Gut microbiota-derived LCA mediates the protective effect of PEDV infection in piglets

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study design
laboratory experiment
Citation
PMID PubMed identifier for scientific articles.
38317217
DOI Digital object identifier for electronic documents.
10.1186/s40168-023-01734-4
URI
Authors
Xing JH, Niu TM, Zou BS, Yang GL, Shi CW, Yan QS, Sun MJ, Yu T, Zhang SM, Feng XZ, Fan SH, Huang HB, Wang JH, Li MH, Jiang YL, Wang JZ, Cao X, Wang N, Zeng Y, Hu JT, Zhang D, Sun WS, Yang WT, Wang CF
Journal
Microbiome
Year
2024
Keywords:
Gut microbiota, Infection resistance, Macrogenomic, Metabolomic, T cell response
BACKGROUND: The gut microbiota is a critical factor in the regulation of host health, but the relationship between the differential resistance of hosts to pathogens and the interaction of gut microbes is not yet clear. Herein, we investigated the potential correlation between the gut microbiota of piglets and their disease resistance using single-cell transcriptomics, 16S amplicon sequencing, metagenomics, and untargeted metabolomics. RESULTS: Porcine epidemic diarrhea virus (PEDV) infection leads to significant changes in the gut microbiota of piglets. Notably, Landrace pigs lose their resistance quickly after being infected with PEDV, but transplanting the fecal microbiota of Min pigs to Landrace pigs alleviated the infection status. Macrogenomic and animal protection models identified Lactobacillus reuteri and Lactobacillus amylovorus in the gut microbiota as playing an anti-infective role. Moreover, metabolomic screening of the secondary bile acids' deoxycholic acid (DCA) and lithocholic acid (LCA) correlated significantly with Lactobacillus reuteri and Lactobacillus amylovorus, but only LCA exerted a protective function in the animal model. In addition, LCA supplementation altered the distribution of intestinal T-cell populations and resulted in significantly enriched CD8+ CTLs, and in vivo and in vitro experiments showed that LCA increased SLA-I expression in porcine intestinal epithelial cells via FXR receptors, thereby recruiting CD8+ CTLs to exert antiviral effects. CONCLUSIONS: Overall, our findings indicate that the diversity of gut microbiota influences the development of the disease, and manipulating Lactobacillus reuteri and Lactobacillus amylovorus, as well as LCA, represents a promising strategy to improve PEDV infection in piglets. Video Abstract.

Experiment 1


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Curated date: 2024/11/06

Curator: Nathcynthia

Revision editor(s): Nathcynthia, Tosin

Subjects

Location of subjects
China
Host species Species from which microbiome was sampled. Contact us to have more species added.
Sus scrofa domesticus
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
Infectious diarrheal disease infectious diarrhea,infectious diarrheal disease,infective diarrhea,Infectious diarrheal disease
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Combination of M-PEDV(min-Porcine epidemic diarrhea virus), L-CON(landrace-control) and L-PEDV(landrace- Porcine epidemic diarrhea virus) pigs
Group 1 name Corresponds to the case (exposed) group for case-control studies
M-CON (min-control) pigs
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Min pigs in china challenged with PBS.
Group 0 sample size Number of subjects in the control (unexposed) group
30
Group 1 sample size Number of subjects in the case (exposed) group
10

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
LEfSe
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
4


Signature 1

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Curated date: 2024/11/07

Curator: Nathcynthia

Revision editor(s): Nathcynthia, Tosin

Source: Fig 2G

Description: Taxa differentially abundant between M-CON (min-control), M-PEDV(min-Porcine epidemic diarrhea virus), L-CON (landrace-control) and L-PEDV(Landrace Porcine epidemic diarrhea virus) pigs.

Abundance in Group 1: increased abundance in M-CON (min-control) pigs

NCBI Quality ControlLinks
Actinomycetota   
Bacteria   
Bacteroidaceae   
Bacteroidales   
Bacteroides   
Bacteroidia   
Bacteroidota   
Bifidobacteriales   
Bifidobacterium   
Oscillospiraceae   
Subdoligranulum   
Unidentified ActinomycetotaUnidentified Actinomycetota
Bifidobacteriaceae   

Revision editor(s): Nathcynthia, Tosin

Experiment 2


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Curated date: 2024/11/07

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Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Combination of M-CON (min-control) , L-CON (landrace-control) and L-PEDV (landrace- Porcine epidemic diarrhea virus) pigs
Group 1 name Corresponds to the case (exposed) group for case-control studies
M-PEDV(min- pigs Porcine epidemic diarrhea virus)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Min pigs challenged with PEDV (Porcine epidemic diarrhea virus).

Lab analysis

Statistical Analysis

Signature 1

EditHistoryDelete
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Needs review

Curated date: 2024/11/07

Curator: Nathcynthia

Revision editor(s): Nathcynthia, Tosin

Source: Fig 2G

Description: Taxa differentially abundant between M-CON (min-control), M-PEDV(min- Porcine epidemic diarrhea virus), L-CON (landrace control) and L-PEDV(Landrace Porcine epidemic diarrhea virus) pigs

Abundance in Group 1: increased abundance in M-PEDV(min- pigs Porcine epidemic diarrhea virus)

NCBI Quality ControlLinks
Erysipelotrichales   
Lachnospiraceae   
Lachnospirales   
Limosilactobacillus   
Prevotella   

Revision editor(s): Nathcynthia, Tosin

Experiment 3


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Curated date: 2024/11/08

Curator: Nathcynthia

Revision editor(s): Nathcynthia, Tosin

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Combination of M-CON (min-control), M-PEDV(min-Porcine epidemic diarrhea virus) and L-PEDV(landrace-Porcine epidemic diarrhea virus) pigs.
Group 1 name Corresponds to the case (exposed) group for case-control studies
L-CON (landrace-control) pigs
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Landrace pigs challenged with PBS.

Lab analysis

Statistical Analysis

Signature 1

EditHistoryDelete
Mark reviewed
Your review change was submitted
Needs review

Curated date: 2024/11/12

Curator: Tosin

Revision editor(s): Tosin

Source: Fig 2G

Description: Taxa differentially abundant between M-CON (min-control), M-PEDV(min-Porcine epidemic diarrhea virus), L-CON (landrace-control) and L-PEDV(landrace Porcine epidemic diarrhea virus) pigs

Abundance in Group 1: increased abundance in L-CON (landrace-control) pigs

NCBI Quality ControlLinks
Clostridia   
Clostridiaceae   
Eubacteriales   
Oscillospiraceae   
Rikenellaceae   
Spirochaetaceae   
Spirochaetales   
Spirochaetia   
Spirochaetota   
Treponema   
unidentified   
UCG 002UCG 002
Prevotellaceae Nk3B31 groupPrevotellaceae Nk3B31 group
Clostridium   

Revision editor(s): Tosin

Experiment 4


EditHistoryDelete
Mark reviewed
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Curated date: 2024/11/11

Curator: Nathcynthia

Revision editor(s): Nathcynthia, Tosin

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Combination of M-CON (min-control), M-PEDV(min-Porcine epidemic diarrhea virus) and L-CON (landrace-control) pigs.
Group 1 name Corresponds to the case (exposed) group for case-control studies
L-PEDV(landrace- Porcine epidemic diarrhea virus) pigs
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Landrace pigs challenged with PEDV (Porcine epidemic diarrhea virus).

Lab analysis

Statistical Analysis

Signature 1

EditHistoryDelete
Mark reviewed
Your review change was submitted
Needs review

Curated date: 2024/11/11

Curator: Nathcynthia

Revision editor(s): Nathcynthia, Tosin

Source: Fig 2G

Description: Taxa differentially abundant between M-CON (min-control), M-PEDV(min-Porcine epidemic diarrhea virus), L-CON (landrace-control) and L-PEDV(landrace-Porcine epidemic diarrhea virus) pigs.

Abundance in Group 1: increased abundance in L-PEDV(landrace- Porcine epidemic diarrhea virus) pigs

NCBI Quality ControlLinks
Agathobacter   
Bacilli   
Bacillota   
Lactobacillaceae   
Lactobacillales   
Lactobacillus   
Megasphaera   
Negativicutes   
Veillonellaceae   
Veillonellales   
Selenomonadales   

Revision editor(s): Nathcynthia, Tosin

Experiment 5


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Curated date: 2024/11/12

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Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
M-CON (min-control) pigs
Group 1 name Corresponds to the case (exposed) group for case-control studies
M-PEDV(min-Porcine epidemic diarrhea virus) pigs
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Min pigs in china challenged with PEDV (Porcine epidemic diarrhea virus).
Group 0 sample size Number of subjects in the control (unexposed) group
10

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
Simpson Estimator of species richness and species evenness: more weight on species evenness
increased
Richness Number of species
increased

Signature 1

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Curated date: 2024/11/12

Curator: Tosin

Revision editor(s): Tosin

Source: Figure 4D

Description: Taxa differentially abundant between M-CON (min-control) and M-PEDV(Porcine epidemic diarrhea virus) pigs.

Abundance in Group 1: increased abundance in M-PEDV(min-Porcine epidemic diarrhea virus) pigs

NCBI Quality ControlLinks
Anaerobutyricum hallii   
Bacteroides sp. CAG:709   
Bacteroides sp. CAG:770   
Bacteroides sp. CAG:927   
Bariatricus massiliensis   
Blautia obeum   
Blautia wexlerae   
Butyricicoccus porcorum   
Chlamydia trachomatis   
Clostridiales bacterium 52_15   
Clostridium sp. CAG:127   
Clostridium sp. CAG:221   
Clostridium sp. CAG:451   
Collinsella aerofaciens   
Dorea longicatena   
Eubacterium coprostanoligenes   
Eubacterium sp. CAG:180   
Faecalibacterium prausnitzii   
Firmicutes bacterium CAG:114   
Firmicutes bacterium CAG:646   
Firmicutes bacterium CAG:124   
Firmicutes bacterium CAG:170   
Firmicutes bacterium CAG:791   
Holdemanella biformis   
Lachnospira eligens   
Lactobacillus amylovorus   
Lactobacillus amylovorus CAG:719   
Lactobacillus helveticus   
Lactobacillus johnsonii   
Lactobacillus kitasatonis   
Limosilactobacillus mucosae   
Limosilactobacillus pontis   
Limosilactobacillus reuteri   
Megasphaera elsdenii   
Mobilibacterium timonense   
Mycoplasma sp. CAG:956   
Oscillibacter sp. CAG:241   
Prevotella sp. CAG:386   
Prevotella sp. CAG:485   
Prevotella sp. CAG:604   
Prevotella sp. CAG:873   
Prevotella sp. CAG:891   
Prevotella sp. P2-180   
Prevotella sp. P3-122   
Prevotella sp. P5-92   
Prevotella sp. S7-1-8   
Roseburia inulinivorans   
Roseburia sp. CAG:197   
Ruminococcus callidus   
Ruminococcus flavefaciens   
Ruminococcus sp. CAG:254   
Ruminococcus sp. JC304   
Subdoligranulum variabile   
Treponema porcinum   
uncultured Blautia sp.   
uncultured Butyricicoccus sp.   
uncultured Clostridium sp.   
uncultured Eubacterium sp.   
uncultured Ruminococcus sp.   

Revision editor(s): Tosin

Signature 2

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Needs review

Curated date: 2024/11/12

Curator: Tosin

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Source: Figure 4D

Description: Taxa differentially abundant between M-CON (min-control) and M-PEDV(Porcine epidemic diarrhea virus) pigs.

Abundance in Group 1: decreased abundance in M-PEDV(min-Porcine epidemic diarrhea virus) pigs

NCBI Quality ControlLinks
Bacteroides eggerthii   
Bacteroides fluxus   
Bacteroides fragilis   
Bacteroides mediterraneensis   
Bacteroides sp. 43_108   
Bacteroides sp. CAG:443   
Bacteroides sp. CAG:875   
Bacteroides uniformis   
Bifidobacterium longum   
Bifidobacterium pseudocatenulatum   
Enterococcus cecorum   
Flavonifractor sp. An306   
Flavonifractor sp. An82   
Gemmiger formicilis   
Gemmiger sp. An120   
Gemmiger sp. An50   
Intestinimonas butyriciproducens   
Leyella stercorea   
Phascolarctobacterium succinatutens   
Phocaeicola coprocola   
Phocaeicola coprophilus   
Phocaeicola massiliensis   
Phocaeicola plebeius   
Phocaeicola plebeius CAG:211   
Phocaeicola vulgatus   
Prevotella sp. CAG:279   
Prevotella sp. CAG:520   
Prevotella sp. tc2-28   
Ruminococcaceae bacterium D16   
Segatella copri   
Segatella copri CAG:164   
Streptococcus gallolyticus   
Subdoligranulum sp. 60_17   
Veillonella magna   
uncultured Bacteroides sp.   
uncultured bacterium   
Unclassified peptacetobacter hiranonisUnclassified peptacetobacter hiranonis

Revision editor(s): Tosin

Experiment 6


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Curated date: 2024/11/14

Curator: Tosin

Revision editor(s): Tosin

Differences from previous experiment shown

Subjects

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

Statistical Analysis

Statistical test
Metastats
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
Not specified

Alpha Diversity

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

Signature 1

EditHistoryDelete
Mark reviewed
Your review change was submitted
Needs review

Curated date: 2024/11/15

Curator: Tosin

Revision editor(s): Tosin

Source: Figure 4B

Description: Analysis of significantly upregulated (top 4) and downregulated (top 4) species in the abundance table between M-CON (min-control) and M-PEDV (min- porcine epidemic diarrhea virus) pigs.

Abundance in Group 1: increased abundance in M-PEDV(min-Porcine epidemic diarrhea virus) pigs

NCBI Quality ControlLinks
Faecalibacterium prausnitzii   
Lactobacillus amylovorus   
Limosilactobacillus reuteri   
Prevotella sp. CAG:604   

Revision editor(s): Tosin

Signature 2

EditHistoryDelete
Mark reviewed
Your review change was submitted
Needs review

Curated date: 2024/11/15

Curator: Tosin

Revision editor(s): Tosin

Source: Figure 4B

Description: Analysis of significantly upregulated (top 4) and downregulated (top 4) species in the abundance table between M-CON and M-PEDV (min- porcine epidemic diarrhea virus) pigs.

Abundance in Group 1: decreased abundance in M-PEDV(min-Porcine epidemic diarrhea virus) pigs

NCBI Quality ControlLinks
Phocaeicola plebeius   
Segatella copri   
Prevotella sp. CAG:520   
Phocaeicola plebeius CAG:211   

Revision editor(s): Tosin

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