The study, published in the Journal of Clinical Endocrinology & Metabolism, found that patients with hypothyroidism had more than double the risk of developing SIBO compared to those with normal thyroid function. The risk was even higher in patients with autoimmune thyroid disease, where the body’s immune system attacks the thyroid gland, but appeared lower in those receiving hormone treatment for the condition.

The findings offer insight into how specific changes in gut bacteria could contribute to disease beyond the gastrointestinal system.

“Studies like this remind us how interconnected the body’s systems are and the important role the microbiome plays in overall health,” said endocrinologist Ruchi Mathur, MD, director of Clinical Research and Clinical Operations for the Medically Associated Science and Technology (MAST) program and the study’s corresponding author.

Mathur sat down with the Cedars-Sinai Newsroom to share key takeaways from the investigation.

What did the study reveal about gut bacteria activity in patients with thyroid disease?

We found that patients with hypothyroidism had different patterns of bacteria in the small intestine compared with those without thyroid disease. In patients with both hypothyroidism and SIBO, we found Klebsiella bacteria dominated rather than the bacterial groups we more commonly see in SIBO. This suggests hypothyroidism may not only increase the risk of SIBO but may also influence the types of bacteria involved.

Could this mean a more severe form of SIBO?

Possibly, more research is needed to confirm this. Previous Cedars-Sinai research has shown that Klebsiella can disrupt the balance and interaction of bacteria in the small intestine more than some other bacterial groups.

How does thyroid hormone treatment affect SIBO risk?

One of the more interesting findings of our study was that patients receiving levothyroxine to treat their thyroid condition appeared to have a lower risk of developing SIBO compared with untreated patients. It is possible that thyroid hormone replacement affects gut motility, which may help reduce bacterial overgrowth in the small intestine. More research is needed, but the finding suggests thyroid treatment may influence digestive health in ways we are only beginning to understand.

Why is it important to study the small intestine directly?

Many microbiome studies rely on stool samples, but the bacteria found in stool can differ significantly from those living in the small intestine. The small intestine plays a central role in digestion, metabolism and hormone function, so studying it directly gives us a much more accurate picture of what may be happening in diseases such as hypothyroidism and SIBO. It also may help researchers identify future therapeutic targets.

What can physicians and patients learn from these new insights?

It is important to recognize the relationship between hypothyroidism and SIBO and address symptoms accordingly. If a patient with hypothyroidism is complaining of gastrointestinal symptoms such as bloating or altered bowel habits, their care team should consider evaluating them for SIBO. Likewise, if a patient presents with bloating, constipation or unexplained gastrointestinal symptoms, thyroid testing may also be appropriate.

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.

Obesity increases the accumulation of senescent cells, aged cells that have stopped dividing but have not died, in several organs and tissues.

“Senescent cells differ depending on the originating cell types, diseases and other factors. Some senescent cells help with wound healing, but others cause harm and are known contributors to age-related diseases,” said Masayoshi Suda, MD, PhD, assistant professor of Medicine at Cedars-Sinai and lead author of the study. “Our goal is to identify and target these harmful types of senescent cells while sparing helpful cells.”

Previous research by the investigators showed that eliminating senescent cells with drugs called senolytics improved metabolic function, the body’s method for turning food and drink into energy.

In the current study, investigators focused on senescent blood vessel cells. They selectively removed these cells from obese laboratory mice and found that the animals’ inflammation and fat mass were reduced—and blood sugar levels improved.

When the investigators transplanted senescent blood vessel cells into lean laboratory mice, those mice developed inflammation in fat tissue and metabolic dysfunction.

Suda said this occurred because senescent blood vessel cells release high levels of inflammatory molecules.

The investigators next treated both groups of mice with fisetin, a naturally occurring senolytic compound, and found that the mice had fewer senescent blood vessel cells and improved diabetic symptoms. Investigators saw a similar decline in senescent blood vessel cells when they treated tissue samples from obese human patients with fisetin.

“Preliminary findings like these are crucial to translating aging research into clinical care,” said James Kirkland, MD, PhD, director of the Center for Advanced Gerotherapeutics and senior author of the study. “While more research is needed, we aim to eventually treat multiple age-related diseases simultaneously by using fisetin and related senolytics for aging and metabolic health.”

Suda said his team will next work to test this approach in clinical trials.

“If we can target senescent cells safely in humans, it could help address not just diabetes but a range of age-related conditions,” he said.

Additional Cedars-Sinai authors include Selim Chaib, Larissa Langhi Prata, Tamar Pirtskhalava, Nino Giorgadze, Sara Espinoza, Nicolas Musi, and Tamar Tchkonia.

Additional authors include Yi Zhu, Utkarsh Tripathi, Karl Paul, Allyson Palmer, Vagisha Kulshreshtha, Christina Inman, Kurt Johnson, Runqing Huang, Carolyn Roos, Luisa Leon-Sanchez, Jordan Miller, Thomas White, Linshan Laux, Laura Niedernhofer, Paul Robbins, Sundeep Khosla and Stefan G. Tullius.

Disclosures: Tamar Tchkonia, Allyson Palmer, Yi Zhu and James L. Kirkland have a financial interest related to this research, including patents and pending patents covering senolytic drugs and their uses held by Mayo Clinic.

Funding: This work was supported by the US National Institutes of Health (NIH) grants R37AG013925, R33AG061456, P01AG062413 (J.L.K., S.K., L.J.N., P.D.R.), U54 AG079754 (P.D.R., S.K., L.J.N), P01AG43376 (P.D.R., L.J.N.), R01AG086085 (S.K.), R01AG087387 (Y.Z.), and R01 AG063543 (L.J.N.). 

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.

“Patients are not usually hospitalized because of diabetes, but because of another condition, so they are not admitted in one specific area of the hospital,” said Roma Gianchandani, MD, medical director of Diabetes Quality and vice chair of Quality and Innovation at Cedars-Sinai. “It’s important that specialized protocols and programs that prioritize diabetes care are available hospital-wide.”

Diabetes affects how the body turns food into energy, sometimes causing high blood sugar, also known as high blood glucose or hyperglycemia. Hospitalized patients who do not have diabetes also can develop high blood glucose—a condition called stress hyperglycemia—which can lead to poor outcomes.

Gianchandani, an endocrinologist, along with Cedars-Sinai Fellow Margaret Wei, MD, authored a paper published in Annals of Internal Medicine about hospital best practices for managing high blood glucose. Gianchandani leads the medical center’s interdisciplinary efforts to improve outcomes for hospitalized patients with diabetes or stress hyperglycemia.

The Cedars-Sinai Newsroom spoke with Gianchandani about these efforts.

What does inpatient diabetes management involve?

Hospitals should use diabetes experts to help patients reach their safest blood sugar levels, which is shown to shorten hospital stays and improve outcomes. There is no single best diabetes team format—institutions should do what works with their own processes—but the most effective teams use experts to manage a patient from admission to discharge and conduct post-discharge follow-ups.

At Cedars-Sinai, we have a heterogeneous team format that includes endocrinologists (faculty and private), endocrinology trainees, diabetes educators, pharmacists and information technologists with a focus on hospital diabetes management. We also are increasingly integrating diabetes technology into our medical ordering system to help non-diabetes practitioners better manage their patients. Our diabetes clinicians are familiar with the latest diabetes technologies and increasingly used devices like continuous glucose monitors.

What’s new about Cedars-Sinai’s approach to inpatient diabetes care?

Collectively, our teams have prioritized several key components that have been shown to improve outcomes. We have standardized care by creating nursing policies for monitoring blood sugar and administering insulin, as well as procedures for addressing low blood sugar.

We are at the forefront of technology integration. We are using a computerized tool to support nurses administering insulin through an IV—the nurse simply enters the patient’s blood sugar, and the tool calculates how much insulin to give without the nurse needing to make that complex calculation. We also have insulin pumps and glucose sensors integrated into the patient’s electronic medical record, so we can monitor patients’ blood sugar as needed after they go home. This would allow us in the future to follow up if the patient needed to adjust their insulin dosage.

I am proud to share that Cedars-Sinai also has a pharmacist surveillance program. A pharmacist reviews abnormally high and low blood sugar levels every morning and reaches out to patients’ physicians if medication orders need to be adjusted.

We also are evaluating predictive algorithms using artificial intelligence tools for managing diabetes. For example, monitoring patients over time, an algorithm could predict when their blood sugar might go too high or too low.

How does Cedars-Sinai educate diabetes patients in the hospital?

A hospital stay provides a unique opportunity for diabetes education. We have several educators in the hospital as well as outpatient educators. Our inpatient educators interact with patients during admission to address any gaps in care they may be experiencing, and they strive to ensure patients go home with the resources they need to maintain safe blood sugar levels.

Read more on the Cedars-Sinai Blog: How to Prevent Insulin Resistance and Keep Blood Sugar Levels Steady

The drugs, known as glucagon-like peptide-1 receptor agonists (GLP-1RAs), are marketed under many brand names. They work by stimulating insulin secretion, slowing down food leaving the stomach, and causing a delay in gastric emptying. As a result, the drugs may help Type 2 diabetes patients manage their blood sugar and help patients with obesity to lose weight.

According to the study, published Oct. 1 in the journal JAMA Network Open, these medications may also lead to problems during upper endoscopies, which involve inserting an endoscope—a long, thin tube with a camera and a light on the end—into a patient’s esophagus, stomach and the beginning of the small intestine under sedation to diagnose diseases and conditions of the digestive system.

Researchers found that patients who regularly took GLP-1RAs were significantly more likely to retain food in their stomachs during the procedure than were patients who did not take the drugs. Food retention can raise the risk of aspiration, a rare but serious complication of surgeries in which stomach contents are introduced into the lungs while a patient is under sedation.  

The researchers found that even though patients in the study, as instructed, stopped taking the GLP-1RAs a week before their upper endoscopies, they were still more likely to retain food than those who did not take these drugs.

"The effects of the GLP-1RA drugs appeared to persist even when patients were asked to stop taking them a week before the procedure," said endocrinologist Ruchi Mathur, MD, professor of Medicine, director of Clinical Research and Clinical Operations for Medically Associated Science and Technology at Cedars-Sinai and the study's corresponding author. She added that although aspiration was not detected in any of the patients, food retention can make aspiration more likely.

A total of 70 individuals taking GLP-1RAs and 139 controls were included in the study.

Results showed that 17% of patients on the drugs who underwent upper endoscopy alone showed food retention, compared with none of the controls. They also observed that patients who underwent both a colonoscopy and an upper endoscopy on the same day, requiring a 24-hour clear liquid and bowel preparation protocol, showed no food retention in either the GLP-1RA group or the controls. "This protective effect against food retention may be due to the preparation typically required for colonoscopies, as opposed to upper endoscopies," Mathur said.

The researchers also found a clear association between GLP-1RA use, which can sometimes produce constipation as a side effect, and unsatisfactory bowel preparation for colonoscopies. Inadequate bowel preparation may contribute to missed lesions, patient dissatisfaction, and cancellation of the procedure.

"Overall, our results support the value of individualizing recommendations for patients and having risk-benefit discussions for patients on these drugs," Mathur said. "Any patients using a GLP-1RA drug should be sure to inform their physicians and anesthesiologists before undergoing gastrointestinal procedures."

Peter Chen, MD, professor of Medicine, the Medallion Chair in Molecular Medicine and interim chair of the Cedars-Sinai Department of Medicine, said, "The rigorous research performed by Dr. Mathur and her team represents an important contribution to our understanding of how these powerful obesity and diabetes medications may impact medical care."

Other Cedars-Sinai authors include Jason Nasser, MD; Ava Hosseini, MPH; Gillian Barlow, PhD; Roma Gianchandani, MD; Ali Rezaie, MD, MSc; and Mark Pimentel, MD.

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