Gut Microbiota Differs in Composition and Functionality Between Children With Type 1 Diabetes and MODY2 and Healthy Control Subjects: A Case-Control Study

Study information

Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

30224347

DOI Digital object identifier for electronic documents.

10.2337/dc18-0253

URI

Authors

Leiva-Gea I, Sánchez-Alcoholado L, Martín-Tejedor B, Castellano-Castillo D, Moreno-Indias I, Urda-Cardona A, Tinahones FJ, Fernández-García JC, Queipo-Ortuño MI

Journal

Diabetes care

Year

2018

OBJECTIVE: Type 1 diabetes is associated with compositional differences in gut microbiota. To date, no microbiome studies have been performed in maturity-onset diabetes of the young 2 (MODY2), a monogenic cause of diabetes. Gut microbiota of type 1 diabetes, MODY2, and healthy control subjects was compared. RESEARCH DESIGN AND METHODS: This was a case-control study in 15 children with type 1 diabetes, 15 children with MODY2, and 13 healthy children. Metabolic control and potential factors modifying gut microbiota were controlled. Microbiome composition was determined by 16S rRNA pyrosequencing. RESULTS: Compared with healthy control subjects, type 1 diabetes was associated with a significantly lower microbiota diversity, a significantly higher relative abundance of Bacteroides, Ruminococcus, Veillonella, Blautia, and Streptococcus genera, and a lower relative abundance of Bifidobacterium, Roseburia, Faecalibacterium, and Lachnospira. Children with MODY2 showed a significantly higher Prevotella abundance and a lower Ruminococcus and Bacteroides abundance. Proinflammatory cytokines and lipopolysaccharides were increased in type 1 diabetes, and gut permeability (determined by zonulin levels) was significantly increased in type 1 diabetes and MODY2. The PICRUSt analysis found an increment of genes related to lipid and amino acid metabolism, ABC transport, lipopolysaccharide biosynthesis, arachidonic acid metabolism, antigen processing and presentation, and chemokine signaling pathways in type 1 diabetes. CONCLUSIONS: Gut microbiota in type 1 diabetes differs at taxonomic and functional levels not only in comparison with healthy subjects but fundamentally with regard to a model of nonautoimmune diabetes. Future longitudinal studies should be aimed at evaluating if the modulation of gut microbiota in patients with a high risk of type 1 diabetes could modify the natural history of this autoimmune disease.

Experiment 1

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Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, Atrayees, ChiomaBlessing

Subjects

Location of subjects: Spain

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 I diabetes mellitus Autoimmune Diabete,Autoimmune Diabetes,Brittle Diabetes Mellitus,Diabete, Autoimmune,diabetes mellitis type 1,diabetes mellitis type I,DIABETES MELLITUS TYPE 01,Diabetes mellitus type 1,Diabetes mellitus type 1 (disorder),Diabetes mellitus type I,Diabetes mellitus type I [insulin dependent type] [IDDM] [juvenile type], not stated as uncontrolled, with unspecified complication,Diabetes mellitus type I [insulin dependent type] [IDDM] [juvenile type], uncontrolled, with unspecified complication,Diabetes Mellitus, Brittle,Diabetes Mellitus, Insulin Dependent,Diabetes Mellitus, Insulin-Dependent,Diabetes Mellitus, Juvenile Onset,Diabetes Mellitus, Juvenile-Onset,Diabetes Mellitus, Ketosis Prone,Diabetes Mellitus, Ketosis-Prone,Diabetes Mellitus, Sudden Onset,Diabetes Mellitus, Sudden-Onset,Diabetes Mellitus, Type 1,Diabetes Mellitus, Type I,Diabetes, Autoimmune,DMI UNSPF NT ST UNCNTRLD,DMI UNSPF UNCNTRLD,IDDM,IDDM - Insulin-dependent diabetes mellitus,immune mediated diabetes,Insulin Dependent Diabetes,insulin dependent diabetes,Insulin dependent diabetes mellitus,insulin dependent diabetes mellitus,Insulin-Dependent Diabetes Mellitus,insulin-dependent diabetes mellitus,Juvenile Diabetes,juvenile diabetes,Juvenile onset diabetes mellitus,Juvenile-Onset Diabetes Mellitus,Ketosis-Prone Diabetes Mellitus,Mellitus, Sudden-Onset Diabetes,Sudden-Onset Diabetes Mellitus,Type 1 Diabetes,type 1 diabetes,Type 1 Diabetes Mellitus,type 1 diabetes mellitus,Type I Diabetes,type I diabetes,type I diabetes mellitus,Type I diabetes mellitus

Group 0 name Corresponds to the control (unexposed) group for case-control studies: maturity-onset diabetes of the young 2 (MODY2) and healthy Controls

Group 1 name Corresponds to the case (exposed) group for case-control studies: Type I Diabetics

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: type 1 diabetes was diagnosed according to the criteria of the American Diabetes Association and the positivity of at least two persistent, confirmed anti-islet autoantibodies (anti-insulin autoantibodies, GAD autoantibodies, or tyrosine phosphatase autoantibodies). MODY2 children were diagnosed by suggestive clinical history, negative anti-islet autoantibodies, and positive genetic testing. Healthy control subjects were children with negative anti-islet autoantibodies,

Group 0 sample size Number of subjects in the control (unexposed) group: 28

Group 1 sample size Number of subjects in the case (exposed) group: 15

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): 3 months

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V2-V3

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).: relative abundances

Statistical test: Mann-Whitney (Wilcoxon)

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

Matched on Factors on which subjects have been matched on in a case-control study: age, body mass index, breastfeeding duration, delivery procedure, race, sex

Signature 1

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Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

Curated date: 2021/01/10

Curator: Yaseen Javaid

Revision editor(s): WikiWorks

Source: Text

Description: differentially abundant taxa of the fecal microbiota in type 1 diabetes, MODY2, and healthy controls

Abundance in Group 1: increased abundance in Type I Diabetics

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Bacteroidota
Bacteroidaceae
Rikenellaceae
Enterobacteriaceae
Blautia
Oscillospiraceae
Veillonellaceae
Streptococcaceae
Bacteroides
Veillonella
Ruminococcus
Streptococcus
Enterobacter
Sutterella

Revision editor(s): WikiWorks

Signature 2

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Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

Curated date: 2021/01/10

Curator: Yaseen Javaid

Revision editor(s): WikiWorks

Source: Text

Description: differentially abundant taxa of the fecal microbiota in type 1 diabetes, MODY2, and healthy controls

Abundance in Group 1: decreased abundance in Type I Diabetics

NCBI	Quality Control	Links
Bacillota
Actinomycetota

Revision editor(s): WikiWorks

Experiment 2

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Reviewed Marked as Reviewed by Shaimaa Elsafoury on 2021/02/09

Curated date: 2021/01/10

Curator: WikiWorks

Revision editor(s): WikiWorks, Atrayees, ChiomaBlessing

Differences from previous experiment shown

Subjects

Group 0 name Corresponds to the control (unexposed) group for case-control studies: healthy Controls

Group 1 name Corresponds to the case (exposed) group for case-control studies: Type I Diabetics and maturity-onset diabetes of the young 2 (MODY2)