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Creeping fat in Crohn's may turn harmful

Even though it is common, the condition has not been studied much.

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Creeping fat — the thickened mesenteric adipose tissue seen in Crohn’s disease — may start as a protective response to bacterial leakage from the gut but later become a driver of fibrosis and strictures, according to research presented by Suzanne Devkota, PhD.
 
During the 2026 Crohn’s & Colitis Congress®, a partnership of AGA and the Crohn's & Colitis Foundation, held in Las Vegas, Dr. Devkota, who directs the Cedars-Sinai Human Microbiome Research Institute in Los Angeles, described new mechanistic data suggesting that certain gut bacteria can migrate into mesenteric fat, survive there and trigger a cycle of fat expansion, immune activation and fibrosis.
 
According to Dr. Devkota, creeping fat is most seen in ileal Crohn’s disease and is closely linked to strictures. Surgeons have long noted that thick fat wraps only around diseased bowel segments, stopping abruptly where inflammation ends. Even though it is common, the condition has not been studied much.
 
Importantly, creeping fat is not typical soft adipose tissue. “It is extremely fibrotic,” Dr. Devkota said, noting that the fat can be as stiff as the scarred intestinal wall itself. Because it cannot expand normally, it may contribute mechanically to luminal narrowing and stricture formation.
 
Bacterial translocation as a trigger
 
Dr. Devkota’s lab studies creeping fat through a microbial lens, focusing on how gut bacteria interact with host tissues. In earlier work, her group showed that bacterial translocation — movement of bacteria across the intestinal barrier — occurs even in healthy individuals but is usually harmless because the immune system clears the microbes.
 
In Crohn’s disease, however, the bacteria that translocate are different, she said, and clearance appears impaired. One species in particular, Clostridium innocuum, was frequently found in mesenteric fat from Crohn’s patients, suggesting it may play a role in creeping fat formation.
 
In unpublished work using human surgical specimens, mouse models and cell culture systems, the researchers found that early mesenteric fat expansion may be beneficial. In animal models, fat expansion appeared to contain bacteria locally and prevent bacterial products from entering the bloodstream.
 
“These were mice we colonized with a minimal bacterial consortium that included C. innocuum,” Dr. Devkota told GI & Hepatology News. “In these mice we could recover C. innocuum from the mesenteric adipose.” Similarly, Crohn’s patients with creeping fat did not show higher levels of bacterial products in blood compared with healthy controls, despite having a leaky intestinal barrier.
 
Over time, however, the response becomes maladaptive. Persistent bacteria within the fat drive immune cell infiltration, collagen deposition and progressive fibrosis, creating a self-reinforcing cycle.
 
Dr. Devkota’s team also investigated how C. innocuum survives the journey from the gut to fat tissue, an environment very different from the anaerobic intestinal lumen.
One adaptation involves lipid metabolism. When exposed to human creeping fat in the laboratory, C. innocuum activated genes involved in beta-oxidation, allowing it to use fat as an energy source. Not all gut bacteria can do this, which may explain why only certain species successfully translocate.
 
Another adaptation is sporulation. Although C. innocuum is classified as a strict anaerobe, the researchers found that exposure to oxygen triggers the bacterium to form spores rather than die. These spores can survive high-oxygen conditions for extended periods and later germinate when they encounter bile acids that signal a lipid-rich environment, such as mesenteric fat.
 
Fat cells are not passive
 
The research also challenges the idea that adipose tissue is merely a passive target. Adipocytes can sense bacterial products and respond actively. In unpublished cell culture experiments, exposure to C. innocuum alone — without hormonal stimulation — caused preadipocytes to differentiate into mature, lipid-filled fat cells.
 
“This suggests the bacteria are not only consuming lipid but also driving fat expansion,” Dr. Devkota said.
 
Taken together, the findings suggest that creeping fat begins as an attempt to wall off bacterial invasion but eventually contributes to fibrosis and strictures when inflammation persists. The findings also underscore the importance of prevention. “Managing inflammation early and aggressively may be critical to preserve the intestinal barrier and reduce the selection of bacteria adapted to survive outside the gut,” Dr. Devkota said.
 
Her group has completed a large, multi-omic analysis of more than 100 surgical cases, with plans to make the data publicly available. She said that future work will focus on identifying therapeutic targets that interrupt the cycle before fibrosis becomes irreversible.
 
Dr. Devkota reported having no relevant disclosures.

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