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. 2024 Feb 21;16(1):2316575. doi: 10.1080/19490976.2024.2316575

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© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The terms on which this article has been published allow the posting of the Accepted Manuscript in a repository by the author(s) or with their consent.

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Figure 1. — Constructing butyrate producing yeasts for the treatment of IBD.

(a) Research shows that the content of butyrate in the intestinal cavity of IBD patients is lower than that of normal individuals.^31,32 BA, butyrate. (b) Based on S. cerevisiae, reconstruct butyrate synthesis pathway and regulate metabolism modules to construct a series of engineering yeasts with different butyrate production capacity. ERG10, acetyl-CoA C-acetyltransferase; MCT1, malonyl-CoA: ACP transferase; MLS1, malate synthase; CIT2, citrate synthase; ACS1, ACS2, acetyl-CoA synthetase; ALD6, cytosolic aldehyde dehydrogenase; ACH1，acetyl-CoA hydrolase; ADH1, ADH4, alcohol dehydrogenase; GPD1, GPD2, glycerol-3-phosphate dehydrogenase; FAA1, FAA4, Long chain fatty acyl-CoA synthetase; FAT1, very long chain fatty acyl-CoA synthetase and fatty acid transporter. (c) The butyrate engineering yeast J16 can restore the butyrate level in the intestinal cavity of patients with IBD to normal levels. The butyrate released, like previous research results,^35–37 can regulate intestinal microbiota homeostasis, increase the abundance of probiotics, and reduce the abundance of harmful bacteria. B. adolescentis, Bifidobacterium_adolescentis; L. johnsonii, Lactobacillus_johnsonii; L. delbrueckii, Lactobacillus_delbrueckii; L. salivarius, Lactobacillus_salivarius. (d) The butyrate engineering yeast J16 can restore the butyrate level in the intestinal cavity of colitis mice to normal levels. The butyrate released, can inhibit the production of pro-inflammatory factors, promote the release of anti-inflammatory factors, and protect the intestinal barrier function from damage as previously reported.^38–40 IL-6, interleukin-6; IL-1β, interleukin-1β; IL-10, interleukin-10; TNF-α, tumor necrosis factor-α; ZO1, Zona Occludens 1; MUC2, Mucin 2.