac Disease When Given in an Open Capsule Format. (Link)
Stool Gluten Peptide Detection Is Superior to Urinary Analysis, Coeliac Serology, Dietary Adherence Scores and Symptoms in the Detection of Intermittent Gluten Exposure in Coeliac Disease: A Randomised, Placebo-Controlled, Low-Dose Gluten Challenge Study. https://doi.org/10.3390/nu16020279
Impaired IgM Memory B Cell Function Is Common in Coeliac Disease but Conjugate Pneumococcal Vaccination Induces Robust Protective Immunity. (Link)
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