Additional file 1 of IL-22 alters gut microbiota composition and function to increase aryl hydrocarbon receptor activity in mice and humans

Autor: Mar, Jordan S., Ota, Naruhisa, Pokorzynski, Nick D., Peng, Yutian, Jaochico, Allan, Sangaraju, Dewakar, Skippington, Elizabeth, Lekkerkerker, Annemarie N., Rothenberg, Michael E., Tan, Man-Wah, Yi, Tangsheng, Keir, Mary E.
Rok vydání: 2023
DOI: 10.6084/m9.figshare.22619468
Popis: Additional file 1: Figure S1. Supplement to IL-22Fc microbiota response in mice. (A) After a two week acclimatization period during which animals were co-housed, six- to eight-week-old, female C57BL/6J mice (n=16) were randomly re-caged on study day 0 into two treatment groups and separately housed for the remainder of the experiment: IL-22Fc treated (n=8, four mice per cage) and control (n=8, four mice per cage). Animals were treated with 50 ug/mouse of either IL-22Fc or anti-ragweed isotype control via intraperitoneal injection three times a week for two weeks (as indicated by the red arrow), and euthanized on day 14. See methods for additional details. (B) Richness following IL-22Fc or aRW treatment. P-values determined by T-test. (C-D) Normalized abundance in control and IL-22Fc treated animals of the top highly IL-22Fc responsive bacterial genera consistently enriched (C) or depleted (D). Statistical significance determined by DESeq2 and corrected for false discovery. * BH-corrected p-value 5, n=13). P-value determined by Rank-Sum test. (D) Fecal AhR Activity (reported as fold change over unstimulated wells) at screening in HV (n=69) moderate UC (mMCS ≤ 5, n=10), and severe UC (mMCS > 5, n=13). P-value determined by T-test. (E) AUC of Log2(fold change from screening) for fecal concentrations of L-Trp, I3C, IPA, and L-Kyn in enrolled UC participants following administration of efmarodocokin alfa (n=9) or placebo (n=5). P-value determined by T-Test. For panel E, only enrolled UC participants with a complete sample collection history (screening, day 29, day 43, day 64, and day 85) were considered for AUC calculations. Figure S7. Supplement to efmarodocokin alfa effect on fecal microbiota in enrolled trial participants. (A) Mean Log2(fold change in abundance at screening between enrolled UC and HV) of the IL-22Fc depleted (n=8) and IL-22Fc enriched (n=5) genera present in the fecal microbiome of enrolled trial participants at screening. P-value determined by T-test. (B) Normalized abundance of highly IL-22Fc depleted (B) or enriched (C) genera in the fecal microbiome of enrolled HV (n=39) and UC (n=24) participants at screening. P-value determined by DESeq2 analysis. Figure S8. Supplement to efmarodocokin alfa effect on fecal microbiota AUC in humans. AUC of Log2(fold change from screening) for normalized abundance of IL-22Fc depleted (A) or enriched (B) genera detected in enrolled UC patients receiving either placebo (n=5) or efmarodocokin alfa (n=9) treatment. Only enrolled UC patients with a complete sample collection history (screening, day 29, day 43, day 64, and day 85) were considered for AUC calculations. Note that CAG-873 was not detected in any enrolled UC patients with a complete sampling history. P-value determined by T-Test.
Databáze: OpenAIRE