IBS affects about 10% of U.S. adults and, while incurable, can be managed through diet, behavioral therapy and medication.

Rezaie, director of Bioinformatics and Biotechnology at the Medically Associated Science and Technology (MAST) Program at Cedars-Sinai, told HCPLive the field is shifting away from a one-size-fits-all approach to symptom treatment and toward therapies tailored to the biological drivers of each patient’s disease.

“Twenty or 30 years ago, we would empirically treat patients, mostly just targeting symptoms,” Rezaie told HCPLive. “Now, we recognize that IBS has multiple underlying pathophysiologies, and depending on the patient, we can tailor therapy more precisely.”

Rezaie told HCPLive research increasingly suggests “a subgroup of IBS patients has disease driven by the gut microbiome,” fueling interest in microbiome-targeted therapies.

Rezaie said that because IBS is a chronic condition often diagnosed when patients are in their 20s, 30s and 40s, it typically requires long-term management of fluctuating symptoms.

“If you start them on a medication,” he told HCPLive, “this is not necessarily a curable disease, so they might be on that medication for years or decades.”

A large real-world study led by Rezaie found that some commonly prescribed IBS medications, particularly antidepressants and certain antidiarrheals, may be associated with an increased long-term mortality risk, underscoring the importance of evaluating safety in a condition often treated for decades.

In a related interview with HCPLive, Rezaie noted that these research findings highlight the need for more informed patient discussions and for future IBS guidelines to better incorporate long-term safety data alongside symptom management.

Read the complete article from HCPLive.

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.

The findings, published in Communications Medicine, are based on nearly two decades of electronic health records from more than 650,000 U.S. adults with IBS, making it the largest real-world study to examine the long-term safety of IBS treatments.

IBS is a chronic gastrointestinal condition affecting about 10% of the U.S. population. There is no cure, but dietary modifications, behavioral therapy and medications can help manage symptoms.

“Many patients are diagnosed with IBS at a young age and may remain on medications for years,” said Ali Rezaie, MD, medical director of the GI Motility Program at Cedars-Sinai and senior author of the study. “However, most clinical trials of these medications last less than a year, so we know very little about their long-term safety. This study begins to address that gap.”

Researchers assessed patients taking Food and Drug Administration-approved IBS medications, as well as antidepressants, antispasmodics and opioid-based antidiarrheal drugs, such as loperamide and diphenoxylate—widely used and recommended in IBS care. They found that long-term antidepressant use was associated with a 35% higher risk of death, and that loperamide and diphenoxylate use were associated with roughly double the risk of death.

The study does not establish that these medications directly cause death; rather, the observed associations may reflect higher rates of adverse outcomes, such as cardiovascular events, falls and stroke, which were more frequent among exposed patients.

Although antidepressants are not FDA-approved for IBS, they are commonly prescribed for IBS patients to help reduce pain, calm symptoms and make the condition easier to manage. The study found that other recommended treatments, including FDA-approved medications and antispasmodics, were not associated with increased mortality risk.

Researchers emphasized that while the increase in risk is significant and may sound concerning, the overall risk to any individual patient is small.

“IBS patients should not panic, but they do need to understand and weigh the small but meaningful risks when considering long-term treatments,” said Rezaie, the director of Bioinformatics at the Medically Associated Science and Technology (MAST) Program at Cedars-Sinai. “Patients should speak with their healthcare provider about the safest and most effective options for managing their symptoms.”

Rezaie said more research is needed to confirm these findings and identify which patients may be at greatest risk. He also called for future treatment guidelines to better address the long-term safety of medications commonly used to manage IBS.

In the meantime, he emphasized a more personalized approach to IBS patient care.

“Treatment for IBS patients should focus on identifying the underlying causes and using the safest, evidence-based options available rather than relying on a single class of medications for long-term management,” Rezaie said.

Additional Cedars-Sinai authors include Sepideh Mehravar, MD, Yee Hui Yeo, MD, and Mark Pimentel, MD.

Other authors include Parnian Naji, MD, Wee Han Ng, Nils Burger, PhD, and Will Takakura, MD.

Conflicts of Interest: Mark Pimentel is also a consultant for and received grant support from Bausch Health. Ali Rezaie reports serving as a consultant for Bausch Health and Ardelyx. In addition, Cedars-Sinai Medical Center has a licensing agreement with Gemelli Biotech. Ali Rezaie and Mark Pimentel have equity in Gemelli Biotech and Good LFE. The remaining authors disclose no conflicts.

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 research tested the elemental diet’s effectiveness and explored whether improving its unappealing taste—a major barrier—could help patients adhere to the diet’s stringent protocol. The investigators’ findings were published in the peer-reviewed journal Clinical Gastroenterology and Hepatology.

The elemental diet is a special low-fat liquid formulation that is designed to be easily digested and contains all the essential nutrients necessary for a healthy diet. A few prior studies have shown that the diet has the potential to improve challenging symptoms associated with digestive issues like small intestinal bacterial overgrowth (SIBO), intestinal methanogen overgrowth (IMO), Crohn’s disease, eosinophilic esophagitis and other gut ailments. The diet likely works by reducing inflammation, balancing the gut microbiome, healing the gut lining, and providing complete nutrition without additives and allergens that typically irritate the gut. Historically, elemental diet has had a low adherence rate because of the strict protocol and unpleasant taste.

SIBO and IMO typically occur when harmful bacteria or methane-producing microbes grow out of control in the gut. While antibiotics are often used to treat these conditions, they don’t always work.

“Elemental diets are designed to give the digestive system a break by providing easily absorbed nutrients,” said Ali Rezaie, MD, the study’s corresponding author and medical director of the GI Motility Program and director of Bioinformatics at the Medically Associated Science and Technology (MAST) Program at Cedars-Sinai. “This reduces stress on the gut, helping it heal and function better.”

In this study, 30 adults ages 18 to 85 diagnosed with SIBO or IMO strictly adhered to only a more palatable version of the elemental diet for two weeks. This was followed by two weeks during which study participants resumed their normal diet. The researchers analyzed changes in the gut microbiome, how well the diet was tolerated, symptom relief and breath test results, along with tracking any side effects.

The results were encouraging. Most participants reported tolerating the diet well, with no serious side effects. A key finding was a reduction in unfavorable microbes linked to gut issues. Methane levels also dropped significantly, with many returning to normal.

In addition, 83% of participants reported feeling better, with significant relief from common symptoms like bloating and discomfort. These findings suggested that a tastier version of the elemental diet helped restore balance in the gut and eased symptoms of SIBO and IMO.

“The study's positive results suggest that enhancing the palatability of the elemental diet could make it more accessible and practical for patients, improving adherence and quality of life for those who face significant challenges with traditional therapies,” said Mark Pimentel, MD, study author and executive director of the MAST Program at Cedars-Sinai.

Rezaie and his team of investigators plan to conduct larger studies to better understand the long-term effects of elemental diets and further address the socioeconomic barriers.

Other Cedars-Sinai authors include: Bianca W. Chang, Juliana de Freitas Germano, Gabriela Leite, Ruchi Mathur, Krystyna Houser, Ava Hosseini, Daniel Brimberry, Mohamad Rashid, Sepideh Mehravar, MJ Villanueva-Millan, Maritza Sanchez, Stacy Weitsman, Cristina M. Fajardo, Ignacio G. Rivera, LiJin Joo, Yin Chan and Gillian M. Barlow.

Funding: This study was in part supported by a research grant from Good LFE and John and Geraldine Cusenza Foundation. These sponsors played no role in the study design or in the collection, analysis, and interpretation of data.

Conflict of interest: Mark Pimentel, MD, is a consultant for Ferring Pharmaceuticals, Inc and Salvo Health, Cylinder Health, Inc has received grant support from Bausch Health, and has equity in Gemelli Biotech, Salvo Health, Cylinder Health, and Good LFE. Ali Rezaie, MD, is a consultant/speaker for Bausch Health and has equity in Gemelli Biotech and Good LFE. Cedars-Sinai has licensing agreements with Hobbs Medical and Gemelli Biotech.

Read more on the Cedars-Sinai Blog: Healthy Bowel Movements: Why You Should Pay Attention to Your Poop

The study, published in Clinical Gastroenterology and Hepatology, showed that disruption in a patient’s gut flora, specifically the overgrowth of archaea—unique microorganisms in the gut microbiome that produce methane—could be the cause.

Researchers hope the study’s findings will help experts root out the cause of constipation instead of merely treating patients’ symptoms. These findings could also aid in developing a personalized treatment plan for a subgroup of patients who experience severe constipation due to intestinal methanogen overgrowth (IMO)—a condition in which archaea excessively grow in the intestines.

“Our study found that patients with IMO are more likely to have constipation, particularly severe constipation, and less likely to have unyielding diarrhea,” said the study’s corresponding author, 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. “Patients, however, also reported several other gut-related symptoms, including bloating, diarrhea, abdominal pain and flatulence.”

Constipation is one of the most common gut-related issues in the United States. About 16% of adults experience bloating, abdominal pain, and difficulty having bowel movements; the numbers nearly double for people over 60. While many things, like medication side effects or lack of dietary fiber, can cause constipation, historically, there has been a shortage of research on the gut microbiome’s role in constipation and other digestive issues. 

“When there is an excessive amount of archaea in your gut, they produce more methane, and some of that methane makes its way to your bloodstream, then to your lungs, and you breathe it out, where it can measured as a diagnostic test,” Rezaie said. “Essentially, people who have excessive amounts of methane have a lot of GI symptoms, including constipation, flatulence, bloating and diarrhea.”

For context, the gut microbiome consists of trillions of microorganisms, such as the community of bacteria, yeast and fungi in the digestive system. When there is an imbalance among the microorganisms populating the gut, it is associated with a host of GI symptoms and diseases.

Experts used electronic databases to identify 19 studies—11 conducted in the U.S. and eight conducted in six other countries—that assessed symptoms for patients with IMO.

“Historically there has been a paucity of information regarding the role of archaea in health and disease. Unique symptom patterns related to IMO should be taken into account when measuring patient-reported outcomes and should be further studied in relation to the microbiome,” said Peter Chen, MD, interim chair of the Department of Medicine at Cedars-Sinai.

For example, taking over-the-counter or prescription laxatives often relieves constipation, but won’t always address other GI symptoms, such as bloating, abdominal pain and diarrhea. In fact, in some cases, taking a laxative could potentially worsen coexisting diarrhea and bloating. 

Researchers explain that the optimal solution for IMO-induced severe constipation is to suppress the archaea overgrowth and keep the organism at bay. This generally involves a combination of antibiotics and a specialized diet to reset the gut microbiome. However, the first step is to diagnose the archaea overgrowth through a noninvasive hydrogen/methane breath test.

According to Rezaie, the study's findings are crucial and will hopefully encourage healthcare providers to utilize precision medicine, conduct clinical trials that target microbiome research and develop strategies to optimize patient care.

“The goal is to move toward developing specific therapies and personalized treatment for a subgroup of people who experience constipation due to IMO,” Rezaie said. “We can start by using breath tests to identify excessive methane production, which can be the first step to detecting archaea overgrowth and could ultimately lead to developing more targeted therapies. It's a big step to move away from the common reflex use of laxatives.”

Additional Cedars-Sinai authors include Sepideh Mehravar, MD; Jiajing Wang, PhD; Jason Nasser, MD; and Mark Pimentel, MD.

Funding: This study was supported in part by funds provided by Nancy Stark and Stanley Iezman in support of the MAST Program's Innovation Project.

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

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