Exploring the gut microbiota in patients with pre-diabetes and treatment naïve diabetes type 2 - a pilot study

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Reviewed Marked as Reviewed by Peace Sandy on 2024-1-24
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Gravdal K, Kirste KH, Grzelak K, Kirubakaran GT, Leissner P, Saliou A, Casèn C
Journal
BMC endocrine disorders
Year
2023
Keywords:
16S rRNA bacterial gene, Bacterial profiling, Microbiota signatures, Prediabetes, Type 2 diabetes
BACKGROUND: Compared to their healthy counterparts, patients with type 2 diabetes (T2D) can exhibit an altered gut microbiota composition, correlated with detrimental outcomes, including reduced insulin sensitivity, dyslipidemia, and increased markers of inflammation. However, a typical T2D microbiota profile is not established. The aim of this pilot study was to explore the gut microbiota and bacteria associated with prediabetes (pre-T2D) patients, and treatment naïve T2D patients, compared to healthy subjects. METHODS: Fecal samples were collected from patients and healthy subjects (from Norway). The bacterial genomic DNA was extracted, and the microbiota analyzed utilizing the bacterial 16S rRNA gene. To secure a broad coverage of potential T2D associated bacteria, two technologies were used: The GA-map® 131-plex, utilizing 131 DNA probes complementary to pre-selected bacterial targets (covering the 16S regions V3-V9), and the LUMI-Seq™ platform, a full-length 16S sequencing technology (V1-V9). Variations in the gut microbiota between groups were explored using multivariate methods, differential bacterial abundance was estimated, and microbiota signatures discriminating the groups were assessed using classification models. RESULTS: In total, 24 pre-T2D patients, 18 T2D patients, and 52 healthy subjects were recruited. From the LUMI-Seq™ analysis, 10 and 9 bacterial taxa were differentially abundant between pre-T2D and healthy, and T2D and healthy, respectively. From the GA-map® 131-plex analysis, 10 bacterial markers were differentially abundant when comparing pre-T2D and healthy. Several of the bacteria were short-chain fatty acid (SCFA) producers or typical opportunistic bacteria. Bacteria with similar function or associated properties also contributed to the separation of pre-T2D and T2D from healthy as found by classification models. However, limited overlap was found for specific bacterial genera and species. CONCLUSIONS: This pilot study revealed that differences in the abundance of SCFA producing bacteria, and an increase in typical opportunistic bacteria, may contribute to the variations in the microbiota separating the pre-T2D and T2D patients from healthy subjects. However, further efforts in investigating the relationship between gut microbiota, diabetes, and associated factors such as BMI, are needed for developing specific diabetes microbiota signatures.

Experiment 1


Reviewed Marked as Reviewed by Peace Sandy on 2024-1-24

Curated date: 2023/10/05

Curator: Kadeniyi

Revision editor(s): Kadeniyi, Peace Sandy

Subjects

Location of subjects
Norway
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 - based on GA- map
Group 1 name Corresponds to the case (exposed) group for case-control studies
Pre-Type 2 Diabetes
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Pre-Type 2 Diabetes patients are Individuals that have blood glucose levels higher than normal but below the threshold for T2D, are often overweight, and have an elevated risk of T2D and cardiovascular disease.
Group 0 sample size Number of subjects in the control (unexposed) group
38
Group 1 sample size Number of subjects in the case (exposed) group
22
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
4 weeks

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V3-V9
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
Mann-Whitney (Wilcoxon)
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.01
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
Yes
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, body mass index, sex, Confounders controlled for: "f-cal" 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.f-cal


Signature 1

Reviewed Marked as Reviewed by Peace Sandy on 2024-1-24

Curated date: 2023/10/10

Curator: Kadeniyi

Revision editor(s): Kadeniyi, Peace Sandy

Source: Table 2

Description: Differentially abundant bacteria – pre-T2D vs. healthy, GA-map® 131-plex

Abundance in Group 1: increased abundance in Pre-Type 2 Diabetes

NCBI Quality ControlLinks
Dorea
Pseudomonadota
Enterobacterales
Escherichia/Shigella sp.

Revision editor(s): Kadeniyi, Peace Sandy

Signature 2

Reviewed Marked as Reviewed by Peace Sandy on 2024-1-24

Curated date: 2023/10/10

Curator: Kadeniyi

Revision editor(s): Kadeniyi, Peace Sandy

Source: Table 2

Description: Differentially abundant bacteria – pre-T2D vs. healthy, GA-map® 131-plex

Abundance in Group 1: decreased abundance in Pre-Type 2 Diabetes

NCBI Quality ControlLinks
Roseburia
Roseburia intestinalis
Faecalibacterium prausnitzii
Dialister invisus
Veillonella
Sutterella wadsworthensis

Revision editor(s): Kadeniyi, Peace Sandy

Experiment 2


Reviewed Marked as Reviewed by Peace Sandy on 2024-1-24

Curated date: 2023/10/11

Curator: Kadeniyi

Revision editor(s): Kadeniyi, Peace Sandy

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Healthy Controls - based on LUMI -Seq data
Group 0 sample size Number of subjects in the control (unexposed) group
48

Lab analysis

16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V1-V9

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
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, body mass index, sex, Confounders controlled for: "F-cal" 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.F-cal


Signature 1

Reviewed Marked as Reviewed by Peace Sandy on 2024-1-24

Curated date: 2023/10/11

Curator: Kadeniyi

Revision editor(s): Kadeniyi, Peace Sandy

Source: Table 3

Description: Diferentially abundant bacteria — pre-T2D and T2D vs. healthy, LUMI-Seq™

Abundance in Group 1: increased abundance in Pre-Type 2 Diabetes

NCBI Quality ControlLinks
Bacilli
Lactobacillales
Streptococcaceae
Streptococcus
Eisenbergiella
Eisenbergiella massiliensis
Neglectibacter
Neglectibacter timonensis

Revision editor(s): Kadeniyi, Peace Sandy

Signature 2

Reviewed Marked as Reviewed by Peace Sandy on 2024-1-24

Curated date: 2023/10/11

Curator: Kadeniyi

Revision editor(s): Kadeniyi, Peace Sandy

Source: Table 3

Description: Diferentially abundant bacteria — pre-T2D and T2D vs. healthy, LUMI-Seq™

Abundance in Group 1: decreased abundance in Pre-Type 2 Diabetes

NCBI Quality ControlLinks
Oscillibacter valericigenes
Phocaeicola coprocola

Revision editor(s): Kadeniyi, Peace Sandy

Experiment 3


Reviewed Marked as Reviewed by Peace Sandy on 2024-1-24

Curated date: 2023/10/12

Curator: Kadeniyi

Revision editor(s): Kadeniyi, Peace Sandy

Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies
Type 2 Diabetes - T2D
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with Type 2 diabetes (T2D)
Group 1 sample size Number of subjects in the case (exposed) group
16

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by Peace Sandy on 2024-1-24

Curated date: 2023/10/12

Curator: Kadeniyi

Revision editor(s): Kadeniyi, Peace Sandy

Source: Table 3

Description: Diferentially abundant bacteria — pre-T2D and T2D vs. healthy, LUMI-Seq™

Abundance in Group 1: increased abundance in Type 2 Diabetes - T2D

NCBI Quality ControlLinks
Dorea
Enterobacterales
Dorea formicigenerans
Dorea longicatena
Erysipelotrichia
Erysipelotrichaceae
Turicibacter
Turicibacter sanguinis

Revision editor(s): Kadeniyi, Peace Sandy

Signature 2

Reviewed Marked as Reviewed by Peace Sandy on 2024-1-24

Curated date: 2023/10/12

Curator: Kadeniyi

Revision editor(s): Kadeniyi, Peace Sandy

Source: Table 3

Description: Diferentially abundant bacteria — pre-T2D and T2D vs. healthy, LUMI-Seq™

Abundance in Group 1: decreased abundance in Type 2 Diabetes - T2D

NCBI Quality ControlLinks
Anaerotignum

Revision editor(s): Kadeniyi, Peace Sandy

Experiment 4


Reviewed Marked as Reviewed by Peace Sandy on 2024-1-24

Curated date: 2024/01/24

Curator: Peace Sandy

Revision editor(s): Peace Sandy

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies
Pre- Type 2 Diabetes individuals
Group 1 name Corresponds to the case (exposed) group for case-control studies
Type 2 Diabetes - T2D Patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Patients with Type 2 Diabetes
Group 0 sample size Number of subjects in the control (unexposed) group
22

Lab analysis

Statistical Analysis

Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, body mass index, sex, Confounders controlled for: "f-cal" 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.f-cal


Signature 1

Reviewed Marked as Reviewed by Peace Sandy on 2024-1-24

Curated date: 2024/01/24

Curator: Peace Sandy

Revision editor(s): Peace Sandy

Source: Table 3

Description: Diferentially abundant bacteria — pre-T2D and T2D vs. healthy, LUMI-Seq™

Abundance in Group 1: increased abundance in Type 2 Diabetes - T2D Patients

NCBI Quality ControlLinks
Dorea
Dorea formicigenerans
Dorea longicatena
Erysipelotrichaceae
Erysipelotrichia
Turicibacter
Turicibacter sanguinis

Revision editor(s): Peace Sandy

Signature 2

Reviewed Marked as Reviewed by Peace Sandy on 2024-1-24

Curated date: 2024/01/24

Curator: Peace Sandy

Revision editor(s): Peace Sandy

Source: Table 3

Description: Diferentially abundant bacteria — pre-T2D and T2D vs. healthy, LUMI-Seq™

Abundance in Group 1: decreased abundance in Type 2 Diabetes - T2D Patients

NCBI Quality ControlLinks
Bacilli
Eisenbergiella
Eisenbergiella massiliensis
Lactobacillales
Neglectibacter
Neglectibacter timonensis
Streptococcaceae
Streptococcus

Revision editor(s): Peace Sandy