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.

Keywords: functional dyspepsia, DGBI, neurogastroenterology, duodenal eosinophilia, eosinophilic duodenitis, gastroparesis, Rome V, amitriptyline, microbiome, cyclic vomiting, SIBO, breath testing, Nick Talley

As always comments, questions, feedback and suggestions please send to:

X: @2guystalkingit

Email: [email protected]

00:19 Intro

03:32 Welcome Nick

04:22 What functional dyspepsia is, and why it's probably several diseases

06:48 Rome V, and why "functional" is a terrible word

08:14 How Nick explains the diagnosis to patients

09:00 Workup and first-line treatment: scoping, routine duodenal biopsies, PPIs, tricyclics, antihistamines

13:21 Adding an antihistamine on top of a PPI

13:49 Duodenal eosinophilia: can your pathologist actually see it?

15:43 EoE and functional dyspepsia: separate pathways

17:03 Six-food elimination, biologics, and the budesonide trial

19:28 The duodenal microbiome and swallowed streptococci

22:20 Refractory disease: mirtazapine, SNRIs, quetiapine, hypnotherapy 26:01 Smoking, alcohol, NSAIDs, exercise and diet

29:08 Exclusive enteral nutrition

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

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:

X: @2guystalkingit

Email: [email protected]

00:00 Intro: Season 2 is here

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

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

ESSENCE trial

Synergy-NASH trial

SURMOUNT-MAINTAIN

Tirzepatide and fat oxidation, Cell Metabolism 2025

GLP-1 receptor agonists and 13 obesity-associated cancers

SELECT trial

FLOW trial

SURMOUNT-OSA

STEP 9: Semaglutide in obesity and knee osteoarthritis

Psoriatic Arthritis paper

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: [email protected]

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

Email: [email protected]

Chapters

05:08 Introduction to Elliot and His Work

08:14 The Power of Social Media in Medical Education

11:10 The Fascination with Pickle Juice and Muscle Cramps

14:00 Innovative Research During COVID-19

17:01 Exploring Non-Pharmaceutical Interventions

20:04 Debunking Myths Around Methotrexate and Liver Disease

23:10 Addressing Misconceptions About Medications

25:56 The Impact of AI on Medical Literature

28:56 The Ammonia Debate in Clinical Practice

30:17 Understanding Ammonia as a Clinical Biomarker

37:28 Assessing Frailty in Liver Disease Patients

44:20 Reevaluating SBP Prophylaxis in Cirrhosis

49:03 The Importance of Diagnostic Paracentesis

52:34 The Positive Side of Hepatology

Keywords

Elliot Tapper, hepatology, liver disease, medical education, social media, muscle cramps, methotrexate, ammonia levels, frailty, antibiotic prophylaxis, diagnostic paracentesis

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.

As always comments, questions and feedback please send to: X: @2guystalkingit

Email: [email protected]

Chapters

00:20 J + J Introduction

05:11 Introduction to the Microbiome  

07:16 Understanding the Gut Microbiome  

10:04 The Dynamic Nature of the Microbiome  

13:21 Factors Influencing the Gut Microbiome  

16:15 Clinical Relevance of Stool Microbiome  

19:24 Microbiome and Disease: Cancer and Liver Health  

22:12 Microbiome in Inflammatory Bowel Disease (IBD) and Metabolism  

25:20 Future Directions in Microbiome Research  

35:20 The Uncertainty of Microbial Therapeutics  

37:10 The Future of Microbiome Research  

42:41 Understanding Prebiotics and Probiotics  

56:49 The Need for Microbiome Clinician specialists

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.

As always comments, questions and feedback please send to: X: @2guystalkingit

Email: [email protected]

Chapters

00:00 Introduction with J & J

4:20 On to our guests... Diet and IBD

05:50 Dietary Patterns for Disease Prevention

08:53 Therapeutic Diets and Active IBD

11:58 Controversies in Dietary Recommendations

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/

A FODMAP Gentle approach: https://www.monashfodmap.com/blog/gentle-fodmap-diet/

The SCOFF Questionnaire: https://ceed.org.au/wp-content/uploads/2024/05/SCOFF.pdf

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

Email: [email protected]

Chapters

00:30 J & J Introduction

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

40:00 Management of Autoimmune Hepatitis: An Art and Science

56:30 Proactive Approaches in Primary Biliary Cholangitis (PBC) Management

1:01:05 Advice for Aspiring Hepatologists

Keywords

Hepatology, Autoimmune Liver Disease, PSC, Ursodeoxycholic Acid, Cancer Surveillance, Inflammatory Bowel Disease, Clinical Trials, Patient Care, Liver Transplantation, PSC Management, pouch studies, autoimmune hepatitis, management, PBC, hepatology, patient choices, liver transplant, treatment options, chronic diseases, clinical trials

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 

Email: [email protected]

Chapters

04:15 Introduction to Simon Gabe  

06:59 Understanding Intestinal Rehabilitation  

09:56 Defining Intestinal Failure  

13:29 Trends in Intestinal Failure Causes  

16:23 Bowel Length and Nutritional Support  

20:26 Managing Short Bowel Syndrome  

26:06 Barriers to Recognizing Intestinal Failure  

30:37 Patient Evaluation Process for Intestinal Failure  

33:07 Empowering Patients in Line Management  

36:21 Managing Line Sepsis: Best Practices  

43:17 Understanding Ehlers-Danlos Syndrome (EDS) and Nutrition  

50:14 Nutritional Support in Cancer Patients  

54:18 Enteral Support in Dementia Patients  

57:15 Addressing Intestinal Ischemia: A Call to Action

Keywords

Intestinal rehabilitation, intestinal failure, nutrition, gastroenterology, patient care, bowel length, short bowel syndrome, nutritional support, clinical practice, healthcare, line management, line sepsis, Ehlers-Danlos Syndrome, nutritional support, cancer patients, dementia, intestinal ischemia, patient empowerment, multidisciplinary team, intravenous nutrition

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:

X: @2guystalkingit

Email: [email protected]

Chapters

03:32 Introduction and Guest Introduction

05:30 Reflections on the ECCO Conference

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

21:44 Dietary Insights and the Mediterranean Diet

23:30 The ADAPT Study on Emulsifiers and IBD

30:00 General dietary recommendations in IBD

33:48 Fiber consumption and Crohn's Disease development

39:40 The Role of Plant-Based Diets in IBD

43:18 Environmental factors in association with IBD

45:53 Understanding Environmental Factors in IBD

47:25 Linking IBD and Neurodegenerative Diseases and Vedolizumab

54:32 Proactive Monitoring in Ulcerative Colitis

Keywords

IBD, ECCO Conference, Bea Gros, PREDICT Study, Mediterranean Diet, Emulsifiers, Disease Prediction, Patient Care, Dietary Studies, Holistic Health, Crohn's Disease, Ulcerative Colitis, plant-based, fiber, environmental factors, probiotics, nutrition

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

16:44 Revisiting Biopsy Techniques and Clinical Observations

19:40 Mucosal Healing and Follow-Up Practices

22:35 Refractory Coeliac Disease: Definitions and Management

26:48 Treatment Strategies for Refractory Coeliac Disease

31:14 Understanding Treatment Targets in Coeliac Disease

32:16 Maintenance Treatment for Refractory Coeliac Disease

33:13 Exploring Alternative Treatment Options

34:12 Balancing Treatment Risks and Benefits

34:59 Advancements in Histology and Scoring Systems

37:05 Future Directions in Coeliac Disease Research

39:01 Innovations in Diagnosis and Screening

41:01 The Role of Gluten Challenges in Diagnosis

43:14 Understanding the Causes of Coeliac Disease

45:14 Patient Management and Follow-Up Care

48:12 Vaccination and Hyposplenism

56:13 Opportunities for Research and Collaboration

Links to papers mentioned

Iron deficiency.(Link)

2020 ESPGHAN Guidelines for diagnosing Coeliac Disease

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)