Trans-ethnic gut microbial signatures of prediabetic subjects from India and Denmark

From BugSigDB
Reviewed Marked as Reviewed by Svetlana up on 2024-12-20
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Pinna NK, Anjana RM, Saxena S, Dutta A, Gnanaprakash V, Rameshkumar G, Aswath S, Raghavan S, Rani CSS, Radha V, Balasubramanyam M, Pant A, Nielsen T, Jørgensen T, Færch K, Kashani A, Silva MCA, Vestergaard H, Hansen TH, Hansen T, Arumugam M, Nair GB, Das B, Pedersen O, Mohan V, Mande SS
Journal
Genome medicine
Year
2021
BACKGROUND: Recent studies have indicated an association of gut microbiota and microbial metabolites with type 2 diabetes mellitus (T2D). However, large-scale investigation of the gut microbiota of "prediabetic" (PD) subjects has not been reported. Identifying robust gut microbiome signatures of prediabetes and characterizing early prediabetic stages is important for the understanding of disease development and could be crucial in early diagnosis and prevention. METHODS: The current study performed amplification and sequencing on the variable regions (V1-V5) of the 16S rRNA genes to profile and compare gut microbiota of prediabetic individuals (N = 262) with normoglycemic individuals (N = 275) from two cohorts in India and Denmark. Similarly, fasting serum inflammatory biomarkers were profiled from the study participants. RESULTS: After correcting for strong country-specific cohort effect, 16 operational taxonomic units (OTUs) including members from the genera Prevotella9, Phascolarctobacterium, Barnesiella, Flavonifractor, Tyzzerella_4, Bacteroides, Faecalibacterium, and Agathobacter were identified as enriched in normoglycaemic subjects with respect to the subjects with prediabetes using a negative binomial Wald test. We also identified 144 OTUs enriched in the prediabetic subjects, which included members from the genera Megasphaera, Streptococcus, Prevotella9, Alistipes, Mitsuokella, Escherichia/Shigella, Prevotella2, Vibrio, Lactobacillus, Alloprevotella, Rhodococcus, and Klebsiella. Comparative analyses of relative abundance of bacterial taxa revealed that the Streptococcus, Escherichia/Shigella, Prevotella2, Vibrio, and Alloprevotella OTUs exhibited more than fourfold enrichment in the gut microbiota of prediabetic subjects. When considering subjects from the two geographies separately, we were able to identify additional gut microbiome signatures of prediabetes. The study reports a probable association of Megasphaera OTU(s) with impaired glucose tolerance, which is significantly pronounced in Indian subjects. While the overall results confirm a state of proinflammation as early as in prediabetes, the Indian cohort exhibited a characteristic pattern of abundance of inflammatory markers indicating low-grade intestinal inflammation at an overall population level, irrespective of glycemic status. CONCLUSIONS: The results present trans-ethnic gut microbiome and inflammation signatures associated with prediabetes, in Indian and Danish populations. The identified associations may be explored further as potential early indicators for individuals at risk of dysglycemia.

Experiment 1


Reviewed Marked as Reviewed by Svetlana up on 2024-12-20

Curated date: 2024/11/05

Curator: KateRasheed

Revision editor(s): KateRasheed

Subjects

Location of subjects
Denmark
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
Normoglycemic (NG) controls - Danish Cohort
Group 1 name Corresponds to the case (exposed) group for case-control studies
Prediabetes (PD) - Danish Cohort
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Prediabetes (PD) - Danish Cohort refers to patients in their early stage of prediabetes.
Group 0 sample size Number of subjects in the control (unexposed) group
138
Group 1 sample size Number of subjects in the case (exposed) group
121
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
4 months

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V1-V5
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Roche454

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
raw counts
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

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-12-20

Curated date: 2024/11/05

Curator: KateRasheed

Revision editor(s): KateRasheed

Source: Additional file 11: Table S9A

Description: Differentially abundant taxa between NG and PD subjects, belonging to the Danish cohort, identified using a negative binomial Wald test.

Abundance in Group 1: increased abundance in Prediabetes (PD) - Danish Cohort

NCBI Quality ControlLinks
Ruminococcaceae_UCG-013Ruminococcaceae_UCG-013
Blautia obeum
Lachnoclostridium
Lachnospiraceae bacterium NK4A136
Ruminococcaceae_UCG-005Ruminococcaceae_UCG-005
Bacteroides fragilis/xylanisolvensBacteroides fragilis/xylanisolvens
Bacteroides fragilis/ovatusBacteroides fragilis/ovatus
Ruminiclostridium_9Ruminiclostridium_9
Ruminiclostridium_5Ruminiclostridium_5
bacterium FCS020
Bacteroides
Blautia
Eisenbergiella
Oscillospiraceae
uncultured Oscillospiraceae bacterium
Lachnospiraceae
Eisenbergiella massiliensis
Eggerthella lenta
Bacteroides intestinalis
Thomasclavelia
Prevotella_2Prevotella_2

Revision editor(s): KateRasheed

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-12-20

Curated date: 2024/11/05

Curator: KateRasheed

Revision editor(s): KateRasheed

Source: Additional file 11: Table S9A

Description: Differentially abundant taxa between NG and PD subjects, belonging to the Danish cohort, identified using a negative binomial Wald test.

Abundance in Group 1: decreased abundance in Prediabetes (PD) - Danish Cohort

NCBI Quality ControlLinks
Oscillibacter
Phascolarctobacterium faecium
rumen bacterium NK4A214
uncultured Mollicutes bacterium
Prevotella_9Prevotella_9
Ruminococcaceae_UCG-005Ruminococcaceae_UCG-005
Ruminococcaceae_UCG-002Ruminococcaceae_UCG-002
Ruminococcus 1Ruminococcus 1
Family XIII AD3011 groupFamily XIII AD3011 group

Revision editor(s): KateRasheed

Experiment 2


Reviewed Marked as Reviewed by Svetlana up on 2024-12-20

Curated date: 2024/11/05

Curator: KateRasheed

Revision editor(s): KateRasheed

Differences from previous experiment shown

Subjects

Lab analysis

Statistical Analysis

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, sex, Confounders controlled for: "waist-to-hip ratio" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.waist-to-hip ratio, Confounders controlled for: "Systolic BP" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.Systolic BP, Confounders controlled for: "IL6" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.IL6, Confounders controlled for: "TNFα" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.TNFα, Confounders controlled for: "LBP" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.LBP, Confounders controlled for: "IAP" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.IAP

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-12-20

Curated date: 2024/11/05

Curator: KateRasheed

Revision editor(s): KateRasheed

Source: Additional file 11: Table S9B

Description: Differentially abundant taxa between NG and PD subjects, belonging to the Danish cohort, identified after correcting for covariates (age, gender, waist-to-hip ratio, Systolic BP, IL6, TNFα, LBP and IAP) using a negative binomial Wald test.

Abundance in Group 1: decreased abundance in Prediabetes (PD) - Danish Cohort

NCBI Quality ControlLinks
Phocaeicola vulgatus
Roseburia
Roseburia faecis
rumen bacterium NK4A214
Ruminococcaceae_UCG-005Ruminococcaceae_UCG-005
Ruminococcaceae_UCG-002Ruminococcaceae_UCG-002
Christensenellaceae_R-7_groupChristensenellaceae_R-7_group
Escherichia/Shigella albertii/boydii/coli/dysenteriae/fergusonii/flexneri/sonnei/vulnerisEscherichia/Shigella albertii/boydii/coli/dysenteriae/fergusonii/flexneri/sonnei/vulneris

Revision editor(s): KateRasheed

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-12-20

Curated date: 2024/11/05

Curator: KateRasheed

Revision editor(s): KateRasheed

Source: Additional file 11: Table S9B

Description: Differentially abundant taxa between NG and PD subjects, belonging to the Danish cohort, identified after correcting for covariates (age, gender, waist-to-hip ratio, Systolic BP, IL6, TNFα, LBP and IAP) using a negative binomial Wald test.

Abundance in Group 1: increased abundance in Prediabetes (PD) - Danish Cohort

NCBI Quality ControlLinks
Lachnoclostridium
Dorea longicatena
Faecalibacterium prausnitzii
Bacteroides fragilis/xylanisolvensBacteroides fragilis/xylanisolvens
Bacteroides
Clostridium
Lachnospiraceae
uncultured Oscillospiraceae bacterium
Bacteroides dorei/fragilisBacteroides dorei/fragilis
Veillonella atypica
Collinsella bouchesdurhonensis
Dialister
Eisenbergiella
Oscillospiraceae

Revision editor(s): KateRasheed

Experiment 3


Reviewed Marked as Reviewed by Svetlana up on 2024-12-20

Curated date: 2024/11/05

Curator: KateRasheed

Revision editor(s): KateRasheed

Differences from previous experiment shown

Subjects

Location of subjects
Denmark
India


Group 0 name Corresponds to the control (unexposed) group for case-control studies
Indian Cohort (IN)
Group 1 name Corresponds to the case (exposed) group for case-control studies
Danish Cohort (DK)
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Danish Cohort (DK) refers to the normoglycemic and prediabetic groups in Danish subjects.
Group 0 sample size Number of subjects in the control (unexposed) group
278
Group 1 sample size Number of subjects in the case (exposed) group
259

Lab analysis

Statistical Analysis

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
Not specified

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-12-20

Curated date: 2024/11/05

Curator: KateRasheed

Revision editor(s): KateRasheed

Source: Additional file 7: Table S5B, Table S5A

Description: Differentially abundant taxa between Indian (IN) and Danish (DK) gut microbiomes identified using a negative binomial Wald test.

Abundance in Group 1: increased abundance in Danish Cohort (DK)

NCBI Quality ControlLinks
Acidaminococcaceae
Akkermansiaceae
Anaeroplasmataceae
Bacteroidaceae
Barnesiellaceae
Beijerinckiaceae
Christensenella
Defluviitaleaceae
Desulfobacteraceae
Marinifilaceae
Muribaculaceae
Nocardiaceae
Oscillospiraceae
Paracoccaceae
Peptococcaceae
Pseudomonadaceae
Puniceicoccaceae
Rikenellaceae
Synergistaceae
Tannerellaceae
Victivallaceae
Xanthobacteraceae
Clostridiales vadinBB60 groupClostridiales vadinBB60 group
Coriobacteriales incertae sedisCoriobacteriales incertae sedis
Family XIFamily XI
Bacillota
Bacteroidota
Mycoplasmatota
Verrucomicrobiota
Cyanobacteriota
Lentisphaerota
Fusobacteriota
Synergistota

Revision editor(s): KateRasheed

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-12-20

Curated date: 2024/11/05

Curator: KateRasheed

Revision editor(s): KateRasheed

Source: Additional file 7: Table S5B, Table S5A

Description: Differentially abundant taxa between Indian (IN) and Danish (DK) gut microbiomes identified using a negative binomial Wald test.

Abundance in Group 1: decreased abundance in Danish Cohort (DK)

NCBI Quality ControlLinks
Actinomycetaceae
Atopobiaceae
Bacillaceae
Bifidobacteriaceae
Burkholderiaceae
Carnobacteriaceae
Caulobacteraceae
Coriobacteriaceae
Eggerthella sinensis
Eggerthellaceae
Elusimicrobiaceae
Enterobacteriaceae
Enterococcaceae
Erysipelotrichaceae
Lachnospiraceae
Lactobacillaceae
Peptostreptococcaceae
Prevotellaceae
Spirochaetaceae
Streptococcaceae
Succinivibrionaceae
Veillonellaceae
Vibrionaceae
Clostridiaceae 1Clostridiaceae 1
Pseudomonadota
Actinomycetota
Spirochaetota
Elusimicrobiota
Lysobacteraceae

Revision editor(s): KateRasheed

Experiment 4


Reviewed Marked as Reviewed by Svetlana up on 2024-12-20

Curated date: 2024/11/05

Curator: KateRasheed

Revision editor(s): KateRasheed

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Normoglycemic (NG) controls - Indian & Danish Cohorts
Group 1 name Corresponds to the case (exposed) group for case-control studies
Prediabetes (PD) - Indian & Danish Cohorts
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Prediabetes (PD) - Indian & Danish Cohorts refers patients in their early stage of prediabetes in both India and Denmark cohorts.
Group 0 sample size Number of subjects in the control (unexposed) group
275
Group 1 sample size Number of subjects in the case (exposed) group
262

Lab analysis

Statistical Analysis

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
geographic area

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-12-20

Curated date: 2024/11/05

Curator: KateRasheed

Revision editor(s): KateRasheed

Source: Additional file 9: Table S7

Description: Differentially abundant taxa between NG and PD subjects, belonging to the Indian and Danish cohorts (pooled together) identified using a negative binomial Wald test (corrected for geography specific cohort effect).

Abundance in Group 1: increased abundance in Prediabetes (PD) - Indian & Danish Cohorts

NCBI Quality ControlLinks
Coprococcus comes
Dorea longicatena
Fusicatenibacter saccharivorans
Dorea formicigenerans
Subdoligranulum
Lachnospiraceae
Blautia
Blautia massiliensis (ex Liu et al. 2021)
Faecalibacterium
Lachnoclostridium
Ruminococcaceae_UCG-005Ruminococcaceae_UCG-005
Ruminococcaceae_UCG-0013Ruminococcaceae_UCG-0013
Blautia faecis
Coprococcus
Lachnospira
Lachnospira pectinoschiza
Intestinimonas
Streptococcus
Agathobacter
Ligilactobacillus ruminis
Oscillospiraceae
Ruminiclostridium_9Ruminiclostridium_9
Senegalimassilia
Intestinibacter bartlettii
Bacteroides
Megasphaera
Roseburia
Bifidobacterium adolescentis/faecale/stercorisBifidobacterium adolescentis/faecale/stercoris
Ruminiclostridium_5Ruminiclostridium_5
Lactobacillus
Klebsiella aerogenes/oxytoca/pneumoniaeKlebsiella aerogenes/oxytoca/pneumoniae
Enterorhabdus
Rhodococcus baikonurensis/boritolerans/degradans/erythropolis/globerulus/hoagii/opacus/qingshengii/rhodochrousRhodococcus baikonurensis/boritolerans/degradans/erythropolis/globerulus/hoagii/opacus/qingshengii/rhodochrous
Rhodococcus
Alistipes inops
Agathobaculum desmolans
Alistipes finegoldii/onderdonkiiAlistipes finegoldii/onderdonkii
Lactobacillus acidophilus/casei/crispatus/kitasatonisLactobacillus acidophilus/casei/crispatus/kitasatonis
Adlercreutzia
Achromobacter insolitus/xylosoxidansAchromobacter insolitus/xylosoxidans
Mitsuokella
Negativibacillus
Blautia wexlerae
Prevotella_9Prevotella_9
Peptococcaceae
Collinsella
Holdemanella
Lactobacillus delbrueckii
Veillonella tobetsuensis
Oscillibacter
Dialister
Anaerotruncus colihominis
Christensenellaceae_R-7_groupChristensenellaceae_R-7_group
Sutterella
Thomasclavelia
Escherichia/Shigella albertii/boydii/coli/dysenteriae/fergusonii/flexneri/sonnei/vulnerisEscherichia/Shigella albertii/boydii/coli/dysenteriae/fergusonii/flexneri/sonnei/vulneris
Veillonella atypica
Prevotella_2Prevotella_2
Bacteroides intestinalis
Eisenbergiella
uncultured Oscillospiraceae bacterium
Candidatus Obscuribacterales
Enterobacter
Veillonella dispar
Staphylococcus epidermidis/haemolyticus/hominisStaphylococcus epidermidis/haemolyticus/hominis
Alloprevotella
Lactobacillus fermentum/mucosaeLactobacillus fermentum/mucosae
Veillonella
Veillonella dispar/parvulaVeillonella dispar/parvula
Enterococcus azikeevi/durans/faecalis/faecium/hirae/lactis/mundtii/raffinosus/ratti/thailandicus/villorumEnterococcus azikeevi/durans/faecalis/faecium/hirae/lactis/mundtii/raffinosus/ratti/thailandicus/villorum
Veillonella parvula
Vibrio cholerae

Revision editor(s): KateRasheed

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-12-20

Curated date: 2024/11/05

Curator: KateRasheed

Revision editor(s): KateRasheed

Source: Additional file 9: Table S7

Description: Differentially abundant OTUs between NG and PD subjects, belonging to the Indian and Danish cohorts (pooled together) identified using a negative binomial Wald test (corrected for geography specific cohort effect).

Abundance in Group 1: decreased abundance in Prediabetes (PD) - Indian & Danish Cohorts

NCBI Quality ControlLinks
Ruminococcaceae_UCG-010Ruminococcaceae_UCG-010
Prevotella 9Prevotella 9
Bacteroides nordii
Oscillospiraceae
Faecalibacterium
Barnesiella intestinihominis
[Clostridium] nexile
Phascolarctobacterium faecium
Muribaculaceae
Christensenellaceae_R-7_groupChristensenellaceae_R-7_group
Flavonifractor plautii
Agathobacter
Ruminococcaceae_UCG-002Ruminococcaceae_UCG-002
Family_XIII_AD3011_groupFamily_XIII_AD3011_group

Revision editor(s): KateRasheed

Experiment 5


Reviewed Marked as Reviewed by Svetlana up on 2024-12-20

Curated date: 2024/11/05

Curator: KateRasheed

Revision editor(s): KateRasheed

Differences from previous experiment shown

Subjects

Location of subjects
India


Group 0 name Corresponds to the control (unexposed) group for case-control studies
Normoglycemic (NG) controls - Indian Cohort
Group 1 name Corresponds to the case (exposed) group for case-control studies
Prediabetes (PD) - Indian Cohort
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Prediabetes (PD) - Indian Cohort refers to patients in their early stage of prediabetes.
Group 0 sample size Number of subjects in the control (unexposed) group
137
Group 1 sample size Number of subjects in the case (exposed) group
141
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

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
Not specified

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-12-20

Curated date: 2024/11/05

Curator: KateRasheed

Revision editor(s): KateRasheed

Source: Additional file 10: Table S8A

Description: Differentially abundant taxa between NG and PD subjects, belonging to the Indian cohort, identified using a negative binomial Wald test.

Abundance in Group 1: increased abundance in Prediabetes (PD) - Indian Cohort

NCBI Quality ControlLinks
Roseburia
Blautia
Fusicatenibacter saccharivorans
Megasphaera elsdenii
Clostridium
Lachnospiraceae
Subdoligranulum
Lachnospiraceae bacterium NK4A136
Lachnospira
Blautia faecis
Faecalibacterium
Ruminococcaceae_UCG-013Ruminococcaceae_UCG-013
Intestinibacter bartlettii
Klebsiella aerogenes/oxytoca/pneumoniaeKlebsiella aerogenes/oxytoca/pneumoniae
Collinsella
Dialister succinatiphilus
Megasphaera
Weissella cibaria/confusa/koreensisWeissella cibaria/confusa/koreensis
Prevotella 9Prevotella 9
Bacteroides
Senegalimassilia
Ligilactobacillus ruminis
Olsenella
Achromobacter insolitus/xylosoxidansAchromobacter insolitus/xylosoxidans
Lactobacillus phage/reuteri/salivariusLactobacillus phage/reuteri/salivarius
Lactobacillus
Streptococcus
Ruminococcus
GKS98 freshwater groupGKS98 freshwater group
Oscillospiraceae
Megamonas
Ruminococcaceae_UCG-002Ruminococcaceae_UCG-002
Dialister
Alloprevotella
Veillonella atypica
Staphylococcus epidermidis/haemolyticus/hominisStaphylococcus epidermidis/haemolyticus/hominis
Phascolarctobacterium succinatutens
Escherichia/Shigella albertii/boydii/coli/dysenteriae/fergusonii/flexneri/sonnei/vulnerisEscherichia/Shigella albertii/boydii/coli/dysenteriae/fergusonii/flexneri/sonnei/vulneris
Lactobacillus fermentum/mucosaeLactobacillus fermentum/mucosae
Enterococcus azikeevi/durans/faecalis/faecium/hirae/lactis/mundtii/raffinosus/ratti/thailandicus/villorumEnterococcus azikeevi/durans/faecalis/faecium/hirae/lactis/mundtii/raffinosus/ratti/thailandicus/villorum
Veillonella dispar
Veillonella dispar/parvulaVeillonella dispar/parvula
Veillonella parvula
Lactobacillus delbrueckii
Vibrio cholerae
Veillonella

Revision editor(s): KateRasheed

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-12-20

Curated date: 2024/11/05

Curator: KateRasheed

Revision editor(s): KateRasheed

Source: Additional file 10: Table S8A

Description: Differentially abundant OTUs between NG and PD subjects, belonging to the Indian cohort, identified using a negative binomial Wald test.

Abundance in Group 1: decreased abundance in Prediabetes (PD) - Indian Cohort

NCBI Quality ControlLinks
Ruminococcaceae_UCG-002Ruminococcaceae_UCG-002
Faecalibacterium
Alloprevotella
Prevotella 9Prevotella 9
Agathobacter
Muribaculaceae

Revision editor(s): KateRasheed

Experiment 6


Reviewed Marked as Reviewed by Svetlana up on 2024-12-20

Curated date: 2024/11/05

Curator: KateRasheed

Revision editor(s): KateRasheed

Differences from previous experiment shown

Subjects

Lab analysis

Statistical Analysis

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, sex, Confounders controlled for: "waist-to-hip ratio" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.waist-to-hip ratio, Confounders controlled for: "Systolic BP" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.Systolic BP, Confounders controlled for: "IL6" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.IL6, Confounders controlled for: "TNFα" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.TNFα, Confounders controlled for: "LBP" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.LBP, Confounders controlled for: "IAP" is not in the list (abnormal glucose tolerance, acetaldehyde, acute graft vs. host disease, acute lymphoblastic leukemia, acute myeloid leukemia, adenoma, age, AIDS, alcohol consumption measurement, alcohol drinking, ...) of allowed values.IAP

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-12-20

Curated date: 2024/11/06

Curator: KateRasheed

Revision editor(s): KateRasheed

Source: Additional file 10: Table S8B

Description: Differentially abundant OTUs between NG and PD subjects , belonging to the Indian cohort, identified after correcting for covariates (age, gender, waist-to-hip ratio, Systolic BP, IL6, TNFα, LBP and IAP) using a negative binomial Wald test.

Abundance in Group 1: increased abundance in Prediabetes (PD) - Indian Cohort

NCBI Quality ControlLinks
Roseburia
Agathobacter
Blautia
Subdoligranulum
Fusicatenibacter saccharivorans
Dorea formicigenerans
Dorea longicatena
Blautia faecis
Marvinbryantia
Collinsella
Slackia
Roseburia faecis
Collinsella aerofaciens
Ruminococcus
Ruminococcaceae_UCG-013Ruminococcaceae_UCG-013
Lachnospiraceae
Ligilactobacillus ruminis
Staphylococcus epidermidis/haemolyticus/hominisStaphylococcus epidermidis/haemolyticus/hominis
Klebsiella aerogenes/oxytoca/pneumoniaeKlebsiella aerogenes/oxytoca/pneumoniae
Veillonella tobetsuensis
Lactobacillus delbrueckii
Lactobacillus delbrueckii/fermentum/ingluviei/oris/parabuchneri/plantarumLactobacillus delbrueckii/fermentum/ingluviei/oris/parabuchneri/plantarum
Veillonella parvula
Blautia wexlerae
GKS98_freshwater_groupGKS98_freshwater_group
Phascolarctobacterium succinatutens
Pseudomonas aeruginosa/denitrificans/fluorescens/mendocina/otitidis/protegens/putida/tropicalisPseudomonas aeruginosa/denitrificans/fluorescens/mendocina/otitidis/protegens/putida/tropicalis
Veillonella atypica
Veillonella dispar
Alloprevotella
Achromobacter insolitus/xylosoxidansAchromobacter insolitus/xylosoxidans
Veillonella dispar/parvulaVeillonella dispar/parvula
Enterococcus azikeevi/durans/faecalis/faecium/hirae/lactis/mundtii/raffinosus/ratti/thailandicus/villorumEnterococcus azikeevi/durans/faecalis/faecium/hirae/lactis/mundtii/raffinosus/ratti/thailandicus/villorum
Veillonella
Kerstersia

Revision editor(s): KateRasheed

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-12-20

Curated date: 2024/11/06

Curator: KateRasheed

Revision editor(s): KateRasheed

Source: Additional file 10: Table S8B

Description: Differentially abundant OTUs between NG and PD subjects , belonging to the Indian cohort, identified after correcting for covariates (age, gender, waist-to-hip ratio, Systolic BP, IL6, TNFα, LBP and IAP) using a negative binomial Wald test.

Abundance in Group 1: decreased abundance in Prediabetes (PD) - Indian Cohort

NCBI Quality ControlLinks
Ruminococcaceae_UCG-005Ruminococcaceae_UCG-005
Ruminococcaceae_UCG-002Ruminococcaceae_UCG-002
Alloprevotella
Prevotella 9Prevotella 9
Clostridium tertium
Agathobacter
Faecalibacterium
Ruminococcus_2Ruminococcus_2

Revision editor(s): KateRasheed

Experiment 7


Reviewed Marked as Reviewed by Svetlana up on 2024-12-20

Curated date: 2024/11/06

Curator: KateRasheed

Revision editor(s): KateRasheed

Differences from previous experiment shown

Subjects

Location of subjects
Denmark
India


Group 0 name Corresponds to the control (unexposed) group for case-control studies
Normoglycemic (NG) controls - Indian & Danish Cohorts
Group 1 name Corresponds to the case (exposed) group for case-control studies
Prediabetes (PD) - Indian & Danish Cohorts
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Prediabetes (PD) - Indian & Danish Cohorts refers patients in their early stage of prediabetes in both India and Denmark cohorts.
Group 0 sample size Number of subjects in the control (unexposed) group
275
Group 1 sample size Number of subjects in the case (exposed) group
262
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
4 months

Lab analysis

Statistical Analysis

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
geographic area

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2024-12-20

Curated date: 2024/11/06

Curator: KateRasheed

Revision editor(s): KateRasheed

Source: Additional file 12: Table S10A, Table S10B, Table S10C

Description: Differentially abundant taxa between NG and PD subjects, belonging to the Indian and Danish cohorts (pooled together) identified using a negative binomial Wald test (corrected for geography specific cohort-effect).

Abundance in Group 1: increased abundance in Prediabetes (PD) - Indian & Danish Cohorts

NCBI Quality ControlLinks
Actinomycetota
Elusimicrobiota
Fusobacteriota
Pseudomonadota
Streptococcaceae
Enterobacteriaceae
Burkholderiaceae
Vibrionaceae
Nocardiaceae
Enterococcaceae
Lactobacillus
Blautia
Streptococcus
Lachnoclostridium
GKS98 freshwater groupGKS98 freshwater group
Escherichia/ShigellaEscherichia/Shigella
Vibrio
Pasteurella
Veillonella
Klebsiella
Rhodococcus
Intestinibacter
Achromobacter
Negativibacillus
Eisenbergiella
Enterococcus

Revision editor(s): KateRasheed

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2024-12-20

Curated date: 2024/11/06

Curator: KateRasheed

Revision editor(s): KateRasheed

Source: Additional file 12: Table S10A, Table S10B, Table S10C

Description: Differentially abundant taxa between NG and PD subjects, belonging to the Indian and Danish cohorts (pooled together) identified using a negative binomial Wald test (corrected for geography specific cohort-effect).

Abundance in Group 1: decreased abundance in Prediabetes (PD) - Indian & Danish Cohorts

NCBI Quality ControlLinks
Bacillota
Bacteroidota
Mycoplasmatota
Verrucomicrobiota
Cyanobacteriota
Spirochaetota
Lentisphaerota
Synergistota
Clostridiales vadinBB60 groupClostridiales vadinBB60 group

Revision editor(s): KateRasheed