Increased dietary protein stimulates amino acid catabolism via the gut microbiota and secondary bile acid production

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Reviewed Marked as Reviewed by Svetlana up on 2025-4-4
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
Authors
Tobón-Cornejo S, Sanchez-Tapia M, Guizar-Heredia R, Velázquez Villegas L, Noriega LG, Furuzawa-Carballeda J, Hernández-Pando R, Vázquez-Manjarrez N, Granados-Portillo O, López-Barradas A, Rebollar-Vega R, Maya O, Miller AW, Serralde A, Guevara-Cruz M, Torres N, Tovar AR
Journal
Gut microbes
Year
2025
Keywords:
Gut microbiota, amino acid catabolism, glucagon, high-protein diet, secondary bile acids
Excess amino acids from a protein-rich diet are mainly catabolized in the liver. However, it is still unclear to what extent the gut microbiota may be involved in the mechanisms governing this catabolism. Therefore, the aim of this study was to investigate whether consumption of different dietary protein concentrations induces changes in the taxonomy of the gut microbiota, which may contribute to the regulation of hepatic amino acid catabolism. Consumption of a high-protein diet caused overexpression of HIF-1α in the colon and increase in mitochondrial activity, creating a more anaerobic environment that was associated with changes in the taxonomy of the gut microbiota promoting an increase in the synthesis of secondary bile acids, increased secretion of pancreatic glucagon. This effect was demonstrated in pancreatic islets, where secondary bile acids stimulated the expression of the PC2 enzyme that promotes glucagon formation. The increase in circulating glucagon was associated with an induction of the expression of hepatic amino acid-degrading enzymes, an effect attenuated by antibiotics. Thus, high protein intake in mice and humans induced the increase of different species in the gut microbiota with the capacity to produce secondary bile acids leading to an increase in secondary bile acids and glucagon levels, promoting amino acid catabolism.

Experiment 1


Reviewed Marked as Reviewed by Svetlana up on 2025-4-4

Curated date: 2025/03/28

Curator: Miss Lulu

Revision editor(s): Miss Lulu

Subjects

Location of subjects
United States of America
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
Colon Hindgut,Large bowel,Posterior intestine,Colon,colon
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Response to diet Response to diet,response to diet
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Low protein group- LP
Group 1 name Corresponds to the case (exposed) group for case-control studies
High protein group- HP
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Dietary regimen constituting of 50% protein for 10 days.
Group 0 sample size Number of subjects in the control (unexposed) group
20
Group 1 sample size Number of subjects in the case (exposed) group
20

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
2

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2025-4-4

Curated date: 2025/03/28

Curator: Miss Lulu

Revision editor(s): Miss Lulu

Source: Figure 4E

Description: Linear discriminant analysis (LDA) shows significant differences in the relative abundance of bacterial species in mice fed different protein concentrations.

Abundance in Group 1: increased abundance in High protein group- HP

NCBI Quality ControlLinks
Escherichia coli
Thomasclavelia cocleata
Parabacteroides distasonis
Mucispirillum schaedleri

Revision editor(s): Miss Lulu

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2025-4-4

Curated date: 2025/03/28

Curator: Miss Lulu

Revision editor(s): Miss Lulu

Source: Figure 4E

Description: Linear discriminant analysis (LDA) shows significant differences in the relative abundance of bacterial species in mice fed different protein concentrations.

Abundance in Group 1: decreased abundance in High protein group- HP

NCBI Quality ControlLinks
Akkermansia muciniphila

Revision editor(s): Miss Lulu

Experiment 2


Reviewed Marked as Reviewed by Svetlana up on 2025-4-4

Curated date: 2025/03/29

Curator: Miss Lulu

Revision editor(s): Miss Lulu, KateRasheed

Differences from previous experiment shown

Subjects

Host species Species from which microbiome was sampled. Contact us to have more species added.
Homo sapiens
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
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Baseline Participants
Group 1 name Corresponds to the case (exposed) group for case-control studies
End of study Participants
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Effect of high protein diet on humans after clinical trial was conducted.
Group 0 sample size Number of subjects in the control (unexposed) group
19
Group 1 sample size Number of subjects in the case (exposed) group
19
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
3 months

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2025-4-4

Curated date: 2025/03/29

Curator: Miss Lulu

Revision editor(s): Miss Lulu

Source: Figure 10D

Description: Linear discriminant analysis (LDA) of the gut microbiota at the species level. Concentration of fecal secondary bile acids

Abundance in Group 1: increased abundance in End of study Participants

NCBI Quality ControlLinks
Anaerorhabdus furcosa
Gemmiger formicilis
Parabacteroides distasonis
[Clostridium] fimetarium
Paraeggerthella hongkongensis
Solobacterium moorei

Revision editor(s): Miss Lulu

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2025-4-4

Curated date: 2025/03/29

Curator: Miss Lulu

Revision editor(s): Miss Lulu

Source: Figure 10D

Description: Linear discriminant analysis (LDA) of the gut microbiota at the species level. Concentration of fecal secondary bile acids

Abundance in Group 1: decreased abundance in End of study Participants

NCBI Quality ControlLinks
Butyricicoccus pullicaecorum
Papillibacter cinnamivorans
Granulicatella balaenopterae
Coprococcus catus
Dorea longicatena
[Ruminococcus] lactaris
Alistipes finegoldii
Alistipes putredinis
Barnesiella intestinihominis
Roseburia inulinivorans
Macellibacteroides fermentans

Revision editor(s): Miss Lulu

Experiment 3


Reviewed Marked as Reviewed by Svetlana up on 2025-4-4

Curated date: 2025/04/01

Curator: Miss Lulu

Revision editor(s): Miss Lulu

Differences from previous experiment shown

Subjects

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
Colon Hindgut,Large bowel,Posterior intestine,Colon,colon
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Normal protein group- NP
Group 1 name Corresponds to the case (exposed) group for case-control studies
High protein group- HP
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Dietary regimen constituting of 50% protein for 10 days.
Group 0 sample size Number of subjects in the control (unexposed) group
20
Group 1 sample size Number of subjects in the case (exposed) group
20
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
Not specified

Lab analysis

Statistical Analysis

Statistical test
ANOVA
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Yes
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
unchanged

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2025-4-4

Curated date: 2025/04/01

Curator: Miss Lulu

Revision editor(s): Miss Lulu

Source: Figure 4D

Description: Gut microbiota is modified by dietary protein concentration in mice (genus)

Abundance in Group 1: increased abundance in High protein group- HP

NCBI Quality ControlLinks
SMB53SMB53
Allobaculum
Sutterella
Lactobacillus

Revision editor(s): Miss Lulu

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2025-4-4

Curated date: 2025/04/01

Curator: Miss Lulu

Revision editor(s): Miss Lulu

Source: Figure 4D

Description: Gut microbiota is modified by dietary protein concentration in mice (genus)

Abundance in Group 1: decreased abundance in High protein group- HP

NCBI Quality ControlLinks
AF12AF12
Rikenella
Coprococcus
Oscillospira

Revision editor(s): Miss Lulu

Experiment 4


Reviewed Marked as Reviewed by Svetlana up on 2025-4-4

Curated date: 2025/04/01

Curator: Miss Lulu

Revision editor(s): Miss Lulu

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Low protein group- LP

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2025-4-4

Curated date: 2025/04/01

Curator: Miss Lulu

Revision editor(s): Miss Lulu

Source: Figure 4D

Description: Gut microbiota is modified by dietary protein concentration in mice (genus)

Abundance in Group 1: increased abundance in High protein group- HP

NCBI Quality ControlLinks
AF12AF12
SMB53SMB53
Allobaculum
Sutterella
Lactobacillus

Revision editor(s): Miss Lulu

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2025-4-4

Curated date: 2025/04/01

Curator: Miss Lulu

Revision editor(s): Miss Lulu

Source: Figure 4D

Description: Gut microbiota is modified by dietary protein concentration in mice (genus)

Abundance in Group 1: decreased abundance in High protein group- HP

NCBI Quality ControlLinks
Rikenella
Coprococcus
Oscillospira

Revision editor(s): Miss Lulu

Experiment 5


Reviewed Marked as Reviewed by Svetlana up on 2025-4-4

Curated date: 2025/04/01

Curator: Miss Lulu

Revision editor(s): Miss Lulu

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
Normal protein group- NP
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Dietary regimen constituting of 20% protein for 10 days.

Lab analysis

Statistical Analysis

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2025-4-4

Curated date: 2025/04/01

Curator: Miss Lulu

Revision editor(s): Miss Lulu

Source: Figure 4D

Description: Gut microbiota is modified by dietary protein concentration in mice (genus)

Abundance in Group 1: increased abundance in Normal protein group- NP

NCBI Quality ControlLinks
AF12AF12
Coprococcus
Oscillospira
Sutterella
Lactobacillus

Revision editor(s): Miss Lulu

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2025-4-4

Curated date: 2025/04/01

Curator: Miss Lulu

Revision editor(s): Miss Lulu

Source: Figure 4D

Description: Gut microbiota is modified by dietary protein concentration in mice.(genus)

Abundance in Group 1: decreased abundance in Normal protein group- NP

NCBI Quality ControlLinks
Rikenella
SMB53SMB53
Allobaculum

Revision editor(s): Miss Lulu