Fig. 6: DAV132 maintains an effective immune response during ATB treatment in mice. | Nature Communications

Fig. 6: DAV132 maintains an effective immune response during ATB treatment in mice.

From: The DAV132 colon-targeted adsorbent does not interfere with plasma concentrations of antibiotics but prevents antibiotic-related dysbiosis: a randomized phase I trial in healthy volunteers

Fig. 6

A Flow cytometry analysis of the total CD8+Tcells and the ratio of CD8+ T cells/Treg population in MCA-205 tumor infiltrating lymphocytes (TILs) from ATB-treated mice recolonized with FMT from D6 samples in four HV (1, 2, 4, and 5) who received CZA alone or CZA + DAV132 at D6 (Fig. 5D, E). Data are presented as mean ± SEM, the Mann–Whitney U test was used to determine significant differences among the different groups. Each dot represents one mouse. B From experiment presented in Fig. 5D, E, UMAP visualization of tumor-infiltrating T cells in the group FMT CZA + DAV132 (Iso-PD-1 or αPD-1) C Heatmap representation of the 26 populations visualized in the UMAP with their respective normalized mean fluorescence intensity of the depicted markers. In grey, the frequency of pooled population for each group and the statistical analysis were done based on the percentage per mouse. D RNAseq of the bulk tumor representing the FMT from CZA-DAV132 + αPD-1 compared to the 3 other groups. n = 5mice/group, samples depicted in first two principal components space. For each of the 2 axes, values within parentheses correspond to explained variance. Ninety-five percent confidence ellipses were added. E ImmuCellAI-mouse extrapolation of central memory CD8+ T cells. The center line indicates the median value, lower and upper hinges represent the 25th and 75th percentiles, respectively, and whiskers denote minimum and maximum. F RNAseq heatmap representing expression of genes differentially expressed on MCA-205 CD8+ T cells sorted n = 5mice/group between CZA-DAV132 + Iso-PD-1 and CZA-DAV132 + αPD-1 and other groups (FDR adjusted p < 0.01). Rows: genes were clustered based on Euclidean distance and « complete » method. Columns: samples were ordered given group membership. G qPCR of ifng gene and the ifng/il-10 ratio in the mesenteric lymph nodes and draining lymph node from the 4 experimental groups, Data are presented as mean ± SEM, the Mann–Whitney U test was used to determine significant differences among the different groups. CZA ceftazidime-avibactam, FMT fecal microbiota transplantation, infg interferon gamma, il10 interleukine-10, PD-1 programmed cell death protein 1, PTZ piperacillin-tazobactam, DAV132 DAV132 12 g po tid. (ns non-significant).

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