Exploring 3-Aminobenzoic Acid as a Therapeutic Dietary Component for Enhancing Intestinal Barrier Integrity in Ulcerative Colitis

Tanaka, M.; Toyonaga, T.; Nakagawa, F.; Iwamoto, T.; Komatsu, A.; Sumiyoshi, N.; Shibuya, N.; Minemura, A.; Ariyoshi, T.; Matsumoto, A.; Oka, K.; Shimoda, M.; Saruta, M.

doi:10.1101/2024.08.18.608525

bioRxiv · 10.1101/2024.08.18.608525

Exploring 3-Aminobenzoic Acid as a Therapeutic Dietary Component for Enhancing Intestinal Barrier Integrity in Ulcerative Colitis

Tanaka, M.·Toyonaga, T.·Nakagawa, F.·Iwamoto, T.·Komatsu, A.·Sumiyoshi, N.·Shibuya, N.·Minemura, A.·Ariyoshi, T.·Matsumoto, A.·Oka, K.·Shimoda, M.·Saruta, M.

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Abstract

BackgroundDietary components and their metabolites produced by intestinal bacteria play a crucial role in maintaining intestinal epithelial integrity. Disrupted epithelial integrity increases permeability and leads to chronic inflammation in the colon, known as ulcerative colitis (UC), in genetically predisposed individuals. However, the gut microbial metabolites regulating epithelial permeability remain unexplored and their metabolism in UC patients is unclear. MethodsA library of 119 gut microbial metabolites was screened for their ability to reduce epithelial permeability in Caco2 cell monolayers. The diet containing 3-aminobenzoic acid (3-ABA) was identified using liquid chromatography with quadrupole time-of-flight mass spectrometry. The abundance of fecal 3-ABA was compared between UC patients and healthy individuals followed by 16S rRNA metagenomic analysis to estimate the gut microbial function in ABA degradation. The anti-inflammatory effect of 3-ABA was examined in a mouse model of dextran sodium sulfate-induced colitis. ResultsStimulation with 3-ABA reduced epithelial permeability and enhanced barrier integrity in Caco2 cells by modulating the tight junctional regulatory pathway. 3-ABA was abundant in beans and decreased in the feces of UC patients. Functional prediction analysis of gut microbiota revealed an accelerated degradation of ABA with significant up-regulation of mabA, a gene encoding a bacterial enzyme involved in 3-ABA degradation, in UC patients. Rectal and oral administration of 3-ABA ameliorated experimental colitis in mice. Conclusion3-ABA abundant in beans enhanced intestinal epithelial integrity and ameliorated experimental colitis in mice. Proactive intake of 3-ABA might be a novel treatment approach for UC.

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Tanaka, M., Toyonaga, T., Nakagawa, F., Iwamoto, T., Komatsu, A., Sumiyoshi, N., Shibuya, N., Minemura, A., Ariyoshi, T., Matsumoto, A., Oka, K., Shimoda, M., Saruta, M.. 2024-08-19. Exploring 3-Aminobenzoic Acid as a Therapeutic Dietary Component for Enhancing Intestinal Barrier Integrity in Ulcerative Colitis. https://doi.org/10.1101/2024.08.18.608525

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