Gut microbiota modulation via fecal microbiota transplantation mitigates hyperoxaluria and calcium oxalate crystal depositions induced by high oxalate diet

From BugSigDB
Needs review
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
An L, Li S, Chang Z, Lei M, He Z, Xu P, Zhang S, Jiang Z, Iqbal MS, Sun X, Liu H, Duan X, Wu W
Journal
Gut microbes
Year
2025
Keywords:
Hyperoxaluria, fecal microbiota transplantation, gut microbiota, high dietary oxalate, metabolome
Hyperoxaluria, including primary and secondary hyperoxaluria, is a disorder characterized by increased urinary oxalate excretion and could lead to recurrent calcium oxalate kidney stones, nephrocalcinosis and eventually end stage renal disease. For secondary hyperoxaluria, high dietary oxalate (HDOx) or its precursors intake is a key reason. Recently, accumulated studies highlight the important role of gut microbiota in the regulation of oxalate homeostasis. However, the underlying mechanisms involving gut microbiota and metabolite disruptions in secondary hyperoxaluria remain poorly understood. Here, we investigated the therapeutic efficacy of fecal microbiota transplantation (FMT) sourced from healthy rats fed with standard pellet diet against urinary oxalate excretion, renal damage and calcium oxalate (CaOx) crystal depositions via using hyperoxaluria rat models. We observed dose-dependent increases in urinary oxalate excretion and CaOx crystal depositions due to hyperoxaluria, accompanied by significant reductions in gut microbiota diversity characterized by shifts in Ruminococcaceae_UCG-014 and Parasutterella composition. Metabolomic analysis validated these findings, revealing substantial decreases in key metabolites associated with these microbial groups. Transplanting microbes from healthy rats effectively reduced HDOx-induced urinary oxalate excretion and CaOx crystal depositions meanwhile restoring Ruminococcaceae_UCG-014 and Parasutterella populations and their associated metabolites. Furthermore, FMT treatment could significantly decrease the urinary oxalate excretion and CaOx crystal depositions in rat kidneys via, at least in part, upregulating the expressions of intestinal barrier proteins and oxalate transporters in the intestine. In conclusion, our study emphasizes the effectiveness of FMT in countering HDOx-induced hyperoxaluria by restoring gut microbiota and related metabolites. These findings provide insights on the complex connection between secondary hyperoxaluria caused by high dietary oxalate and disruptions in gut microbiota, offering promising avenues for targeted therapeutic strategies.

Experiment 1


Needs review

Curated date: 2025/03/18

Curator: Dorcas-od

Revision editor(s): Dorcas-od

Subjects

Location of subjects
China
Host species Species from which microbiome was sampled. Contact us to have more species added.
Rattus norvegicus
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
Oxalate measurement Oxalate measurement,oxalate measurement
Group 0 name Corresponds to the control (unexposed) group for case-control studies
5%K2Ox-0day
Group 1 name Corresponds to the case (exposed) group for case-control studies
5%K2Ox-45day
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Rats exposed to a 5% K2Ox diet that induces hyperoxaluria, evidenced by increased urinary oxalate excretion and renal CaOx crystal deposition
Group 0 sample size Number of subjects in the control (unexposed) group
8
Group 1 sample size Number of subjects in the case (exposed) group
8

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
MaAsLin2
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
No
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
3.5

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

Needs review

Curated date: 2025/04/01

Curator: Dorcas-od

Revision editor(s): Dorcas-od

Source: Figure 1e

Description: The differential genera between the Normal group and the HDOx groups at day 45.

Abundance in Group 1: increased abundance in 5%K2Ox-45day

NCBI Quality ControlLinks
Lactobacillus
Roseburia
Ruminococcaceae_UCG-014Ruminococcaceae_UCG-014
Ruminiclostridium_6Ruminiclostridium_6
Ruminococcaceae_NK4A214_groupRuminococcaceae_NK4A214_group
Ruminiclostridium_9Ruminiclostridium_9
Ruminococcus_2Ruminococcus_2
Eubacterium coprostanoligenes

Revision editor(s): Dorcas-od

Signature 2

Needs review

Curated date: 2025/04/01

Curator: Dorcas-od

Revision editor(s): Dorcas-od

Source: Figure 1e-h

Description: (e, f) The differential genera between the Normal group and the HDOx groups at day 45.

Abundance in Group 1: decreased abundance in 5%K2Ox-45day

NCBI Quality ControlLinks
Parasutterella
Ruminococcaceae_UCG-005Ruminococcaceae_UCG-005

Revision editor(s): Dorcas-od

Experiment 2


Needs review

Curated date: 2025/03/18

Curator: Dorcas-od

Revision editor(s): Dorcas-od

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
5%Hyp-0day
Group 1 name Corresponds to the case (exposed) group for case-control studies
5%Hyp-45day

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

Needs review

Curated date: 2025/04/02

Curator: Dorcas-od

Revision editor(s): Dorcas-od

Source: Figure 1f

Description: The differential genera between the Normal group and the HDOx groups at day 45.

Abundance in Group 1: increased abundance in 5%Hyp-45day

NCBI Quality ControlLinks
Lactobacillus
Ruminococcaceae_UCG-014Ruminococcaceae_UCG-014
Eubacterium coprostanoligenes

Revision editor(s): Dorcas-od

Signature 2

Needs review

Curated date: 2025/04/02

Curator: Dorcas-od

Revision editor(s): Dorcas-od

Source: Figure 1f

Description: The differential genera between the Normal group and the HDOx groups at day 45.

Abundance in Group 1: decreased abundance in 5%Hyp-45day

NCBI Quality ControlLinks
Blautia
Ruminococcaceae_UCG-005Ruminococcaceae_UCG-005
Bacteroidia
Parasutterella
Alloprevotella
Fusicatenibacter
Oscillospira

Revision editor(s): Dorcas-od

Experiment 3


Needs review

Curated date: 2025/04/04

Curator: Dorcas-od

Revision editor(s): Dorcas-od

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Normal-45day
Group 1 name Corresponds to the case (exposed) group for case-control studies
5%K2Ox-45day

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

Needs review

Curated date: 2025/04/05

Curator: Dorcas-od

Revision editor(s): Dorcas-od

Source: Figure 1g

Description: The different genera between the day 0 and day 45 of HDOx groups. ns: no significance. & : p < 0.05. ### : p < 0.001. **** ,#### ,^^^^ and &&&& : p < 0.001.

Abundance in Group 1: increased abundance in 5%K2Ox-45day

NCBI Quality ControlLinks
Ruminiclostridium_6Ruminiclostridium_6
Ruminococcaceae_UCG-005Ruminococcaceae_UCG-005
Ruminococcaceae_UCG-014Ruminococcaceae_UCG-014
Ruminococcus_2Ruminococcus_2
Eubacterium coprostanoligenes
Ruminiclostridium_9Ruminiclostridium_9
Ruminococcaceae_NK4A214_groupRuminococcaceae_NK4A214_group
Eubacterium xylanophilum
Candidatus Saccharimonas
Prevotella_9Prevotella_9

Revision editor(s): Dorcas-od

Signature 2

Needs review

Curated date: 2025/04/05

Curator: Dorcas-od

Revision editor(s): Dorcas-od

Source: Figure 1g

Description: The different genera between the day 0 and day 45 of HDOx groups. ns: no significance. & : p < 0.05. ### : p < 0.001. **** ,#### ,^^^^ and &&&& : p < 0.001.

Abundance in Group 1: decreased abundance in 5%K2Ox-45day

NCBI Quality ControlLinks
Prevotellaceae_NK3B31_groupPrevotellaceae_NK3B31_group
Coriobacteriaceae_UCG-002Coriobacteriaceae_UCG-002
Parasutterella
Prevotellaceae_UCG-001Prevotellaceae_UCG-001
Alistipes
Oscillospira
Butyricimonas
Papillibacter
Holdemania

Revision editor(s): Dorcas-od

Experiment 4


Needs review

Curated date: 2025/04/05

Curator: Dorcas-od

Revision editor(s): Dorcas-od

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
5%Hyp-45day

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

Needs review

Curated date: 2025/04/05

Curator: Dorcas-od

Revision editor(s): Dorcas-od

Source: Figure 1h

Description: The different genera between the day 0 and day 45 of HDOx groups. ns: no significance. & : p < 0.05. ### : p < 0.001. **** ,#### ,^^^^ and &&&& : p < 0.001.

Abundance in Group 1: increased abundance in 5%Hyp-45day

NCBI Quality ControlLinks
Ruminiclostridium_6Ruminiclostridium_6
Ruminococcaceae_UCG-014Ruminococcaceae_UCG-014
Ruminococcus_2Ruminococcus_2
Prevotella_9Prevotella_9
Oscillibacter
Candidatus Saccharimonas
Marvinbryantia
Shuttleworthella
Erysipelotrichaceae_UCG-003Erysipelotrichaceae_UCG-003
Streptococcus

Revision editor(s): Dorcas-od

Signature 2

Needs review

Curated date: 2025/04/05

Curator: Dorcas-od

Revision editor(s): Dorcas-od

Source: Figure 1h

Description: The different genera between the day 0 and day 45 of HDOx groups. ns: no significance. & : p < 0.05. ### : p < 0.001. **** ,#### ,^^^^ and &&&& : p < 0.001.

Abundance in Group 1: decreased abundance in 5%Hyp-45day

NCBI Quality ControlLinks
Akkermansia
Alloprevotella
Bacteroides
Butyricimonas
Oscillospira
Papillibacter
Parasutterella
Prevotellaceae_UCG-001Prevotellaceae_UCG-001
Clostridium_sensu_ stricto_1Clostridium_sensu_ stricto_1
Acidobacteria bacterium RB41Acidobacteria bacterium RB41

Revision editor(s): Dorcas-od

Experiment 5


Needs review

Curated date: 2025/04/05

Curator: Dorcas-od

Revision editor(s): Dorcas-od

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Response to transplant Response to transplant,response to transplant
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Normal Group
Group 1 name Corresponds to the case (exposed) group for case-control studies
5%K2Ox

Lab analysis

Statistical Analysis

Statistical test
ANOVA
LEfSe
Spearman Correlation
Welch's T-Test

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

Needs review

Curated date: 2025/04/05

Curator: Dorcas-od

Revision editor(s): Dorcas-od

Source: Figure 4a

Description: The effects of FMT on gut microbiota and metabolism.

Abundance in Group 1: increased abundance in 5%K2Ox

NCBI Quality ControlLinks
Bacteroidota
Pseudomonadota
Actinomycetota

Revision editor(s): Dorcas-od

Signature 2

Needs review

Curated date: 2025/04/05

Curator: Dorcas-od

Revision editor(s): Dorcas-od

Source: Figure 4a

Description: The effects of FMT on gut microbiota and metabolism.

Abundance in Group 1: decreased abundance in 5%K2Ox

NCBI Quality ControlLinks
Bacillota

Revision editor(s): Dorcas-od

Experiment 6


Needs review

Curated date: 2025/04/05

Curator: Dorcas-od

Revision editor(s): Dorcas-od

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
5%K2OxFMT

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

Needs review

Curated date: 2025/04/05

Curator: Dorcas-od

Revision editor(s): Dorcas-od

Source: Figure 4a

Description: The effects of FMT on gut microbiota and metabolism.

Abundance in Group 1: increased abundance in 5%K2OxFMT

NCBI Quality ControlLinks
Actinomycetota
Bacteroidota
Pseudomonadota

Revision editor(s): Dorcas-od

Signature 2

Needs review

Curated date: 2025/04/05

Curator: Dorcas-od

Revision editor(s): Dorcas-od

Source: Figure 4a

Description: The effects of FMT on gut microbiota and metabolism.

Abundance in Group 1: decreased abundance in 5%K2OxFMT

NCBI Quality ControlLinks
Bacillota

Revision editor(s): Dorcas-od

Experiment 7


Needs review

Curated date: 2025/04/05

Curator: Dorcas-od

Revision editor(s): Dorcas-od

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
5%K2Ox

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

Needs review

Curated date: 2025/04/06

Curator: Dorcas-od

Revision editor(s): Dorcas-od

Source: Figure 4a

Description: The effects of FMT on gut microbiota and metabolism.

Abundance in Group 1: increased abundance in 5%K2OxFMT

NCBI Quality ControlLinks
Bacillota

Revision editor(s): Dorcas-od

Experiment 8


Needs review

Curated date: 2025/04/06

Curator: Dorcas-od

Revision editor(s): Dorcas-od

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Normal Group
Group 1 name Corresponds to the case (exposed) group for case-control studies
5%Hyp

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

Needs review

Curated date: 2025/04/06

Curator: Dorcas-od

Revision editor(s): Dorcas-od

Source: Figure 4a

Description: The effects of FMT on gut microbiota and metabolism.

Abundance in Group 1: increased abundance in 5%Hyp

NCBI Quality ControlLinks
Bacteroidota
Verrucomicrobiota

Revision editor(s): Dorcas-od

Experiment 9


Needs review

Curated date: 2025/04/06

Curator: Dorcas-od

Revision editor(s): Dorcas-od

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
5%Hyp
Group 1 name Corresponds to the case (exposed) group for case-control studies
5%HypFMT
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
The effects of FMT on gut microbiota and metabolism.

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

Needs review

Curated date: 2025/04/06

Curator: Dorcas-od

Revision editor(s): Dorcas-od

Source: Figure 4a

Description: The effects of FMT on gut microbiota and metabolism.

Abundance in Group 1: increased abundance in 5%HypFMT

NCBI Quality ControlLinks
Bacillota

Revision editor(s): Dorcas-od

Signature 2

Needs review

Curated date: 2025/04/06

Curator: Dorcas-od

Revision editor(s): Dorcas-od

Source: Figure 4a

Description: The effects of FMT on gut microbiota and metabolism.

Abundance in Group 1: decreased abundance in 5%HypFMT

NCBI Quality ControlLinks
Bacteroidota
Verrucomicrobiota

Revision editor(s): Dorcas-od

Experiment 10


Needs review

Curated date: 2025/04/06

Curator: Dorcas-od

Revision editor(s): Dorcas-od

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
5%K2Ox
Group 1 name Corresponds to the case (exposed) group for case-control studies
5%K2OxFMT
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Rats exposed to a 5% K2Ox diet that induces hyperoxaluria, evidenced by increased urinary oxalate excretion and renal CaOx crystal deposition

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 11


Needs review

Curated date: 2025/04/07

Curator: Dorcas-od

Revision editor(s): Dorcas-od

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
5%Hyp
Group 1 name Corresponds to the case (exposed) group for case-control studies
5%HypFMT
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Not specified
Group 0 sample size Number of subjects in the control (unexposed) group
Not specified
Group 1 sample size Number of subjects in the case (exposed) group
Not specified
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
Rats exposed to a 5% K2Ox diet that induces hyperoxaluria, evidenced by increased urinary oxalate excretion and renal CaOx crystal deposition

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

Needs review

Curated date: 2025/04/07

Curator: Dorcas-od

Revision editor(s): Dorcas-od

Source: Figure 4c

Description: The effects of FMT on gut microbiota and metabolism.

Abundance in Group 1: increased abundance in 5%HypFMT

NCBI Quality ControlLinks
Parasutterella

Revision editor(s): Dorcas-od