Fecal Microbiota Composition, Their Interactions, and Metagenome Function in US Adults with Type 2 Diabetes According to Enterotypes

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Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
Authors
Park S, Zhang T, Kang S
Journal
International journal of molecular sciences
Year
2023
Keywords:
fecal bacteria, metagenome analysis, pooling data, type 2 diabetes, western diet
T2DM etiology differs among Asians and Caucasians and may be associated with gut microbiota influenced by different diet patterns. However, the association between fecal bacterial composition, enterotypes, and T2DM susceptibility remained controversial. We investigated the fecal bacterial composition, co-abundance network, and metagenome function in US adults with T2DM compared to healthy adults based on enterotypes. We analyzed 1911 fecal bacterial files of 1039 T2DM and 872 healthy US adults from the Human Microbiome Projects. Operational taxonomic units were obtained after filtering and cleaning the files using Qiime2 tools. Machine learning and network analysis identified primary bacteria and their interactions influencing T2DM incidence, clustered into enterotypes, Bacteroidaceae (ET-B), Lachnospiraceae (ET-L), and Prevotellaceae (ET-P). ET-B showed higher T2DM incidence. Alpha-diversity was significantly lower in T2DM in ET-L and ET-P (p < 0.0001), but not in ET-B. Beta-diversity revealed a distinct separation between T2DM and healthy groups across all enterotypes (p < 0.0001). The XGBoost model exhibited high accuracy and sensitivity. Enterocloster bolteae, Facalicatena fissicatena, Clostridium symbiosum, and Facalibacterium prausnitizii were more abundant in the T2DM group than in the healthy group. Bacteroides koreensis, Oscillibacter ruminantium, Bacteroides uniformis, and Blautia wexlerae were lower in the T2DM than in the healthy group regardless of the enterotypes in the XGBoost model (p < 0.0001). However, the patterns of microbial interactions varied among different enterotypes affecting T2DM risk. The interaction between fecal bacteria was more tightly regulated in the ET-L than in the ET-B and ET-P groups (p < 0.001). Metagenomic analysis revealed an inverse association between bacteria abundance in T2DM, energy utility, butanoate and propanoate metabolism, and the insulin signaling pathway (p < 0.0001). In conclusion, fecal bacteria play a role in T2DM pathogenesis, particularly within different enterotypes, providing valuable insights into the link between gut microbiota and T2DM in the US population.

Experiment 1


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Curated date: 2025/02/24

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.
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
Type II diabetes mellitus adult onset diabetes,Adult-Onset Diabetes,adult-onset diabetes,Adult-Onset Diabetes Mellitus,diabetes mellitis type 2,diabetes mellitis type II,DIABETES MELLITUS TYPE 02,diabetes mellitus type 2,Diabetes Mellitus, Adult Onset,Diabetes Mellitus, Adult-Onset,Diabetes Mellitus, Ketosis Resistant,Diabetes Mellitus, Ketosis-Resistant,Diabetes Mellitus, Maturity Onset,Diabetes Mellitus, Maturity-Onset,Diabetes Mellitus, Non Insulin Dependent,Diabetes Mellitus, Non-Insulin-Dependent,Diabetes Mellitus, Noninsulin Dependent,diabetes mellitus, noninsulin-dependent,Diabetes Mellitus, Slow Onset,Diabetes Mellitus, Slow-Onset,Diabetes Mellitus, Stable,Diabetes Mellitus, Type 2,diabetes mellitus, type 2,diabetes mellitus, type 2, protection against,Diabetes Mellitus, Type II,Diabetes, Type 2,diabetes, type 2,insulin resistance, susceptibility to,Ketosis-Resistant Diabetes Mellitus,Maturity Onset Diabetes Mellitus,maturity-onset diabetes,Maturity-Onset Diabetes Mellitus,MODY,NIDDM,Non-Insulin Dependent Diabetes,non-insulin dependent diabetes,Non-Insulin Dependent Diabetes Mellitus,non-insulin dependent diabetes mellitus,non-insulin-dependent diabetes mellitus,noninsulin dependent diabetes,noninsulin-dependent diabetes mellitus,Slow-Onset Diabetes Mellitus,Stable Diabetes Mellitus,T2DM - Type 2 Diabetes mellitus,T2DM - type 2 diabetes mellitus,Type 2 Diabetes,type 2 diabetes,Type 2 Diabetes Mellitus,type 2 diabetes mellitus,Type 2 Diabetes Mellitus Non-Insulin Dependent,type 2 diabetes mellitus non-insulin dependent,Type II Diabetes,type II diabetes,type II diabetes mellitus,Type II diabetes mellitus
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Healthy controls in Total participants
Group 1 name Corresponds to the case (exposed) group for case-control studies
Type 2 diabetes (T2DM) in Total Participants
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Participants were Caucasians with T2DM aged over 30 years.
Group 0 sample size Number of subjects in the control (unexposed) group
872
Group 1 sample size Number of subjects in the case (exposed) group
1039

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
Not specified
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
Decision Trees (xgBoost Statistical test: "Decision Trees (xgBoost" is not in the list (ANCOM, ANCOM-BC, ANOSIM, ANOVA, Beta Binomial Regression, Chi-Square, Cox Proportional-Hazards Regression, Decision Trees (xgBoost, gradient boosting), Dunn's test, DESeq2, ...) of allowed values.
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.001
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
Simpson Estimator of species richness and species evenness: more weight on species evenness
unchanged

Signature 1

Needs review

Curated date: 2025/02/24

Curator: Miss Lulu

Revision editor(s): Miss Lulu

Source: Figures 2B

Description: Fecal bacteria composition in total participants.

Abundance in Group 1: increased abundance in Type 2 diabetes (T2DM) in Total Participants

NCBI Quality ControlLinks
Bacteroides koreensis
Bacteroides uniformis
Fusicatenibacter saccharivorans
Gemmiger formicilis
Oscillibacter ruminantium
Phocaeicola vulgatus

Revision editor(s): Miss Lulu

Signature 2

Needs review

Curated date: 2025/02/24

Curator: Miss Lulu

Revision editor(s): Miss Lulu

Source: Figure 2B

Description: Fecal bacteria composition in total participants.

Abundance in Group 1: decreased abundance in Type 2 diabetes (T2DM) in Total Participants

NCBI Quality ControlLinks
Bacteroides koreensis
Oscillibacter ruminantium
Bacteroides uniformis
Fusicatenibacter saccharivorans
Gemmiger formicilis
Blautia wexlerae
Mediterraneibacter gnavus
Phocaeicola vulgatus
Parabacteroides merdae
Kineothrix alysoides
Collinsella aerofaciens

Revision editor(s): Miss Lulu

Experiment 2


Needs review

Curated date: 2025/02/24

Curator: Miss Lulu

Revision editor(s): Miss Lulu

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Diabetes mellitus biomarker Diabetes mellitus biomarker,diabetes mellitus biomarker
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Healthy controls in ET-B
Group 1 name Corresponds to the case (exposed) group for case-control studies
Type 2 diabetes (T2DM) in ET-B
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Participants were Caucasians with T2DM aged over 30 years. (ET-B).
Group 0 sample size Number of subjects in the control (unexposed) group
416
Group 1 sample size Number of subjects in the case (exposed) group
533

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
Richness Number of species
unchanged

Signature 1

Needs review

Curated date: 2025/02/24

Curator: Miss Lulu

Revision editor(s): Miss Lulu

Source: Figure 3B

Description: Fecal bacteria composition in Enterotype Bacteroidaceae (ET-B)

Abundance in Group 1: increased abundance in Type 2 diabetes (T2DM) in ET-B

NCBI Quality ControlLinks
Oscillibacter ruminantium
Bacteroides koreensis
Agathobacter rectalis

Revision editor(s): Miss Lulu

Signature 2

Needs review

Curated date: 2025/02/24

Curator: Miss Lulu

Revision editor(s): Miss Lulu

Source: Figure 3B

Description: Fecal bacteria composition in Enterotype Bacteroidaceae (ET-B)

Abundance in Group 1: decreased abundance in Type 2 diabetes (T2DM) in ET-B

NCBI Quality ControlLinks
Oscillibacter ruminantium
Bacteroides koreensis
Phocaeicola vulgatus
Romboutsia timonensis
Agathobacter rectalis
Dialister invisus
Roseburia intestinalis L1-82
Roseburia inulinivorans
Blautia luti
Bacteroides xylanisolvens
Collinsella aerofaciens

Revision editor(s): Miss Lulu

Experiment 3


Needs review

Curated date: 2025/02/24

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
Healthy controls in ET-L
Group 1 name Corresponds to the case (exposed) group for case-control studies
Type 2 diabetes (T2DM) in ET-L
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Participants were Caucasians with T2DM aged over 30 years in Enterotype Lachnospiraceae (ET-L).
Group 0 sample size Number of subjects in the control (unexposed) group
329
Group 1 sample size Number of subjects in the case (exposed) group
411

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
Richness Number of species
increased

Signature 1

Needs review

Curated date: 2025/02/24

Curator: Miss Lulu

Revision editor(s): Miss Lulu

Source: Figure 4B

Description: Fecal bacteria composition in Enterotype Lachnospiraceae (ET-L)

Abundance in Group 1: increased abundance in Type 2 diabetes (T2DM) in ET-L

NCBI Quality ControlLinks
Oscillibacter ruminantium
Blautia wexlerae
Bacteroides koreensis
Blautia faecis
Sporobacter termitidis
Akkermansia muciniphila

Revision editor(s): Miss Lulu

Signature 2

Needs review

Curated date: 2025/02/24

Curator: Miss Lulu

Revision editor(s): Miss Lulu

Source: Figure 4B

Description: Fecal bacteria composition in Enterotype Lachnospiraceae (ET-L).

Abundance in Group 1: decreased abundance in Type 2 diabetes (T2DM) in ET-L

NCBI Quality ControlLinks
Oscillibacter ruminantium
Bacteroides koreensis
Blautia faecis
Sporobacter termitidis
Hungatella effluvii
Monoglobus pectinilyticus
Ruminococcus champanellensis
Enterocloster hominis (ex Hitch et al. 2024)

Revision editor(s): Miss Lulu

Experiment 4


Needs review

Curated date: 2025/02/24

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
Healthy controls in ET-P
Group 1 name Corresponds to the case (exposed) group for case-control studies
Type 2 diabetes (T2DM) in ET-P
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Participants were Caucasians with T2DM aged over 30 years in Enterotype Prevotellaceae (ET-P).
Group 0 sample size Number of subjects in the control (unexposed) group
127
Group 1 sample size Number of subjects in the case (exposed) group
95

Lab analysis

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
MGISEQ-2000

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
Simpson Estimator of species richness and species evenness: more weight on species evenness
decreased

Signature 1

Needs review

Curated date: 2025/02/24

Curator: Miss Lulu

Revision editor(s): Miss Lulu

Source: Figure 5B

Description: Fecal bacteria composition in Enterotype Prevotellaceae (ET-P).

Abundance in Group 1: decreased abundance in Type 2 diabetes (T2DM) in ET-P

NCBI Quality ControlLinks
Oscillibacter ruminantium
Bacteroides koreensis
Dorea longicatena
Bacteroides faecis
Blautia wexlerae
Parabacteroides merdae
Kineothrix alysoides
Segatella copri

Revision editor(s): Miss Lulu

Signature 2

Needs review

Curated date: 2025/02/24

Curator: Miss Lulu

Revision editor(s): Miss Lulu

Source: Figure 5B

Description: Fecal bacteria composition in Enterotype Prevotellaceae (ET-P).

Abundance in Group 1: increased abundance in Type 2 diabetes (T2DM) in ET-P

NCBI Quality ControlLinks
Oscillibacter ruminantium
Bacteroides koreensis
Dorea longicatena
Bacteroides faecis
Parabacteroides merdae

Revision editor(s): Miss Lulu