The regulatory effect of chitooligosaccharides on islet inflammation in T2D individuals after islet cell transplantation: the mechanism behind Candida albicans abundance and macrophage polarization
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Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Zhang Y, Ji X, Chang K, Yin H, Zhao M, Zhao L
Journal
Gut microbes
Year
2025
Keywords:
Candida albicans, Islet cell transplantation, chitooligosaccharides, islet inflammation, macrophages
Islet cell transplantation (ICT) represents a promising therapeutic approach for addressing diabetes mellitus. However, the islet inflammation during transplantation significantly reduces the surgical outcome rate, which is related to the polarization of macrophages. Chitooligosaccharides (COS) was previously reported which could modulate the immune system, alleviate inflammation, regulate gut microecology, and repair the intestinal barrier. Therefore, we hypothesized COS could relieve pancreatic inflammation by regulating macrophage polarization and gut microbiota. First, 18S rDNA gene sequencing was performed on fecal samples from the ICT population, showing abnormally increased amount of Candida albicans, possibly causing pancreatic inflammation. Functional oligosaccharides responsible for regulating macrophage polarization and inhibiting the growth of Candida albicans were screened. Afterwards, human flora-associated T2D (HMA-T2D) mouse models of gut microbiota were established, and the ability of the selected oligosaccharides were validated in vivo to alleviate inflammation and regulate gut microbiota. The results indicated that ICT significantly decreased the alpha diversity of gut fungal, altered fungal community structures, and increased Candida albicans abundance. Moreover, Candida albicans promoted M1 macrophage polarization, leading to islet inflammation. COS inhibited Candida albicans growth, suppressed the MyD88-NF-κB pathway, activated STAT6, inhibited M1, and promoted M2 macrophage polarization. Furthermore, COS-treated HMA-T2D mice displayed lower M1 macrophage differentiation and higher M2 macrophage numbers. Additionally, COS also enhanced ZO-1 and Occludin mRNA expression, reduced Candida albicans abundance, and balanced gut microecology. This study illustrated that COS modulated macrophage polarization via the MyD88/NF-κB and STAT6 pathways, repaired the intestinal barrier, and reduced Candida albicans abundance to alleviate islet inflammation.
Experiment 1
Reviewed Marked as Reviewed by Svetlana up on 2025-4-3
Subjects
- Location of subjects
- China
- 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
- Response to transplant Response to transplant,response to transplant
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Con (Control) group
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- ICT (islet cell transplantation) group
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Patients with T2D (type 2 diabetes) who underwent ICT (islet cell transplantation)
- Group 0 sample size Number of subjects in the control (unexposed) group
- 16
- 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)
- Current use of antibiotics
Lab analysis
- Sequencing type
- 18S
- 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
- LEfSe
- 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)?
- No
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- 2
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- decreased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- increased
- Richness Number of species
- decreased
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-4-3
Source: Figure 2I
Description: Differential abundant taxa between CON (control) and ICT (islet cell transplantation) groups by LeFse.
Abundance in Group 1: increased abundance in ICT (islet cell transplantation) group
Revision editor(s): Tosin
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2025-4-3
Source: Figure 2I
Description: Differential abundant taxa between CON (control) and ICT (islet cell transplantation) groups by LeFse.
Abundance in Group 1: decreased abundance in ICT (islet cell transplantation) group
| NCBI | Quality Control | Links |
|---|---|---|
| Hannaella luteola | ||
| Imbricatea | ||
| Leucosporidiaceae | ||
| Leucosporidiales | ||
| Leucosporidium | ||
| Leucosporidium yakuticum | ||
| Polygonaceae | ||
| Rheum | ||
| Rheum spiciforme |
Revision editor(s): Tosin
Experiment 2
Reviewed Marked as Reviewed by Svetlana up on 2025-4-3
Differences from previous experiment shown
Subjects
Lab analysis
Statistical Analysis
- Statistical test
- T-Test
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
- Chao1 Abundance-based estimator of species richness
- decreased
- Simpson Estimator of species richness and species evenness: more weight on species evenness
- increased
- Richness Number of species
- decreased
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-4-3
Source: Figure 2d, F and H
Description: Comparison of microbial distribution histogram at genus, species level. (d), (f) and (h) the significant analysis of gut fungi.
Abundance in Group 1: increased abundance in ICT (islet cell transplantation) group
| NCBI | Quality Control | Links |
|---|---|---|
| Ascomycota | ||
| Candida albicans | ||
| Candida |
Revision editor(s): Tosin
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2025-4-3
Source: Figure 2d, 2F and 2H
Description: Comparison of microbial distribution histogram at genus, species level. (d), (f) and (h) the significant analysis of gut fungi.
Abundance in Group 1: decreased abundance in ICT (islet cell transplantation) group
| NCBI | Quality Control | Links |
|---|---|---|
| Ciliophora | ||
| Basidiomycota | ||
| Quercus | ||
| Russula | ||
| Russula exalbicans | ||
| Quercus lobata |
Revision editor(s): Tosin
Experiment 3
Reviewed Marked as Reviewed by Svetlana up on 2025-4-3
Differences from previous experiment shown
Subjects
- Host species Species from which microbiome was sampled. Contact us to have more species added.
- Mus musculus
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Treatment outcome measurement Treatment outcome measurement,treatment outcome measurement
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- RA (Rapamycin alone) treatment group of HMA-T2D (Human Microbiota associated type 2 diabetes) mice
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- RC (Rapamycin + Chitooligosaccharides ) treatment group of HMA-T2D (Human Microbiota associated type 2 diabetes) mice
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- The HMA-T2D (Human Microbiota associated type 2 diabetes) mice gavaged with Rapamycin (RAPA) 5 mg/kg every other day and Chitooligosaccharides (COS) 350 mg/kg/day.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 8
- Group 1 sample size Number of subjects in the case (exposed) group
- 8
- 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
- Statistical test
- LEfSe
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- increased
- Richness Number of species
- unchanged
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-4-3
Source: Figure 8B and 8C
Description: Analysis of the gut fungal community abundance differences between the RA (Rapamycin alone) and RC (Rapamycin + Chitooligosaccharides) groups of HMA-T2D (Human Microbiota associated type 2 diabetes) mice by LEfSe analysis
Abundance in Group 1: increased abundance in RC (Rapamycin + Chitooligosaccharides ) treatment group of HMA-T2D (Human Microbiota associated type 2 diabetes) mice
Revision editor(s): Tosin
Signature 2
Reviewed Marked as Reviewed by Svetlana up on 2025-4-3
Source: Figure 8B and 8C
Description: Analysis of the gut fungal community abundance differences between the RA (Rapamycin alone) and RC (Rapamycin + Chitooligosaccharides) groups of HMA-T2D (Human Microbiota associated type 2 diabetes) mice by LEfSe analysis
Abundance in Group 1: decreased abundance in RC (Rapamycin + Chitooligosaccharides ) treatment group of HMA-T2D (Human Microbiota associated type 2 diabetes) mice
| NCBI | Quality Control | Links |
|---|---|---|
| Arxiozyma telluris | ||
| Candida albicans | ||
| Hanseniaspora | ||
| Hanseniaspora uvarum | ||
| Kazachstania | ||
| Mattesia | ||
| unclassified Mattesia |
Revision editor(s): Tosin
Experiment 4
Reviewed Marked as Reviewed by Svetlana up on 2025-4-3
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- CA (Candida albicans Alone) treatment group of HMA-T2D (Human Microbiota associated type 2 diabetes) mice
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- CC (Candida albicans + Chitooligosaccharides) treatment group of HMA-T2D (Human Microbiota associated type 2 diabetes) mice
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- The HMA-T2D (Human Microbiota associated type 2 diabetes) mice Gavaged with Candida albicans (2 × 108 CFU/0.2 mL every other day) and COS (chitooligosaccharides) 350 mg/kg/day
Lab analysis
Statistical Analysis
- Statistical test
- T-Test
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- Not specified
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- increased
- Richness Number of species
- unchanged
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-4-3
Source: Figure 8e
Description: The significance analysis of the fungi in the CA (Candida albicans Alone) and CC ( (Candida albicans + Chitooligosaccharides) groups of HMA-T2D (Human Microbiota associated type 2 diabetes) mice
Abundance in Group 1: decreased abundance in CC (Candida albicans + Chitooligosaccharides) treatment group of HMA-T2D (Human Microbiota associated type 2 diabetes) mice
| NCBI | Quality Control | Links |
|---|---|---|
| Candida albicans |
Revision editor(s): Tosin
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