NIDDK

Recent Advances & Emerging Opportunities

2025

Digestive Diseases
and Nutrition
U.S. Department of Health and Human Services
National Institutes of Health
National Institute of Diabetes & Digestive & Kidney Diseases NIH Publication Number: 25-DK-7962
DIGESTIVE DISEASES AND NUTRITION...........50 A Pancreatic Stent Lowers Risk
of Pancreatitis Following
Exploring Intestinal Function ..................................53 Endoscopic Procedure.......................................58

Study Upends Conventional Wisdom Discovering Factors Involved in

by Revealing Five Intestinal Regions ...............53 Liver Inflammation .....................................................58

Understanding Gut Inflammation ..........................53 Key Protein Drives Liver Inflammation

and Fibrosis..........................................................58

Gut Bacteria and T Cells of the Immune

System Contribute to Development Understanding the Effects of

of Serious Intestinal Inflammation, Genetic Differences on Liver Immune

Colitis, After Certain Cancer Treatments .......53 Cells Involved in Inflammation.........................59

A Genetic Risk Factor for Predicting Liver Disease Outcomes .......................59

Crohn’s Disease Could Disrupt

Intestinal Healing................................................54 Using Non-Invasive Liver Stiffness
Measurement to Predict Liver
Uncovering Key Players in Celiac Disease ............55 Disease Outcomes ............................................59

New Celiac Disease Model Reveals Feature: Study Explores Factors

Insights About Immune Underlying Healing of Crohn’s

Response to Gluten............................................55 Disease in Children ....................................................61

Treating Diarrheal Disease in Children ..................56 Feature: New Clinical Trial Aims to
Compare Endoscopy Approaches

Addressing Provider Misperceptions for Preventing Esophageal Cancer .........................62

Could Limit Deaths in Children From

Diarrheal Diseases..............................................56 Personal Perspective: Alicia—Crafting
a Life With Gastroparesis .........................................64

Understanding How Diet Affects Health ..............56

Feeding the Microbiome Helps Children

Grow After Malnutrition....................................56

Switching to Vegan or Ketogenic

Diet Rapidly Impacts Immune System
and Metabolism ..................................................57

Preventing Pancreatic Disease ...............................58

NIDDK Recent Advances & Emerging Opportunities 2025 5

Any basic anatomy class will teach that there are three regions of the small intestine: the duodenum, the jejunum, and
the ileum. These regions were first defined in ancient times, mostly by their overall appearance. As described in this
chapter, researchers have challenged this conventional wisdom by using modern molecular-based techniques to map
out the entire length of both the human and mouse small intestine. They found that they are divided into not three,
but five separate regions, with each region performing a unique step in digestion. The top panel in the image above
shows a mouse small intestine, coiled tightly to display its entire length from its beginning where it joins the stomach
(“proximal,” labeled as “P”), to its end where it empties into the colon (“D,” or “distal”). The colors in the image show
three out of the five regions: The pink color marks two regions that are involved in absorbing fatty acids, and the green
color labels a region that is important for absorbing cholesterol. The bottom two panels are higher magnifications of
the sections marked as “a” and “b” in the top panel, showing the fingerlike projections (villi) in the intestinal lining that
are critical for absorbing nutrients. Because gastrointestinal diseases commonly affect some intestinal regions more
than others, this new way of looking at the small intestine is likely to be valuable for understanding, diagnosing, and
treating disorders of the digestive system.

From: Zwick RK, Kasparek P, Palikuqi B,…Klein OD. Epithelial zonation along the mouse and human small intestine defines five discrete metabolic domains.
Nat Cell Biol 26:250-262, 2024, Springer Nature.

NIDDK Recent Advances & Emerging Opportunities 2025: Digestive Diseases and Nutrition 50
Digestive Diseases and Nutrition
Digestive diseases are among the leading causes of doctor visits, hospitalizations, and disability in
the United States each year. These conditions span a wide spectrum of disorders that affect the
gastrointestinal (GI) tract, liver, gallbladder, and pancreas, as well as obesity and other
nutrition-related disorders. To reduce the burden of digestive diseases, NIDDK-supported scientists
are pursuing research to better understand how widespread these diseases are across the United
States and in specific population groups; identify their causes and how they progress; and test new
interventions for prevention and treatment, including drugs, surgery, and behavior modification.

Digestive diseases can exact a significant toll on Crohn’s disease and ulcerative colitis, is marked by
individuals across the lifespan, resulting in a lower damaging intestinal inflammation that can cause rectal
quality of life, years lost due to premature death, and bleeding, diarrhea, nutritional deficiencies, and other
costs associated with hospitalization and pharmaceutical serious complications. IBD often strikes early in life,
and surgical interventions. The burden of digestive with a peak age of onset in adolescence or young
diseases in the United States is substantial: Based on adulthood. The continued discovery of predisposing
recent data, it is estimated that digestive disease is the genetic variations, potential autoimmune and microbial
primary diagnosis in a total of 66 million ambulatory influences, and new methods to repair damaged
care visits to physicians’ offices and hospital emergency intestinal tissue will help predict the best course of
and outpatient departments in the United States each treatment and catalyze the design of novel, more
year.1 Similarly, analyses with 2021 national inpatient personalized therapeutic strategies.
samples identified 3.6 million hospitalizations with a
primary diagnosis of digestive diseases and 15.6 million
hospitalizations with a primary or secondary diagnosis Scientists are investigating the complex
of digestive diseases.2 In addition, analyses focusing interactions among the genetic, environmental,
specifically on the clinical and economic burden of immune, microbial, and other factors that
emergency department visits identified 16.2 million contribute to, or protect against,
emergency department visits with a primary diagnosis the development of inflammatory
of digestive diseases and costs totaling $123.8 billion in bowel disease.
2021.3 (Note that, similar to 2020 statistics during the
pandemic, the 2021 statistics are likely underestimates
due to continuing pandemic-related health care
challenges.)
1
Centers for Disease Control and Prevention. National Ambulatory
Medical Care Survey (NAMCS). https://www.cdc.gov/nchs/namcs/
Annual estimates of the burden of digestive about/index.html. Accessed October 16, 2024.
diseases list these diseases as the primary 2
Agency for Healthcare Research and Quality. Healthcare Cost and
diagnosis in 66 million ambulatory care visits to Utilization Project (HCUP) National Inpatient Sample (NIS).
physicians’ offices and hospital emergency and http://www.hcup-us.ahrq.gov/nisoverview.jsp.
outpatient departments. Accessed October 7, 2024.
3
Agency for Healthcare Research and Quality. Healthcare Cost and
Utilization Project (HCUP) Nationwide Emergency Department Sample
Inflammatory bowel disease (IBD), an umbrella term (NEDS). http://www.hcup-us.ahrq.gov/nedsoverview.jsp.
for chronic and painful intestinal diseases that include Accessed October 7, 2024.

NIDDK Recent Advances & Emerging Opportunities 2025: Digestive Diseases and Nutrition 51
Diseases of the stomach and intestines also include factors such as age, geography, diet, and antibiotic usage.
peptic ulcer disease, which is typically caused by In acute and chronic pancreatitis, digestive enzymes
infection with the bacterium Helicobacter pylori or attack the pancreas from within, causing inflammation,
use of nonsteroidal anti-inflammatory drugs. Other loss of function, and severe pain. Advanced pancreatitis
stomach and intestinal disorders include functional can be debilitating and may lead to cancer or diabetes,
GI disorders, such as irritable bowel syndrome (IBS), and because pancreatitis is difficult to detect in its early
which can cause abdominal pain and altered bowel stages, many cases are advanced by the time they are
habits. Gastroesophageal reflux disease, in which diagnosed. Research has elucidated genetic and other
caustic stomach acids rise up into the esophagus, factors contributing to pancreatitis that may lead to ways
can lead to a heightened risk of esophageal cancer. to treat or prevent this disease.
Gastroparesis is characterized by delayed emptying of
food from the stomach, resulting in nausea, vomiting, Serious adverse health effects can occur when the
and abdominal discomfort. Fecal incontinence, or liver is functionally compromised by disease, which
impaired bowel control, is a very prevalent condition, sometimes leads to scarring. Severe scarring (cirrhosis)
and because it is difficult to talk about, many people can result in complete liver failure (end-stage liver
suffer without seeking treatment. Scientists continue disease). Some liver diseases primarily affect children,
to strive for a deeper understanding of the causes such as biliary atresia (a progressive inflammatory
of GI disorders, which will lead to improvements in liver disease). Others generally affect adults, such as
diagnosis and management. In individuals with celiac nonalcoholic fatty liver disease or NAFLD (also referred
disease, the immune system reacts to ingestion of to as metabolic dysfunction-associated steatotic liver
gluten—a protein component of wheat, barley, and disease or MASLD), or its more severe form, nonalcoholic
rye—resulting in chronic diarrhea, bloating, anemia, steatohepatitis or NASH (also referred to as metabolic
and, in children, slower growth and short stature. The dysfunction-associated steatohepatitis or MASH). In
only current treatment for celiac disease is maintenance recent years, however, NAFLD/MASLD in the United
of a strict gluten-free diet, which is difficult for many States has been increasingly diagnosed in children as
people. Research advances in the understanding of well, concurrent with rising rates of overweight and
genes and environmental triggers that are involved in obesity. NAFLD/MASLD is also associated with health
the development of celiac disease may contribute to disparities: While the disease occurs in people of all
improved diagnosis and treatment. races and ethnicities, in the United States it is more
likely to affect those of Hispanic ethnicity. Some forms
of liver disease are caused by viral infection, as in most
Research to advance understanding of genes cases of hepatitis, or by genetic mutations such as
and environmental triggers involved in the alpha-1-antitrypsin deficiency; others arise from factors
development of celiac disease may contribute to such as autoimmune reactions, drug toxicity, bile duct
improved diagnosis and therapy. obstruction, and other triggers, some of which are
unknown. Many liver diseases, such as chronic hepatitis
B and C, place individuals at elevated risk for developing
The microbes that inhabit the GI tract—also known as liver cancer. When liver disease reaches the end
the gut microbiome—are important in maintaining the stage, the only effective treatment is a liver transplant.
balance between digestive health and disease. These Research is critical to identify liver disease early, find
bacteria, viruses, and other microorganisms can affect methods to preserve liver function in people with liver
long-term health and nutritional status, depending disease, and develop and further study new treatment
on their interactions with each other, with intestinal options, including experimental, cell-based approaches
cells, and with nutrients ingested by their human host. to liver regeneration.
Disruptions in this microbial ecosystem are associated
with diseases such as IBD or infections by the harmful
bacterium Clostridium difficile. Scientists are gaining In recent years, nonalcoholic fatty liver
insights into the ways these GI microbes influence the disease, also referred to as metabolic
development and function of the digestive tract and dysfunction-associated steatotic liver disease,
other systems throughout the body, such as those with has been increasingly diagnosed in children and
immune and metabolic functions, as well as how the adults in the United States, concurrent with
composition of the GI microbial community changes with rising rates of overweight and obesity.

NIDDK Recent Advances & Emerging Opportunities 2025: Digestive Diseases and Nutrition 52
NIDDK also funds research on nutrition-related nutrients), with the help of a type of computational
disorders, including those that involve specific, artificial intelligence called “machine learning” that can
inherited alterations in nutrient metabolism. NIDDK- be used to identify patterns in complex data. They
supported research has enhanced knowledge of how mapped the different gene activity to specific locations,
these nutritional disorders develop and how they can creating a kind of atlas that shows all the functional
best be treated. Investigators also conduct basic, regions of the intestine. They found that the small
clinical, and translational research on the requirements, intestine in both mice and humans is actually divided
bioavailability, and metabolism of nutrients and other into five functional regions (which they labeled A to E),
dietary components to understand dietary needs in rather than the conventional three, each with its own
health and disease. NIDDK staff work collaboratively population of enterocytes that specialize in processing
with representatives from across NIH, including in specific types of nutrients. For example, the cells in
NIH’s Office of Nutrition Research, to advance nutrition region C showed higher activity in genes important for
research efforts. processing carbohydrates, while region E appeared to
be important for processing cholesterol. Experiments
in mice showed that the activity of genes associated
EXPLORING INTESTINAL FUNCTION with each region was affected by diet; genes associated
with region C were boosted in response to a diet high
Study Upends Conventional Wisdom by Revealing Five in carbohydrates, for instance. The researchers also
Intestinal Regions: A recent study has provided a new identified three populations of intestinal stem cells that
perspective on the small intestine in humans and mice, are programmed to give rise to all the enterocytes in
showing its length is divided into five functional regions, each region, which is important because knowing the
rather than the conventional three, with each region origin of these cells could provide the basis for future
having a specific role in digestion. therapies that aim to help heal the intestine.

Since ancient times, the human small intestine has Overall, these findings present a new, more complex
traditionally been divided into three regions: the view of the small intestine. Because gastrointestinal
duodenum, the jejunum, and the ileum. Each segment diseases commonly affect some intestinal regions more
is believed to have specific roles in digestion, working than others, this knowledge is likely to be valuable for
together to break down food and absorb nutrients in understanding, diagnosing, and treating disorders of the
a stepwise manner. Exactly how this division of labor digestive system.
works is unclear, however, because the boundaries
separating the three regions are not well defined, and it Zwick RK, Kasparek P, Palikuqi B,…Klein OD. Epithelial zonation along the
is difficult to map out all the different steps of digestion. mouse and human small intestine defines five discrete metabolic domains.
Nat Cell Biol 26: 250-262, 2024.

A recent study has provided a new perspective

on the small intestine in humans and mice, UNDERSTANDING GUT INFLAMMATION
showing that its length is divided into five
functional regions, rather than the traditional Gut Bacteria and T Cells of the Immune System
three, each having a specific role in digestion. Contribute to Development of Serious Intestinal
Inflammation, Colitis, After Certain Cancer Treatments:
Researchers recently developed a mouse model
One way to gain a better understanding of how the work to analyze how colitis (a painful and often serious
of the small intestine is divided along its length would inflammation of the large intestine) develops following
be to compare gene activity from many different regions certain cancer treatments. Cancer cells frequently
of the intestine, since cells use different combinations produce chemical signals that dampen the anti-tumor
of genes to perform different tasks—like using a specific response of the immune system. Targeting these signals
set of tools from a toolbox. Researchers recently did with a group of drugs that work via a process called
this comprehensive analysis by collecting samples immune checkpoint blockade (ICB) allows immune
spanning the entire length of the intestine—from both cells to remain active against the cancer. However,
female and male mice and humans—and comparing gene these drugs can also lead to unrestrained immune cell
activity among enterocytes (intestinal cells that absorb activation in the gut. Overactivity of the gut’s immune

NIDDK Recent Advances & Emerging Opportunities 2025: Digestive Diseases and Nutrition 53
system can lead to inflammation and colitis, which can be Lo BC, Kryczek I, Yu J,…Nuñez G. Microbiota-dependent activation of
so severe that ICB therapy must be halted. Understanding CD4+ T cells induces CTLA-4 blockade-associated colitis via Fcγ receptors.
why this off-target effect occurs can help uncover options Science 383: 62-70, 2024.
for preventing colitis with ICB therapy and ultimately
make this cancer treatment more tolerable and effective. A Genetic Risk Factor for Crohn’s Disease Could Disrupt
Intestinal Healing: Researchers have discovered how a
genetic risk factor for Crohn’s disease can slow down
Scientists have discovered why certain cancer healing of damaged intestinal tissue in mice, providing
drugs can cause intestinal inflammation, paving new insight into the healing process and offering ways to
the way for developing better therapies. pursue novel treatments.

Crohn’s disease, a form of inflammatory bowel disease,

For this study, researchers first developed an animal is a chronic (long-lasting) disease that causes painful
model that mimicked human ICB-associated colitis. inflammation in the gut. This inflammation leads to
Laboratory mouse colonies are typically maintained tissue damage, resulting in patchy lesions that can
under “specific pathogen–free” conditions to develop anywhere in the digestive tract. Scientists have
prevent disease-causing microbes from interfering been trying to understand why these lesions occur—and
with experimental results. However, the lack of mend so slowly—with the hope that new treatments
environmental pathogens also results in a community of can be developed. Research has shown that blood
microbes in the gut of these animals (“the microbiome”) clotting within lesions typically launches a sequence of
that does not resemble what is seen in the wild. This events that ultimately causes the cells of the intestinal
can affect how the mice respond to both disease- lining (epithelial cells) to move into and fill the site of
causing stimuli and therapeutic drugs. Therefore, the injury. However, genetic variations—particularly those
researchers utilized mice with microbiomes obtained found more commonly in people with inflammatory
from wild-caught mice, as this microbiome helps the bowel disease—could cause defects in this process. The
animals more closely mimic human immune responses. specific effects of these variations have been difficult
These mice developed colitis when given ICB therapy, to identify, though, because scientists are still trying
which enabled the scientists to study the role of the to piece together all the steps that link blood clotting
gut-resident immune cells in this pathology. The to epithelial cell movement and ultimately the repair of
scientists found that one group of immune cells, T cells, intestinal tissue.
was particularly affected in the guts of mice given ICB.
There are several types of T cells, some of which cause
inflammation while others work to regulate or turn off Researchers have discovered how a genetic
immune responses. Researchers found that mice with risk factor for Crohn’s disease can slow down
ICB-induced colitis had lower numbers of the regulatory the healing of damaged intestinal tissue,
T cells and higher activation of the inflammatory offering new paths toward the development of
T cells. This increased the amount of a protein called treatments.
interferon gamma, which causes intestinal inflammation.
Importantly, they found that a small modification to
the ICB drug could prevent these changes in the gut Using a mouse model and blood samples from people
by avoiding inflammatory T-cell activation while still with Crohn’s disease, researchers recently uncovered
maintaining the drug’s tumor-fighting abilities. an important component of the gastrointestinal healing
puzzle. They focused on a genetic variation associated
These insights into why ICB causes colitis could help with a higher risk of Crohn’s disease that affects a
scientists continue to develop new cancer therapies protein known to play an important role in the wound-
with fewer off-target consequences, making cancer healing process. This protein, called hepatocyte growth
treatments more tolerable and effective. The results factor activator (HGFAC), is switched on by blood
also provide a deeper understanding of colitis, including clotting. HGFAC then activates another protein called
the role of the microbiome, which could lead to the macrophage-stimulating protein (MSP), which, the
development of more therapies for all people living with scientists found, triggers changes in epithelial cells that
this debilitating condition. enable them to move into the damaged tissue. Additional

NIDDK Recent Advances & Emerging Opportunities 2025: Digestive Diseases and Nutrition 54
experiments showed these mobile epithelial cells human gut, which includes multiple layers consisting of
release a chemical called retinoic acid, which stimulates not only epithelial cells but also immune cells that play
the rebuilding of the intricate molecular network that a critical role in celiac disease.
surrounds cells and helps maintain the tissue’s shape.
The scientists found that the genetic variation results Recently, a team of researchers, including scientists
in a modified version of HGFAC that cannot effectively from NIDDK’s Intestinal Stem Cell Consortium,
activate MSP, thereby crippling the movement of developed the first laboratory model that faithfully
epithelial cells, inhibiting the release of retinoic acid, and replicates the complex interactions between human
slowing down the tissue’s ability to heal itself. intestinal epithelial and immune cells. The cells
were collected from intestinal biopsies provided by
The researchers also showed that the HGFAC variation 135 female and male volunteers (81 with diagnosed
affected MSP activation in blood samples from people celiac disease and 54 without the disease but who
who carry the variation, but more research is needed had undergone biopsies for a different condition).
to confirm that this genetic variation has the same The majority of participants were female, as celiac
effect in people with Crohn’s disease as it does in mice. disease is more common in females than in males.
Nevertheless, these results do suggest there may be The researchers discovered how to cultivate the cells
ways to bypass the defect, such as providing active in clusters, called “organoids,” in a way that enabled
MSP. These findings also help researchers understand survival of both epithelial cells and underlying immune
the complicated steps involved in repairing damaged cells. When gliadin (a component of gluten) was added
tissue, which could lead to additional new therapies, not to the organoids from people with celiac disease, the
only for Crohn’s disease but also for other diseases that immune cells reacted rapidly and similarly to how they
feature defects in healing. would in the body, attacking the epithelial cells. The
researchers found that a chemical called IL-7, released
Nakata T, Li C, Mayassi T,…Xavier RJ. Genetic vulnerability to Crohn’s by the organoids’ immune cells in response to gliadin,
disease reveals a spatially resolved epithelial restitution program. Sci Transl is vital to their destruction of the epithelial cells.
Med 15: eadg5252, 2023. Importantly, the researchers confirmed the validity of
this discovery by showing that IL-7—which was not
previously associated with celiac disease—is ramped up
UNCOVERING KEY PLAYERS IN in the intestinal samples of people with active disease,
CELIAC DISEASE which means it could potentially be a target for therapy.

New Celiac Disease Model Reveals Insights About

Immune Response to Gluten: Using intestinal cells Researchers have developed a more accurate
from study volunteers, researchers have developed a laboratory model of celiac disease using human
more accurate and personalized laboratory model of cells, leading to new insights into mechanisms
celiac disease, leading to the discovery of a chemical underlying the disease.
signal’s important role in the gut’s immune response
to gluten.
As demonstrated in this study, this promising model
Celiac disease is caused by gut immune cells reacting can help identify the important players in celiac disease.
abnormally to gluten in dietary grains such as wheat, It will also likely be a useful tool to test potential
rye, and barley. The resulting inflammation ravages therapeutics before moving them forward into more
the small intestine, destroying epithelial cells lining the complicated and expensive clinical trials. And, because
intestine and causing abdominal pain, diarrhea, and the cells are from a person with celiac disease, it may
other potentially severe symptoms. Finding ways to eventually be possible to predict whether a certain
treat celiac disease—other than adhering to a very strict, therapy has a better chance of working in a specific
burdensome gluten-free diet—has been challenging, individual—a step toward developing personalized
largely because of a lack of accurate laboratory models medicine approaches for celiac disease.
to help scientists understand the disease and test
potential therapeutics. Typically, intestinal cells grown Santos AJM, van Unen V, Lin Z,…Kuo CJ. A human autoimmune organoid
in the lab do not replicate the environment of the model reveals IL-7 function in coeliac disease. Nature 632: 401-410, 2024.

NIDDK Recent Advances & Emerging Opportunities 2025: Digestive Diseases and Nutrition 55
TREATING DIARRHEAL DISEASE This study helps to identify why ORS prescription for
IN CHILDREN treating childhood diarrhea is low despite its known
benefits. These findings will hopefully inform the design
Addressing Provider Misperceptions Could Limit Deaths of interventions to encourage ORS use, either through
in Children From Diarrheal Diseases: Researchers informing health care providers or promoting more
recently worked to understand why health care providers communication of preferences by caregivers that will
do not prescribe a common treatment for childhood ultimately benefit thousands of young people at risk of
diarrheal diseases despite knowledge of its benefits. diarrhea around the globe.
Diarrhea is a leading cause of death in young children
worldwide. A low-cost, widely available treatment Wagner Z, Mohanan M, Zutshi R, Mukherji A, Sood N. What drives poor
called oral rehydration salts (ORS)—a mix of sugar and quality of care for child diarrhea? Experimental evidence from India.
electrolytes dissolved in water—is available and well Science, 383: eadj9986, 2024.
accepted, but health care providers do not prescribe it in
almost half of cases where it could be efficacious, despite
these providers identifying it as the standard of care. UNDERSTANDING HOW DIET
AFFECTS HEALTH
To study barriers that prevent the prescription of ORS,
researchers implemented a randomized controlled trial Feeding the Microbiome Helps Children Grow After
in India, where nearly a quarter of the world’s diarrhea- Malnutrition: A recent study found a diet that included
associated deaths in children occur despite more than complementary foods tailored toward promoting the
75 percent of caregivers seeking medical advice for the expansion of healthy bacteria in infants’ guts can help
condition. The study aimed to determine if financial increase growth after malnutrition. Malnutrition remains
incentives (i.e., clinics receiving higher payments for a global public health concern, as it accounts for nearly
antibiotics versus ORS prescribing), supply issues, or half of deaths in children under the age of 5. Infants
patient prescribing preferences influenced whether that experience either acute or prolonged malnutrition
a health care provider recommended ORS. With the have an increased risk of infection, dampened immune
approval of an institutional review board, trained male response, and physical and cognitive growth deficits that
actors sought care from 2,282 private, mostly male can persist through the lifespan.
health care providers across 253 medium-sized towns
throughout two, culturally diverse northern and southern
states of India. These actors pretended to be the father Researchers have found a diet containing a
of a 2-year-old child with diarrhea, describing details complementary food formulated to nurture the
to suggest the underlying cause was viral instead of gut microbiome can increase growth in infants
bacterial, therefore warranting treatment with ORS over with malnutrition in the early years of life.
antibiotics. Different scripts were employed at different
visits to test the potential barriers to ORS prescription.
The bacteria that populate the gut—referred to as the
The results indicate that provider misperceptions of “microbiome”—play an important role in growth and
patient preferences are the strongest barrier to ORS development. Children that experience malnutrition
prescription. When the people portraying caregivers have decreased growth and diversity of the microbiome
signaled a preference for ORS, they were twice as likely as they switch from milk to solid foods, which has been
to be given it. This perceived patient preference was shown to slow child development. Therefore, researchers
6 to 10 times more important than either financial aimed to determine if early dietary intervention to
incentives or supply issues in explaining the providers’ promote a healthy microbiome could help overcome
underutilization of ORS, and it was especially important malnutrition-associated growth deficits. A total of 118
when the would-be caregivers visited clinics that 12- to 18-month-old Bangladeshi male and female
employed providers with no formal medical training. infants with malnutrition participated in a 3-month
Importantly, these results could extend to other areas study that compared feeding of microbiome-promoting
of the world where diarrheal diseases are common or complementary food containing local ingredients with a
to countries where health care providers receive limited conventional supplemental food, in addition to the infants’
formal training. background diet of solid food or breastmilk. Despite

NIDDK Recent Advances & Emerging Opportunities 2025: Digestive Diseases and Nutrition 56
the microbiome-promoting food having less calories processed foods. Each person ate as much as desired
than the conventional one, infants receiving the former of one diet (vegan or keto) for 2 weeks, followed by as
had a significantly higher improvement in their rate of much as desired of the other diet for 2 weeks. People on
weight gain compared to those given the latter. Analysis the vegan diet voluntarily consumed fewer calories than
of the infants’ stools revealed specific types of bacteria those on the keto diet. Throughout the study, blood,
were associated with growth of the children, and the urine, and stool were collected for analysis. The effects of
abundance of these changed in the children consuming the diets were examined using a “multi-omics” approach
the microbiome-promoting food. Additionally, the stool that analyzed multiple data sets to assess the body’s
analysis showed that the microbiome-promoting food biochemical, cellular, metabolic, and immune responses, as
changed how the bacteria convert carbohydrates (one well as changes to the microbiome. Participants remained
of the basic building blocks of food) into energy, creating on site for the entire month-long study, allowing for
different byproducts that could affect both the gut bacteria careful control of the dietary interventions. The scientists
and the infant. found that the vegan diet prompted responses linked
to innate immunity—the body’s non-specific first line
This study provides some clues as to why a microbiome- of defense against pathogens. The keto diet prompted
promoting supplemental food proves superior to the responses associated with adaptive immunity—pathogen-
conventional one for increasing growth in these infants specific immunity built through exposures in daily life
with malnutrition. Additionally, it suggests that different and vaccination. Metabolic shifts in the participants and
bacteria may process carbohydrates from food in different their microbiomes were also observed. For example, the
ways to promote child growth. This may help inform keto diet was associated with changes in participants’
efforts to create even better, culturally relevant diets for amino acid metabolism—an increase in human metabolic
those who are living with malnutrition. pathways for the production and degradation of amino
acids and a reduction in microbial pathways for these
Hibberd MC, Webber DM, Rodionov DA,…Gordon JI. Bioactive glycans in processes—which might reflect the higher amounts of
a microbiome-directed food for children with malnutrition. Nature 625: protein consumed by people on this diet.
157-165, 2024.

Switching to Vegan or Ketogenic Diet Rapidly Impacts Only a few weeks on either a vegan or
Immune System and Metabolism: Researchers observed ketogenic diet prompted distinct changes in
rapid and distinct immune system changes in a small study immune function and metabolism in adult
of people who switched to a vegan or a ketogenic (also study participants.
called keto) diet, opening the way to potential further study
to determine effects on health. The vegan diet eliminates
animal products and tends to be high in fiber and low in The distinct metabolic and immune system changes caused
fat, while the keto diet is a low-carbohydrate diet that by the two diets were observed despite the diversity of
is generally high in fat. Understanding of how specific the participants, which shows that dietary changes can
foods impact the human immune system and microbiome cause consistent effects to multiple pathways in the
(communities of microbes living in the gut) has been limited. body. This study demonstrates that the immune system
Therapeutic nutritional interventions—which involve responds surprisingly rapidly to nutritional interventions.
changing the diet to improve health—are also not well More research is needed to determine if these changes
understood, and few studies have directly compared the are beneficial or detrimental and what effects they may
effects of different dietary patterns on the immune system. have on nutritional interventions for different diseases.
Such research could lead to the development of more
This study comparing immune system and other responses personalized diets to prevent or treat disease.
to vegan and keto diets was conducted by researchers
from NIDDK and NIH’s National Institute of Allergy and Link VM, Subramanian P, Cheung F,…Belkaid Y. Differential peripheral
Infectious Diseases at the Metabolic Clinical Research immune signatures elicited by vegan versus ketogenic diets in humans. Nat
Unit in the NIH Clinical Center. The 20 adult participants Med 30: 560-572, 2024.
were diverse with respect to ethnicity, race, gender, body
mass index, and age. Both diets contained a healthy This writeup was adapted from an NIH News Release authored by the
amount of non-starchy vegetables and minimized highly NIDDK Media Team and NIAID News & Science Writing Branch.

NIDDK Recent Advances & Emerging Opportunities 2025: Digestive Diseases and Nutrition 57
PREVENTING PANCREATIC DISEASE researchers found that the group receiving indomethacin
alone had a 32 percent higher risk of developing post-
A Pancreatic Stent Lowers Risk of Pancreatitis Following ERCP pancreatitis (14.9 percent of those who received
Endoscopic Procedure: A large clinical trial recently found indomethacin alone developed pancreatitis compared
that the combination of an anti-inflammatory drug and the to 11.3 percent of those who received the combination
insertion of a pancreatic stent is more effective than the treatment). This means the combination treatment was
anti-inflammatory drug alone at preventing pancreatitis more effective than indomethacin alone, and people
after an endoscopic procedure called endoscopic at high risk for pancreatitis following ERCP would
retrograde cholangiopancreatography (ERCP). likely benefit from a pancreatic stent. More research is
needed to develop additional (and perhaps even more
A series of ducts connects the liver, gallbladder, and effective) ways to limit the risk of pancreatitis following
pancreas to the intestine to allow the flow of bile ERCP and to better understand and predict who is more
acids and digestive enzymes into the gut. ERCP likely to develop pancreatitis. Nevertheless, despite the
is a valuable and effective procedure that uses an preliminary evidence suggesting that indomethacin may
endoscope (a long, thin, flexible tube fitted with a eliminate the need for stent placement, the results of
tiny camera), in combination with X-ray imaging, to this important, large, multiregional clinical trial support
see and treat disorders of these biliary and pancreatic pancreatic stent placement in addition to indomethacin
ducts. Pancreatitis—a painful inflammation of the in high-risk patients, in accordance with clinical practice
pancreas—is one of the most common and potentially guidelines.
serious complications associated with ERCP, with
risk varying from person to person. The medical Elmunzer BJ, Foster LD, Serrano J,…Durkalski-Mauldin V; on behalf of
community recommends several measures to prevent the SVI Study Group. Indomethacin with or without prophylactic stent
pancreatitis following ERCP, including hydration and placement to prevent pancreatitis after ERCP: a randomized non-inferiority
anti-inflammatory drugs such as indomethacin, which trial. Lancet 403: 450-458, 2024.
has shown some promise to be an effective deterrent.
It is also recommended that individuals considered
to be at high risk for ERCP-associated pancreatitis be DISCOVERING FACTORS INVOLVED IN
given a temporary stent (a small, tubular support) in the LIVER INFLAMMATION
pancreatic duct, in addition to indomethacin, although
the stenting procedure also carries risk of complications. Key Protein Drives Liver Inflammation and Fibrosis:
It was not clear, however, whether indomethacin Researchers identified the role of a particular protein in
alone is as effective as the combination treatment of orchestrating the processes of liver inflammation and
indomethacin plus a pancreatic stent. Importantly, fibrosis that occur as part of the liver disease nonalcoholic
treatment with indomethacin alone, if equally effective steatohepatitis, or NASH (also referred to as metabolic
as the combination treatment, would avoid the additional dysfunction-associated steatohepatitis, or MASH), in
risks and high costs associated with inserting a stent. studies in mice and cells. Nonalcoholic fatty liver disease
(also referred to as metabolic dysfunction-associated
steatotic liver disease) and its more severe form of
A large clinical trial recently found that NASH are common diseases experienced by adults and
administering an anti-inflammatory drug children in the United States and around the world. A
along with a pancreatic stent is more leading cause of liver transplantation and liver cancer,
effective at preventing pancreatitis after NASH is marked by excess fat accumulation in the liver,
an endoscopic procedure than the inflammation, and fibrosis, or scar tissue formation. In
anti-inflammatory drug alone. addition to diet and exercise, the first drug to treat NASH
with liver scarring was recently approved by the U.S. Food
and Drug Administration (FDA). Further research on
To compare the effectiveness of these two approaches, disease pathways could lead to the identification of new
1,950 women and men deemed to be at high risk for potential therapeutic targets and strategies to prevent
ERCP-associated pancreatitis—at 20 sites across the scarring and other serious effects of the disease.
United States—were given either the combination
treatment (indomethacin plus a pancreatic stent) or The liver inflammation and scarring of NASH are
indomethacin alone when they underwent ERCP. The driven by a complex interplay of factors among and

NIDDK Recent Advances & Emerging Opportunities 2025: Digestive Diseases and Nutrition 58
within liver and immune cells. Mechanisms driving this infection and injury originating outside and within the
process, or how to halt or possibly reverse it, are not cell into an inflammatory response.
fully understood. One research team looking at liver
disease processes set their sights on a protein secreted Delving deeply into the complex cellular machinery at
by liver cells called CYR61. This protein is produced work, researchers used three genetically different mouse
in greater quantities in livers from people with NASH, strains—one that is resistant to NASH and two that are
and is known to communicate with nearby immune and susceptible to NASH to varying degrees when fed a diet
fibrosis-causing cells. However, the protein’s effects on high in fat, cholesterol, and sugar—and compared the
liver fibrosis are unclear. The studies were conducted activity of genes in the mice. They observed that Kupffer
in a mouse model of NASH, in which the mice are fed a cells in these strains responded differently to this diet,
diet high in fat, cholesterol, and sugar, resulting in excess in terms of regulating their activation of certain genes.
liver fat and injected with a chemical that simulates They then asked what factors influence gene activity in
fibrosis. Both female and male mice, some of which were the Kupffer cells in response to different conditions by
genetically altered to lack the CYR61 protein in the main comparing the NASH-resistant mice with the mice that
functional cells of the liver, were used for some of the were the most susceptible to NASH. They found that
studies, while only male mice were used for others. The the answer was: It depends. Under conditions where
researchers observed that, among mice lacking CYR61, cells were maintaining normal function, the researchers
those fed the NASH-inducing diet had reduced liver found that much of the gene activity variation between
inflammation and fibrosis. By marking and examining the Kupffer cells of the mouse strains resulted from the
specific cell types in studies of the mice and of cells influence of factors coming from outside of the Kupffer
grown in dishes, the researchers showed that CYR61 cells, such as signals from other cells, with some effects
activated certain immune cells to promote inflammation from factors within the Kupffer cells acting indirectly to
and fibrosis. Conversely, blocking CYR61’s activity with influence gene expression. But when the researchers
an antibody reduced fibrosis. tested a different inflammatory condition in response
to a bacterial protein, they found that strain-specific
This research illuminates the cellular pathways utilized responses within the Kupffer cells derived more from
by CYR61 to promote liver inflammation and fibrosis. the genetic variations within the Kupffer cells having
CYR61 and the cellular pathways it affects could serve direct effects on the genes that were differentially active.
as targets for developing future treatments that improve This study shows how genetic differences associated
outcomes and limit the progression of NASH. with disease risk can influence cell functioning—either
by altering gene expression through direct or indirect
Mooring M, Yeung GA, Luukkonen P,…Yimlamai D. Hepatocyte CYR61 effects within the cells of interest or by influencing
polarizes profibrotic macrophages to orchestrate NASH fibrosis. Sci Transl expression of factors in different cell types that can then
Med 15: eade3157, 2023. act on the cells of interest. This insight can lead to a
better understanding of disease processes and may have
Understanding the Effects of Genetic Differences implications for developing new therapies.
on Liver Immune Cells Involved in Inflammation:
Researchers studied a type of liver immune cell These findings are relevant not only to defining cellular
involved in inflammation and parsed the impacts of mechanisms involved in liver inflammation and disease,
genetic differences between mice on the expression but also may be applied to studies of other cell types and
of genes within these cells under different conditions, disease processes.
providing clues as to how these cells may affect liver
disease progression. The liver contains different types Bennett H, Troutman TD, Zhou E,…Glass CK. Discrimination of cell-intrinsic
of macrophages, a type of immune cell that engulfs and environment-dependent effects of natural genetic variation on Kupffer
pathogens and activates other immune cells. Kupffer cell epigenomes and transcriptomes. Nat Immunol 24: 1825-1838, 2023.
cells, named for the scientist who discovered them, are
the most common type of liver macrophage, and play
a key role in disease processes such as inflammation PREDICTING LIVER DISEASE OUTCOMES
associated with the liver disease nonalcoholic
steatohepatitis, or NASH (also referred to as metabolic Using Noninvasive Liver Stiffness Measurement to
dysfunction-associated steatohepatitis or MASH). Still Predict Liver Disease Outcomes: In a study of adults
unknown is exactly how Kupffer cells translate signals of with nonalcoholic fatty liver disease or NAFLD (also

NIDDK Recent Advances & Emerging Opportunities 2025: Digestive Diseases and Nutrition 59
referred to as metabolic dysfunction-associated steatotic 1,400 women and men, approximately 80 percent
liver disease or MASLD), NIDDK’s NASH Clinical identifying as White and 11 percent as Hispanic,
Research Network found that liver stiffness, measured participating in the NASH Clinical Research Network
noninvasively, may serve as an indicator for risk of at nine clinical centers across the United States.
outcomes such as liver cancer, liver failure requiring Participants received baseline and annual exams
transplantation, or death. NAFLD, currently the most with liver stiffness measures for an average of over 4
common form of liver disease in the United States, is a years, during which information was collected on the
condition where fat accumulates in the liver. Its most number and types of liver-related adverse events they
severe form—known as nonalcoholic steatohepatitis, experienced. These events included liver cancer, liver
or NASH (also referred to as metabolic dysfunction- failure requiring transplantation, liver-related death,
associated steatohepatitis or MASH)—involves excess and other clinical outcomes of NAFLD. The researchers
fat accumulation in the liver, as well as inflammation observed that people whose liver stiffness measures
and fibrosis (scar tissue formation), and is the leading increased during the study above a certain threshold—
reason for adult liver transplantation in the country. suggesting liver disease progression—had a four-fold
Early detection of liver disease is challenging because it increase in liver-related events compared to people
requires a biopsy, and monitoring disease progression whose liver stiffness remained under the threshold.
requires a series of biopsies. Researchers have been Conversely, people whose liver stiffness measures
working for years on developing noninvasive but highly started above the threshold but fell below it during the
informative ways to diagnose and monitor the liver same period had a 75 percent decrease in their risk
health of people with NAFLD. of liver-related events relative to people whose liver
stiffness stayed above the threshold.

A study in adults participating in NIDDK’s Based on these study results, the investigators view
NASH Clinical Research Network found that measures of liver stiffness over time as a useful
liver stiffness measures may serve as a non- noninvasive indicator of the direction of clinical
invasive indicator for risk of clinical outcomes outcomes from NASH. These measures can be used
from liver disease progression. to improve clinical care by helping to identify people
with NAFLD at risk for worse outcomes and to facilitate
testing responses to new therapies in clinical trials.
In this study, a research team assessed whether
measuring liver stiffness using a noninvasive technology Gawrieh S, Vilar-Gomez E, Wilson LA,…Chalasani N; for the NASH Clinical
called vibration-controlled transient elastography, or Research Network. Increases and decreases in liver stiffness measurement
VCTE, could accurately predict increasing or decreasing are independently associated with the risk of liver-related events in NAFLD.
risk of chronic liver disease. They studied more than J Hepatol 81: 600-608, 2024.

NIDDK Recent Advances & Emerging Opportunities 2025: Digestive Diseases and Nutrition 60
 FEATURE
Study Explores Factors Underlying
Healing of Crohn’s Disease in Children
A new NIDDK-supported clinical trial is looking to
better understand why some children with Crohn’s
disease experience complete healing after receiving a
common therapy, while others do not.

Crohn’s disease is a form of inflammatory bowel

disease (IBD) that causes lesions in the lining of the States and Canada, in partnership with the hundreds
small intestine and/or colon in both children and of children ages 6 to 17 enrolled in the study
adults. Symptoms may include abdominal cramping, and their families. The study is investigating the
diarrhea, blood in the stool, weight loss, and delayed association between patients’ pre-treatment clinical,
growth in children. While the cause is unclear, it is radiologic (detectable with imaging such as MRI or
thought to stem from overactivity of the intestinal X-ray), genomic, and microbial features and how well
immune system in policing potential pathogens, so their bodies are able to completely heal in response
doctors typically use anti-inflammatory treatments to treatment. The children receive anti-TNF therapy
to address the disease and ideally heal the gut. for 1 year, guided by a computer program to optimize
Some of the most common treatments inhibit the dosing for each patient. Participants provide
inflammatory molecule called TNF, but responses vary periodic blood, stool, and tissue biopsy samples to
across individuals, and these treatments come with measure pre-treatment factors and test for signs
high costs and the risk of side effects. Some children of inflammation. Study participants also undergo
with Crohn’s disease treated with TNF-blocking regular colonoscopies and a special type of MRI
drugs show complete intestinal healing, while others called magnetic resonance enterography, or MRE.
continue to experience symptoms or even progression These procedures allow the researchers to assess
of their disease, sometimes requiring surgery. how much intestinal healing is occurring in response
Understanding the characteristics that determine to the treatment. Currently, the study is continuing
whether the treatment will result in complete healing to enroll study participants, but once completed, the
has the potential to profoundly influence patient care study’s impact will be amplified through availability
and outcomes. of data and samples to investigators in the broader
research community for additional studies.
To address this need for more knowledge, NIDDK
launched a new study in 2023 called the Clinical, The hope of the CAMEO study is that its findings
Imaging, and Endoscopic Outcomes of Children Newly will help to determine the likelihood that pediatric
Diagnosed with Crohn’s Disease Study, or CAMEO. Crohn’s disease patients will experience responses
The study aims to identify features present at the time and remissions with current treatments, as well as to
when children are diagnosed with Crohn’s disease inform future treatment development. These study
that can predict whether their disease will be healed efforts serve the larger goal of developing better ways
in response to treatment. It is being conducted at to care for children with Crohn’s disease.
26 clinical centers researching IBD across the United

NIDDK Recent Advances & Emerging Opportunities 2025: Digestive Diseases and Nutrition 61
 FEATURE
New Clinical Trial Aims to Compare
Endoscopy Approaches for
Preventing Esophageal Cancer
Esophageal cancer is one of the deadliest cancers in
the United States. The disease starts when cancer
cells form in the esophagus (the muscular tube
that carries food and liquids from the mouth to the
stomach), with symptoms usually not appearing until
the cancer has spread to other organs. This makes
the disease very difficult to treat, so major goals for
NIDDK-supported scientists are to come up with
ways to detect changes in esophageal cells before
the cancer has a chance to develop and to compare routinely monitor the cells in Barrett’s esophagus
approaches to intervene at these early stages to by surveillance endoscopy. This procedure uses a
prevent cancer. long, thin, flexible tube fitted with a tiny camera and
other tools to see inside and collect small biopsy
Prior studies have shown that one of the earliest samples from the esophagus. If abnormal cells are
changes that could lead to esophageal cancer is found, doctors can use a treatment called endoscopic
Barrett’s esophagus, a relatively common condition eradication therapy (EET) to remove the precancerous
wherein the cells in the esophagus take on cells. Studies have shown that using EET is effective
characteristics of intestinal cells. Barrett’s esophagus for preventing esophageal cancer in people with high-
does not cause perceptible symptoms, though many grade dysplasia, but it is unclear whether it should be
with this condition also experience gastroesophageal used for low-grade dysplasia, since most cases of low-
reflux disease. While most people with Barrett’s grade dysplasia do not progress to cancer, and EET is
esophagus do not develop esophageal cancer, they are costly and carries risk of complications.
at higher risk for the disease.
To determine whether EET would be more beneficial
When Barrettʼs esophagus transitions to cancer, it than the surveillance type of endoscopy alone
does so in a stepwise fashion. The first step is that for people with low-grade dysplasia, NIDDK is
the cells undergo dysplasia, or irreversible changes sponsoring a large, multi-center clinical trial called
that typically start as “low-grade,” which means the Surveillance Versus Endoscopic Eradication Therapy
cells have some characteristics of cancer cells but are Trial (SURVENT). Adult participants with low-grade
not defined as cancer. Low-grade dysplasia is fairly dysplasia will undergo either surveillance for 1 to 4
common in people with Barrett’s esophagus, and years or EET (followed by surveillance endoscopy).
only some people progress to the next step—“high- By monitoring (and treating) any progression toward
grade” dysplasia—in which esophageal cells look very cancer, the researchers can determine if there are
abnormal and have a higher chance of becoming benefits to using EET at this early stage.
cancerous. As a preventive measure, doctors will

NIDDK Recent Advances & Emerging Opportunities 2025: Digestive Diseases and Nutrition 62
 FEATURE
The SURVENT trial also provides researchers with will be to determine how accurately these markers
an opportunity to find new ways to predict if a predict if a person is at high risk for developing cancer,
person with Barrett’s esophagus has a high chance so appropriate treatment decisions can be made.
of eventually developing esophageal cancer. Studies
have shown that certain molecular and cellular Overall, the SURVENT trial aims to help guide
markers linked to cancer can appear in some people treatment decisions for Barrett’s esophagus, with the
with Barrett’s esophagus years before dysplasia is ultimate goal of preventing esophageal cancer. It will
detectable, which means these markers could act as also inform the management of Barrett’s esophagus,
very early warning signs that cancer is likely to develop improving the lives of millions of people in the United
in the future. Thus, another aim of the SURVENT trial States living with this condition.

NIDDK Recent Advances & Emerging Opportunities 2025: Digestive Diseases and Nutrition 63
 PERSONAL PERSPECTIVE
Alicia: Crafting a Life With
Gastroparesis
gastroparesis—a potentially debilitating condition
wherein the stomach empties too slowly. (For more
information on gastroparesis, see the info box at the
end of this feature.)

ON THE OTHER SIDE OF CLINICAL

RESEARCH

Alicia found herself navigating a new and unfamiliar

diagnosis as the COVID-19 pandemic lockdowns
began in March 2020. “I got diagnosed right when
everything shut down, so I kind of was handed a diet,
and it was like, ʽWeʼll see you when the world opens
back up,ʼ” she says.

As a lab researcher with a biology degree working at

a pharmaceutical company, Alicia was knowledgeable
about clinical research. But even for someone with
Alicia is participating in the Gastroparesis Clinical Research Consortium, her background, being on the other side as a patient
which aims to catalyze research and test new diagnostics and therapies proved challenging in the months after her diagnosis
for gastroparesis as she continued to experience symptoms while taking
the prescribed medications and consulting with a
nutritionist.
Dealing with a newly diagnosed disease is daunting—
even more so during a global pandemic. In early 2020, In December 2020, Alicia saw Dr. Henry Parkman, a
at age 24, Alicia went to see a gastroenterologist leading gastroparesis specialist at Temple University.
for what she thought was worsening of the chronic He prescribed a targeted treatment plan for her
heartburn she had experienced since adolescence. type of gastroparesis, which is “idiopathic,” or of
Her frequent symptoms of feeling overly full and unknown cause. Like many individuals with these
nauseated were affecting her quality of life and types of disorders, Alicia’s treatment journey was
ability to work. “It was getting to the point where I not straightforward. After trying a few different
just wouldn’t want to eat breakfast in the morning medications, her nausea and vomiting persisted,
… because I was afraid that I was going to feel ill, so in 2022, she underwent surgery to widen the
and I wouldn’t be able to get through my workday,” opening between her stomach and small intestine.
she recalls. Her doctor prescribed different acid Simultaneously, surgeons placed a gastric stimulator—
reflux medications and ran many tests, including an electrical device that sends mild pulses to the
one for gastric emptying that confirmed she had a stomach—in Alicia’s abdomen. The surgeries helped,
chronic gastrointestinal (GI) motility disorder called but she continued experiencing nausea, acid reflux,

NIDDK Recent Advances & Emerging Opportunities 2025: Digestive Diseases and Nutrition 64
 PERSONAL PERSPECTIVE
and weight loss—a common problem for people with with a specialized nutritional formula to supplement
gastroparesis. Reluctantly, she had another surgery what she is able to eat during the day, used in
to place a plastic jejunostomy tube, or J tube, into her tandem with the gastric electrical stimulator and
small intestine so she could directly ingest nutrients. medications. The J tube has the added benefit of
Afterwards, she was hospitalized while recovering from allowing her medications to be readily available in
a postoperative ileus, a potential surgical complication the intestine for absorption.
where the bowels stop moving, and was prescribed
medication for severe constipation—another common Alicia’s health has improved to the point where she
condition for some individuals with gastroparesis. has gained 20 pounds in 1 year and hopes to soon
reach her target healthy weight. “I was terrified when
they said I had to get a tube and I hated it at first,”
“I was terrified when they said I had to get a says Alicia. “And then I started feeling so good that
tube and I hated it at first,” says Alicia, who I’m grateful I did it.” She’s applied her newfound
underwent treatments for her gastroparesis, energy to her lifelong interest in doing “any and all
including placement of a tube in her small crafts” while cozying up with her cat, Mittens, and
intestine to supply more nutrition. “And has donated hand-sewn “tubie pads”—reusable fabric
then I started feeling so good that I’m pads that fit around various types of feeding tubes,
grateful I did it.” including J tubes, and help minimize leakage and
irritation—to nonprofits that provide them in kids’
care packages.
While receiving what she viewed as excellent care
at Temple, staff told Alicia about a registry study
as part of NIDDK’s Gastroparesis Clinical Research “It can feel like youʼre just one person,” says
Consortium, involving several clinical sites around Alicia of her life with gastroparesis and why
the country. The study goals are to understand she chose to participate in the Gastroparesis
the prevalence, progression, and outcomes of Clinical Research Consortium adult registry
gastroparesis. “I had worked on the other side of study, “but when a bunch of people come
clinical research for so long…. I was pretty adamant together and participate, it brings together
that I wanted to help contribute more data and to all of these data points that then can
enroll,” says Alicia. She has participated in the study be used to better help others with these
ever since, traveling to Temple a few times a year to conditions.”
give blood samples, fill out symptom questionnaires,
and undergo testing. Her family, many of whom
experience acid reflux issues, have supported her Though Alicia is still mindful about eating an easy-
participation and are now well-informed about to-digest diet, she has learned how to manage this
gastroparesis. Alicia has even enjoyed some study in social settings. “Thatʼs been the biggest change
procedures, such as a special gastric emptying test for me—to kind of keep that socialization while also
where she viewed her stomach movement. protecting myself and not feeling ill,” she says. Alicia
has also met others with gastroparesis through
social media to raise awareness, and often shares
NOURISHING A NEW APPROACH TO LIFE resources on gastroparesis, such as the International
Foundation for Gastrointestinal Disorders. “Itʼs
Alicia has emerged from the challenging period of made me feel a lot better about it, having people
her pandemic-era diagnosis with a new approach to to talk to who also have the condition and who
nourishing herself—physically and socially. She is understand what itʼs like to go through a day with it,”
thriving on her regimen of nightly J tube feedings she says.

NIDDK Recent Advances & Emerging Opportunities 2025: Digestive Diseases and Nutrition 65
 PERSONAL PERSPECTIVE
THE VALUE OF RESEARCH Alicia says of her motivation for
participating in the Gastroparesis Clinical
Participating in research as a patient has given Alicia a
Research Consortium adult registry study,
renewed appreciation for her chosen line of work. “I
“If it was to help with developing better
think clinical research is so important,” she remarks.
treatment options for people, and they were
“[Living with gastroparesis] can feel like youʼre just
able then to get their lives back, I feel like
one person,” she says, “but when a bunch of people
that would be really rewarding.”
come together and participate, it brings together
all of these data points that then can be used to
better help others with these conditions.” One of Alicia’s self-care and study participation have
Alicia’s motivations for enrolling in the study was to paid off. “Now I can go out with friends … go to
answer remaining research questions, particularly the Renaissance fair with my sister for the day,”
those needed to better understand what drives her she says. “I am now excited to go on our beach
idiopathic form of gastroparesis. vacation because I know Iʼll have the energy to
walk the boardwalk and actually enjoy it with my
Although life with gastroparesis has been challenging, family,” Alicia shares. Although her health is much
Alicia remains optimistic that research can lead to improved, she remains vigilant. “Itʼs something
even better options for treatment and prevention. that I canʼt not think about, especially since food is
She adds about her study participation that “if it was such a big part of our lives, and I donʼt really have a
to help with developing better treatment options for traditional meal during the day,” says Alicia. “But I
people, and they were able then to get their lives feel like itʼs finally manageable, and I finally feel like
back, I feel like that would be really rewarding.” myself again.”

More Information on Gastroparesis and the

Gastroparesis Clinical Research Consortium
Gastroparesis is a chronic disorder where movement cancer treatments. But in many cases, the cause is
of food by the stomach into the intestine slows unknown or “idiopathic.” The disorder is uncommon,
down or stops without any signs of physical but in the United States it is most prevalent in
blockage. The unremitting digestive symptoms women and in those at higher risk for diabetes.
and pain that often result can limit overall health Symptoms of nausea, feeling full soon after eating,
and quality of life. Research supported by NIDDK and abdominal pain can lead to serious issues with
contributes toward more fully understanding this dehydration from repetitive vomiting, fluctuating
disorder and finding better ways to manage it. blood sugar (glucose), malnutrition in terms of calories
and vitamins, and weight loss. The delayed stomach
Gastroparesis may result from diabetes; surgical emptying of gastroparesis is diagnosed by tracking
injury to the vagus nerve that connects the brain to an ingested meal or wireless capsule. No dedicated
the digestive system; hypothyroidism; autoimmune therapies for gastroparesis have been approved by
or nervous system diseases; viral infections; or some the U.S. Food and Drug Administration. However,

NIDDK Recent Advances & Emerging Opportunities 2025: Digestive Diseases and Nutrition 66
 PERSONAL PERSPECTIVE
treatment can include new dietary habits or starting of gastroparesis, as well as genetic factors, all of
on oral, nasal intravenous, or direct intestinal tube which could lead to new ways to diagnose or treat
feeding; medications to control blood sugar or to the disorder. Clinical trials have tested therapeutic
improve stomach muscle function, control nausea and approaches for idiopathic and diabetic gastroparesis,
vomiting, and reduce abdominal pain; or surgeries to tracked outcomes with treatments such as gastric
reduce stomach pressure or install a device delivering electrical stimulation, and developed new tools,
mild electrical impulses to the stomach. including a diagnostic instrument for children.
Through the NIDDK Central Repository, NIDDK
In 2006, NIDDK established the Gastroparesis provides broad researcher access to consortium
Clinical Research Consortium to catalyze research samples and data for ancillary studies. The
and test new diagnostics and therapies. Now in Institute also funds several investigator-initiated
its fourth iteration, the consortium encompasses gastroparesis studies, such as clinical trials of new
six adult clinical centers, six pediatric centers, and therapies and studies utilizing advanced imaging and
a scientific data research center. In addition to cellular technologies.
clinical trials, the consortium oversees gastroparesis
registries for adults and, more recently, for children, NIDDK is continuing support for the consortium to
to enable ongoing studies on epidemiology, natural enable its ongoing studies, as well as advance new
history, and clinical outcomes. The consortium efforts, including an annotated sample repository
maintains the largest repository of gastroparesis data to identify disease biomarkers. NIDDK is also
and samples in the world. partnering with industry and advocacy groups, such
as the International Foundation for Gastrointestinal
Consortium studies have proven invaluable Disorders, to increase patient engagement in the
for informing gastroparesis care by improving consortium. Through the consortium and other
understanding of the clinical spectrum, symptom efforts, research will continue to inform advances
severity, and physical and mental impacts in people in clinical care that improve the lives of people with
with this gastrointestinal disorder. Studies have gastroparesis.
identified several factors associated with disease
course, including gender, age, race and ethnicity, For information on the Gastroparesis Clinical Research
viral illness, depression, and weight. They have Consortium: https://jhuccs1.us/gpcrc
found neuronal, muscular, and immune drivers

NIDDK Recent Advances & Emerging Opportunities 2025: Digestive Diseases and Nutrition 67