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Comment
. 2023 May 16;4(5):101039.
doi: 10.1016/j.xcrm.2023.101039.

From bugs to drugs: Bacterial 3-IAA enhances efficacy of chemotherapy in pancreatic cancer

Y David Seo  1 , Jennifer A Wargo  2
Affiliations
Comment

From bugs to drugs: Bacterial 3-IAA enhances efficacy of chemotherapy in pancreatic cancer

Y David Seo et al. Cell Rep Med. .

Abstract

Tintelnot et al.1 identified enrichment of indole-3-acetic acid (3-IAA), a tryptophan metabolite produced by gut microbiota, as a predictor of chemotherapy response in pancreatic adenocarcinoma. Recapitulated in mouse models, 3-IAA represents a novel potential therapeutic approach for chemotherapy sensitization.

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Conflict of interest statement

Declaration of interests J.A.W. is an inventor on a US patent application (PCT/US17/53.717); reports compensation for speaker’s bureau and honoraria from Imedex, Dava Oncology, Omniprex, Illumina, Gilead, PeerView, MedImmune, and Bristol-Myers Squibb; serves as a consultant/advisory board member for Roche/Genentech, Novartis, AstraZeneca, GlaxoSmithKline, Bristol-Myers Squibb, Merck, Biothera Pharmaceuticals, and Micronoma. J.A.W. holds stock options from Micronoma.

Figures

Figure 1
Figure 1
Proposed mechanism of action of gut microbiota-mediated 3-IAA chemosensitization Indole-3-acetic acid (3-IAA) is a metabolite of tryptophan broken down by gut microbiota, and higher serum 3-IAA levels were found in pancreatic cancer patients who responded to chemotherapy. The gut microbiome of responders was enhanced in 3-IAA producers (including Bacteroides). Through multiple loss-of- and gain-of-function pre-clinical experiments, the authors demonstrate neutrophil-mediated accumulation of reactive oxygen species, which led to improved response to chemotherapy.
See this image and copyright information in PMC

Comment on

  • Microbiota-derived 3-IAA influences chemotherapy efficacy in pancreatic cancer.
    Tintelnot J, Xu Y, Lesker TR, Schönlein M, Konczalla L, Giannou AD, Pelczar P, Kylies D, Puelles VG, Bielecka AA, Peschka M, Cortesi F, Riecken K, Jung M, Amend L, Bröring TS, Trajkovic-Arsic M, Siveke JT, Renné T, Zhang D, Boeck S, Strowig T, Uzunoglu FG, Güngör C, Stein A, Izbicki JR, Bokemeyer C, Sinn M, Kimmelman AC, Huber S, Gagliani N. Tintelnot J, et al. Nature. 2023 Mar;615(7950):168-174. doi: 10.1038/s41586-023-05728-y. Epub 2023 Feb 22. Nature. 2023. PMID: 36813961 Free PMC article.

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