Episode 63: AIP for IBD — The Gene Expression Study & Patient Experience Survey

What happens inside the body when someone follows the Autoimmune Protocol—and how does AIP actually feel to people using it in real life?

In this episode of the Autoimmune Wellness Podcast, Mickey Trescott reviews two important follow-up studies from the Scripps research team, led by Dr. Gauree Konijeti, that expand our understanding of AIP for inflammatory bowel disease beyond symptom improvement alone.

The first study examined gene expression changes in intestinal tissue after an AIP intervention in ulcerative colitis. The second explored real-world patient experiences using AIP for Crohn’s disease and ulcerative colitis through a large survey. Together, these studies shed light on both the biological shifts and the lived experience of AIP for IBD.

In this episode, you’ll learn:

1. Why researchers examined gene expression changes after AIP
2. What the RNA substudy revealed about immune and healing pathways
3. Why these findings matter despite a small sample size
4. How people with IBD experience AIP outside of clinical trials
5. Common patterns in symptom improvement and medication use
6. How personalization and reintroduction typically unfold in real life
7. What these studies add to the growing AIP research landscape

Resources:

Scripps RNA Gene Expression Study (2019): An Integrative Clinical Pilot Study to Evaluate RNA Expression Changes in Inflammatory Bowel Disease Following the Autoimmune Protocol Diet

AIP IBD Patient Experience Survey (2021): Experience Using the Autoimmune Protocol Diet in Inflammatory Bowel Disease: A Patient Survey

AIP Foundation Series – Free 5-day email course with printable guides, meal plans, and beginner resources.

The New Autoimmune Protocol (Book) – Updated research, Core and Modified AIP guidance, and step-by-step meal plans (available for pre-order).

Episode Timeline:

00:00 – Introduction: looking beyond symptoms

02:23 – Overview of the RNA and patient experience studies

03:42 – RNA substudy participant profile

06:51 – The AIP intervention used in the RNA analysis

07:41 – Clinical outcomes observed in the RNA subgroup

10:32 – How RNA gene expression was analyzed

13:07 – Results: gene expression and immune pathways

16:47 – Introducing the IBD patient experience survey

20:21 – Survey results: symptom changes and medication use

24:00 – Survey results: food reintroductions

28:08 – Recap: what these studies add to AIP research

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.

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.

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.

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.

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.

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.

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.

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

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?

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.

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.

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.

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

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.

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And if today's episode sparked your curiosity about the science,

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Protocol Coming this May.

It pulls together all of the updated medical research and pairs it

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