Understanding Gluten vs. Fructan Intolerances in IBS with Dr. Biesiekierski

Gluten sensitivity remains one of the most debated topics in the management of irritable bowel syndrome (IBS). Despite growing public awareness and clinical discussion on gluten, controlled dietary trials increasingly suggest that physiological gluten-specific effects outside of celiac disease are rare. 

Instead of gluten, fermentable carbohydrates, particularly fructans, consistently drive digestive symptoms. This disconnect between perception and evidence has important implications for dietary guidance, behavioral interventions and long-term patient outcomes.

To get the latest insights on where the science currently stands, we spoke with Dr. Jessica Biesiekierski, Associate Professor and Head of Human Nutrition at the University of Melbourne. Her work integrates randomized controlled dietary trials with mechanistic studies of gut physiology and gut–brain interaction. 

In this discussion, Dr. Biesiekierski shares evidence-based insights on differentiating gluten sensitivity from fructan intolerance, the role of expectation and nocebo effects in symptom generation, and how clinicians can apply nuanced, personalized strategies, rather than blanket restrictions, to support patients with IBS.

Thank you for joining us today to share your expertise. To begin, walk us through your background. What is the focus of your research?

I am an Associate Professor and Head of Human Nutrition at the University of Melbourne. I am a nutrition scientist with international research experience, including postdoctoral training with KU Leuven in Belgium. I lead a globally collaborative program that integrates randomized controlled dietary trials with mechanistic studies to understand how diet influences gut biology and gut-brain communication. My work focuses on gastrointestinal conditions such as irritable bowel syndrome (IBS) and functional dyspepsia, with the overarching aim of developing evidence-based, sustainable nutrition interventions that improve symptoms while avoiding unnecessary dietary restriction.

What questions drive your work on gluten, FODMAPs, and IBS?

My work is driven by the question of what truly causes food-related symptoms, and how we can manage them precisely without unnecessary restriction. In IBS and related disorders, symptoms often emerge from interactions between diet, gut physiology, and how the brain processes gut signals. Understanding where dietary factors including gluten, fermentable carbohydrates and expectation each fit into that picture is critical for designing effective, proportionate dietary strategies.

Gluten sensitivity continues to generate debate. Based on your research, what are we learning about the prevalence of gluten vs. fructan sensitivity and how each contributes to symptoms?

Across controlled studies, gluten-specific effects outside celiac disease appear uncommon, whereas fermentable carbohydrates such as fructans more consistently trigger symptoms in people with IBS. Importantly, many individuals experience symptoms even when gluten is absent, highlighting that wheat-related symptoms are often driven by broader dietary and gut–brain mechanisms rather than gluten itself.

In your clinical research, what methods are most effective for teasing apart true gluten sensitivity from nocebo effects or from fructan-related symptoms?

The most informative approach combines careful exclusion of celiac disease, stabilization of background diet, and structured dietary challenges. Without controlling for fermentable carbohydrates and expectation effects, it is not possible to reliably attribute symptoms to gluten. This is why well-designed trials and dietitian-guided testing are essential in both research and clinical practice.

You’ve published really interesting findings lately on non-celiac gluten sensitivity and fructan intolerances. What findings surprised you most from this research?

One of the most striking findings has been how strongly expectation shapes symptom experience. In several well-controlled studies, symptom severity aligned more closely with what participants believed they were consuming than with the actual dietary exposure. This reinforces that symptoms are real, but their drivers are often more complex than a single food component.

What do we know about whether non-celiac gluten sensitivity is a distinct condition? Or do current data suggest most cases are FODMAP-related?

Current evidence suggests that non-celiac gluten sensitivity is not a single, clearly defined biological condition. Instead, it overlaps substantially with IBS and other disorders of gut-brain interaction. While a small subgroup may respond specifically to gluten, for most people symptoms appear to reflect broader diet-gut–brain processes.

What are the most common myths or misunderstandings about gluten sensitivity? About FODMAPs?

A persistent myth is that gluten is broadly harmful or inflammatory for the general population. Another is that feeling better on a gluten-free diet proves gluten sensitivity. In reality, symptom improvement often reflects changes in overall diet composition, fermentation load, and food-related anxiety rather than gluten itself.

We know wheat is a complicated food when it comes to IBS. What role do non-gluten wheat components — like FODMAPs, amylase-trypsin inhibitors, or other proteins — play in symptom generation?

Wheat is a complex food, and focusing solely on gluten oversimplifies symptom generation. The strongest human evidence points to fermentable carbohydrates, particularly fructans, as key symptom triggers in IBS. Other wheat components, such as amylase-trypsin inhibitors (ATIs), have shown immune effects in laboratory and animal studies, but their relevance to symptoms in humans remains unproven, as well-controlled human challenge data are lacking. Clinically, this means it is rarely helpful to single out one “toxic” component of wheat; instead, symptoms are best understood as arising from how different wheat constituents interact with gut physiology, sensitivity, and gut–brain processes.

How can healthcare providers help patients with IBS or food-related digestive symptoms differentiate gluten sensitivity from fructan intolerance?

Clinicians can help by shifting the focus from blanket avoidance to structured, time-limited experimentation. A critical first step is testing for celiac disease before any gluten is removed, as premature restriction can compromise diagnosis and has lifelong implications if missed. Once celiac disease and wheat allergy are excluded, differentiation is best achieved through dietitian-guided dietary trials that stabilize the background diet, incorporate short-term elimination, and support systematic reintroduction. Framing this process within an understanding of gut–brain interaction helps reduce fear around food, improves diagnostic clarity, protects nutritional adequacy, and leads to better long-term outcomes.

Why do you think gluten has become such a dominant “culprit” in the public narrative, even though research suggests fructans often play a significant role in symptoms?

Gluten offers a simple narrative in a complex space. Media amplification, wellness culture, and the gluten-free market have reinforced its prominence, even as scientific evidence points to more nuanced mechanisms underlying symptoms.

In your view, what are the biggest risks of self-diagnosing gluten sensitivity or following a gluten-free diet when it’s not necessary?

Unnecessary restriction can increase cost, reduce dietary quality, and reinforce anxiety around eating. Over time, this can make symptoms harder to manage rather than easier, particularly in people with gut–brain interaction disorders.

What’s your perspective on the low FODMAP diet? What are its strengths, limitations, and what do people often get wrong about it?

The low FODMAP diet is a valuable clinical tool when used as intended: short-term, structured, and personalized. Problems arise when it becomes a permanent avoidance strategy rather than a pathway to understanding individual tolerance.

How can healthcare providers help patients manage fructan-related symptoms without excessive diet restriction? What about gluten-related symptoms?

Effective management often involves adjusting portions, timing, and food combinations rather than full exclusion. The goal is flexibility and confidence around food, not perfection.

What role can digestive enzymes play in supporting people with fructan intolerance? With gluten sensitivity?

Digestive enzymes can be a useful adjunct for some people, particularly to reduce symptom burden in real-world eating situations. They are great tools that support dietary flexibility (rather than substitutes for understanding individual triggers).

Where do you see the field heading next? What research questions still need answers when it comes to gluten, fructans, and IBS?

The field is moving toward integrated, multidisciplinary models of care that recognize food-related symptoms as emerging from interactions between diet, gut physiology, and gut-brain processes. Key unanswered questions include how to predict who will respond best to dietary approaches versus gut-brain therapies, and how to combine these strategies effectively rather than positioning them as alternatives.

Ongoing research, including trials of exposure-based cognitive behavioral therapy alongside dietary interventions, is helping clarify how targeting both diet and the brain’s interpretation of gut signals can improve long-term outcomes. We are currently recruiting for an international study open to adults with IBS in Australia and the USA, where participants are randomized to either a dietary intervention or exposure-based CBT, with 12 weeks of free, personalized treatment delivered online (www.gutresearchstudy.com).

Based on your research, what do you wish both clinicians and patients better understood about wheat-related symptoms overall?

I wish there was broader understanding that wheat-related symptoms are rarely explained by a single ingredient, and that effective management often requires more than diet alone. For many people, symptoms persist not because the “right” food hasn’t been eliminated, but because gut sensitivity, expectation, and learned responses continue to amplify gut signals. Integrating dietary strategies with psychological approaches, allows patients to regain confidence with food, reduce fear-driven avoidance, and achieve more durable symptom relief.

If you could offer advice to healthcare providers who support patients with IBS and other digestive symptoms, what would it be?

Take a multidisciplinary, proportionate approach that targets the underlying drivers of symptoms. Diet is a powerful tool when used in a structured, time-limited way and paired with education about gut-brain interaction. I think that for patients with persistent symptoms or high food-related anxiety, integrating gut–brain therapies alongside dietitian-led care leads to better outcomes than dietary restriction alone.