Food-derived compound fights inflammatory bowel disease by restoring gut balance: Study

Researchers from Harbin's Northeast Agricultural University demonstrate that supplementing diet with the short-chain fatty acid isobutyrate eases intestinal inflammation and restores gut balance in a pig model of colitis, pointing to a promising new avenue for treating inflammatory bowel disease (IBD). The study outcome addresses the unmet need for IBD treatments that avoid the long-term side effects of current drugs while targeting underlying gut dysbiosis and barrier dysfunction.

Urgent Call for Safer IBD Solutions: Tackling Chronic Inflammation Beyond Drugs

IBD—including Crohn's disease and ulcerative colitis-afflicts millions worldwide, causes chronic pain and diarrhea, and often requires lifelong medication with serious side effects. Discovering a safe, food-derived compound that restores healthy gut bacteria and directly calms gut inflammation could improve patient care, reduce reliance on steroids or immunosuppressants, and inform dietary or supplement strategies for clinicians and public health.

Restoring Lost Metabolite: Low Isobutyrate Levels Linked to Gut Imbalance, Supplement Reverses Damage in Models

Results showed that the levels of isobutyrate were significantly lower in human patients with Crohn's disease and in animal models of colitis, including both mice and pigs. In pigs given dietary isobutyrate before inducing colitis, researchers observed reduced diarrhea, bleeding, weight loss, and colon shortening compared to untreated animals. The supplement also shifted the gut microbiome toward beneficial bacteria, notably increasing Lactobacillus reuteri and its production of anti-inflammatory compounds such as indole-3-lactic acid (ILA) and 3-hydroxybutyrate. Measures of intestinal barrier health revealed that tight-junction proteins, such as Claudin-1, were preserved, and blood levels of gut-leakage markers (D-lactic acid, DAO, LPS) remained low in the isobutyrate-treated group. At the immune level, isobutyrate indirectly activated the aryl hydrocarbon receptor (AhR) via ILA, promoting the recruitment of regulatory T cells, and directly stimulated GPR109A to strengthen the barrier while suppressing the pro-inflammatory TLR4/MyD88/NF-κB pathway.

“We've long known that gut metabolites play a central role in intestinal health, but seeing isobutyrate supplementation both rebalance the microbiome and strengthen barrier defenses in a pig model was truly encouraging,” says Prof. Baoming Shi. “This points to a realistic, food-derived approach that could one day reduce patients' reliance on harsh drugs and improve quality of life for those with IBD.”

Pig Study Reveals How Dietary Isobutyrate Reshapes Microbiome and Fortifies Gut Barrier

Researchers fed young pigs either a standard diet or the same diet supplemented with isobutyrate for two weeks. They then triggered colitis by administering dextran sulfate sodium (DSS), a chemical that inflames the gut. Over five days, they monitored clinical signs, collected stool samples for bacterial and metabolite analysis, and examined tissue under a microscope. State-of-the-art genetic sequencing and chemical profiling revealed how isobutyrate altered microbes and their products, while lab tests measured barrier proteins, immune markers, and inflammatory signals.

Published in Research in May 2025, this study demonstrates that restoring a typically low gut metabolite, isobutyrate, can fortify the intestinal ecosystem, bolster its physical defenses, and recalibrate immune responses, thereby preventing or mitigating colitis. As pig guts closely mimic those of humans, these findings lay a solid groundwork for future clinical trials and suggest that dietary or supplemental isobutyrate may one day become a safe, low-cost treatment to ease the burden of IBD.

Reference:

Xiuyu Fang, Haiyang Liu, Junling Liu, Yongqing Du, Zihan Chi, Yiqi Bian, Xuan Zhao, Teng Teng, Baoming Shi. Isobutyrate Confers Resistance to Inflammatory Bowel Disease through Host–Microbiota Interactions in Pigs. Research. 2025;8:0673.DOI:10.34133/research.0673