investigators linked higher coffee consumption with lower risk of cirrhosis, liver cancer and liver-related death.

“Previous studies suggested that coffee might benefit the liver, but most were smaller or looked at only one piece of the puzzle,” said hepatologist Hyunseok Kim, MD, MPH, PhD, assistant professor of Medicine at Cedars-Sinai and corresponding author of the study. “We followed hundreds of thousands of people for more than a decade and looked at their health outcomes along with liver MRI scans and blood protein analyses. Together, those findings help explain the biological mechanisms behind coffee’s association with better liver health.”

A Cedars-Sinai study of more than 355,000 adults found that drinking coffee was associated with lower risks of cirrhosis, liver cancer and liver-related death. The investigators analyzed data from 354,957 UK Biobank participants who did not have cirrhosis or liver cancer at the start of the study. Over a median follow-up of 13 years, researchers tracked new diagnoses of cirrhosis, liver cancer and liver-related death through linked health records.

Compared with people who did not drink coffee, those who drank five or more cups of coffee a day had a 32% lower risk of cirrhosis, a 47% lower risk of liver cancer and a 42% lower risk of liver-related death. Participants who drank more coffee also had lower levels of liver fat, liver iron, fibrosis and liver inflammation in MRI scans. And coffee drinkers’ blood tests showed higher levels of proteins tied to healthy liver function and lower levels of proteins linked to scarring and inflammation.

While liver health risk decreased as coffee consumption increased, researchers noted that benefits were seen even at one to two cups per day and appeared strongest around three to four cups per day. They emphasized that while the highest intake group (five or more cups daily) showed benefit, they would not recommend increasing consumption to that level specifically.

Similar protective associations were observed for caffeinated and decaffeinated coffee, suggesting that caffeine itself is unlikely to be the only active component, and that other naturally occurring compounds in coffee may contribute to the benefits. Because the study was observational, investigators noted it does not prove that coffee itself prevents liver disease. And they emphasized that coffee should complement—not replace—established strategies for preventing liver disease.

“Our findings support moderate coffee consumption for people who already enjoy and tolerate it well,” said study senior author Ju Dong Yang, MD, medical director of the Liver Cancer Program at Cedars-Sinai. “However, we would not recommend that someone begin drinking coffee solely for liver protection based on this study alone. Prevention should continue to focus on maintaining a healthy weight, limiting alcohol, exercising regularly, and managing blood sugar, blood pressure and cholesterol.”

Because caffeine isn’t appropriate for everyone, people with uncontrolled high blood pressure, certain heart rhythm disorders, severe anxiety, insomnia or other conditions that require limiting caffeine should consult their healthcare provider before increasing their coffee consumption.

“The next step in our research is to identify the specific compounds in coffee that are responsible for these liver-protective associations,” said study author Shelly Lu, MD, the Women’s Guild Chair in Gastroenterology and director of the Karsh Division of Gastroenterology and Hepatology at Cedars-Sinai. “Our findings point to biological pathways involving inflammation and scarring and highlight molecular targets that future research can explore to better understand how coffee may influence liver health and who stands to benefit the most.”

Additional Cedars-Sinai authors include Yufeng Wang, Abdelrahman M. Attia, Minsun Kwak, Seungwon Burm, Derin Celtik, Daniel Legaspi, Osama Khattab, Naomy Kim, Beza M. Mengistu, Kelsey N. Larios, Walid Ayoub, Alexandar Kuo, Paul Martin, Aarshi Vipani, Yun Wang, Debiao Li and Stephen Pandol.

Other authors include Mohammad Saeid Rezaee-Zavareh, David Sooik Kim and Suthat Liangpunsakul.

Conflicts of Interest: Ju Dong Yang reports the following conflicts of interest: consulting service for AstraZeneca, Eisai, Exact Sciences, and Fujifilm Medical Sciences.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

Alcohol‐associated liver disease, which is caused by chronic alcohol use, can lead to inflammation and scarring of the liver. In severe cases it can lead to liver failure, with some patients requiring a liver transplant. The condition accounts for nearly half of the liver-disease-related deaths in the U.S., according to the National Institutes of Health.

“We do not have effective therapies for alcohol‐associated liver disease,” said Shelly Lu, MD, the Women's Guild Chair in Gastroenterology and director of the Karsh Division of Gastroenterology and Hepatology. “Abstaining from alcohol can arrest this condition but this is often difficult to achieve. To save lives, we need to target drivers of alcohol-associated liver disease that promote inflammation and scarring. ”

Lu is co-corresponding author of a study, published in Hepatology, which connected a protein called FOXM1 with scarring and inflammation in alcohol‐associated liver disease. Another recent Cedars-Sinai study, published in Science Advances, showed that alcohol caused an enzyme known as SRC to alter the liver’s immune responses.

In Lu’s study, investigators examined alcohol-exposed human liver tissue samples and cells, and those of laboratory mice. They found that the FOXM1 protein controlled a network of genes and proteins that worked together to cause liver scarring and inflammation. FOXM1 is known to be involved in multiple liver diseases, including cancer. When the investigators suppressed the action of FOXM1, liver scarring was reversed.

“We found that FOXM1 is a key regulator of alcohol-associated liver disease progression and represents a promising target for therapeutic intervention,” Lu said.

The Science Advances study demonstrated how alcohol exposure—through the action of the enzyme SRC and the protein called UBC9—triggered inflammation and immune changes in the liver. When investigators used gene editing or enzymes to block SRC activity,  inflammation was reduced.

“The strong effect of enzymes suggests the possibility of therapeutic targets against alcohol‐associated liver disease,” said Maria Lauda Tomasi, PhD, associate professor of Medicine and Biomedical Sciences at Cedars-Sinai and the study’s co-corresponding author.

The findings also highlight UBC9 as a key regulator of the immune response, which could have implications beyond the liver for cancer and other inflammatory diseases, Tomasi said.

“These rigorous studies contribute greatly to our understanding of alcohol‐associated liver disease,” said David E. Cohen, MD, PhD, chair of the Department of Medicine. “The findings could open new pathways for the development of urgently needed treatments.”

Other Cedars-Sinai authors of the Hepatology study include Bing Yang, Liqing Lu, Jiaohong Wang, Lucía Barbier-Torres, Jing Zhang, Jyoti Chhimwal, Sonal Sinha, Brent Beadel, Guo Zhang, Takashi Tsuchiya, Maria Lauda Tomasi and Heping Yang. The other author was Ting Liu.

Funding: This work was supported by NIH grant R01AA026759 (Shelly C. Lu, Heping Yang, and Maria Lauda Tomasi).

Other Cedars-Sinai authors of the Science Advances study include Swati Chandla, Youngyi Lim, Andrea Floris, Michael Mazarei, Xi Yang, Takashi Tsuchiya, Manisha Dagar, Alfonso Darmawan, Monica Justo, Ramachandran Murali, Alexandra Gangi, Nirmala Mavila and Komal Ramani. The other author was Ivan Tomasi.

Funding: This work was supported by the National Institutes of Health, grant 

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

Digestive Disease Week is the largest international gathering of physicians and scientists in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery.

Cedars-Sinai is a nationally recognized leader in gastroenterology and gastrointestinal surgery. Digestive and liver disease experts attending the conference are available to discuss a wide variety of research, including these presentations.

Late-Breaking Trial Shows Progress in Difficult Ulcerative Colitis

Maria T. Abreu, MD, executive director of the F. Widjaja Inflammatory Bowel Disease Institute, will present late-breaking results from a clinical trial evaluating two targeted biologic therapies for ulcerative colitis used together. The study focused on patients whose disease had not responded to multiple advanced treatments and found that the combination led to higher rates of clinical remission and healing of the intestinal lining compared with either drug alone.

“We studied patients whose disease has already proven difficult to treat and found that using two therapies together led to stronger outcomes than either alone, without increasing side effects,” Abreu said.

Irritable Bowel Syndrome (IBS)

Ali Rezaie, MD, medical director of the GI Motility Program, will present research that found palatable elemental diet nutrition replacement reduced abdominal pain and related symptoms in people with irritable bowel syndrome after two weeks.

Zoe Krut, MHDS, a clinical research coordinator with the Center for Outcomes Research and Education at Cedars-Sinai Health Sciences University, will present research from a multicenter randomized trial showing that virtual reality-delivered cognitive behavioral therapy improved symptoms of IBS and was well accepted by patients. Study leader Christopher Almario, MD, MSHPM, assistant professor of Medicine and Health Systems Research, will also be on hand to discuss the research.

Interventional Gastroenterology

Barham K. Abu Dayyeh, MD, MPH, director of Interventional Gastroenterology, will share results of a study in which a less invasive laparoscopic procedure for hiatal hernia-associated GERD (gastroesophageal reflux disease) was used. It achieved results similar to standard surgery, with fewer complications. The abstract has been selected for the “Best of DDW” session held at the end of the meeting, highlighting 6 of the top studies presented.

Abu Dayyeh will also share results of another study in which a novel endoscopic therapy used pulsed electric fields to treat the lining of the small intestine. Results reveal improvements in blood sugar control and weight management for nearly one year in adults with Type 2 diabetes.

Inflammatory Bowel Disease

Talin Haritunians, PhD, a research associate professor of Medicine, will present results of a study that found patients with inflammatory bowel disease (IBD) have distinct genetic variants linked to an increased risk for cardiovascular disease, independent of traditional risk factors.

Allistair Clark, MA, a clinical research data specialist at Cedars-Sinai Health Sciences University, will share results of an investigation that found an AI-powered virtual reality therapy reduced pain and anxiety in patients with inflammatory bowel disease (IBD) in both inpatient and outpatient settings.

Small Intestinal Bacterial Overgrowth (SIBO)

Ruchi Mathur, MD, an endocrinologist, and Gabriela Leite, PhD, a research scientist, will present research linking changes in the small bowel microbiome to Type 2 diabetes. These include strong associations with small intestinal bacterial overgrowth (SIBO) and higher glucose levels. Mathur and Leite are with the Medically Associated Science and Technology (MAST) Program.

Diagnostics: Breath Testing

Mark Pimentel, MD, gastroenterologist, and project scientist Maria Jesus Villanueva-Millan, PhD, of the MAST program, are available to discuss their research t directly comparing breath and small-intestine gases in the same patients, showing that hydrogen sulfide levels reflect those in the small intestine and are linked to specific microbes and diarrhea severity.

Liver Disease

Hyunseok Kim, MD, MPH, PhD, hepatologist and assistant professor, Medicine, will present results of research examining biomarkers that may help predict cirrhosis and liver disease progression in people with alcohol-associated liver disease.

Ju Dong Yang, MD, medical director of the Liver Cancer Program, and clinical research data specialist Osama Khattab, MD, are available to discuss their research showing that transarterial radioembolization (TARE) achieved survival outcomes comparable to ablation in early-stage liver cancer, suggesting it may offer an alternative treatment option for patients.

Media Contact

To schedule an interview with a Cedars-Sinai expert during the conference, please contact Laura Coverson Laura.Coverson@cshs.org or 310-562-1112.

program to residents of 39 states, giving people across the U.S. fast, convenient, at-home access to expert medical insights on treatment options for more than 600 health conditions.

The expansion comes at a pivotal moment in medical history: Many regions are experiencing shortages of medical specialists, people are increasingly comfortable using online health resources, and more people are seeking reliable information as they take active roles in their healthcare decisions.

“People feel more comfortable asking for a virtual second opinion when they know the process will be fast, convenient, and of high quality,” said emergency medicine physician Shoma Desai, MD, executive director of Digital Innovation at Cedars-Sinai. “A virtual second opinion from a national center of excellence like Cedars-Sinai gives participants confidence and empowers them to make decisions about their treatment.”

A Participant Finds Answers

For Gregory Rothaus, of Nevada, Cedars-Sinai’s Virtual Second Opinion program provided much-needed clarity. In early 2024, after several weeks of illness, Rothaus’ local physician suggested he “probably” had ulcerative colitis.

“I didn’t want ‘probably,’” Rothaus said. “I wanted certainty.”

With limited specialists in his area, Rothaus found the Virtual Second Opinion option especially appealing. Being able to quickly get a written second opinion report from a Cedars-Sinai specialist was a valued option. He also appreciated the optional virtual education session to clarify his questions about the written report.

“It gave me peace of mind that nothing was being overlooked,” said Rothaus, who, with the support of his local, treating physician, underwent additional tests referenced in the virtual second opinion report.

Within a month, the treating physician was able to give Rothaus a more accurate diagnosis: Crohn’s colitis.

His condition is now in remission.

Rothaus said the virtual second opinion made him feel more in control of his healthcare.  

“It’s about having the security that you’re on the right treatment path,” Rothaus said. “I’m the CEO of my health.”

How Virtual Second Opinion Works

More than 150 Cedars-Sinai specialists across key areas—including cancer, digestive diseases, heart and vascular conditions, lung conditions, neurology, orthopedics, pediatrics, spine conditions, and women’s health—provide virtual second opinions through a secure and private platform.

Participants begin by completing a short questionnaire and speaking with a Cedars-Sinai nurse coordinator, who collects relevant medical records. The Virtual Second Opinion program then identifies a physician specialist whose expertise aligns with the participant’s area of concern. That physician reviews the prior medical records and prepares a detailed written report analyzing the participant’s medical history and prior recommendations and answering any specific questions.

Participants also may choose to join an optional 30-minute virtual education session with the Cedars-Sinai specialist to ask questions related to the report.

Most participants receive their full written report within five days of completing their medical record collection. Satisfaction is high—94% in recent surveys—with participants citing convenience and speed as key benefits.

National surveys highlight the growing need for quicker, easier-to-access second opinions. The National Coalition for Cancer Survivorship reports that roughly one-quarter to one-third of U.S. cancer patients seek a second opinion, though many hesitate because of concerns about potential treatment delays or geographic barriers.

Virtual second opinions help overcome these challenges by efficiently and quickly identifying specialists who have expertise in a participant’s area of concern.

At present, Cedars-Sinai’s Virtual Second Opinion program is available to residents in Alabama, Arizona, Arkansas, California, Colorado, Connecticut, Delaware, District of Columbia, Florida, Hawaii, Idaho, Illinois, Indiana, Iowa, Kansas, Kentucky, Louisiana, Maryland, Massachusetts, Minnesota, Mississippi, Missouri, Nebraska, Nevada, New Hampshire, New Jersey, New Mexico, New York, North Carolina, North Dakota, Oklahoma, Oregon, Pennsylvania, South Carolina, Tennessee, Utah, Virginia, Washington, West Virginia and Wisconsin. 

There is a one-time fee to access a Virtual Second Opinion at Cedars-Sinai. Although it is not covered by insurance, most FSA and HSA plans may reimburse the cost.

Read more from Cedars-Sinai Stories and Insights: Virtual Second Opinion—Healing the Heart With Every Step

The findings are published in the journal Gastroenterology.

“Among Hispanic patients, higher African ancestry was associated with more severe Crohn’s disease throughout the digestive tract, while higher Amerindian ancestry was linked to disease affecting primarily the colon,” said Talin Haritunians, PhD, the corresponding author of the study and a research associate professor of Medicine at Cedars-Sinai.

Many Hispanic individuals have mixed genetic ancestry that can include Indigenous American ancestry, plus European and African contributions that are the result of centuries of migration and colonization. Amerindian Hispanics have ancestry from indigenous Maya, Aztec and Inca civilizations—and from Spain. 

“Our findings show that genetic ancestry can help explain important differences we see in how inflammatory bowel disease affects patients, even within a single ethnic group,” Haritunians said.

An estimated 3 million people in the U.S. have inflammatory bowel disease, according to the Centers for Disease Control and Prevention. The disorder can produce chronic, painful and often destructive inflammation in the digestive tract. The two most common forms of IBD are Crohn’s disease, which can impact any part of the gastrointestinal system, and ulcerative colitis which affects just the colon and rectum.

Ancestry-Aware Analysis

Investigators analyzed genetic and clinical data from more than 7,300 Hispanic patients from the U.S., including Puerto Rico, who had IBD. They also analyzed the same data from patients without the disease. Using a new method of genomic analysis that takes specific ancestry into account, investigators examined how genetic risk and disease presentation and severity varied across ancestral backgrounds.

Hispanic populations often include individuals with mixed genetic ancestry, reflecting a mosaic of Indigenous American, European, and African genetic contributions, the result of centuries of migration and colonization.

“Our group has had a longstanding commitment to extending studies to include diverse populations. Here, we were able to identify ancestry-specific variations in IBD patterns that may be overlooked in broader genetic studies, which often focus on European populations,” said Dermot McGovern, MD, PhD, a co-author of the study and director of Translational Research in the Inflammatory Bowel and Immunobiology Research Institute.

One group in the genetic study was found to be at higher risk for developing a serious and painful form of inflammatory bowel disease.

“Increased risk of penetrating Crohn’s disease was associated with higher African ancestry among Hispanic patients. It is a severe form of IBD in which inflammation extends through the layers of intestinal wall and increases the risk of complications that often require surgery,” McGovern said.

The findings also highlight the importance of examining genetic risk alongside other factors, such as diet and environment, to better understand inflammatory bowel disease across diverse populations.

“Largescale genetic studies that include diverse patients and populations historically underrepresented in research are essential for advancing our understanding of IBD and helping patients,” Haritunians said. “Expanding research in this way will help us move toward more inclusive approaches with the potential to improve treatment options and the lives of patients.”

Additional Cedars-Sinai authors include Dalin Li, PhD; Shaohong Yang, MD; Sweta Sinha, MPH; Emebet Mengesha; Maria A. Quintero, MD; Stephan R. Targan, MD; Shervin Rabizadeh, MD; and Maria T. Abreu, MD.

Other authors include Ashley H. Beecham, PhD; Steven W. Brugger, PhD; Mary F. Davis, PhD; Esther A. Torres, MD; Lissette Gomez, MSc; Paola Lopez-Marte, MD; Mark Daly, PhD; Christine R. Stevens; James S. Leavitt, MD; Oriana M. Damas, MD; Ksenija Sabic; Judy H. Cho, MD; and Jacob L. McCauley, PhD.

Funding: This work was supported by the F. Widjaja Foundation Inflammatory Bowel Disease Institute; the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (NIH/NIDDK) through grants U01 DK062413, U24 DK062429-18, U01 DK062422-18, U01 DK062431, and DK062432; the Leona M. and Harry B. Helmsley Charitable Trust; the Fred L. Hartley Family Foundation; the Micky & Madeline Arison Family Foundation Crohn’s & Colitis Discovery Laboratory; the Sanford J. Grossman Charitable Trust; and the National Institutes of Health through grants U54HG003067 and 5UM1HG008895.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about university.

Pimentel points out that the days between Thanksgiving and New Year’s are among the riskiest for food poisoning, especially as large meals, buffets and leftovers become part of the festivities. Each year, about 48 million Americans—roughly 1 in 6—get sick from foodborne illnesses, leading to an estimated 128,000 hospitalizations and 3,000 deaths, according to the Centers for Disease Control and Prevention.

Pimentel and Cedars-Sinai clinical dietitian Albert Abayev, RD, who works with patients undergoing weight loss surgery and general surgery, serve up answers to common holiday food safety questions.

What new insights have emerged in recent years about food poisoning—its causes, risks and prevention?

Pimentel: Foodborne illness continues to result from contamination with bacteria such as E. coli, Salmonella, Shigella or Campylobacter jejuni. Improper handling remains a major source of contamination. Foods left out for hours—common during buffets and large gatherings—create ideal conditions for bacterial growth.

Abayev: Many holiday-related food safety issues stem from outdated traditions or rushed environments. Long stretches of food left out on counters, undercooked poultry or stuffing, crowding the refrigerator, thawing meats on the counter, and multitasking that can lead to cross contamination are among the most frequent problems.

How long does it take to get food poisoning—and is the last meal always to blame?

Pimentel: Symptoms do not always appear immediately. Certain infections may take up to 48 hours to incubate. When determining the likely source, consider foods eaten in the prior two days and whether others who shared them also became ill.

How long does food poisoning usually last—and is it contagious?

Pimentel: Most cases resolve within a few days. E. coli often clears quickly, while Salmonella and Campylobacter may last a week or longer. Foodborne illness is not contagious like a virus, but contamination can occur if a sick person prepares food for others. Those with any symptoms should avoid preparing meals until fully recovered.

What are the biggest food safety mistakes people make in holiday kitchens?

Abayev: Allowing food to sit at room temperature for extended periods is the most common issue. Once food has been out for more than two hours, bacteria grow quickly. Undercooking turkey, stuffing and casseroles is another frequent problem; all dishes should reach 165 degrees Fahrenheit. Cross contamination, refrigerator overcrowding and improper thawing also add to the risk.

How reliable are the 'smell test' or 'eye test' when judging leftovers, and how long do leftovers stay safe?

Abayev: Appearance and smell are not reliable indicators of safety. Many harmful bacteria do not alter a food’s odor or color. Leftovers should be refrigerated within two hours, used within three to four days and reheated to 165 degrees. Also, freezing the food preserves quality for several months.

How should people with digestive conditions—or those using GLP-1 medications for weight loss—approach holiday meals safely?

Pimentel: Individuals with irritable bowel syndrome, inflammatory bowel disease or other chronic gastrointestinal conditions are more susceptible to foodborne illness, and an infection can worsen symptoms or trigger flares. Careful food handling, thorough cooking and choosing low-risk foods are especially important.

Abayev: GLP-1 users on weight management programs may experience slower stomach emptying, making heavy holiday foods more likely to cause discomfort. Smaller portions, slower eating, prioritizing protein and staying upright after meals can help. Because food remains in the stomach longer, contamination may result in stronger symptoms.

What should people do to recover from food poisoning?

Pimentel: Recovery starts with hydration. Small, frequent sips of water, electrolyte drinks or broth help replace losses. Bland foods like toast, rice, bananas or broth-based soups can be added as symptoms improve. Medical care is appropriate if symptoms last more than a couple of days or if there is high fever, blood in the stool or signs of dehydration.

What is one of the biggest food safety concerns this year?

Pimentel: Improved monitoring has reduced contamination in meat but produce now poses growing concern. Field conditions may limit workers’ access to proper hygiene, and many vegetables are eaten raw, eliminating the safety benefit of cooking.

What is the most important takeaway for holiday hosts and guests?

Abayev: Temperature control is the foundation of food safety. Hot foods should stay hot, cold foods should stay cold and leftovers should be refrigerated promptly.

Pimentel: Better safe than sorry; no one wants a side of food poisoning with their holiday meal.

Read more on the Cedars-Sinai Blog: Weight-Loss Drugs—What to Know Now

But gravity does much more than that, according to Brennan Spiegel, MD, MSHS, director of Health Services Research for Cedars-Sinai, whose new book makes the case that gravity affects every system in our bodies, and especially our digestive health. 

Spiegel, a gastroenterologist, is the author of a new theory—published in the American Journal of Gastroenterology and detailed in his book—that irritable bowel syndrome (IBS) and other digestive system conditions could be the result of the body’s inability to manage gravity.

Spiegel’s book, Pull: How Gravity Shapes Your Body, Steadies the Mind and Guides Our Health, expands on his theory, using the term “gravity intolerance” and describing how every part of our body—not just the gut— evolved to manage this fundamental force.

“If you’ve ever felt unusually fatigued after a long day on your feet, gotten dizzy standing up too quickly, dealt with persistent back pain, noticed swelling around your ankles, or had indigestion lying flat in bed—you’ve felt the effects of what I call gravity intolerance,” Spiegel said.

Spiegel, Cedars-Sinai’s George and Dorothy Gourrich Chair in Digital Health Ethics, describes how a family member’s declining health led him to his gravity intolerance theory.  

Spiegel’s mother-in-law was living in an assisted living facility and spending much of her time lying down in bed. Simultaneously, she was experiencing depression and worsening digestive issues like bloating and constipation. Spiegel theorized that human bodies aren’t designed to lie flat all day but are meant to get up and move.

“Our abdominal contents are heavy, like carrying a sack of potatoes in our bellies for a lifetime. Thankfully, evolution equipped us with systems to manage this load when we’re standing upright,” Spiegel said. “But lying down for too long compresses the intestines, slows digestion, and can create a feedback loop of discomfort between the gut and brain. I started to wonder: Was my mother-in-law’s time in bed causing her symptoms, or was it the other way around? Her story revealed a much larger picture to me about how gravity affects the body—and how many of my patients’ struggles might connect back to it.”

“The human relationship to gravity is much like a fish’s relationship to water,” Spiegel explained. “We live our entire lives in it, are shaped by it, yet rarely notice its constant influence on our existence.”

This insight led Spiegel to think more about gravity and the gut. “Might gravity intolerance explain why physical activity—like core strengthening, tai chi or aerobic activity—can often improve IBS symptoms, more than some medication? Could it also explain why some patients get lightheaded when they stand up quickly, or why so many also suffer from lower back pain—a consequence of gravity strain—or get worse at high altitude, where gravity’s grip on the atmosphere is diminished, or have abdominal obesity, weighing down the belly?” Spiegel said. “I began to suspect that gravity’s relentless pull might be a common thread in conditions I’d been studying for years.”  

Gravity intolerance, according to Spiegel, can affect our mental wellbeing as well. He describes mental gravity as a condition in which negative thoughts and emotions make us feel weighed down, as if gravity’s pull has intensified. More than a metaphor, Spiegel explains how the “gut feelings” many people feel when anxious also occur when falling on a roller coaster, or even when “falling” in love, revealing a deeper link between mind, body and gravity.

In Pull, Spiegel discusses gravity management and how to build gravity resilience to improve health and overall wellness, not just for gut health, but for overall mind-body resilience. He mentions flotation tanks, standing desks, inverted yoga poses, core strengthening and small adjustments people can make to improving gut health, like using footstools to create a more gravity-friendly posture. He also explains the idea of biogravitational medicine, a new field he hopes to develop to understand how gravity influences the human body and mind.

Other Cedars-Sinai leaders are intrigued by the new theory. Shelly Lu, MD, the Women's Guild Chair in Gastroenterology and director of the Division of Digestive and Liver Diseases at Cedars-Sinai, looks forward to the hypothesis being tested. “This could be a game changer in how we think about IBS and possibly how it’s treated.”

Itai Danovitch, MD, chair of the Cedars-Sinai Department of Psychiatry and Behavioral Neurosciences, says it offers a unifying framework for understanding why so many psychiatric conditions involve both mental and physical symptoms. “We've long known that gut health affects mood, that posture influences confidence, that movement helps depression—but conceptualizing these through the lens of gravity management is genuinely novel. This framework could  point toward new interventions that can be rigorously tested and evaluated.”

Spiegel is already looking ahead to proving his theory.

“Gravity was here long before we were, and it will remain long after we’re gone,” Spiegel said. “It stands to reason that mastering gravity was essential for life to evolve on Earth, and we survive and thrive by standing up and staying up as long as we can, and as well as we can.”

Read More on the Cedars-Sinai Blog: Causes and Treatments for Irritable Bowel Syndrome

“In the morning, we will host a clinician track on best practices for treating women with IBD,” Khanna said. “In the afternoon, patients and families are invited to a dedicated session covering pregnancy, fertility, nutrition, mental health and more. There is also time for patients and providers to connect.”

An estimated 3 million people in the U.S. have inflammatory bowel disease, according to the Centers for Disease Control and Prevention. The disorder produces chronic and often destructive inflammation in the digestive tract. The two most common forms of IBD are Crohn’s disease and ulcerative colitis. While some cases can be mild and manageable, many IBD patients are faced with a constellation of health problems including severe diarrhea, malnutrition, dangerous blood clots, and extensive and painful scarring.

IBD occurs in men and women at about the same rate, but the disease can leave women facing unique health challenges. There can be difficult decisions about proceeding with certain drug therapies while trying to conceive or during pregnancy and menopause. 

“For women living with IBD, simply knowing that their needs are recognized and that there is a community and program designed for them can be incredibly empowering,” Khanna said.

The Cedars-Sinai Newsroom interviewed Khanna about how IBD impacts the health and wellbeing of women, including finding a good healthcare provider and effective therapies available to them.

In what ways can IBD impact women and men differently?

While inflammatory bowel disease occurs at about the same rate in both sexes, women often present differently. After age 30, Crohn’s disease is more common in women than in men. We also see sex-specific patterns: Women are more likely to have Crohn’s limited to the colon, less extensive ulcerative colitis, and more frequent extraintestinal conditions, such as eye inflammation and skin disorders. Recognizing these differences is critical for timely diagnosis and effective management.

Are there differences in diagnosis, disease course or treatment protocols for women?

The diagnostic workup for IBD is the same regardless of sex and typically involves colonoscopy, imaging, lab testing. However, the course of the illness can vary. Women may experience flares around hormonal changes, such as those occurring during menstruation or pregnancy.

Treatment approaches are generally the same for men and women, but side effects can differ. For example, women are more likely to develop drug-induced lupus with certain biologic therapies. Providers must stay alert to sex-based responses to various treatments for IBD. For women of childbearing age, therapy selection must consider whether a medication is safe in pregnancy. Most of them are, but not all.

Does IBD impact a woman’s reproductive life, including menstruation, fertility and pregnancy?

Absolutely. Many women report worsening symptoms during menstruation due to hormone fluctuations. Fertility can be reduced in women with active inflammation or prior pelvic surgery, although more research is needed on that front. Pregnancy outcomes are best when disease is in remission for at least three to six months before conception. Interestingly, we have found that some women with IBD may actually experience improvement in symptoms during pregnancy.

Most IBD medications can be safely continued during pregnancy, particularly when the disease is under control. Methotrexate, an immunosuppressant medication, should be avoided. There are other classes of medications, such as JAK inhibitors, whose safety and use should be discussed with your provider. At Cedars-Sinai, our IBD Pregnancy and Fertility Clinic brings gastroenterology and obstetrics together so women receive coordinated care.

Do women find it challenging to get an accurate IBD diagnosis? What advice would you offer?

Many women do face delays. They may see multiple providers before reaching a gastroenterologist who recognizes their symptoms as inflammatory bowel disease. My advice is to advocate for yourself. If you are not being heard, seek a second opinion, ideally at a dedicated IBD center. A colonoscopy and appropriate testing are essential to confirm the condition.

How do IBD patients benefit from a multidisciplinary approach to care?

One young woman in her 20s came to me after years of aggressive Crohn’s disease. She had seen specialists across the country, endured multiple treatments, and was facing another surgery. She broke down in tears, telling me she felt abandoned by her doctors. I reassured her and then brought her case to our weekly IBD meeting where top experts could collaborate on her care. That sense of not being given up on, and of building a trusted partnership with a care team, can be life-changing for patients living with a chronic illness.

The Women and IBD conference will take place at Cedars-Sinai on Saturday, Sept. 13. Attendance is free but registration is required. Those interested in attending can email groupibdwomensprogram@cshs.org to register and receive more information.

Read more on the Cedars-Sinai Blog: A Good Grip on Crohn’s Disease

Melmed told Everyday Health a gastroenterologist who specializes in inflammatory bowel diseases can provide expert treatment for ulcerative colitis. They also can perform colonoscopies, “a very important tool for understanding, evaluating and assessing the state of colitis, which enables treatment decisions,” he said.

Melmed told Everyday Health that a primary care physician can recommend a gastroenterologist and that patients may want to do some research to find out the specialist’s experience treating the disease.

Because up to 30% of people with ulcerative colitis may need surgery to control their symptoms, Melmed said making a plan early on, just in case—such as finding a surgeon and medical center that specialize in bowel diseases and that are included in the patient’s insurance network—is important.

Melmed told Everyday Health patients should bring their medical records, including colonoscopy reports, imaging and medication history, to their first visit with a new physician.

“It can be tricky for a doctor to see new patients when the records aren’t available,” he said.

It also may be helpful to bring a list of questions to that first appointment, as well as a health history summary and a journal detailing symptoms.

Click here to read the complete article from Everyday Health.

highlight a potential link between pandemic-related stress on the gut-brain axis.

“Using data from a national online study, we found that rates of digestive issues such as irritable bowel syndrome and chronic idiopathic constipation rose significantly,” said Christopher V. Almario, MD, MSHPM, lead author and gastroenterologist at Cedars-Sinai. “These findings underscore the significant toll the pandemic has taken on digestive health.”

Also known as disorders of gut-brain interaction, conditions like irritable bowel syndrome and chronic idiopathic constipation are common gastrointestinal disorders driven by complex interactions between the gut and nervous system.

Nearly 40% of people in the U.S. are estimated to meet diagnostic criteria for at least one disorders of gut-brain interaction, making these conditions a major source of healthcare burden and reduced quality of life.

“These disorders involve chronic gastrointestinal symptoms that are often triggered or worsened by psychological stress,” said Almario.

To better understand how the viral infection might be linked with digestive health, researchers analyzed data from over 160,000 adults across the U.S. who participated in a national online survey conducted from May 2020 to May 2022.

Participants completed detailed questionnaires covering digestive symptoms, mental health and lifestyle changes. By tracking responses over time, the researchers observed a steady rise in gut-related health issues that began early in the pandemic and persisted throughout the survey period.

Key findings showed that:

• Rates of irritable bowel syndrome increased from around 6% among U.S. adults in May 2020 to about 11% in May 2022.
• Chronic idiopathic constipation rose slightly from 6.0% to 6.4%.
• Among adults who reported IBS, investigators noted that the prevalence of mixed IBS, a subtype of IBS where a person experiences both diarrhea and constipation, was most commonly reported. The investigators did not observe significant increases in other types of functional digestive disorders.

As doctors uncover the long-term health effects of COVID-19, study investigators hope this study may draw attention to how the virus’ impact on mental health may affect the gut—potentially triggering or worsening disorders like IBS and other gut-brain conditions.

“This research calls for a renewed focus on gastrointestinal health in the post-pandemic era,” said Brennan Spiegel, MD, MSHS, corresponding author of the study and director of Health Services Research for Cedars-Sinai.

Spiegel, director of the Cedars-Sinai Master's Degree Program in Health Delivery Science and the George and Dorothy Gourrich Chair in Digital Health Ethics, says even those who did not get COVID-19 but endured significant psychological distress also may have had alterations in their gut-brain axis.

“Healthcare providers must be vigilant in recognizing and addressing the long-term effects of the pandemic on digestive health,” said Spiegel.

Other Cedars-Sinai authors include So Yung Choi. Other authors include William D. Chey.

Funding: Support for this study was received from Ironwood Pharmaceuticals and Salix Pharmaceuticals in the form of institutional research grants to Cedars-Sinai. Brennan M.R. Spiegel, MD, MSHS is the guarantor of this article.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

The monoclonal antibody therapy, developed at Cedars-Sinai, is called tulisokibart. The experimental treatment also recently showed promising results in a separate Phase II study in treating ulcerative colitis.

Crohn’s disease and ulcerative colitis are chronic inflammatory bowel diseases that affect the digestive tract and impact approximately 1% of the U.S. population. There is no cure, and response to current treatments is variable.

“These findings, together with the recently published positive results in ulcerative colitis, strongly support this approach as a completely new therapy for people with inflammatory bowel diseases,” said clinician-scientist and geneticist Dermot McGovern, MD, PhD, director of Translational Research in the F. Widjaja Inflammatory Bowel Disease Institute at Cedars-Sinai and senior author of the study.

McGovern, the Joshua L. and Lisa Z. Greer Chair in Inflammatory Bowel Disease Genetics and the director of Precision Health at Cedars-Sinai, together with colleagues at Cedars-Sinai, helped develop tulisokibart.

“This mechanism was identified through both genetic and immunological work, the vast majority of which came from the inflammatory bowel diseases group at Cedars-Sinai,” he said.

In the Phase II-A trial, called APOLLO-CD, 55 adults with Crohn’s disease received tulisokibart in varying doses over 12 weeks. The results showed that nearly 50% of patients achieved clinical remission, compared to about 16% in historical studies.

The investigational therapy also may target fibrosis—a process that leads to narrowing in the gut and often requires surgery. Fibrosis is a major problem in Crohn’s disease and other diseases and cannot currently be prevented or reversed.

Stephan Targan, MD, former executive director of the F. Widjaja Inflammatory Bowel Disease Institute at Cedars-Sinai and a study author, said the therapy’s ability to target fibrosis has broad implications.

“Fibrosis is a major issue in many chronic medical conditions and can cause serious complications,” said Targan, the Feintech Family Chair in Inflammatory Bowel Disease. “So, there is great interest in seeing whether the drug we developed may have benefits even beyond inflammatory bowel disease.”

McGovern added that data from the APOLLO-CD study indicated that response to tulisokibart was rapid—patients’ inflammatory markers dropped within a week of beginning the therapy.

“This is promising news, because in addition to getting people well and helping them stay in remission, we want to help them get well as quickly as possible,” he said.

Also promising: Tulisokibart was developed with a diagnostic tool to help identify people who are most likely to benefit from the drug, which would introduce precision medicine to inflammatory bowel disease care.

McGovern, Targan and a team of researchers at Cedars-Sinai, including Janine Bilsborough, PhD, director of Inflammatory Bowel Disease Drug Discovery and Development, have long studied the role of TL1A in contributing to inflammation and fibrosis in inflammatory bowel disease patients. 

Bilsborough, also a study author, said, “We’ve dedicated our careers to pursuing innovative therapies for people affected by inflammatory bowel disease. It’s very fulfilling to see scientific progress that could help Crohn’s and ulcerative colitis patients reach lasting remission and live a life without limitation.”

Further studies are in progress in larger groups of people with both Crohn’s disease and ulcerative colitis: The double-blind, placebo-controlled Phase III trials will determine the effectiveness and safety of tulisokibart as a treatment to bring about and maintain remission in people with IBD.

Other authors involved in the study include Prof. Brian G. Feagan, MD; Prof. Bruce E. Sands, MD; Prof. Corey A. Siegel, MD; Prof. Marla C. Dubinsky, MD; Randy S. Longman, MD, PhD; João Sabino, MD; Olivier Laurent, PhD; Allison Luo, MD; Jiandong Lu, PhD; Deanna D. Nguyen, MD; Ernesto J. Muñoz-Elias, PhD; Heather Llewellyn, PhD; Tony (Yong) Wang, PhD; InSock Jang, PhD; Ron Marchelletta, PhD; Fadi Towfic, PhD; Mark Yen, MD; Jaclyn K. Anderson, DO; Aaron DuVall, MD; Prof. Jaroslaw Kierkus, MD; Prof. Marek Woynarowski, MD; and Houssam Al Kharrat, MD.

This research was supported by Prometheus Biosciences, a subsidiary of Merck & Co.

Conflicts of Interest: McGovern, Targan and Bilsborough have consulted for Merck, Prometheus Biosciences (acquired by MERCK) and Prometheus Labs. Cedars-Sinai has a financial interest due to the right to receive future royalties for patient rights from MERCK, Inc.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

Following a comprehensive national search, Cedars-Sinai has appointed David E. Cohen, MD, PhD, as the new chair of the Department of Medicine, effective July 1. Cohen, a longtime leader, scholar and mentor in academic medicine, has focused his research and clinical practice on obesity-related

“Dr. Cohen has dedicated his career to advancing the highest-quality clinical care, biomedical research, medical education and program building,” said Shlomo Melmed, MB, ChB, executive vice president of Medicine and Health Sciences and dean of the Medical Faculty. “He is admired by students and colleagues alike as a kind and patient teacher who leads by example. We wish Dr. Cohen every success as he guides our Department of Medicine to its next level of achievement.”

Cohen joins Cedars-Sinai from Brigham and Women’s Hospital in Boston, where he is chief of the Division of Gastroenterology, Hepatology and Endoscopy, and from Harvard Medical School, where he is professor of Medicine. He also previously was chief of the Division of Gastroenterology and Hepatology and the Vincent Astor Distinguished Professor of Medicine at Weill Cornell Medicine and NewYork-Presbyterian Hospital.

“It is my honor to lead the Department of Medicine at Cedars-Sinai, among the most prestigious medical institutions in the world,” Cohen said. “I look forward to collaborating with faculty and staff as we provide the highest-quality care to patients and lead the innovative research that will improve their lives.”

For nearly three decades, Cohen led a successful National Institutes of Health-funded laboratory studying how fats control the way the liver processes nutrients and maintains the body’s energy balance, with a goal of finding new ways to manage obesity and related health problems, such as liver disease and Type 2 diabetes. He developed small molecules to help treat liver disease, diabetes and problems related to metabolic syndrome, which increases the risk of heart disease, diabetes, stroke and other conditions.

Cohen’s research has been published in prestigious peer-reviewed journals, including Nature Medicine, Nature Communications, Cell Metabolism, Journal of Clinical Investigation, Science Signaling, Hepatology and PNAS. He recently completed a five-year term as editor-in-chief of Hepatology.

Earlier in Cohen’s career, he was director of Hepatology at Brigham and Women’s Hospital and director of the Harvard-MIT Division of Health Sciences and Technology. He also held joint appointments in the departments of Medicine and Biochemistry at the Albert Einstein College of Medicine in New York.

Cohen is the recipient of the American Liver Foundation Distinguished Scientific Achievement Award, the American Liver Foundation Research Prize, an American Liver Foundation Liver Scholar Award, an International HDL Research Award, a Hirschl Career Scientist Award and an NIH MERIT Award. He also was an Established Investigator of the American Heart Association.

He is a fellow of the American Gastroenterological Association and of the American Association for the Study of Liver Diseases, and an elected member of the American Society for Clinical Investigation, the Association of American Physicians and the Interurban Clinical Club.

Cohen received his medical degree from Harvard Medical School and the Harvard-MIT Program in Health Sciences and Technology, and a PhD in physiology and biophysics from Harvard University. He completed an internal medicine residency as well as gastroenterology and hepatology fellowships at Brigham and Women’s Hospital.

Read more in Cedars-Sinai’s Discoveries Magazine: The Worst Disease You’ve Never Heard Of

, her mentor and a former research colleague from more than two decades ago.

In her new role, Abreu will direct inflammatory bowel disease (IBD) teaching and clinical activities, as well as basic, translational and clinical research. She also will collaborate with multiple stakeholders across Cedars-Sinai Health System to advance leading-edge care for patients.

“We warmly welcome Dr. Abreu back to our Cedars-Sinai community and look forward to her continued brilliant scientific and clinical contributions to the IBD field,” said Shlomo Melmed, MB, ChB, executive vice president of Medicine and Health Sciences and dean of the Medical Faculty at Cedars-Sinai. “We also extend our warmest gratitude and admiration to Dr. Targan for his decades-long record of pioneering innovation and exceptional leadership.”

Abreu is president of the American Gastroenterological Association. She has authored more than 300 peer-reviewed articles published in high-impact medical journals and is a recipient of the 2019 Sherman Prize from the Bruce and Cynthia Sherman Charitable Foundation for her outstanding achievements in treating and researching inflammatory bowel disease.

Abreu returns to Cedars-Sinai from the University of Miami, where she was the Martin Kalser Endowed Chair of Gastroenterology; professor of Medicine, Microbiology and Immunology; and director of the Crohn’s and Colitis Center. Prior to her current position she was director of the Crohn’s and Colitis Center at Mount Sinai Medical Center in New York. While at Cedars-Sinai, Abreu was director of Basic and Translational Research in the Inflammatory Bowel Disease Center.

“My fundamental training as a physician-scientist occurred at Cedars-Sinai, and I believe it’s my destiny to return,” Abreu said. “With many of the current faculty having trained with me—whether at Cedars-Sinai or at the University of Miami—it is very exciting to be back among this expert team, and especially with Dr. Targan, who first inspired me to study IBD.”

Targan, also a Sherman Prize recipient, is a highly respected physician-scientist noted for developing biologic drugs that have revolutionized patient care, pioneering a multisystem approach to IBD, discovering biomarkers used to classify IBD disorders, and advancing care for IBD patients worldwide. He will remain on the Cedars-Sinai faculty as a distinguished professor of Medicine.

Abreu earned her medical degree from the University of Miami Miller School of Medicine. She completed her internship and residency at Brigham and Women’s Hospital in Boston and a fellowship in gastroenterology at UCLA.

In 2020, she received the Mentoring Award from the Immunology, Microbiology and Inflammatory Bowel Diseases Section of the American Gastroenterological Association. She also received the Healio Lifetime Disruptor Award, honoring a gastroenterologist who consistently pushes the field forward through innovative treatments, practice management, patient care and research. In 2023, Abreu was honored with the Women Empowering and Embracing Women Award from the South Florida Hispanic Chamber of Commerce.

Read more on the Cedars-Sinai Blog: IBD Dietitian Apprenticeship—Improving Access to Nutrition Care

. The eight-week program, known as IBS VR, makes use of cognitive behavioral therapy (CBT) to help patients manage symptoms such as pain and stress.

In an ongoing clinical trial, Cedars-Sinai gives VR headsets and the IBS VR app to patients, who get access to new virtual “treatment rooms” every few days. In the treatment rooms, patients learn relaxation strategies and other tactics to help manage their IBS symptoms.

“We want to raise awareness of the opportunity to think beyond the pill and particularly think about VR,” said Brennan Spiegel, MD, MSHS, director of Health Services Research at Cedars-Sinai and senior author of the study. “IBS is a gut-brain interaction disorder, and we know that calming the nervous system using cognitive behavioral therapy helps keep the gut calm. We want to add IBS VR to the cognitive behavioral therapy toolbox, particularly because IBS VR is more easily accessible to all patients. We are bringing the clinic to the patient.”

The app-based treatment will now undergo testing funded by a $1 million, three-year grant from the National Institutes of Health.

Additional authors: Karisma K. Suchak, Christopher V. Almario, Omer Liran, Robert Chernoff

Funding: Drs. Brennan Spiegel and Omer Liran co-developed SynerGI using internal resources from Cedars-Sinai Medical Center with additional support from the Marc and Sheri Rapaport Fund for Digital Health Science and Precision Health at Cedars-Sinai.

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Liver fibrosis can be triggered by many factors, including viruses that cause hepatitis (infection and inflammation in the liver), long-term alcohol use or some metabolic disorders. Because it produces few or no symptoms at first, the condition typically progresses slowly for years, going undetected until it has caused serious organ damage. At that stage, liver transplantation may be the only effective treatment. The ability to undo the scarring would be a major breakthrough for patient care.

In their study, published in the peer-reviewed journal Nature Communications, Cedars-Sinai investigators examined three genes and the proteins that they made. One of them, FOXM1, is known to cause liver cancer, inflammation and fibrosis when it becomes overactive in hepatocytes, a type of liver cell. The two other genes, MAT2A and MAT2B, are required to activate another type of cell, hepatic stellate cells, which plays a key role in liver fibrosis. The study demonstrated that the proteins coded by these three genes interact and that all three are needed to produce liver fibrosis.

“We discovered that these proteins ‘talk’ with each other inside liver cells,” said Shelly Lu, MD, director of the Karsh Division of Gastroenterology and Hepatology at Cedars-Sinai and corresponding author of the study. “They even influence nearby cells through extracellular vesicles—fat molecules filled with genetic fragments, proteins and other biological materials that act as messengers between cells. Working together, that is how these proteins stimulate each other, driving liver inflammation and fibrosis.”

These discoveries raised the possibility that inactivating just one of the three proteins might block liver fibrosis. To test that theory, the team induced liver inflammation and fibrosis in laboratory mice and treated them with a substance known as FDI-6 that blocks the FOXM1 protein. In a series of experiments, they showed that FDI-6 could prevent liver fibrosis from developing, halt further progression and even reverse the condition, resulting in the scarring disappearing.

Although both mice and humans have all three genes, and these genes also are more highly expressed in human liver fibrosis and cirrhosis, the study did not prove that a similar treatment would work in patients with liver fibrosis. Reaching that conclusion would require additional research and testing, Lu said. 

“What we achieved was to unveil the axis of FOXM1, MAT2A and MAT2B as a potential target for developing drugs to treat liver fibrosis,” Lu said. “Our findings suggest that blocking any of these proteins might be useful in treating this condition.”

Peter Chen, MD, professor of Medicine, the Medallion Chair in Molecular Medicine and interim chair of the Cedars-Sinai Department of Medicine, said, “This highly original study significantly advances our understanding of an insidious condition that too often leaves patients and doctors with few treatment options. It is emblematic of Cedars-Sinai’s innovative scientific work.”

Other Cedars-Sinai authors include Bing Yang, Liqing Lu, Ting Xiong, Wei Fan, Jiaohong Wang, Lucía Barbier-Torres, Jyoti Chhimwal, Sonal Sinha, Takashi Tsuchiya, Nirmala Mavila, Maria Lauda Tomasi, DuoYao Cao, Jing Zhang, Hui Peng, Komal Ramani, Jenny Han, Ekihiro Seki and Heping Yang. Additional authors include Jose M. Mato, Ting Liu, Xi Yang and Vladimir V. Kalinichenko.

Funding was provided by the National Institutes of Health grant P01CA233452 to S.C. Lu, H. Yang and E. Seki; Plan Nacional of I + D SAF2017-88041-R to J.M. Mato; and the National Natural Science Foundation of China 82070632 to Liu T.

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“The ACG annual meeting is an important opportunity for our expert researchers and clinicians to share their innovative research with other leaders in this space to drive the field forward and continue improving patient care,” said Shelly Lu, MD, the Women’s Guild Chair in Gastroenterology and director of the Karsh Division of Gastroenterology and Hepatology at Cedars-Sinai.

Cedars-Sinai is ranked #1 in California and #2 in the nation for Gastroenterology and GI Surgery, according to U.S. News & World Report’s “Best Hospitals 2024-2025” rankings.

Cedars-Sinai Highlights at ACG 2024

Brennan Spiegel, MD, MSHS, the George and Dorothy Gourrich Chair in Digital Health Ethics and director of Health Services Research at Cedars-Sinai, co-authored a series of new books for ACG titled, Guide to the Guidelines, and is hosting an educational session to enhance knowledge of ACG guidelines and improve clinicians’ medical practice.

Ali Rezaie, MD, medical director of the Cedars-Sinai GI Motility Program and director of Bioinformatics at the Medically Associated Science and Technology (MAST) program at Cedars-Sinai, is receiving the ACG Outstanding Research Award in the Small Intestine Category for his research, “Achieving Organoleptic Acceptability With Elemental Formula: A Prospective Single-Blind Comparative Study.” Rezaie also is presenting research into the effects of GLP-1 agonists on surgical outcomes.

Srinivas Gaddam, MD, associate director of Pancreatic Biliary Research at Cedars-Sinai, is presenting a poster on the risk of pancreatic cancer after a diagnosis of gallbladder disease.

Andres Yarur, MD, a gastroenterologist and associate professor of Medicine at Cedars-Sinai, is lecturing in the postgraduate course, giving an oral abstract presentation and exhibiting several posters about inflammatory bowel disease.

Amrit K. Kamboj, MD, a gastroenterologist at Cedars-Sinai, is presenting research data on esophageal conditions including Barrett’s esophagus, which is caused by damage from stomach acid.

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Results from the multicenter Phase II study, ARTEMIS-UC, were published in The New England Journal of Medicine.

Ulcerative colitis is a type of inflammatory bowel disease (IBD) that damages the digestive tract, causing stomach cramping, diarrhea, weight loss and rectal bleeding. It affects as many as 900,000 people in the U.S., and current treatments are often only minimally effective.

“Findings from this study are poised to have a remarkable impact on treatment for ulcerative colitis and IBD overall,” said study senior author and IBD research pioneer Stephan Targan, MD, the Feintech Family Chair in Inflammatory Bowel Disease and executive director of the F. Widjaja Inflammatory Bowel Disease Institute at Cedars-Sinai. “The investigational therapy was generated based on the concept of precision medicine; it shows promise as being both anti-inflammatory and anti-fibrotic; it represents a potential turning point in drug development and discovery; and it could change how this complex disease is treated in the future.”

The study evaluated a therapy developed by Cedars-Sinai clinician-scientists called tulisokibart (previously PRA023)—a man-made monoclonal antibody that acts like endogenous antibodies. It is designed to target and block a protein called TL1A, which can contribute to the severity of ulcerative colitis. The antibody reduces inflammation and targets fibrosis, which causes many of the complications and severity of disease.

“Unlike other IBD treatments that can exacerbate inflammation or suppress the body’s natural anti-inflammatory responses, our findings suggest that tulisokibart modulates inflammation and the body's anti-inflammatory mechanisms,” Targan said. “This dual action could lead to more balanced and effective management of ulcerative colitis.”

Notably, the role of TL1A as a master regulator of inflammation was discovered by Targan and collaborators at Cedars-Sinai. In groundbreaking work spanning two decades, the researchers found that while TL1A protects against invading pathogens, at high levels it also contributes to inflammation and fibrosis in IBD.  

ARTEMIS-UC was a 12-week study involving 178 adults from 14 countries. It also included a genetic-based companion diagnostic test to help predict response to the therapy.

A Phase III study will further examine safety and test effectiveness of tulisokibart in patients who take it longer than 12 weeks.

Clinician-scientist and geneticist Dermot McGovern, MD, PhD, director of Translational Research in the F. Widjaja Inflammatory Bowel Disease Institute at Cedars-Sinai and one of the study authors, has focused his career on identifying genetic variants associated with ulcerative colitis and other autoimmune diseases, exploring drug targets and working to revolutionize treatment through a precision medicine approach.

Nearly 20 years ago at Oxford University, McGovern and colleagues, in the first-ever genome-wide association study in IBD, identified that a variation in the TNF superfamily 15 (TNFSF15) gene was associated with developing both ulcerative colitis and Crohn’s disease. The protein TL1A, simultaneously being studied by Targan at Cedars-Sinai, is encoded by TNFSF15. McGovern left Oxford to collaborate with Targan and team at Cedars-Sinai in the effort to bring scientific breakthroughs to IBD.

“Findings from the ARTEMIS-UC study exemplify how combining genetics and biology can transform IBD care,” said McGovern, the Joshua L. and Lisa Z. Greer Chair in Inflammatory Bowel Disease Genetics and the director of Precision Health at Cedars-Sinai.

McGovern, who was recently awarded the prestigious Sherman Prize for his pioneering work in advancing understanding of the genetic architecture of IBD in diverse populations, says the uniqueness of this target and the way tulisokibart was designed to interact with that target represent significant advancements in how clinicians approach IBD treatment.

“Previously we have only been able to prescribe a medication to a patient that we think will work well, but going forward we could imagine telling the patient, ‘Actually, the genetic test suggests that you would be more likely to respond to this therapy,’” McGovern said.

Targan and McGovern also noted that ARTEMIS-UC involved multiple countries and diverse populations, reflecting the global nature of IBD. The F. Widjaja Inflammatory Bowel Disease Institute has invested significant resources in extending genetic research in IBD to diverse populations.

“It’s taken a village—supported by Cedars-Sinai’s integrated science culture—to reach this point,” said Targan, a 2017 recipient of the Sherman Prize. “We’ve devoted our careers to getting better treatments to IBD patients, and now we’re closer than ever to helping all patients with ulcerative colitis get their disease into remission so they can get back to enjoying life.”

Other authors involved in the study include Bruce E. Sands, MD; Brian G. Feagan, MD; Laurent Peyrin-Biroulet, MD, PhD; Silvio Danese, MD; David T. Rubin, MD; Olivier Laurent, PhD; Allison Luo, MD; Deanna D. Nguyen, MD; Jiandong Lu, PhD; Mark Yen, MD; Jaroslaw Leszczyszyn, MD, PhD; Radosław Kempiński, MD, PhD; Christopher Ma, MD; and Timothy E. Ritter, MD.  

This research was supported by Prometheus Biosciences, a subsidiary of MERCK.

Conflict of Interest: Targan and McGovern have consulted for MERCK, Prometheus Biosciences (acquired by MERCK) and Prometheus Labs.

Read more on the Cedars-Sinai Blog: Is It IBS or IBD?

McGovern, the Joshua L. and Lisa Z. Greer Chair in Inflammatory Bowel Disease Genetics and director of Precision Health at Cedars-Sinai, is one of two 2024 Sherman Prize recipients. The Prize, established by the Bruce and Cynthia Sherman Charitable Foundation, recognizes visionary clinicians, surgeons, researchers and academics who have made exceptional contributions in transforming IBD research and improving patient care.

“Receiving the Sherman Prize is an incredible honor,” McGovern said. “To be listed alongside previous awardees, people I greatly admire, is very special to me. Much of the credit for this honor goes to my outstanding team—I’m very lucky to be working with such smart and dedicated people to help improve the lives of those with IBD.”

Over the past 15 years, McGovern has been a key driver in many pivotal IBD genetic studies.  

“Dr. McGovern is a brilliant researcher who is working to elucidate the complexities of IBD to meaningfully improve the lives of people around the world who suffer from the disorder,” said Shlomo Melmed, MB, ChB, executive vice president of Medicine and Health Sciences, dean of the Medical Faculty and distinguished professor of Medicine at Cedars-Sinai. “Our institution is an international leader in IBD research and treatment, largely due to our talented faculty—exemplified by Dr. McGovern’s visionary leadership and dedication. Heartiest congratulations on his receipt of the distinguished Sherman Prize.”

McGovern began his career at Oxford University. He remembers a patient asking how he knew the treatment being prescribed was the right one. That question sparked McGovern’s yearslong quest to identify drug targets and associated biomarkers so he could match each patient with the most effective medicine.

While at Oxford, McGovern and collaborators identified a gene involved in IBD pathophysiology called TNF Superfamily 15. At the same time, Stephan Targan, MD, the Feintech Family Chair in Inflammatory Bowel Disease and director of the F. Widjaja Inflammatory Bowel Disease Institute at Cedars-Sinai—also a past recipient of the Sherman Prize—had discovered and was studying a protein encoded by the TL1A  gene.

After a chance meeting between the two, McGovern joined Targan and team at Cedars-Sinai.

Today, McGovern leads his own lab, the Translational Genomics Group, at Cedars-Sinai. After 20 years of collaboration with Targan on an anti-TL1A therapy, McGovern’s dream of delivering personalized medicine to IBD patients is gaining momentum. A new investigative treatment that differs from existing therapies while also addressing fibrosis (excessive scar tissue) in Crohn’s disease and ulcerative colitis—forms of IBD—is being studied in Phase III clinical trials. And, for the first time in IBD care, the disease has a companion diagnostic tool, which matches a patient to a specific medication.

If the therapy is approved, it will be the first approved personalized medicine for people with IBD.

McGovern says collaborations enable advances for patients. Now, he is working on other game-changing projects in his lab—such as improving the IBD classification system—with an eye toward broad global application.

He believes that the most pressing challenge for the field is bringing IBD advances to all parts of society. To that end, he has led the effort to extend largely European ancestry studies and advances to African American, Hispanic/Latino and East Asian populations. He also recently created a consortium to conduct genetic studies in sub-Saharan Africa.

“The Sherman Prize will allow me to enhance our collaborations across sub-Saharan Africa so that we can study the evolution of IBD in African populations,” McGovern said.

Improving patients’ quality of life, regardless of where they live, their ethnicity, social status or gender, inspires McGovern.

“A fundamental aspect of our work to advance our understanding of the causes of Crohn’s disease and ulcerative colitis and develop strategies to translate these discoveries into the clinic is our philosophy that these advances should be available to all populations,” McGovern said. “This has motivated us to invest resources and pioneer studies in diverse populations and ensure we are addressing disparities in research and clinical care.”

Read more from the Cedars-Sinai Blog: A Good Grip on Crohn’s Disease

Cedars-Sinai investigators have identified significant variations in the microbes of the small bowel (small intestine) are strongly associated with various body weights, from a normal body mass index, or BMI, to having obesity.

The gut microbiome includes the bacteria, fungi, and viruses that inhabit the human gastrointestinal tract. Imbalances in these microbial populations have previously been observed in the stool samples of patients with obesity-related diseases. This is the first study to fully examine the small bowel microbiome in normal weight, overweight and obesity, according to investigators.

“Using specialized techniques, we did a deeper dive into the microbial universe and  found the small bowel was significantly, and specifically, altered in participants who were overweight or had obesity, when compared to those of normal weight. Some of these changes were progressive, moving from normal weight to overweight to having obesity,” said endocrinologist Ruchi Mathur, MD, a professor of Medicine at Cedars-Sinai and corresponding author of the study.

The paper is published in the American Journal of Gastroenterology.

“Many functions related to food metabolism and nutrient absorption converge in the small bowel, as do many endocrine and immune functions that may influence weight gain. We think that changes in the balances of small bowel microbial populations may have a greater impact on weight gain and the development of obesity than previously understood,” said Mathur, also the director of the Diabetes Outpatient Teaching Education Center.

Using specimens obtained from esophagogastroduodenoscopies, blood samples and patient questionnaires, investigators examined the small bowel microbiomes of 214 patients stratified by body mass index. Study participants were classified according to the Centers for Disease Control and Prevention (CDC) guidelines of a normal weight having a BMI of 18.5-24.9, overweight individuals a BMI of 25-29.9, and for those classified as having obesity, with a BMI of 30 or higher.

The microbial populations of the duodenum, the first part of the small bowel where nutrition absorption begins, were analyzed in all three groups. Shotgun metagenomic sequencing was used to obtain a comprehensive evaluation of all the organisms present.

“A key finding was that one bacterial population, Lactobacillus, in the duodenum exhibited differing and highly species-specific associations in subjects classified as overweight or having obesity. These microbiome changes related to weight gain may be of particular importance because many people regularly consume Lactobacillus-containing products, including dairy-based foods, probiotics and certain vegan cuisine such as fermented tempeh,” said Gabriela Leite, PhD, the lead author of the study and lead project scientist for Cedars-Sinai’s Medically Associated Science and Technology (MAST) Program.

An estimated 182 million adults in the U.S. are overweight or have obesity, according to the CDC. The global number exceeds 1 billion. The causes are multifactorial and associated with serious health problems, including cardiovascular disease, metabolic syndrome and Type 2 diabetes. Genetics, epigenetics, gut hormones and gut microbiomes are involved in the pathophysiology of obesity, which can also be influenced by socioeconomic and psychosocial factors.

Investigators believe understanding the influences and activity of the microbes that populate our small bowel microbiome may offer an important path to improving the health and lives of millions of people.

“Identifying changes in the populations, and activity, of small bowel microbial species associated with overweight or having obesity is part of a key initiative to develop new therapeutic targets and to personalize medicine,” said gastroenterologist and study co-author Mark Pimentel, MD, executive director of Cedars-Sinai’s MAST Program.

“More research will be needed to identify the cause-and-effect relationships between the changes we observed, but the goal is to develop treatments and interventions that help people lower their risk for obesity related disease and improve their overall health,” Pimentel said.

Additional Cedars-Sinai authors involved in the study are Gillian M. Barlow, PhD; Mohamad Rashid, MD; Ava Hosseini, MPH; Daniel Cohrs, MD; Gonzalo Parodi; Walter Morales; Stacy Weitsman, MS; and Ali Rezaie, MD.

This research was funded in part by the Monica Lester Charitable Trust and the Elias, Genevieve, and Georgianna Atol Charitable Trust.

Read more from the Cedars-Sinai Blog: Cedars-Sinai Investigators Exploring the Connection Between the Microbiome and Diabetes

Investigators found glucagon-like peptide-1 receptor agonists (GLP-1RAs)—medications like Ozempic and Wegovy that are used to treat diabetes and obesity—are associated with an increased risk of aspiration pneumonia following endoscopy. The large, population-based study is published in the leading peer-reviewed journal Gastroenterology. 

Aspiration pneumonia is caused by inhaling foreign materials—including food in the stomach, or secretions from the mouth and nose—into the lungs. Endoscopy is a medical procedure in which a physician puts a tube-like scope down a patient’s throat and into the body to look inside.

One way the new obesity medications work is by slowing digestion, so people feel full longer, causing them to eat less. This also means that food sits in the stomach longer. As a result, the stomach may not empty completely during the usual duration of fasting that is recommended ahead of a surgical procedure to decrease risk of aspiration, explained the study’s corresponding author, Ali Rezaie, MD, medical director of the GI Motility Program and director of bioinformatics at the MAST Program at Cedars-Sinai.

“Aspiration during or after endoscopy can be devastating,” Rezaie said. “If significant, it can lead to respiratory failure, ICU admission and even death. Even mild cases may require close monitoring, respiratory support and medications including antibiotics. It is important we take all possible precautions to prevent aspiration from occurring.” 

The study analyzed data from nearly 1 million de-identified U.S. patients who underwent upper or lower endoscopy procedures between January 2018 and December 2020. Patients who were prescribed GLP-1RA medications had a 33% higher chance of experiencing aspiration pneumonia than those who did not take these medications before the procedure. This comparison also considered other variables that could influence the outcome to ensure a fair comparison between the two groups.

“When we apply this risk to the more than 20 million endoscopies that are performed in the U.S. each year, there may actually be a large number of cases where aspiration could be avoided if the patient safely stops their GLP-1RA medication in advance,” Rezaie said.

“The results of this study could change clinical practice,” said Yee Hui Yeo, MD, first author of the study and a clinical fellow in the Karsh Division of Gastroenterology and Hepatology at Cedars-Sinai. “Patients taking these medications who are scheduled to undergo a procedure should communicate with their healthcare team well in advance to avoid unnecessary and unwanted complications.”

Additional Cedars-Sinai authors involved in the study are Srinivas Gaddam, MD, MPH; Ruchi Mathur, MD; Rabindra Watson, MD; and Jamil Samaan, MD. Additional authors include Wee Han Ng; Pin-Chia Huang, BS; and Kevin Sheng-Kai Ma, DDS.

Read more from the Cedars-Sinai Blog: Weight-Loss Drugs – What to Know Now

The study is published in the journal Gastroenterology.

“We found that being female, smoking, or having a history of surgeries to treat Crohn’s disease or ulcerative colitis puts patients more at risk for developing other serious inflammatory conditions,” said Talin Haritunians, PhD, co-senior author of the study and an associate professor of Medicine at Cedars-Sinai.

“Genetic variations of IBD, as well as the location of the disease in the gastrointestinal tract, were also associated with developing debilitating extraintestinal manifestations of the disease affecting the eyes, joints, skin, liver and spine,” Haritunians said.

The multi-center study involved over 12,000 subjects: the largest study of extraintestinal manifestations of IBD to date, according to investigators. The scientists looked at patients who had at least one of seven different conditions occurring outside the gut, including psoriasis, inflammation of the eye, and ankylosing spondylitis, a condition which can degrade the spine or hips.

Investigators also identified genetic, clinical and immunological factors associated with primary sclerosing cholangitis—a condition which damages the liver—and with painful peripheral arthritis that affects both the small and large joints of the body.

“These inflammatory manifestations outside the gut impact about 40% of our patients with IBD. The disorders can have a very significant effect on quality of life and, in some instances, are life-threatening. Our findings will help us identify those at risk of developing these related conditions,” said Dermot McGovern, MD, PhD, the corresponding author of the study and director of Translational Research in the Cedars-Sinai F. Widjaja Inflammatory Bowel Disease Institute. 

McGovern expects the findings will also provide a guide to developing novel therapeutic treatments for the other disorders and may also address the underlying gut inflammation.

“Our clinical findings in this study shed light on the risk factors for morbidity associated with IBD. Our genetic findings highlight pathways that are targets for existing drugs or therapeutics in development. These discoveries are critical for developing more personalized approaches to the management of IBD and its various manifestations,” said McGovern, who holds the Joshua L. and Lisa Z. Greer Chair in Inflammatory Bowel Disease Genetics and is the director of Precision Health at Cedars-Sinai.

Other Cedars-Sinai authors involved in the study include Michelle Khrom, Shishir Dube, Gregory J. Botwin, Shaohong Yang, Emebet Mengesha, Dalin Li, Takeo Naito, Nirupama N. Bonthala, Christina Ha, Gil Melmed, Shervin Rabizadeh, Gaurav Syal, Stephan R. Targan Eric Vasiliauskas and David Ziring. Other authors include Millie Long, Lori Robbins, Steven R. Brant, Judy Cho, Richard H. Duerr, John Rioux, Phil Schumm, Mark Silverberg, Ashwin N. Ananthakrishnan, William A. Faubion, Bana Jabri, Sergio A. Lira, Rodney D. Newberry, Robert S. Sandler, Ramnik J. Xavier, Subra Kugathasan, David Hercules and R. Balfour Sartor.

This research was supported in part by the F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute. The Cedars-Sinai MIRIAD IBD Biobank is supported by the F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (NIH/NIDDK) grants (P01 DK046763 and U01 DK062413), and The Leona M and Harry B Helmsley Charitable Trust (DPBM and SHARE Consortium).

Conflict of Interest: Dermot McGovern is a consultant for MERCK, Prometheus Biosciences (acquired by MERCK), Takeda and Prometheus Labs.

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Read more in Discoveries Magazine: Ancestry Matters in IBD

The study is published in JAMA Network Open.

“We found that patients in the early stages of steatotic liver disease could consume less than 7.4 grams of alcohol a day without elevating their risk for advanced liver fibrosis which is associated with severe health problems including liver cancer, organ failure and even death,” said Yee Hui Yeo, MD, first author of the study and a clinical fellow in the Karsh Division of Gastroenterology and Hepatology at Cedars-Sinai.

“That amount is equivalent to about 6 ounces of beer, 2.5 ounces of wine and less than 1 ounce of a distilled spirit, like vodka or tequila,” Yeo said.

Steatotic liver disease is the most common chronic liver condition in the U.S., according to the American Liver Foundation, which estimates that 1 in 4 adults have the condition, which is often undiagnosed. Patients are advised to abstain from alcohol consumption, which can further damage the organ. But abstinence can be challenging for many people, even those who are light drinkers and or who have alcohol use disorder, according to the study authors.

“A critical gap in our understanding of steatotic liver disease progression has been the lack of concrete data to define a 'safe' level of alcohol consumption for those patients who can’t quit drinking. Our study addresses this unmet need by providing empirical evidence on the relationship between alcohol intake levels and the progression of early-stage disease,” Yeo said.

In the cohort study, Yeo—working with medical scientists in China—evaluated data from the U.S. National Health and Nutrition Examination Survey III. Investigators reviewed the health surveys from nearly 3,000 people with steatotic liver disease to identify a safe threshold for alcohol consumption.

Yeo emphasizes the findings are not a recommendation that patients with steatotic liver disease continue to drink but are intended to guide their care if abstinence is challenging.

“There has been ambiguity about the extent to which alcohol consumption exacerbates steatotic liver disease. We want to reduce this uncertainty by providing evidence-based information. We favor abstinence as the safest course of action for these patients. But for those who are not able to stop drinking, these findings provide concrete guidelines for making decisions about their health and lifestyle,” Yeo said.

In addition to limiting alcohol consumption, Yeo advises patients with steatotic liver disease improve their diet, get regular physical exercise and manage risk factors, which include hypertension, obesity, diabetes and prediabetes.

“While it is still best to counsel abstinence for patients with this liver disease, the study defines a threshold beyond which alcohol consumption can increase mortality. The results provide new guidance for clinicians and patients,” said Shelly Lu, MD, the Women's Guild Chair in Gastroenterology and director of the Division of Digestive and Liver Diseases at Cedars-Sinai.

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Read more on the Cedars-Sinai Blog: Fatty Liver Disease: Know Your Risk.

The findings of the single center randomized controlled trial are published in Scientific Reports.

“We found that Cedars-Sinai patients in the P.A.I.N.-Sparing group received significantly less opioids and had greater physical activity during their hospitalization, when compared with IBD patients whose pain was treated with as-needed opioids. Also, those receiving the P.A.I.N. protocol tended to have lower overall pain scores while in the hospital,” said Gil Melmed, MD, principal investigator of the study and director of Inflammatory Bowel Disease Clinical Research at Cedars-Sinai.

The P.A.I.N.-Sparing treatment approach developed by investigators was based on a review of the literature on pain management and included scheduled, non-opioid pain medications tailored to the severity of a patient’s reported discomfort. Melmed said that if this approach were not sufficient to control pain, the IBD patients could request opioid pain medications, as needed.

Inflammation, severe diarrhea, malnutrition and acute and chronic pain are leading causes of repeat hospitalizations for IBD patients. Pain is rated by these patients as one of the most burdensome aspects of the disease, yet there is insufficient evidence to support a pain management strategy that is effective.

“Opioid use is more prevalent in IBD than in any other chronic gastrointestinal condition. In spite of the widespread use of these medications, our previous studies have found that opioids do not meaningfully reduce the pain these patients experience. Additionally, there are the known risks associated with using these medications for chronic conditions, including misuse, overdose, infection, hospital readmission and even death,” said Melmed, a professor of Medicine.

Larger, multicenter trials would be useful to further validate the efficacy of the P.A.I.N.-Sparing protocol for IBD patients, Melmed said. He is also encouraged by the emergence of new tools for managing pain.

“There are novel, non-pharmacologic strategies being rigorously studied for their potential to control acute and chronic pain. Biofeedback, virtual reality and other modalities could be incorporated into a proactive approach for addressing the pain and quality of care of our hospitalized IBD patients,” Melmed said.

Additional (current) Cedars-Sinai investigators: Devin Patel, MD; Rajalakshmi Govalan, MD; Shao-Chi Greg Huang; Catherine Bresee; and Teryl K. Nuckols, MD.

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The findings are published in the journal Gastroenterology.

“Even though biologic medications have significantly improved outcomes for our patients with Crohn’s disease or ulcerative colitis, some people do not respond well to these therapies. In our study, we found that the patients with higher amounts of internal abdominal fat were less likely to improve and experience remission from their disease,” said gastroenterologist Andres J. Yarur, MD, the corresponding author of the study.

Unlike some conventional anti-inflammatory drugs which treat inflammation in a non-selective way, biologics work by blocking specific targets that cause inflammation in the body.

Patients in the study with higher visceral fat levels had lower concentrations of the biologic medications in their blood after treatment, and lower rates of steroid-free remission and bowel healing.

“It may not be body weight or body mass index [BMI] that is the reason some of our patients benefit from these approved biologic medications. It seems the fat tissue on the inner side of the abdomen, in particular, impacts treatment, so we may need to use higher doses of the drugs to help these patients,” said Gil Melmed, MD, a co-author of the study and director of Inflammatory Bowel Disease Clinical Research at Cedars-Sinai.

Investigators treated 141 IBD patients with one of three biologic medications: infliximab, ustekinumab or vedolizumab. Reliable body composition measurements were taken for both the IBD group and the 51 healthy control subjects to ensure fat composition for the two groups were similar.

“We found that higher visceral adiposity was associated with higher levels of pro-inflammatory cytokines, suggesting that fat tissue promotes inflammation, the opposite of what we want, and increases resistance to biologic drug therapy. More research is needed because we don’t know whether lowering visceral fat or giving higher doses of the medications would improve drug efficacy,” said Melmed.

Yarur, the study’s principal investigator, agrees, adding that a different kind of medication may be more effective in patients with a high intra-abdominal visceral fat. 

“We need to investigate drugs with different mechanisms of action, especially other small molecules, to see if our findings hold. As the prevalence of obesity and metabolic syndrome increases in our population, we need to find interventions that would improve the body composition of these IBD patients who are not currently helped by these biologic treatments,” said Yarur.

DOI: https://doi.org/10.1053/j.gastro.2023.06.036

Funding: The pilot study for this investigation was funded by a grant from the Digestive Disease Center at the Medical College of Wisconsin.

Conflicts of Interest:  Andres Yarur is a consultant, and member of the advisory board, for Takeda, which manufactures vedolizumab, and for Celltrion Healthcare, which produces one biosimilar of infliximab. Gil Melmed is also a consultant to Takeda and Janssen Immunology, the makers of infliximab and ustekinumab.

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Read more on Discoveries Magazine: Ancestry Matters: Genetic Risk Factors for IBD