Metabolism Is Disrupted in Intestinal Inflammation

Inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis lead to persistent, recurring diarrhea, fever, and pain, as well as severe psychological distress. Despite significant advances and modern medications, treatment remains difficult. Only a portion of patients respond to individual medications.

A central problem in the treatment of IBD is that the underlying metabolism between the body and the microbiome, i.e., the totality of microbes living in the gut, is profoundly disrupted. This has now been demonstrated in detail for the first time using comprehensive data analyses by a Kiel research team. The researchers from the Medical Faculty of Kiel University (CAU) and the University Medical Center Schleswig-Holstein (UKSH), Kiel Campus, published their results this week in the journal Nature Communications .

"Established IBD therapies mostly target processes in the immune system, as these diseases are based on a misguided immune response. But because many patients do not respond adequately to these therapies, it is important to also understand disease mechanisms that go beyond the immune system – for example, at the metabolic level," explains Professor Christoph Kaleta from the Institute of Experimental Medicine (IEM) at Kiel University and the University Hospital Schleswig-Holstein (UKSH), head of the study and member of the PMI Cluster of Excellence.

The scientists examined stool and blood samples from IBD patients before and after the start of therapy. They combined various molecular analysis levels—including metagenomics, transcriptomics, and metabolomics—with detailed computational network analyses to obtain a comprehensive picture of the biochemical processes in the patients' metabolism. Their key finding: Metabolic activity in both the intestinal tissue of those affected and the intestinal microbiome is dramatically reduced and closely linked. 

Energy supply and communication between host and microbiome break down

"We were able to show that in IBD, there is a breakdown in metabolic interactions between host and microbiome," explains Kaleta. "This disrupted communication contributes to the failure of important protective mechanisms and further exacerbation of inflammation."

Among other things, the team observed that certain metabolic products – such as tryptophan and choline – were significantly reduced in the patients' blood. These substances are necessary for the production of important cellular energy sources: NAD and ATP. At the same time, the bacterial utilization of amino acids and fiber, whose breakdown products serve as energy sources for intestinal cells, also changed.

"Our results show that the microbiome produces fewer essential nutrients due to the reduced metabolic performance, which forces human intestinal and immune cells to adjust their own metabolism. This imbalances both metabolism and the immune system. This makes treatment of these diseases particularly complex," explains Dr. Jan Taubenheim, lead author of the study and postdoc at the IEM. 

Individual nutrition as part of therapy

In an exploratory part of the study, the researchers used computer models to simulate whether targeted dietary changes, such as reducing certain carbohydrates or amino acids, could have a positive effect on the disturbed metabolic balance. "Our models suggest that a targeted change in diet could alter the microbiome and thereby slow down pro-inflammatory metabolic processes," says Dr. Samer Kadib Alban, another lead author of the study. "However, our results also show that there is no single diet that can effectively reduce inflammation. The diet would have to be individually adapted to the metabolism of each patient."

"With this study, we have laid the foundation for better understanding the metabolic changes in IBD patients," Taubenheim continues. The next step will be to test the findings in the laboratory and, based on these findings, develop specific therapies to counteract the metabolic changes.

The study is part of the DFG Cluster of Excellence Precision Medicine in Chronic Inflammation (PMI), the DFG-funded clinical research group miTarget (FOR 5042: The microbiome as a therapeutic target in inflammatory bowel diseases), the BMBF-funded initiative iTREAT (Development of individualized treatment pathways for psoriasis and inflammatory bowel diseases through systems medicine approaches) and Try-IBD (Multi-dimensional resolution of tryptophan-dependent immunometabolism as a new pathophysiological principle in inflammatory bowel diseases).

Reference: Taubenheim J, Kadibalban AS, Zimmermann J, et al. Metabolic modeling reveals a multi-level deregulation of host-microbiome metabolic networks in IBD. Nat Commun. 2025;16(1):5120. doi: 10.1038/s41467-025-60233-2

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