Introduction
Disruption of the intestinal barrier and subsequent translocation of microbial products are key features of inflammatory bowel disease (IBD) 1,2. Circulating lipopolysaccharide-binding protein (LBP) reflects systemic exposure to bacterial components and may serve as a biomarker of disease activity and therapeutic response 3-5. Its clinical relevance during biological therapy with infliximab (IFX) and vedolizumab (VEDO) remains insufficiently defined.
Aims & Methods
We aimed to determine whether LBP levels are associated with disease activity and treatment response in IBD, and to assess its potential value alongside established inflammatory markers.
Patients with active IBD initiating induction therapy with IFX or VEDO were prospectively included. Serum LBP, C-reactive protein (CRP), and faecal calprotectin (FCP) were measured at baseline and during induction. Clinical response at week 14 and biological treatment persistence at 1 year were recorded. Patients continuing therapy beyond 1 year were classified as long-term biological users; those discontinuing within 1 year as short-term users. Associations between LBP, inflammatory markers, and treatment outcomes were evaluated using longitudinal mixed-effects models, correlation analyses, and logistic regression.
Results
Sixty-five patients were included (Crohn’s disease: n=32; ulcerative colitis: n=33), treated with IFX (n=34) or VEDO (n=31). In the total cohort, median LBP levels declined significantly by week 14 (p<0.05), paralleling reductions in CRP and FCP. IFX-treated patients showed significant decreases in LBP, whereas in VEDO-treated patients only FCP declined (both p<0.05). Stratified by IBD type, LBP decreased significantly in CD patients receiving IFX and in UC patients receiving VEDO (p<0.05). In the overall cohort, reductions in LBP from baseline to week 14 were associated with long-term biological use (p<0.05). Long-term users demonstrated a significant decline in LBP during induction, while no change was observed in short-term users (p=0.86). This association was driven by IFX-treated patients, in whom LBP reductions differed markedly between long- and short-term users (p<0.001); no such pattern was observed with VEDO.
Conclusion
Circulating LBP decreases in a response-dependent manner during induction therapy with IFX and VEDO. Early reductions in LBP are associated with long-term IFX treatment persistence, suggesting potential utility as an indicator of treatment durability. Baseline LBP levels did not predict short-term clinical response. These findings support the value of longitudinal LBP monitoring—rather than single baseline measurements—as a complementary biomarker during early IFX treatment evaluation. Prospective validation in larger cohorts is warranted.
References
1. Antoni L., Nuding S., Wehkamp J., Stange EF. Intestinal barrier in inflammatory bowel disease. World J Gastroenterol 2014;20(5):1165–79. Doi: 10.3748/wjg.v20.i5.1165.
2. Wells JM., Rossia O., Meijerink M., Van Baarlen P. Epithelial crosstalk at the microbiota-mucosal interface. Proc Natl Acad Sci U S A 2011;108(SUPPL. 1):4607–14. Doi: 10.1073/pnas.1000092107.
3. Ghosh SS., Wang J., Yannie PJ., Ghosh S. Intestinal barrier dysfunction, LPS translocation, and disease development. J Endocr Soc 2020;4(2). Doi: 10.1210/jendso/bvz039.
4. Rojo ÓP., Román ALS., Arbizu EA., de la Hera Martínez A., Sevillano ER., Martínez AA. Serum lipopolysaccharide-binding protein in endotoxemic patients with inflammatory bowel disease. Inflamm Bowel Dis 2007;13(3):269–77. Doi: 10.1002/ibd.20019.
5. Toris LD., Minsart CF., Husson CP., Franchimont DP., Liefferinckx CL. Lipopolysaccharide-binding protein in Crohn’s disease patients: a promising noninvasive biomarker monitoring disease activity. Eur J Gastroenterol Hepatol 2024;36(9):1093–100. Doi: 10.1097/MEG.0000000000002811.
Disclosure
G.D. received research grants from Royal DSM, Takeda, and Janssen Pharmaceuticals, and speaker fees from AbbVie, Pfizer, Takeda, and Janssen Pharmaceuticals. A.R.B. received speaker and advisory board fees from AbbVie and Ferring Pharmaceuticals. R.L. has received speaker’s fees from Cablon Medical and Galapagos, and served on the advisory board at Cablon Medical. All other authors declare no conflicts of interest.
