Ketogenic Diets Alter the Gut Microbiome Resulting in Decreased Intestinal Th17 Cells

From BugSigDB
Needs review
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
Authors
Ang QY, Alexander M, Newman JC, Tian Y, Cai J, Upadhyay V, Turnbaugh JA, Verdin E, Hall KD, Leibel RL, Ravussin E, Rosenbaum M, Patterson AD, Turnbaugh PJ
Journal
Cell
Year
2020
Keywords:
Th17 cells, adipose tissue, bifidobacteria, intestinal immunity, ketogenic diet, ketone bodies, ketone ester, microbiome, β-hydroxybutyrate
Very low-carbohydrate, high-fat ketogenic diets (KDs) induce a pronounced shift in metabolic fuel utilization that elevates circulating ketone bodies; however, the consequences of these compounds for host-microbiome interactions remain unknown. Here, we show that KDs alter the human and mouse gut microbiota in a manner distinct from high-fat diets (HFDs). Metagenomic and metabolomic analyses of stool samples from an 8-week inpatient study revealed marked shifts in gut microbial community structure and function during the KD. Gradient diet experiments in mice confirmed the unique impact of KDs relative to HFDs with a reproducible depletion of bifidobacteria. In vitro and in vivo experiments showed that ketone bodies selectively inhibited bifidobacterial growth. Finally, mono-colonizations and human microbiome transplantations into germ-free mice revealed that the KD-associated gut microbiota reduces the levels of intestinal pro-inflammatory Th17 cells. Together, these results highlight the importance of trans-kingdom chemical dialogs for mediating the host response to dietary interventions.

Experiment 1


Needs review

Curated date: 2022/11/21

Curator: Fatima

Revision editor(s): Fatima, Lwaldron, Peace Sandy, Joan Chuks

Subjects

Location of subjects
United States of America
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
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Response to ketogenic diet Response to ketogenic diet,response to ketogenic diet
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Overweight/Obese Men on Baseline Diet (BD)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Overweight/Obese Men on Ketogenic Diet (KD)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Overweight or class I Obese non-diabetic men who consumed an isocaloric ketogenic diet for 4weeks
Group 0 sample size Number of subjects in the control (unexposed) group
17
Group 1 sample size Number of subjects in the case (exposed) group
17
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
No

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
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
DESeq2
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)?
Yes


Signature 1

Needs review

Curated date: 2022/11/21

Curator: Fatima

Revision editor(s): Fatima, Lwaldron, Joan Chuks

Source: Figure 1E

Description: Bacterial taxa identified by DESeq2 as differentially abundant in Overweight/class I Obese non-diabetic Men, who consumed an isocaloric ketogenic diet for 4weeks Versus the same Overweight/class I Obese non-diabetic Men on Baseline Diet for 4weeks.

Abundance in Group 1: increased abundance in Overweight/Obese Men on Ketogenic Diet (KD)

NCBI Quality ControlLinks
Escherichia/Shigella sp.
Faecalitalea
Flavonifractor
Fusobacterium
Intestinibacter
Intestinimonas
Megamonas
Negativibacillus
Parasutterella
Prevotella sp. 1-8
Thomasclavelia

Revision editor(s): Fatima, Lwaldron, Joan Chuks

Signature 2

Needs review

Curated date: 2024/03/14

Curator: Joan Chuks

Revision editor(s): Joan Chuks

Source: Figure 1E

Description: Bacterial taxa identified by DESeq2 as differentially abundant in Overweight/class I Obese non-diabetic Men, who consumed an isocaloric ketogenic diet for 4weeks Versus the same Overweight/class I Obese non-diabetic Men on Baseline Diet for 4weeks.

Abundance in Group 1: decreased abundance in Overweight/Obese Men on Ketogenic Diet (KD)

NCBI Quality ControlLinks
Agathobacter
Anaerostipes
Bifidobacterium
Dialister
Lachnospiraceae
Oscillospiraceae
Streptococcus
Ruminococcus sp.

Revision editor(s): Joan Chuks

Experiment 2


Needs review

Curated date: 2024/03/17

Curator: Joan Chuks

Revision editor(s): Joan Chuks

Differences from previous experiment shown

Subjects

Host species Species from which microbiome was sampled. Contact us to have more species added.
Mus musculus


Group 0 name Corresponds to the control (unexposed) group for case-control studies
Mice fed on High-fat Diet (HFD)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Mice fed on Ketogenic Diet (KD)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Wild-type C57BL/6J mice of both sexes, between age 5 - 10 weeks, fed on ketogenic diet for 3 weeks.
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

Statistical Analysis

Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.1
Matched on Factors on which subjects have been matched on in a case-control study
diet


Signature 1

Needs review

Curated date: 2024/03/17

Curator: Joan Chuks

Revision editor(s): Joan Chuks

Source: Figure 3G + Figure S4F + Figure 5I

Description: Bacterial taxa identified by DESeq2 as differentially abundant in Wild-type and Mucin 2( Muc2-/-) deficient Mice fed on Ketogenic Diet(KD) Versus the Mice fed on High-Fat Diet (HFD).

Abundance in Group 1: increased abundance in Mice fed on Ketogenic Diet (KD)

NCBI Quality ControlLinks
Acetatifactor
Butyricicoccus
Clostridium sp.
Enterorhabdus
Eubacteriales
Intestinimonas
Mucispirillum
Candidatus Stoquefichus
clostridiales vadinBB60 groupclostridiales vadinBB60 group

Revision editor(s): Joan Chuks

Signature 2

Needs review

Curated date: 2024/03/17

Curator: Joan Chuks

Revision editor(s): Joan Chuks

Source: Figure 3G + Figure S4F

Description: Bacterial taxa identified by DESeq2 as differentially abundant in Wild-type and Mucin 2( Muc2-/-) deficient Mice fed on Ketogenic Diet(KD) Versus Wild-type and Mucin 2( Muc2-/-) deficient Mice fed on High-Fat Diet (HFD).

Abundance in Group 1: decreased abundance in Mice fed on Ketogenic Diet (KD)

NCBI Quality ControlLinks
Bifidobacterium
Dubosiella
Lactobacillus
Marvinbryantia
Muribaculaceae
Ruminiclostridium
lachnospiraceae FCS020 grouplachnospiraceae FCS020 group
Lachnospiraceae bacterium NK4A136

Revision editor(s): Joan Chuks

Experiment 3


Needs review

Curated date: 2024/03/19

Curator: Joan Chuks

Revision editor(s): Joan Chuks

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Mice fed on High-fat Diet (HFD-control)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Mice fed High-fat Diet + Ketone Ester (HFD-KE)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
C57BL/6J mice fed on High-fat diet that was supplemented with a synthetic Ketone ester(KE), beta-hydroxybutyrate(bHB).
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

Lab analysis

Statistical Analysis

Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05


Signature 1

Needs review

Curated date: 2024/03/19

Curator: Joan Chuks

Revision editor(s): Joan Chuks

Source: Figure 5I + Figure 5M

Description: Bacterial taxa identified by DESeq2 as differentially abundant in C57BL/6J mice fed on High-fat diet supplemented with Ketone ester(KE), beta-hydroxybutyrate(bHB) Versus Mice fed on only High-Fat Diet (HFD).

Abundance in Group 1: increased abundance in Mice fed High-fat Diet + Ketone Ester (HFD-KE)

NCBI Quality ControlLinks
Acetatifactor
Bacteroides
Faecalibacterium
Parabacteroides
Prevotella

Revision editor(s): Joan Chuks

Signature 2

Needs review

Curated date: 2024/03/19

Curator: Joan Chuks

Revision editor(s): Joan Chuks

Source: Figure 5M

Description: Bacterial taxa identified by DESeq2 as differentially abundant in C57BL/6J mice fed on High-fat diet supplemented with Ketone ester(KE), beta-hydroxybutyrate(bHB) Versus Mice fed on only High-Fat Diet (HFD).

Abundance in Group 1: decreased abundance in Mice fed High-fat Diet + Ketone Ester (HFD-KE)

NCBI Quality ControlLinks
Bifidobacterium
Collinsella
Enterococcus
Escherichia/Shigella sp.
Lactobacillus
Streptococcus
Turicibacter
Clostridium_sensu_stricto_1Clostridium_sensu_stricto_1

Revision editor(s): Joan Chuks