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Spencer, Paige N.; Brown, Monica E.; Smith, Erin P.; Wang, Jiawei; Kim, William; Spiga, Luisella; Tasneem, Naila; Simmons, Alan J.; Kim, Taewoo; Yang, Yilin; Xu, Yanwen; Zheng, Lin; Ro, James; Kaur, Harsimran; Kang, Seung Woo; Helou, Matthew D.; Lee, Mason A.; Arceneaux, Deronisha; Mueller, Katherine D.; Kuddar, Ozge S.; Harned, Mariah H.; Li, Jing; Banerjee, Amrita; Markham, Nicholas O.; Wilson, Keith T.; Coburn, Lori A.; Goettel, Jeremy A.; Liu, Qi; Washington, M. Kay; Valdivia, Raphael H.; Zhu, Wenhan; Lau, Ken S. (2026). The Journal of Clinical Investigation, 136(7), 1. 

This study investigates why Crohn’s disease (CD), a type of inflammatory bowel disease, affects some parts of the gut more than others. The gastrointestinal tract (digestive system) has different structures and functions along its length, but the reasons for region-specific inflammation are not well understood. Using a mouse model genetically prone to inflammation, the researchers found that a specific bacterium, Chlamydia muridarum (a mouse equivalent of a human infectious bacterium), can trigger inflammation specifically in the upper (ascending) colon, a common site of Crohn’s disease.

They showed that in genetically susceptible individuals, this bacterium activates certain intestinal cells called goblet cells, which normally help produce mucus to protect the gut lining. These cells respond by increasing a metabolic process involving tryptophan (an amino acid) through an enzyme called IDO1 (indoleamine 2,3-dioxygenase 1), which contributes to inflammation. Importantly, the researchers found a similar pattern in humans: patients with active Crohn’s disease had higher levels of IDO1 in the lining of the ascending colon, but not in another commonly affected region, the terminal ileum.

Overall, the study shows how a combination of genetic susceptibility and specific microbes can drive inflammation in particular regions of the gut. This helps explain why Crohn’s disease can appear in specific locations and provides a useful model for studying and potentially targeting disease in the ascending colon.

Figure 1. Crohn’s-like disease in the PC is associated with murine housing facility.

(A) Representative H&E-stained intestinal sections from WT (N = 3) and Tnf^{Δ´¡¸é·¡/+} mice from SPF-B (N = 4) and CONV facilities (N = 5). WT samples are from the CONV facility, and all mice are age-matched (34–42 weeks). (B) Colitis scores from histopathological analysis of murine colons from A. (CÌý²¹²Ô»åÌýD) Colitis scores by colonic regions of CONV Tnf^{Δ´¡¸é·¡/+} mice (N = 4 for 12 weeks in C;ÌýN = 5 for 34–42 weeks in D). (E) Representative H&E-stained PC sections from aged (37 weeks) SPF-B mice (N = 3 WT, N = 4 Tnf^{Δ´¡¸é·¡/+}) transferred and cohoused/fostered as pups in the CONV facility with a WT or Tnf^{Δ´¡¸é·¡/+}foster dam. (F) Representative H&E-stained PC sections from adult (32–54 weeks) SPF-B mice (N = 2 WT, N = 3 Tnf^{Δ´¡¸é·¡/+}) transferred and cohoused in the CONV facility in mixed-sex conditions until experimental collection. All scale bars: 200 μm. Data are shown as the mean ± SEM in quantifications. Statistical significance was determined using an ordinary 1-way ANOVA with Dunnett’s multiple-comparison test with CONV WT as the control group (B) or using paired 2-tailed t tests (CÌý²¹²Ô»åÌýD). *P < 0.05, ****P < 0.0001.