Targeted discovery of gut microbiome-remodeling compounds for the treatment of systemic inflammatory response syndrome

From BugSigDB
Reviewed Marked as Reviewed by Svetlana up on 2024-12-9
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Liu L, Ma L, Liu H, Zhao F, Li P, Zhang J, Lü X, Zhao X, Yi Y
Journal
mSystems
Year
2024
Keywords:
gut inflammation, gut microbiome remodeling, in vitro screening, systemic inflammation response syndrome
Systemic inflammatory response syndrome (SIRS) is a severe inflammatory response that can lead to organ dysfunction and death. Modulating the gut microbiome is a promising therapeutic approach for managing SIRS. This study assesses the therapeutic potential of the Xuanfei Baidu (XFBD) formula in treating SIRS. The results showed that XFBD administration effectively reduced mortality rates and inflammation in SIRS mice. Using 16S rRNA sequencing and fecal microbiota transplantation (FMT), we substantiated that the therapeutic effects of XFBD are partly attributed to gut microbiota modulation. We conducted in vitro experiments to accurately assess the gut microbiome remodeling effects of 51 compounds isolated from XFBD. These compounds exhibited varying abilities to induce a microbial structure that closely resembles that of the healthy control group. By quantifying their impact on microbial structure and clustering their regulatory patterns, we devised multiple gut microbiome remodeling compound (GMRC) cocktails. GMRC cocktail C, comprising aucubin, gentiopicroside, syringic acid, gallic acid, p-hydroxybenzaldehyde, para-hydroxybenzoic acid, and isoimperatorin, demonstrated superior efficacy in treating SIRS compared to a single compound or to other cocktails. Finally, in vitro experiments showcased that GMRC cocktail C effectively rebalanced bacteria composition in SIRS patients. This study underscores XFBD's therapeutic potential in SIRS and highlights the importance of innovative treatment approaches for this disease by targeting the gut microbiota.IMPORTANCEDeveloping effective treatment strategies for systemic inflammatory response syndrome (SIRS) is crucial due to its severe and often life-threatening nature. While traditional treatments like dexamethasone have shown efficacy, they also come with significant side effects and limitations. This study makes significant strides by demonstrating that the Xuanfei Baidu (XFBD) formula can substantially reduce mortality rates and inflammation in SIRS mice through effective modulation of the gut microbiota. By quantitatively assessing the impact of 51 compounds derived from XFBD on the gut microbiome, we developed a potent gut microbiome remodeling compound cocktail. This cocktail outperformed individual compounds and other mixtures in efficacy against SIRS. These findings highlight the potential of XFBD as a therapeutic solution for SIRS and underscore the critical role of innovative strategies targeting the gut microbiota in addressing this severe inflammatory condition.

Experiment 1


Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/15

Curator: Aishat

Revision editor(s): Aishat, Ifeanyisam

Subjects

Location of subjects
China
Host species Species from which microbiome was sampled. Contact us to have more species added.
Mus musculus
Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Systemic inflammatory response syndrome Inflammatory Response Syndrome, Systemic,Sepsis Syndrome,SIRS,Systemic inflammatory response syndrome,systemic inflammatory response syndrome
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Control Group
Group 1 name Corresponds to the case (exposed) group for case-control studies
LPS-induced SIRS (systemic inflammatory response syndrome) group
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Lipopolysaccharide-induced SIRS group represent the disease model receiving treatment. They serve as the primary target for testing the efficacy of therapeutic interventions aimed at reducing inflammation and restoring gut microbiota balance.
Group 0 sample size Number of subjects in the control (unexposed) group
6
Group 1 sample size Number of subjects in the case (exposed) group
6

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V3-V4
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
relative abundances
Statistical test
ANOVA
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
decreased
Chao1 Abundance-based estimator of species richness
decreased

Experiment 2


Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/21

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
LPS-induced SIRS (systemic inflammatory response syndrome) group
Group 1 name Corresponds to the case (exposed) group for case-control studies
FMT-L Group
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
The (Xuanfei Baidu)XFBD-fed group containing live microbiota

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Chao1 Abundance-based estimator of species richness
increased

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/21

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Source: Figure S2D

Description: Specific genus variations used for Fecal Microbiota Transplantation effects of SIRS mice.

Abundance in Group 1: decreased abundance in FMT-L Group

NCBI Quality ControlLinks
unclassified Oscillospiraceae

Revision editor(s): Ifeanyisam

Experiment 3


Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/21

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
FMT-L Group
Group 1 name Corresponds to the case (exposed) group for case-control studies
FMT-HK Group
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
The (Xuanfei Baidu)XFBD-fed group containing heat-killed microbiota

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
decreased
Chao1 Abundance-based estimator of species richness
decreased

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/21

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Source: Figure S2A

Description: Specific genus variations used for the Fecal Microbiota Transplantation effects on microbiota in SIRS mice.

Abundance in Group 1: increased abundance in FMT-HK Group

NCBI Quality ControlLinks
Bacteroides

Revision editor(s): Ifeanyisam

Experiment 4


Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/21

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
LPS-induced SIRS (systemic inflammatory response syndrome) group

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/21

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Source: Figure S2A

Description: Specific genus variations used for the Fecal Microbiota Transplantation effects on microbiota in SIRS mice.

Abundance in Group 1: increased abundance in FMT-HK Group

NCBI Quality ControlLinks
Bacteroides

Revision editor(s): Ifeanyisam

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/21

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Source: Figure S2D

Description: Specific genus variations used for the Fecal Microbiota Transplantation effects on microbiota in SIRS mice.

Abundance in Group 1: decreased abundance in FMT-HK Group

NCBI Quality ControlLinks
unclassified Oscillospiraceae

Revision editor(s): Ifeanyisam

Experiment 5


Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/21

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
N (uncultured control)
Group 1 name Corresponds to the case (exposed) group for case-control studies
M (Uncultured Model)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
SIRS fecal sample before in vitro culture
Group 0 sample size Number of subjects in the control (unexposed) group
3
Group 1 sample size Number of subjects in the case (exposed) group
3

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
decreased
Chao1 Abundance-based estimator of species richness
unchanged

Experiment 6


Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/22

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
M (Uncultured Model Group)
Group 1 name Corresponds to the case (exposed) group for case-control studies
MD (Cultured Model Group)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Microbial composition from the fecal content of LPS-induced SIRS mice after the in vitro culturing process.

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
decreased
Chao1 Abundance-based estimator of species richness
decreased

Experiment 7


Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/22

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
ND (cultured control)
Group 1 name Corresponds to the case (exposed) group for case-control studies
MD (cultured model)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Microbial composition from the fecal content of LPS-induced SIRS mice after the in vitro culturing process

Lab analysis

Statistical Analysis

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/23

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Source: Figure S5D

Description: The relative abundance in genus levels after cocktail treatment

Abundance in Group 1: increased abundance in MD (cultured model)

NCBI Quality ControlLinks
Bacteroides
Enterobacter
Escherichia/Shigella sp.

Revision editor(s): Ifeanyisam

Experiment 10


Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/23

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
N
Group 1 name Corresponds to the case (exposed) group for case-control studies
M
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Uncultured Model

Lab analysis

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
raw counts
Statistical test
DESeq2
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Yes

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
decreased
Chao1 Abundance-based estimator of species richness
decreased

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/23

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Source: Figure 5B

Description: A waterfall plot of significantly altered genus between model and control showing consistent trend in uncultured groups.

Abundance in Group 1: increased abundance in M

NCBI Quality ControlLinks
Bacteroides
Proteus
Butyricimonas
Escherichia/Shigella sp.
Parabacteroides
Bilophila
Enterococcus
Clostridium
Asaccharospora
Thomasclavelia

Revision editor(s): Ifeanyisam

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/23

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Source: Figure 5B

Description: A waterfall plot of significantly altered genus between model and control showing consistent trend in uncultured groups

Abundance in Group 1: decreased abundance in M

NCBI Quality ControlLinks
Allobaculum
Candidatus Saccharimonas
Ruminiclostridium
Turicibacter
uncultured Oscillospiraceae bacterium
ruminococcus 1ruminococcus 1
lachnospiraceae UCG-001lachnospiraceae UCG-001

Revision editor(s): Ifeanyisam

Experiment 11


Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/23

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
ND
Group 1 name Corresponds to the case (exposed) group for case-control studies
MD
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Cultured model

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/23

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Source: Figure 5B

Description: A waterfall plot of significantly altered genus between model and control showing consistent trend in cultured groups

Abundance in Group 1: increased abundance in MD

NCBI Quality ControlLinks
Bacteroides
Proteus
Butyricimonas
Escherichia/Shigella sp.
Parabacteroides
Clostridium
Bilophila
Enterococcus
Asaccharospora
Thomasclavelia

Revision editor(s): Ifeanyisam

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/23

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Source: Figure 5B

Description: A waterfall plot of significantly altered genus between model and control showing consistent trend in cultured groups

Abundance in Group 1: decreased abundance in MD

NCBI Quality ControlLinks
Ruminiclostridium
ruminococcus 1ruminococcus 1
Allobaculum
Turicibacter
Candidatus Saccharimonas
uncultured Oscillospiraceae bacterium
lachnospiraceae UCG-001lachnospiraceae UCG-001

Revision editor(s): Ifeanyisam

Experiment 12


Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/23

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
MD (cultured model)
Group 1 name Corresponds to the case (exposed) group for case-control studies
A2.1 (gut microbiome remodeling compound)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Gut Microbiome Remodeling Compound cocktail concentrations simplified from XFBD formula

Lab analysis

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
relative abundances
Statistical test
ANOVA

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
decreased
Chao1 Abundance-based estimator of species richness
unchanged

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/24

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Source: Figure S5D

Description: The relative abundance in genus levels after cocktail treatment

Abundance in Group 1: decreased abundance in A2.1 (gut microbiome remodeling compound)

NCBI Quality ControlLinks
Bacteroides
Enterobacter
Escherichia/Shigella sp.

Revision editor(s): Ifeanyisam

Experiment 13


Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/23

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
A2.2(gut microbiome remodeling compound)

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Chao1 Abundance-based estimator of species richness
unchanged

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/23

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Source: Figure S5D

Description: The relative abundance in genus levels after cocktail treatment

Abundance in Group 1: decreased abundance in A2.2(gut microbiome remodeling compound)

NCBI Quality ControlLinks
Bacteroides
Escherichia/Shigella sp.

Revision editor(s): Ifeanyisam

Experiment 14


Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/23

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
B2.1 (gut microbiome remodeling compound)

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
decreased
Chao1 Abundance-based estimator of species richness
unchanged

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/24

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Source: Figure S5D

Description: The relative abundance in genus levels after cocktail treatment

Abundance in Group 1: decreased abundance in B2.1 (gut microbiome remodeling compound)

NCBI Quality ControlLinks
Bacteroides
Enterobacter
Escherichia/Shigella sp.

Revision editor(s): Ifeanyisam

Experiment 15


Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/23

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
PD1 (Patient sample 1 with DMSO)
Group 1 name Corresponds to the case (exposed) group for case-control studies
PC1 (Patient sample 1 treated with cocktail c)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patient sample treated with cocktail c

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Chao1 Abundance-based estimator of species richness
unchanged

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/23

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Source: Figure S6A

Description: The relative abundance in Phylum Levels

Abundance in Group 1: decreased abundance in PC1 (Patient sample 1 treated with cocktail c)

NCBI Quality ControlLinks
Bacillota
Enterobacter

Revision editor(s): Ifeanyisam

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/23

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Source: Figure S6A

Description: The relative abundance in Phylum Levels

Abundance in Group 1: increased abundance in PC1 (Patient sample 1 treated with cocktail c)

NCBI Quality ControlLinks
Pseudomonadota

Revision editor(s): Ifeanyisam

Experiment 16


Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/23

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
PD2 (Patient sample 2 with DMSO)
Group 1 name Corresponds to the case (exposed) group for case-control studies
PC2 (Patient sample 2 treated with cocktail c)

Lab analysis

Statistical Analysis

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Not specified

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
unchanged

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/23

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Source: Figure S6A and S6C

Description: The relative abundance in Phylum and genera levels

Abundance in Group 1: decreased abundance in PC2 (Patient sample 2 treated with cocktail c)

NCBI Quality ControlLinks
Bacteroides
Bacteroidia
Parabacteroides
Pseudomonadota

Revision editor(s): Ifeanyisam

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/23

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Source: Figure S6A

Description: The relative abundance level in Phylum levels

Abundance in Group 1: increased abundance in PC2 (Patient sample 2 treated with cocktail c)

NCBI Quality ControlLinks
Bacillota

Revision editor(s): Ifeanyisam

Experiment 17


Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/23

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
PD4 (Patient sample 4 with DMSO)
Group 1 name Corresponds to the case (exposed) group for case-control studies
PC4 (Patient sample 4 treated with cocktail c)

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
decreased
Chao1 Abundance-based estimator of species richness
unchanged

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/23

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Source: Figure S6A and S6C

Description: the relative abundance in Phylum and genera levels

Abundance in Group 1: decreased abundance in PC4 (Patient sample 4 treated with cocktail c)

NCBI Quality ControlLinks
Bacteroides
Enterobacter
Pseudomonadota
Bacteroidia

Revision editor(s): Ifeanyisam

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/23

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Source: figure S6A and S6C

Description: The relative abundance in Phylum and genera levels

Abundance in Group 1: increased abundance in PC4 (Patient sample 4 treated with cocktail c)

NCBI Quality ControlLinks
Bacillota
Escherichia/Shigella sp.

Revision editor(s): Ifeanyisam

Experiment 18


Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/23

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
PD5 (Patient sample 5 with DMSO)
Group 1 name Corresponds to the case (exposed) group for case-control studies
PC5 (Patient sample 5 treated with cocktail c)

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
unchanged

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/23

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Source: Figure S6A

Description: The relative abundance in phylum levels

Abundance in Group 1: decreased abundance in PC5 (Patient sample 5 treated with cocktail c)

NCBI Quality ControlLinks
Bacillota

Revision editor(s): Ifeanyisam

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/23

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Source: Figure S6A

Description: The relative abundance in phylum levels

Abundance in Group 1: increased abundance in PC5 (Patient sample 5 treated with cocktail c)

NCBI Quality ControlLinks
Pseudomonadota

Revision editor(s): Ifeanyisam

Experiment 19


Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/23

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
PD6 (Patient sample 6 with DMSO)
Group 1 name Corresponds to the case (exposed) group for case-control studies
PC6 (Patient sample 6 treated with cocktail c)

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
unchanged

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/23

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Source: Figure S6A and S6C

Description: The relative abundance in Phylum and genera levels

Abundance in Group 1: decreased abundance in PC6 (Patient sample 6 treated with cocktail c)

NCBI Quality ControlLinks
Pseudomonadota
Parabacteroides

Revision editor(s): Ifeanyisam

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/23

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Source: Figure S6A

Description: The relative abundance in Phylum levels

Abundance in Group 1: increased abundance in PC6 (Patient sample 6 treated with cocktail c)

NCBI Quality ControlLinks
Bacillota

Revision editor(s): Ifeanyisam

Experiment 20


Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/23

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
PD8 (Patient sample 8 with DMSO)
Group 1 name Corresponds to the case (exposed) group for case-control studies
PC8 (Patient sample 8 treated with cocktail c)

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
decreased
Chao1 Abundance-based estimator of species richness
decreased

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/23

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Source: Figure S6A and S6C

Description: The relative abundance in Phylum and genera levels

Abundance in Group 1: decreased abundance in PC8 (Patient sample 8 treated with cocktail c)

NCBI Quality ControlLinks
Pseudomonadota
Escherichia/Shigella sp.

Revision editor(s): Ifeanyisam

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/23

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Source: Figure S6A and S6C

Description: The relative abundance in Phylum and genera levels

Abundance in Group 1: increased abundance in PC8 (Patient sample 8 treated with cocktail c)

NCBI Quality ControlLinks
Bacillota
Bifidobacterium

Revision editor(s): Ifeanyisam

Experiment 21


Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/23

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
H (Healthy Volunteers)
Group 1 name Corresponds to the case (exposed) group for case-control studies
P (Patients with SIRS)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with SIRS
Group 0 sample size Number of subjects in the control (unexposed) group
10
Group 1 sample size Number of subjects in the case (exposed) group
8

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/23

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Source: Figure 8C

Description: Abundance comparison of key genera between SIRS patients and healthy volunteers.

Abundance in Group 1: increased abundance in P (Patients with SIRS)

NCBI Quality ControlLinks
Enterococcus
Lactobacillus
Bacteroides
Enterobacter
Lachnoclostridium
Escherichia/Shigella sp.
Akkermansia
Pseudomonas
Ralstonia
Dysgonomonas

Revision editor(s): Ifeanyisam

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/23

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Source: Figure 8C

Description: Abundance comparison of key genera between SIRS patients and healthy volunteers

Abundance in Group 1: decreased abundance in P (Patients with SIRS)

NCBI Quality ControlLinks
Bifidobacterium
Streptococcus
Blautia
Fusicatenibacter
Faecalibacterium
Dorea
Agathobacter
Romboutsia

Revision editor(s): Ifeanyisam

Experiment 22


Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/24

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
MD (cultured model)
Group 1 name Corresponds to the case (exposed) group for case-control studies
B2.2 (gut microbiome remodeling compound)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Gut Microbiome Remodeling Compound cocktail concentrations simplified from XFBD formula
Group 0 sample size Number of subjects in the control (unexposed) group
3
Group 1 sample size Number of subjects in the case (exposed) group
3

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
decreased
Chao1 Abundance-based estimator of species richness
unchanged

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/24

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Source: Figure S5D

Description: The relative abundance in genus levels after cocktail treatment

Abundance in Group 1: decreased abundance in B2.2 (gut microbiome remodeling compound)

NCBI Quality ControlLinks
Bacteroides
Escherichia/Shigella sp.

Revision editor(s): Ifeanyisam

Experiment 23


Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/24

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
C2.1 (gut microbiome remodeling compound)

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
decreased
Chao1 Abundance-based estimator of species richness
unchanged

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/24

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam, Victoria

Source: Figure S5D

Description: The relative abundance in genus levels after cocktail treatment

Abundance in Group 1: decreased abundance in C2.1 (gut microbiome remodeling compound)

NCBI Quality ControlLinks
Enterobacter
Escherichia/Shigella sp.
Bacteroides

Revision editor(s): Ifeanyisam, Victoria

Experiment 24


Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/24

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
C2.2 (gut microbiome remodeling compound)

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Chao1 Abundance-based estimator of species richness
unchanged

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/24

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam, Victoria

Source: Figure S5D

Description: The relative abundance in genus levels after cocktail treatment

Abundance in Group 1: decreased abundance in C2.2 (gut microbiome remodeling compound)

NCBI Quality ControlLinks
Bacteroides
Enterobacter
Escherichia/Shigella sp.

Revision editor(s): Ifeanyisam, Victoria

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/24

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Source: Figure S5D

Description: The relative abundance in genus levels after cocktail treatment

Abundance in Group 1: increased abundance in C2.2 (gut microbiome remodeling compound)

NCBI Quality ControlLinks
Enterococcus

Revision editor(s): Ifeanyisam

Experiment 25


Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/24

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
D2.1 (gut microbiome remodeling compound)

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
decreased
Chao1 Abundance-based estimator of species richness
unchanged

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/24

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam, Victoria

Source: Figure S5D

Description: the relative abundance in genus levels after cocktail treatment

Abundance in Group 1: decreased abundance in D2.1 (gut microbiome remodeling compound)

NCBI Quality ControlLinks
Escherichia/Shigella sp.

Revision editor(s): Ifeanyisam, Victoria

Experiment 26


Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/24

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
D2.2 (gut microbiome remodeling compound)

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased
Chao1 Abundance-based estimator of species richness
unchanged

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/24

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Source: Figure S5D

Description: The relative abundance in genus levels after cocktail treatment

Abundance in Group 1: increased abundance in D2.2 (gut microbiome remodeling compound)

NCBI Quality ControlLinks
Enterococcus

Revision editor(s): Ifeanyisam

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/24

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Source: Figure S5D

Description: The relative abundance in genus levels after cocktail treatment

Abundance in Group 1: decreased abundance in D2.2 (gut microbiome remodeling compound)

NCBI Quality ControlLinks
Bacteroides
Escherichia/Shigella sp.

Revision editor(s): Ifeanyisam

Experiment 27


Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/24

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
E2.1 (gut microbiome remodeling compound)

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
decreased
Chao1 Abundance-based estimator of species richness
unchanged

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/24

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Source: Figure S5D

Description: The relative abundance in genus levels after cocktail treatment

Abundance in Group 1: decreased abundance in E2.1 (gut microbiome remodeling compound)

NCBI Quality ControlLinks
Escherichia/Shigella sp.
Bacteroides
Enterobacter

Revision editor(s): Ifeanyisam

Experiment 28


Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/24

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
E2.2 (gut microbiome remodeling compound)

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
decreased
Chao1 Abundance-based estimator of species richness
unchanged

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/24

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam, Victoria

Source: Figure S5D

Description: the relative abundance in genus levels after cocktail treatment

Abundance in Group 1: decreased abundance in E2.2 (gut microbiome remodeling compound)

NCBI Quality ControlLinks
Enterobacter
Escherichia/Shigella sp.
Bacteroides

Revision editor(s): Ifeanyisam, Victoria

Experiment 29


Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/24

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
F2.1 (gut microbiome remodeling compound)

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
decreased
Chao1 Abundance-based estimator of species richness
unchanged

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/24

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Source: Figure S5D

Description: The relative abundance in genus levels after cocktail treatment

Abundance in Group 1: decreased abundance in F2.1 (gut microbiome remodeling compound)

NCBI Quality ControlLinks
Escherichia/Shigella sp.
Bacteroides
Enterobacter

Revision editor(s): Ifeanyisam

Experiment 30


Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/24

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
F2.2 (gut microbiome remodeling compound)

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged
Chao1 Abundance-based estimator of species richness
unchanged

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-12-9

Curated date: 2024/10/24

Curator: Ifeanyisam

Revision editor(s): Ifeanyisam, Victoria

Source: Figure S5D

Description: The relative abundance in genus levels after cocktail treatment

Abundance in Group 1: decreased abundance in F2.2 (gut microbiome remodeling compound)

NCBI Quality ControlLinks
Bacteroides
Escherichia/Shigella sp.

Revision editor(s): Ifeanyisam, Victoria