Below is the full transcript of Episode 63 of the Autoimmune Wellness Podcast.
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AIP for IBD: The Gene Expression Study & Patient Experience Survey (Ep 063)

[00:00:00] Introduction: Looking to Mechanisms & Experiences

In the earlier episodes of this series, we’ve been reviewing the first medical research studies on the Autoimmune Protocol, including what improvements were seen for people who used AIP from symptom burden to quality of life. Today, we’re taking the next step in that research conversation. We’re looking at research that points to how those changes might be happening inside the body, and just as importantly, what people report experiencing as they use AIP in the real world, outside of a clinical study.

That question was on the minds of the research team at Scripps and to explore it, they designed a first of its kind study that went beyond symptoms alone. Using RNA gene expression analysis before and after the AIP intervention, they examined how immune pathways were being turned up or dialed down, at a molecular level. This gave researchers some of the earliest clues into the biological mechanisms that might help explain AIP’s effects in inflammatory bowel disease.

And to round out their inquiry into AIP for IBD, the Scripps team also conducted a patient experience survey, gathering detailed insights from people who used AIP to manage their Crohn’s or ulcerative colitis. They looked at trends in symptom changes, medication use, diet sustainability, and how people approached food reintroductions after the elimination phase, which is something that has not been studied yet.

These two studies don’t get talked about nearly as often as the original pilot trial, but together they offer a deeper look at both how AIP might work biologically, and how people experience it in real life. They take us beyond symptom charts and into immune signaling, patient motivation, barriers, and long-term patterns, insights that are especially meaningful for anyone navigating IBD or other autoimmune conditions today.

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Welcome back to the Autoimmune Wellness Podcast. I’m your host, Mickey Trescott, and this is the third episode in our AIP Medical Research Review series where I walk you through the published medical research on the Autoimmune Protocol: what was examined, the results, and what it all means for people living with autoimmune disease today.

As always, this podcast is for informational and educational purposes only, and is not a substitute for medical advice. Make sure to talk to your healthcare provider before making any changes to your treatment plan.

[00:02:23] Episode Overview: The AIP IBD RNA & Patient Experience Studies

In today’s episode, we’re diving into two additional studies from the Scripps research team, again led by Dr. Gauree Konijeti, studies that build on the original IBD pilot trial and offer a deeper look at how AIP may work and how patients experience it in real life.

The two papers we will be discussing are: An Integrative Clinical Pilot Study to Evaluate RNA Expression Changes in Inflammatory Bowel Disease Following the Autoimmune Protocol Diet, which was published in 2019.

And Experience Using the Autoimmune Protocol Diet in Inflammatory Bowel Disease, a Patient Survey, published in 2021.

If you’d like to follow along, I’ve included direct links to both open access papers in the show notes.

We’re going to walk through what the researchers set out to examine the methods they used and what they discovered from changes in immune-related gene pathways to patient reported patterns in symptom management, medication use, and food reintroductions after completing the elimination phase of AIP.

By the end of this episode, you will have a clear understanding not only of what happened in these studies, but why they matter for the future of AIP, for patient empowerment, and for expanding the scientific conversation around nutrition and autoimmune disease.

[00:03:42] Study Participant Profile: Who Took Part in the RNA Expression Substudy

So first we’ll discuss the RNA expression, AIP and IBD substudy. And before we look at what changed on a molecular level, let’s start with who was actually included, because just like in the previous episodes, the participant profile really does shape how we interpret results.

This RNA analysis drew from the same cohort used in the original Scripps AIP IBD pilot study. That study enrolled 15 adults with active inflammatory bowel disease, including both Crohn’s disease and ulcerative colitis. Now, these were not mild cases. Participants had longstanding disease, documented active inflammation, and many were being treated with standard medications such as mesalamine, biologics, or steroids.

But for this specific RNA substudy, only a smaller group was eligible. They enrolled participants who had active disease at baseline, underwent a colonoscopy or sigmoidoscopy, both before and after the intervention, and had mucosal biopsies successfully collected at both time points. So if a patient went through the trial and they had all of those factors, they were included.

And so ultimately, four participants with ulcerative colitis met the criteria and were included in the RNA analysis. This means that this sample represents a subset of just the ulcerative colitis participants. All four of them had documented mucosal inflammation before starting AIP. All of them were on mesalamine-only therapy, which reduces the confounding from biologics or systemic immunosuppression.

This is important because it allowed the researchers to look at transcriptional changes in the intestinal tissue without the added effects of immune-modifying medications.

So what was their disease activity like at baseline? They had a mean partial Mayo score of 5.5, which indicated active disease. Their Mayo endoscopic subscores showed mild to moderately active colitis. Their fecal calprotectin levels were elevated, averaging 414 µg/g. And in other words, these participants had clear objective evidence of inflammation both clinically and endoscopically.

And unlike the broader pilot study, the RNA substudy was specifically designed to look at molecular signatures of inflammation in the colon itself. So this is just looking at the tissue. Focusing on a very small, consistent subset– these uc patients on mesalamine– helped reduce variability and make the gene expression analysis more meaningful. It also means the findings tell us something specific: how intestinal tissue and ulcerative colitis might respond to AIP at the cellular level.

Yes, it’s a very small sample and the researchers acknowledge that, but it’s also the very first time that anyone has examined changes in mucosal RNA expression before and after any dietary intervention in active ulcerative colitis, making it a unique and foundational study in the field.

[00:06:51] The AIP RNA Study Intervention

Next, let’s talk about the intervention used in this RNA substudy, because this wasn’t a separate protocol or a different diet. The RNA analysis was conducted on participants who took part in that original Scripps IBD pilot study. So they followed the same structured, phased program we covered in the first episode covering that pilot study.

As a review here, the intervention consisted of a six week staged elimination followed by a five week maintenance phase for a total of 11 weeks. Now, this is what the researchers called it in the paper, but we know these as the transition and the elimination phases of Core AIP. And I’m not going to repeat all the details of that AIP intervention here, but if you’re interested, you can check out the very first medical research review episode where I cover the intervention itself in depth.

[00:07:41] Clinical Outcomes Observed in the RNA Substudy

And before we look at the gene expression findings, it’s important to understand the clinical outcomes observed in this subgroup, because these are the changes that set the stage for what researchers saw later at the molecular level.

First, the partial Mayo score improved dramatically. The partial Mayo score is a widely used tool for evaluating ulcerative colitis activity based on symptoms like stool frequency and rectal bleeding. Their baseline mean score was 5.5, again, indicating active disease by week six. So that is just at the end of the transition phase, it was 0.5. In week 11, which is at the end of the elimination phase, it was 0.25. So these changes were statistically significant and a shift from 5.5 to nearly zero represents a substantial improvement in symptoms and aligns with the remission rates reported in the larger pilot study.

Next, the endoscopic scores improved, so the researchers also looked at the Mayo endoscopic sub score MES, which reflects what inflammation looks like when they go in there with a colonoscopy. The baseline mean was 1.25, and post the intervention it was 0.5. So while this improvement didn’t reach statistical significance, the individual results are notable. Three participants improved by at least one full point in their endoscopic score, and one participant had no change but didn’t worsen. And for such a small sample, these improvements suggest a meaningful shift in visible mucosal inflammation.

Next fecal calprotectin decreased. Fecal calprotectin is a stool marker that reflects neutrophil driven inflammation in the gut. Their baseline mean FC was 414 µg/g. By week six, it was 88 µg/g, and then week 11 it was 70  µg/g. So again, these reductions didn’t meet statistical significance, but the direction of change in the size of the drop was suggestive of a potential decrease in intestinal inflammation.

Now biopsies taken during colonoscopy also showed encouraging changes. At baseline, all four had that mild to moderately active chronic colitis and post-intervention, three showed chronic minimally active colitis and one showed benign colonic mucosa. So that histologic improvement adds another layer of evidence that inflammation was decreasing across multiple measures.

This pattern mirrors the results of the full pilot trial where 73% of participants achieved clinical remission by week six. And these improvements help contextualize the RNA findings: when symptoms and inflammation improve at the surface level, what’s happening deeper in the immune system.

[00:10:32] How the RNA Analysis Was Conducted

Now let’s look at how the researchers measured the changes inside the gut on a cellular level. The original paper describes a very technical process, but the basic idea is pretty straightforward, and I want to explain it to you. The goal of the substudy was to see how gene activity in the intestinal aligning changed from before AIP to after AIP.

To do that, the researchers used a process called RNA sequencing, which is simply a way of measuring which genes are turned on or turned off in a tissue sample. Here’s the process in simple terms: first, they collected tiny samples of intestinal tissue, before starting AIP, and again after. Participants had a colonoscopy or a sigmoidoscopy, and during that procedure, the doctor took a very small biopsy of the colon lining, just a little piece of tissue, similar to what would be taken to check inflammation. These samples are what the researchers use to look at the gene activity.

Next in the lab, the team isolated the RNA from each tissue sample. You can think of RNA, kind of as the activity log of the cell. It shows which genes are currently being used and therefore what the tissue is working on in that moment, like fighting inflammation, repairing itself, or responding to stress. And then third, that extracted RNA was then prepared, so it could be read by a sequencing machine.

This step mostly involves cleaning up the samples and organizing the RNA so that the machine can interpret it. The next step is that each sample was run through a high powered sequencing machine that reads millions of pieces of RNA. This gave the researchers a detailed snapshot of what genes were active in the colon before these people did AIP, and what genes were active after.

Once that sequencing was done, the researchers used statistical tools to look for changes. They examined which genes were more active after AIP, which genes were less active, and which patterns showed up consistently across the participants. This step helped them identify meaningful shifts rather than normal day-to-day variation.

And then finally, the researchers grouped the changed genes onto biological pathways, things like inflammation, immune function, tissue repair, or metabolism. This helps translate a long list of gene names into a big picture understanding of what was happening inside the intestines. Instead of looking at 324 individual genes, they could say things like pathways related to inflammation were turned down, or pathways related to tissue repair were turned up. And this is where the story of the RNA study emerges, and it’s the part we’ll walk through next.

[00:13:07] Results – RNA Gene Expression Findings

Now let’s talk about what the researchers actually found, because this is where things get really interesting. In total, the researchers found 324 genes that changed activity after the AIP intervention, 167 of those genes became less active, and 157 became more active. That’s a lot of movement for such a small sample and those shifts didn’t happen randomly, they clustered around a few key biological themes that help explain the symptom improvements seen in the trial and in the earlier outcomes we reviewed.

Here’s what stood out. First, one of the strongest findings from the RNA analysis was a downregulation of pathways linked to inflammation, especially those involving T cells, which play a major role in ulcerative colitis. This aligns beautifully with the clinical improvements the participants experienced. Lower symptom scores, improved endoscopic appearance and reductions in fecal calprotectin. It suggests that AIP might help shift the immune system away from a pro-inflammatory state.

Next, researchers also saw increased activities and pathways related to regulatory T-cells. Now don’t get confused. T cells and regulatory T cells are very different. These are the cells that help calm and balance the immune system. Think of them as the peacekeeping cells of the immune system. When regulatory T cells are functioning well, inflammation tends to settle rather than escalate. Seeing these pathways turn up suggests that AIP might support the immune system’s ability to self-regulate and not just suppress.

Another notable finding was increased activity and pathways involved in DNA repair: protein synthesis, fatty acid metabolism and general mucosal healing processes. These pathways help the intestinal lining repair itself after inflammation, which is essential in conditions like ulcerative colitis. This is especially meaningful because the colonic biopsies from these participants also showed improved histology: three shifted from moderately active colitis to minimal activity and one biopsy normalized completely.

The researchers also noted an upregulation in certain pathways labeled inflammatory response. At first glance, that sounds contradictory, but here’s the nuance. These pathways often include regulated, functional immune responses, the kind that help the body respond to damage or repair tissue, not the chaotic inflammation seen in UC flares.

And when you put all of these findings together, the picture becomes clearer. After 11 weeks of AIP, the gene activity in the intestines shifted in a direction consistent with less inflammation and more healing. Now, this does not mean AIP cures UC, and the researchers are careful to say that far larger studies are needed.

But this small analysis offers us something that we rarely see in nutrition research: a biological mechanism, directly measured in the tissue affected by the disease, showing changes consistent with clinical improvement. And it is the very first of its kind in IBD dietary research, and it provides early evidence that AIP might influence disease at the cellular level, not just at the symptom level.

So far we’ve looked at the clinical outcomes and the molecular changes seen in the intestinal tissue, findings that suggest AIP might influence inflammation and healing both on the surface and deep within the immune system.

But the Scripps team didn’t stop there. While the RNA substudy helped illuminate how AIP might work at a biological level, there was still another critical piece of the puzzle to explore. How do people actually experience AIP in real life?

[00:16:47] The AIP IBD Patient Experience Survey

To round out their investigation into AIP for inflammatory bowel disease. The Scripps team conducted a different kind of study, not a controlled intervention, but an anonymous, online survey of people who had already used AIP in the past as part of their IBD management. This distinction is important. Unlike the pilot study, where participants followed a structured program with coaching lab work and clinical oversight, this survey captured real world experiences from people who chose to use AIP on their own outside of a research setting.

Their responses reflected a wide variety of approaches, levels of adherence and timelines, and this project was also a collaboration with Autoimmune Wellness, and Angie and I helped share the survey with the AIP community so that researchers could hear directly from these patients. And if you were someone who participated, thank you so much, your input helped create one of the first data sets documenting how people with Crohn’s and ulcerative colitis actually use AIP in their daily lives.

Understanding real world experience is crucial because even a highly effective diet in a clinical setting won’t matter much if it isn’t sustainable or if patients find it too difficult to maintain. So here’s what the research team aimed to learn.

First, the survey looked at symptom patterns before and after starting AIP. Participants reported on abdominal pain, stool frequency, and rectal bleeding at three different points in time: before they started AIP, at the six week mark, and again, when they completed the survey. This allowed researchers to see not only whether symptom improvements were common, but also whether those improvements tended to last.

The survey also gathered information about medication use before and after adopting AIP. Because treatment for inflammatory bowel disease often includes steroids, immunosuppressants, or biologic therapies, participants were asked about their past steroid exposure, their current medications, and whether anything changed after they began AIP. This helped paint a clearer picture of how people were using diet alongside standard medical care.

Another important focus was how people actually implemented AIP in real life. Respondents shared whether they followed the protocol exactly or made modifications, how long they stayed in the elimination phase, and what day-to-day implementation looked like for them. This context matters because AIP outside of a trial is often individualized rather than perfectly uniform.

Next, the survey explored food reintroduction patterns. Participants reported when they began reintroducing foods, which foods they were able to tolerate, and which ones triggered symptoms. Together, these responses offered insight into how people moved beyond elimination and began shaping a more personalized and long-term approach. This is the very first attempt to systematically document reintroductions in IBD, and an area of AIP that is rarely studied, but deeply relevant to sustainability.

And lastly, patient perceived remission and benefit. The survey also asked whether participants felt AIP helped them into remission or maintain it. Because this was not a controlled trial, the results do not tell us how AIP performs under clinical supervision. But instead, they tell us something different and incredibly useful. How real people with IBD use AIP on their own, what results they perceive and how they adapt the protocol over time. Next, we’ll look at what the survey participants reported and the key themes that emerged from their experiences.

[00:20:21] Survey Results: What Patients Reported Using AIP for IBD

A total of 78 people completed the survey. On average participants were 39.4 years old, living with IBD for over 13 years, and 78% had used steroids at some point in their treatment history. This group represented a wide range of disease journeys and levels of medical treatment.

Symptom improvements were common, and often within the first six weeks. Here’s what patients reported: for Crohn’s disease, by week six, 77% reported improvement in abdominal pain, 57% reported improvement in stool frequency, 57% reported improvement in bleeding. By the time of the survey, which is much later in their journey, 70% still reported less abdominal pain, 53% had improved stool frequency and 57% had reduced bleeding. And worsening symptoms were rare, only about 7% or less reported worsening in any category.

Now for ulcerative colitis: by week six, 72% reported less abdominal pain, 79% reported improved stool frequency, and 65% reported less bleeding. And then by the time of the survey, 65% still reported improved abdominal pain, 67% improved stool frequency and 58% reduced bleeding. And again, in this group worsening was uncommon and reported by only 5% of respondents depending on the symptom.

So across both Crohn’s and ulcerative colitis, these patterns match what we saw in the original clinical study. Many people notice improvements early, often within the first six weeks of AIP, and one of the most striking findings was that: 73% of the survey respondents believed they achieved clinical remission because of AIP. And that’s not a typo. That’s actually the same percentage that they saw in the clinical study. It’s interesting seeing that number come up twice, both in the clinical observation group and then the survey group.

Next, they found that steroid discontinuation was common after AIP steroid use is a major issue in IBD due to the long-term side effects, so this finding is particularly meaningful. 32% of participants reported discontinuing steroids after starting AIP.

And the next finding is also really interesting. When asked how they implemented AIP, 73% of participants followed the protocol as written, and at the time there was only Core AIP, so we’re talking about Core AIP here, and 27% personalized or modified it. This mix reflects something that we saw often in the AIP community. Some people adapt the protocol based on their symptoms, their preferences, their resources, their capacity, or their healthcare provider guidance. And this is really important to highlight at this moment because we have learned so much over the last decade about long-term sustainability, food freedom, and reducing unnecessary restriction.

Modified AIP, which is the newer, gentler, and more flexible version of the protocol has been a widely embraced approach because it helps people get meaningful benefits without needing to maintain the full elimination long term. Seeing more than a quarter of survey participants adjust the protocol to fit their real lives reinforces something that we now emphasize all the time. AIP is a framework, not a forever diet. Personalization isn’t just allowed, it’s expected, and it’s been a part of how people have been implementing the protocol all along.

[00:24:00] Survey Results: Reintroductions

Next we learned that unsurprisingly, food reintroductions happened on many different timelines. One of the most fascinating parts of the survey was the data on reintroductions, an area where we usually only have anecdotal reports. So 8% of people reported reintroducing foods from week zero to week four, which is before we actually recommend, so seems like these guys went rogue. 23% reintroduced from week five to eight, which is a pretty standard second month of the protocol. 24% reported reintroducing from months two to six, which is actually pretty far out. 23% reported from month six to 12, and then even 13% reported reintroducing after 12 months, which is an extremely long time.

For anyone listening who hasn’t done AIP yet, we usually recommend one to three months in the elimination phase. So this very short and very long timelines are actually not what we generally recommend. This wide variation shows us that there is no single timeline that everyone is using. A lot of people are actually taking it very slowly. Reintroductions can be highly individualized, and the survey also cataloged which reintroductions were most and least successful, a helpful starting point for understanding patterns, even though personal variability is always high.

Looking at the foods that people couldn’t bring back successfully, here’s how the category’s ranked from the least tolerated to the most tolerated. Almost 60% of people said that they could not tolerate gluten containing grains, which should surprise nobody. I’m actually surprised that number is so low. Processed foods, 52% were unable to reintroduce. I’m not really sure why they used this as a category, because we don’t really use it as a AIP reintroduction food group, but the researchers did what they did.

Nightshades, 46% were unable to reintroduce, which is something that we commonly see with people with IBD. Dairy, 42% were unable to reintroduce. Non-gluten grains, 29% were unable to reintroduce, which is a much better tolerance rate than gluten grains, but they still had an effect on a lot of people, so it is important to reintroduce those separately. And then fruit 3.85% unable to reintroduce, fruit is already allowed on AIP, so this category was a little unusual.

Just a general note on the food categories, while these results are really helpful, I think that the categories that they chose for this survey were a little unusual. For example, the grains, which we’ve already discussed, were split into gluten and non-gluten, which I think was great. But the other essential AIP reintroduction groups were missing, such as eggs, nuts, and seeds, legumes, coffee, alcohol. These are really common food sensitivities and their absence limits the usefulness of this reintroduction data.

And additionally, categories like processed foods and fruit aren’t really standard AIP reintroduction groups, which makes the interpretation a little tricky. But even with those limitations, the big picture is pretty clear. Gluten was by far the least tolerated. Dairy and nightshades were big triggers for this group. Non-gluten grains were surprisingly still a trigger, even though they were much better than gluten grains and fruit was rarely problematic, which we should already know that.

So taken together, the survey results tell us that many people with IBD experience meaningful symptom improvement using AIP. Improvements often begin within the first six weeks. A sizable percentage of IBD patients report achieving remission using AIP. Steroid reduction is common. People implement AIP flexibly based on their needs. And reintroductions are approached at many different timelines and there is a wide variability in what is actually tolerated by each person. So while this is not a controlled study, it offers valuable insights into how AIP functions outside of clinical trials and how people feel that it influences their lives.

[00:28:08] Recap and Wrap-Up

Taken together these two lesser known studies, the RNA gene expression analysis and the patient experience survey add important depth to the early AIP research. The RNA study offers something we rarely see in nutrition and autoimmune disease, a glimpse at how a dietary and lifestyle intervention might influence the immune system at the tissue level.

Even though the sample was small, the patterns pointed in the same direction as the clinical outcomes: less inflammatory activity, and more signs of healing. It begins to answer the question that so many of us have asked: how might AIP work?

And then the patient survey fills in a different but equally important piece of the puzzle. It shows what AIP looks like in the real world, how people implement it, when they see improvements, how they personalize it, and which foods they can or can’t add back. It also reinforces a major theme of AIP today: people benefit most when the protocol becomes a flexible framework rather than a long-term, highly restrictive diet.

So together these studies help validate what many in the AIP community have experienced firsthand: that AIP can be both impactful and adaptable, and that improvements are not only measurable in symptoms and quality of life, but may also have underlying biological signatures.

They also highlight something essential as we look ahead. The future of AIP isn’t just about proving that it works, it’s about understanding how for whom and how to make it as sustainable and personalized as possible.

So that brings us to the end of today’s episode. Thank you so much for joining me as we explored these two lesser known, but incredibly insightful studies from the Scripps research team.

If you’d like to read either paper for yourself, you’ll find direct links to both studies in the show notes. And if you enjoyed this episode, it would mean so much if you subscribe to the podcast or left a quick review. It helps more people discover this information and supports the work we’re doing here.

And if you’re new to AIP or looking for resources to get started, download my AIP Foundation Series at theautoimmuneprotocol.com/foundations. It’s a free, five day email course with over 60 pages of resources and guides. Once you download it, you automatically receive a breakdown every time a new AIP study is published so that you can stay up to date with the science as it evolves.

And if today’s episode sparked your curiosity about the science, you’ll definitely want to check out my new book, The New Autoimmune Protocol Coming this May. It pulls together all of the updated medical research and pairs it with new recipes and step-by-step meal plans, so you can actually apply what we talk about here. Pre-orders are open now and they make a huge difference in helping this information reach more people who need it.

Thanks again for listening, and I’ll see you in the next episode.