Donor Microbiota Metabolic Capacity Determines Engraftment Dynamics and Modulates Gut–Brain Signaling in Recipient Mice
Paper
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The authors' code
R · 188 lines · 5.1 KB · MIT
- library(MicrobiotaProcess)
- library(phyloseq)
- library(tidyverse)
- library(ggtree)
- library(ggtreeExtra)
- library(patchwork)
- library(ggnewscale)
- library(vegan)
- library(coin)
- pdf("all_plots.pdf", width = 11.69, height = 11.69)
- # -------------------------------------------------------------------------
- # colors
- # -------------------------------------------------------------------------
- cols <- c(
- "Co.Donor" = "#56b4e9",
- "Co" = "#9cd866",
- "BIP.Donor"= "#fcda52",
- "BIP" = "#f6659e"
- )
- cols_o <- scales::alpha(cols, .5)
- cols_h <- scales::darken(cols, .2)
- tax_cols <- colorRampPalette(c(
- "#9cd866","#fcda52","#E69F00","#0072B2","#F0E442",
- "#b366d8","#D55E00","gray","#56b4e9","#CC79A7","#009E73"
- ))(30)
- # -------------------------------------------------------------------------
- # functions
- # -------------------------------------------------------------------------
- import_qiime <- function(prefix){
- mp_import_qiime2(
- otuqza = file.path("Data","QIIME2", paste0("feature_table", prefix, ".qza")),
- taxaqza = file.path("Data","QIIME2", paste0("taxonomic_classification", prefix, ".qza")),
- mapfilename = file.path("Data","QIIME2", paste0("metadata", prefix, ".tsv")),
- treeqza = file.path("Data","QIIME2", paste0("rooted_tree", prefix, ".qza"))
- ) %>%
- filter(
- !Phylum %in% c("p__un_k__Bacteria","p__Chloroflexi","p__un_k__Unknown"),
- !Order %in% "o__Chloroplast",
- !Family %in% "f__Mitochondria"
- )
- }
- prep_alpha <- function(x){
- x %>%
- mp_rrarefy(.abundance = Abundance, raresize = 52500, seed = 123) %>%
- mp_cal_rarecurve(.abundance = RareAbundance, chunks = 500) %>%
- mp_cal_alpha(.abundance = RareAbundance) %>%
- mp_cal_pd_metric(.abundance = RareAbundance)
- }
- calc_beta <- function(x, method){
- x %>%
- mp_cal_dist(.abundance = RareAbundance, distmethod = method) %>%
- mp_cal_pcoa(.abundance = RareAbundance, distmethod = method)
- }
- ord_plot <- function(x, title=NULL){
- mp_plot_ord(
- x, .ord = pcoa, .group = Group,
- .color = Group, .size = PD, ellipse = TRUE
- ) +
- scale_color_manual(values = cols) +
- scale_fill_manual(values = cols) +
- theme_bw() +
- ggtitle(title)
- }
- # -------------------------------------------------------------------------
- # import
- # -------------------------------------------------------------------------
- mpse <- import_qiime("")
- mpse_m <- import_qiime("_mouse")
- # -------------------------------------------------------------------------
- # alpha diversity
- # -------------------------------------------------------------------------
- mpse <- prep_alpha(mpse)
- mpse_m <- prep_alpha(mpse_m)
- alpha_tbl <- as.data.frame(colData(mpse)) |>
- select(SID, Group, Observe, Shannon, Pielou, PD)
- write.table(alpha_tbl, "alpha_diversity.tsv", sep="\t", quote=FALSE, col.names=NA)
- p_alpha_human <- mp_plot_rarecurve(
- mpse,
- .rare = RareAbundanceRarecurve,
- .alpha = Observe,
- .group = Group,
- plot.group = TRUE
- ) +
- scale_color_manual(values = cols)
- p_alpha_mouse <- mp_plot_alpha(
- mpse_m,
- .alpha = c(Observe, Shannon, PD, Pielou),
- .group = Group
- ) +
- scale_fill_manual(values = cols_o)
- (p_alpha_human | p_alpha_mouse)
- # -------------------------------------------------------------------------
- # beta diversity
- # -------------------------------------------------------------------------
- methods <- c("bray","unifrac","wunifrac")
- beta_stats <- map_dfr(methods, function(m){
- tmp <- calc_beta(mpse_m, m)
- tmp %<>%
- mp_adonis(.abundance = RareAbundance,
- distmethod = m,
- .formula = ~ Group,
- permutation = 999)
- stat <- tmp %>%
- mp_extract_internal_attr(name = adonis) %>%
- mp_fortify()
- stat$method <- m
- ord_plot(tmp, toupper(m))
- stat
- })
- write.table(beta_stats, "beta_diversity.tsv", sep="\t", quote=FALSE, col.names=NA)
- # -------------------------------------------------------------------------
- # abundance
- # -------------------------------------------------------------------------
- mpse %<>%
- mp_cal_abundance(.abundance = Abundance, relative = TRUE, force = TRUE) %>%
- mp_cal_abundance(.abundance = Abundance, .group = Group, relative = TRUE, force = TRUE)
- p_abund <-
- mp_plot_abundance(
- mpse,
- .abundance = Abundance,
- taxa.class = Genus,
- topn = 30,
- .group = Group,
- plot.group = TRUE
- ) +
- scale_fill_manual(values = tax_cols)
- p_abund
- # -------------------------------------------------------------------------
- # differential abundance (mouse)
- # -------------------------------------------------------------------------
- mpse_m_da <- import_qiime("_mouse") %>%
- mp_filter_taxa(.abundance = Abundance, min.abun = 10, min.prop = 0.1) %>%
- mp_cal_abundance(.abundance = Abundance, relative = TRUE, force = TRUE)
- mpse_m_da %<>%
- mp_diff_analysis(
- .abundance = RelAbundanceBySample,
- .group = Group,
- tip.level = "Species",
- first.test.method = "kruskal_test",
- second.test.method = "wilcox_test",
- ml.method = "lda",
- ldascore = 3,
- action = "add"
- )
- mp_plot_diff_boxplot(mpse_m_da, .group = Group) +
- set_diff_boxplot_color(values = cols)
- # -------------------------------------------------------------------------
- dev.off()
16s_processing.R at commit 2d689c6, under MIT · at the source
Overview
Abstract
This study performs patient-to-mouse fecal microbiota transplantation (FMT) as an experimental platform to investigate gut-brain axis alterations with potential relevance to psychiatric disorders, integrating metabolic modeling with measured metabolites and multi-layer molecular profiling. Microbial communities of a stool sample associated with bipolar disorder (BD) displayed a reduced ecological diversity and diminished metabolic potential, particularly within glutamate, aspartate, and GABA biosynthetic pathways. Upon transplantation with BD patient microbiota, recipient mice displayed a markedly altered microbiome characterized by loss of Akkermansia and expansion of Alloprevotella, alongside disruptions in amino acid and carbohydrate metabolism not evident in mice colonized by a healthy donor microbiota. Metabolic microbiome alterations in BD-recipient mice were also correlated to reduced glutathione levels in gut tissue, likely indicating increased oxidative stress, and decreased mRNA expression of key enteroendocrine hormones, including peptide YY and glucagon. Brain metabolomic profiling of BD-recipient mice revealed significant depletion of glycine, choline, and methionine levels connected to anxiety-like phenotypes in elevated plus-maze and light-dark box behavioral tests. Akkermansia abundance positively correlated with physical activity and exploratory behavior, highlighting an important role of this taxon in gut-brain signaling. Collectively, these findings identify distinct microbial, metabolic, and neurobehavioral signatures transmittable from humans to mice via FMT and demonstrate that differences in donor microbiome diversity and metabolic capacity shape engraftment dynamics in recipient mice, which contribute to differences in gut-brain signaling.
Reproduced under the paper's license (CC BY), from the paper cited above.
Repository
Its files are read in the Code ↔ Paper reader above.
marijazmf/BP_paper_analysis
2d689c64d7f4e71af7d7a83dae2e77b89b961564, 6 March 2026Availability: 1 check, the latest on 28 September 2026: the link answers
- 28 September 2026: the link answers
12 files
- Scripts/
16s_processing.R , R, 188 lines - Scripts/
ASV_sharing.R , R, 133 lines - Scripts/
CorrelationFunction.R , R, 136 lines - Scripts/
Differential_growthRate. , R, 127 linesR - Scripts/
MICOM_Human.sh , Shell, 31 lines - Scripts/
MICOM_Mouse.sh , Shell, 31 lines - Scripts/
Maaslin_Metabolites.R , R, 58 lines - Scripts/
SharedGenera.R , R, 165 lines - Scripts/
Shared_ASV.ipynb , Jupyter, 70 lines - Scripts/
growthRate_RelAbundance. , R, 190 linesR - LICENSE, License, 21 lines
- README.md, Text, 2 lines
The paper's code and data availability statement is in the Data section.
Tracing map
Proposed by the machine: these links were found in the paper and verified at the source, without human review. The map will receive a Zenodo DOI once one of the paper's authors has validated it with their ORCID.
What the map holds:
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Its JSON (tracing-map.json) is deposited on Zenodo with its DOI once the map is validated.
Data
No dataset and no data link were found in the paper.
Data and code availability
Datasets and scripts used in this work are accessible through the GitHub repository: https://
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
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Version 1, 28 September 2026: the first record
Recorded: type, journal, dates, 20 authors, 79 references.
Cite
This paper
Farzi, A., Durdevic, M., Fellendorf, F., Schimmel, P., Kuehnast, T., Bukowski-Thall, G., Gorkiewicz, S., Ip, C. K., Habisch, H., Fischer, S., Mörkl, S., Wagner-Skacel, J., Bengesser, S., Lenger, M., Dalkner, N., Hoegenauer, C., Madl, T., Moissl-Eichinger, C., Gorkiewicz, G., & Reininghaus, E. (2026). Donor Microbiota Metabolic Capacity Determines Engraftment Dynamics and Modulates Gut–Brain Signaling in Recipient Mice. Research Square (preprint). https://
BibTeX
@article{farzi2026donor,
author = {Farzi, Aitak and Durdevic, Marija and Fellendorf, Frederike and Schimmel, Patrick and Kuehnast, Torben and Bukowski-Thall, Grace and Gorkiewicz, Sarah and Ip, Chi Kin and Habisch, Hansjörg and Fischer, Sophia and Mörkl, Sabrina and Wagner-Skacel, Jolana and Bengesser, Susanne and Lenger, Melanie and Dalkner, Nina and Hoegenauer, Christoph and Madl, Tobias and Moissl-Eichinger, Christine and Gorkiewicz, Gregor and Reininghaus, Eva},
title = {{Donor Microbiota Metabolic Capacity Determines Engraftment Dynamics and Modulates Gut–Brain Signaling in Recipient Mice}},
journal = {Research Square (preprint)},
year = {2026},
month = may,
publisher = {Research Square},
issn = {2693-5015},
doi = {10.21203/
url = {https://
}
RIS
TY - JOUR
AU - Farzi, Aitak
AU - Durdevic, Marija
AU - Fellendorf, Frederike
AU - Schimmel, Patrick
AU - Kuehnast, Torben
AU - Bukowski-Thall, Grace
AU - Gorkiewicz, Sarah
AU - Ip, Chi Kin
AU - Habisch, Hansjörg
AU - Fischer, Sophia
AU - Mörkl, Sabrina
AU - Wagner-Skacel, Jolana
AU - Bengesser, Susanne
AU - Lenger, Melanie
AU - Dalkner, Nina
AU - Hoegenauer, Christoph
AU - Madl, Tobias
AU - Moissl-Eichinger, Christine
AU - Gorkiewicz, Gregor
AU - Reininghaus, Eva
TI - Donor Microbiota Metabolic Capacity Determines Engraftment Dynamics and Modulates Gut–Brain Signaling in Recipient Mice
T2 - Research Square (preprint)
J2 - Res Sq
PY - 2026
DA - 2026/
SN - 2693-5015
PB - Research Square
DO - 10.21203/
UR - https://
ER -
CSL-JSON
{
"id": "10.21203/
"type": "article",
"title": "Donor Microbiota Metabolic Capacity Determines Engraftment Dynamics and Modulates Gut–Brain Signaling in Recipient Mice",
"container-title": "Research Square (preprint)",
"author": [
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"family": "Farzi",
"given": "Aitak"
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