Hyperglycemia is associated with duodenal dysbiosis and altered duodenal microenvironment

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Reviewed Marked as Reviewed by Svetlana up on 2025-3-3
Citation
PMID PubMed identifier for scientific articles.
N/A
DOI Digital object identifier for electronic documents.
URI
Authors
Aarti Darra, Anish Bhattacharya, Anupam Kumar Singh, Anuraag Jena, Anurag Agrawal, Pankaj Gupta, Priyanka Popli, Ritambhra Nada, Sanjay Kumar Bhadada, Usha Dutta, Vandana Singh, Vishal Sharma
Journal
Scientific reports
Year
2023
Pages:
First page:
Keywords:
The gut microbiome influences the pathogenesis and course of metabolic disorders such as diabetes. While it is likely that duodenal mucosa associated microbiota contributes to the genesis and progression of increased blood sugar, including the pre-diabetic stage, it is much less studied than stool. We investigated paired stool and duodenal microbiota in subjects with hyperglycemia (HbA1c ≥ 5.7% and fasting plasma glucose > 100 mg/dl) compared to normoglycemic. We found patients with hyperglycemia (n = 33) had higher duodenal bacterial count (p = 0.008), increased pathobionts and reduction in beneficial flora compared to normoglycemic (n = 21). The microenvironment of duodenum was assessed by measuring oxygen saturation using T-Stat, serum inflammatory markers and zonulin for gut permeability. We observed that bacterial overload was correlated with increased serum zonulin (p = 0.061) and higher TNF-α (p = 0.054). Moreover, reduced oxygen saturation (p = 0.021) and a systemic proinflammatory state [increased total leukocyte count (p = 0.031) and reduced IL-10 (p = 0.015)] characterized the duodenum of hyperglycemic. Unlike stool flora, the variability in duodenal bacterial profile was associated with glycemic status and was predicted by bioinformatic analysis to adversely affect nutrient metabolism. Our findings offer new understanding of the compositional changes in the small intestine bacteria by identifying duodenal dysbiosis and altered local metabolism as potentially early events in hyperglycemia.

Experiment 1


Reviewed Marked as Reviewed by Svetlana up on 2025-3-3

Curated date: 2025/02/06

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Subjects

Location of subjects
India
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
Duodenum Proximal intestine,Upper intestine,Duodenum,duodenum
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Hyperglycemia High blood glucose,High blood sugar,Hyperglycemia,hyperglycemia
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Normoglycemic group
Group 1 name Corresponds to the case (exposed) group for case-control studies
Hyperglycemic group
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
The hyperglycemic group consists of subjects with fasting plasma glucose(FPG) > 100 mg/dl and hemoglobin A1C (HbA1c) ≥ 5.7%.
Group 0 sample size Number of subjects in the control (unexposed) group
21
Group 1 sample size Number of subjects in the case (exposed) group
33
Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
6–8 weeks

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).
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
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
age, Confounders controlled for: "sequencing batch effects" 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.sequencing batch effects

Alpha Diversity

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

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2025-3-3

Curated date: 2025/02/06

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Source: Figure 3C

Description: Histograms showing the differential abundant features in duodenal microbiota obtained using DESeq2 in hyperglycemic and normoglycemic subjects at order, family, and genus-species level.

Abundance in Group 1: increased abundance in Hyperglycemic group

NCBI Quality ControlLinks
Escherichia/Shigella sp.
Acinetobacter haemolyticus
Turicibacter sanguinis
Dolosigranulum pigrum
Neisseria subflava
Veillonella tobetsuensis
Streptococcus cristatus

Revision editor(s): Aleru Divine

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2025-3-3

Curated date: 2025/02/06

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Source: Figure 3C

Description: Histograms showing the differential abundant features in duodenal microbiota obtained using DESeq2 in hyperglycemic and normoglycemic subjects at order, family, and genus-species level.

Abundance in Group 1: decreased abundance in Hyperglycemic group

NCBI Quality ControlLinks
Lactococcus
Acinetobacter junii
Lachnoanaerobaculum
Campylobacter concisus
Brachybacterium muris
Epilithonimonas hominis
Prevotella histicola
Gordonia
Akkermansia muciniphila
Parafannyhessea umbonata
Collinsella aerofaciens
Bacteroides
Lancefieldella parvula
Pseudomonadales
Pseudonocardiales
Caulobacterales
Pseudonocardiaceae
Tannerellaceae
Caulobacteraceae
Nocardiaceae
Akkermansiaceae
Coriobacteriaceae

Revision editor(s): Aleru Divine

Experiment 2


Reviewed Marked as Reviewed by Svetlana up on 2025-3-3

Curated date: 2025/02/06

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Differences from previous experiment shown

Subjects

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Feces , Duodenum 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,Proximal intestine,Upper intestine,Duodenum,duodenum
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Sampling site Sampling site,sampling site
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Stool samples
Group 1 name Corresponds to the case (exposed) group for case-control studies
Biopsy samples
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Duodenal biopsy samples from 54 participants.
Group 0 sample size Number of subjects in the control (unexposed) group
54
Group 1 sample size Number of subjects in the case (exposed) group
54

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2025-3-3

Curated date: 2025/02/06

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Source: Supplementary Table 1

Description: Table depicting differentially abundant species in biopsy compared to stool, analyzed using DESeq2 package.

Abundance in Group 1: increased abundance in Biopsy samples

NCBI Quality ControlLinks
Carnobacterium maltaromaticum
Serratia
Granulicatella elegans
Stenotrophomonas
Acinetobacter
Hoylesella nanceiensis
Sphingomonas
Acinetobacter johnsonii
Peptostreptococcus stomatis
Porphyromonas pasteri
Gemella
Bacillus
Segatella salivae
Prevotella melaninogenica
Lactobacillus iners
Alcaligenes faecalis
Corynebacterium
Prevotella histicola
Epilithonimonas hominis
Phascolarctobacterium faecium
Burkholderia
Acinetobacter bouvetii
Prevotella nigrescens
Neisseria
Prevotella
Gemella morbillorum
Pseudonocardia
Lachnoanaerobaculum
Prevotella pallens
Streptococcus
Fusobacterium periodonticum
Fusobacterium
Exiguobacterium
Capnocytophaga leadbetteri
Ochrobactrum
Proteus
Fusobacterium nucleatum
Pseudonocardia alni subsp. carboxydivorans
Providencia
Flectobacillus roseus
Roseateles
Nesterenkonia xinjiangensis
Dialister pneumosintes
Parvimonas micra
Dolosigranulum pigrum
Paracoccus sphaerophysae
Streptococcus cristatus
Oribacterium parvum
Acinetobacter haemolyticus
Stomatobaculum longum
Leptotrichia wadei
Rothia
Rothia mucilaginosa
Helicobacter pylori
Curtobacterium
Oribacterium sinus
Hoylesella shahii
Acinetobacter junii
Porphyromonas endodontalis
Rothia dentocariosa
Gemella sanguinis
Aggregatibacter segnis
Haemophilus
Campylobacter
Lactococcus
Campylobacter concisus
Neisseria subflava
Veillonella atypica
Veillonella
Veillonella dispar
Veillonella rogosae
Megasphaera micronuciformis
Veillonella tobetsuensis
Neisseria mucosa
Aeromonas
Haemophilus parainfluenzae
Haemophilus sputorum
Dialister invisus
[Eubacterium] brachy
[Eubacterium] sulci
Filifactor alocis
Veillonella parvula
Micrococcus lylae
Corynebacterium mucifaciens
Gemella parahaemolysans
Lautropia mirabilis
Klebsiella pneumoniae
Sphingobacterium alimentarium
Solilutibacter tolerans
Gordonia
Methylobacterium jeotgali
Microbacterium
Brachybacterium muris
Schaalia odontolytica

Revision editor(s): Aleru Divine

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2025-3-3

Curated date: 2025/02/06

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Source: Supplementary Table 2

Description: Table depicting differentially abundant species in stool compared to biopsy analysed using DESeq2 package.

Abundance in Group 1: decreased abundance in Biopsy samples

NCBI Quality ControlLinks
Megasphaera
Bacteroides uniformis
Faecalibacterium prausnitzii
Ruminococcus bromii
Bifidobacterium longum
Dorea longicatena
Bacteroides thetaiotaomicron
Alistipes putredinis
Faecalibacterium
Lactobacillus delbrueckii
Blautia
Segatella copri
Blautia massiliensis (ex Liu et al. 2021)
Lachnospira eligens
Roseburia faecis
Coprococcus comes
Eshraghiella crossota
Coprococcus catus
Sutterella wadsworthensis
Anaerobutyricum hallii
Bacteroides
Mitsuokella multacida
Fusicatenibacter saccharivorans
Bacteroides stercoris
Roseburia inulinivorans
Odoribacter splanchnicus
Mitsuokella jalaludinii
Blautia obeum
Ruminococcus
Romboutsia
Blautia faecis
Slackia isoflavoniconvertens
Coprococcus eutactus
Roseburia hominis
Bilophila wadsworthia
Roseburia intestinalis
Alistipes senegalensis
Alistipes communis
Anaerostipes hadrus
Holdemanella biformis
Ligilactobacillus ruminis
Ruminococcus callidus
Dorea formicigenerans
Flavonifractor plautii
Clostridium
Ruminococcus bicirculans (ex Liu et al. 2021)
Lachnospiraceae bacterium
Allisonella histaminiformans
Parasutterella excrementihominis
Bifidobacterium
Parabacteroides distasonis
Intestinibacter bartlettii
Escherichia/Shigella sp.
Alistipes shahii
Klebsiella
Bifidobacterium angulatum

Revision editor(s): Aleru Divine

Experiment 3


Reviewed Marked as Reviewed by Svetlana up on 2025-3-3

Curated date: 2025/02/07

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Differences from previous experiment shown

Subjects

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Duodenal biopsy samples from participants with hyperglycemia.
Group 0 sample size Number of subjects in the control (unexposed) group
33
Group 1 sample size Number of subjects in the case (exposed) group
33

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2025-3-3

Curated date: 2025/02/07

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Source: Supplementary Figure 1

Description: Boxplot showing the comparison of top taxa between hyperglycemic and normoglycemic groups in stool and duodenum samples at Phylum, Class, Order and Family levels.

Abundance in Group 1: increased abundance in Biopsy samples

NCBI Quality ControlLinks
Pseudomonadota
Actinomycetota
Fusobacteriota
Acidimicrobiia
Alphaproteobacteria
Bacilli
Epsilonproteobacteria
Fusobacteriia
Gammaproteobacteria
Negativicutes
BetaproteobacterialesBetaproteobacteriales
Pasteurellales
Selenomonadales
Pseudomonadales
Lactobacillales
Enterobacterales
Micrococcales
Burkholderiaceae
Pasteurellaceae
Veillonellaceae
Pseudomonadaceae
Carnobacteriaceae
Neisseriaceae

Revision editor(s): Aleru Divine

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2025-3-3

Curated date: 2025/02/07

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Source: Supplementary Figure 1

Description: Boxplot showing the comparison of top taxa between hyperglycemic and normoglycemic groups in stool and duodenum samples at Phylum, Class, Order and Family levels.

Abundance in Group 1: decreased abundance in Biopsy samples

NCBI Quality ControlLinks
Aeromonadales
Bacillota
Bacteroidales
Bacteroidia
Bacteroidota
Clostridia
Erysipelotrichia
Eubacteriales
Lachnospiraceae
Oscillospiraceae
Prevotellaceae
Succinivibrionaceae

Revision editor(s): Aleru Divine

Experiment 4


Reviewed Marked as Reviewed by Svetlana up on 2025-3-3

Curated date: 2025/02/07

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Differences from previous experiment shown

Subjects

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Duodenal biopsy samples from normoglycemic participants.
Group 0 sample size Number of subjects in the control (unexposed) group
21
Group 1 sample size Number of subjects in the case (exposed) group
21

Lab analysis

Statistical Analysis

Signature 1

Reviewed Marked as Reviewed by Svetlana up on 2025-3-3

Curated date: 2025/02/07

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Source: Supplementary Figure 1

Description: Boxplot showing the comparison of top taxa between hyperglycemic and normoglycemic groups in stool and duodenum samples at Phylum, Class, Order and Family levels.

Abundance in Group 1: increased abundance in Biopsy samples

NCBI Quality ControlLinks
Pseudomonadota
Actinomycetota
Fusobacteriota
Acidimicrobiia
Alphaproteobacteria
Bacilli
Epsilonproteobacteria
Fusobacteriia
Gammaproteobacteria
Negativicutes
BetaproteobacterialesBetaproteobacteriales
Pasteurellales
Selenomonadales
Pseudomonadales
Lactobacillales
Enterobacterales
Micrococcales
Burkholderiaceae
Pasteurellaceae
Veillonellaceae
Pseudomonadaceae
Carnobacteriaceae
Neisseriaceae

Revision editor(s): Aleru Divine

Signature 2

Reviewed Marked as Reviewed by Svetlana up on 2025-3-3

Curated date: 2025/02/07

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Source: Supplementary Figure 1

Description: Boxplot showing the comparison of top taxa between hyperglycemic and normoglycemic groups in stool and duodenum samples at Phylum, Class, Order and Family levels.

Abundance in Group 1: decreased abundance in Biopsy samples

NCBI Quality ControlLinks
Bacteroidota
Bacillota
Bacteroidia
Clostridia
Erysipelotrichia
Bacteroidales
Aeromonadales
Eubacteriales
Prevotellaceae
Succinivibrionaceae
Lachnospiraceae
Oscillospiraceae

Revision editor(s): Aleru Divine