Hyperglycemia is associated with duodenal dysbiosis and altered duodenal microenvironment

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Needs review
Citation
PMID PubMed identifier for scientific articles.
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 4


Needs review

Curated date: 2025/02/07

Curator: Aleru Divine

Revision editor(s): Aleru Divine

Differences from previous experiment shown

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
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
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 normoglycemic participants.
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
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


Signature 1

Needs review

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

Needs review

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