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

Leiva-Gea, Isabel; Sánchez-Alcoholado, Lidia; Martín-Tejedor, Beatriz; Castellano‐Castillo, Daniel; Moreno-Indias, Isabel; Urda-Cardona, Antonio; Tinahones, Francisco J.; Fernández‐García, José Carlos

doi:10.2337/dc18-0253

Cited by 190 publications

(208 citation statements)

References 43 publications

(36 reference statements)

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“…However, conflicting data with regard to F/B ratio in individuals diagnosed with T1D have been published too (28,29), which may be attributed to different sample sizes, data analysis approaches, and geographical location. Another common gut microbiome shift associated with the T1D development is the decreased microbial diversity, which has been reported both in T1D children (30,31) and in autoantibodypositive children (26,27,32). It was further found that the decline in bacterial diversity was specific to seroconverters that eventually developed into T1D but not in undeveloped seroconverters (33).…”

Section: Aberrant Gut Microbiota Composition In Human T1dmentioning

confidence: 86%

“…A decrease in Bifidobacterium was also reported in T1D subjects by several studies. In a study investigating the bacterial compositional differences among children with T1D and maturity-onset diabetes of the young 2 (MODY2) and healthy control subjects by 16S ribosomal RNA (rRNA) gene sequencing, the authors concluded that T1D children presented with a reduced level of Bifidobacterium, and perhaps even more interestingly, it was observed that the intestinal microbiota profile of T1D patients was different from not only healthy subjects but also subjects with MODY2 (30). Another study also using 16S rRNA gene sequencing concluded the similar trends regarding Bifidobacterium (37).…”

Section: Aberrant Gut Microbiota Composition In Human T1dmentioning

confidence: 99%

“…It was identified that butyrate could reduce gut permeability by promoting the assembly of tight junctions (TJ) (155) as well as inducing mucin synthesis (131), and the role of butyrate in restoring TJ barrier was achieved by affecting the expression of TJ proteins comprising claudin-2, occludin, cingulin, and zonula occludens (ZO) proteins (156). Despite the great variability of intestinal microbiota associated with T1D, most published studies have found that Bacteroides were positively associated with T1D development (24,27,28,30,32,34,38). These bacteria are able to ferment glucose and lactate to propionate, acetate, and succinate (157), which cannot induce the biosynthesis of mucin-like butyrate (158).…”

Section: Impact Of Gut Microbiota On Intestinal Permeabilitymentioning

confidence: 99%

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Evaluating the Causal Role of Gut Microbiota in Type 1 Diabetes and Its Possible Pathogenic Mechanisms

et al. 2020

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Type 1 diabetes (T1D) is a multifactorial autoimmune disease mediated by genetic, epigenetic, and environmental factors. In recent years, the emergence of high-throughput sequencing has allowed us to investigate the role of gut microbiota in the development of T1D. Significant changes in the composition of gut microbiome, also termed dysbiosis, have been found in subjects with clinical or preclinical T1D. However, whether the dysbiosis is a cause or an effect of the disease remains unclear. Currently, increasing evidence has supported a causal link between intestine microflora and T1D development. The current review will focus on recent research regarding the associations between intestine microbiome and T1D progression with an intention to evaluate the causality. We will also discuss the possible mechanisms by which imbalanced gut microbiota leads to the development of T1D.

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Section: Aberrant Gut Microbiota Composition In Human T1dmentioning

confidence: 86%

Section: Aberrant Gut Microbiota Composition In Human T1dmentioning

confidence: 99%

Section: Impact Of Gut Microbiota On Intestinal Permeabilitymentioning

confidence: 99%

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Evaluating the Causal Role of Gut Microbiota in Type 1 Diabetes and Its Possible Pathogenic Mechanisms

et al. 2020

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“…Patterns of dysbiosis have often been assessed by changes in richness and diversity with variable findings in different disease conditions. For instance, the richness and diversity of gut microbiota was found to be reduced in arteriosclerosis, hypertension [21], diabetic patients [22] and animal model, whereas increased diversity was associated with atrial fibrillation [23] myocardial infarction, stroke and transient ischemic attacks. Interestingly alterations associated with autism [24] and obesity [25] was found to be inconsistent.…”

Section: Discussionmentioning

confidence: 99%

Non-uinform gut microbiota alteration patterns associated with therapeutic outcomes in an Alzheimer's disease animal model

Wang¹,

Amakye²,

Cao³

et al. 2019

Preprint

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Background: Dysbiosis of gut microbiota is associated with the progression of beta-amyloid (Aβ) pathology in Alzheimer’s disease (AD). We aimed to identify uniform Aβ-responsible gut microbiota status as possible guideline for gut microbiota manipulation and the prediction of outcomes of microbiota targeted treatments. Six months old APP/PS1 mice from the same genetic background, housing and feeding conditions were then daily gavage with Metformin, peptides WN5 or PW5 to manipulate the gut microbiota for 12 weeks. Aβ pathology and gut microbiota were then explored and compared. Results: Fecal microbiota transplantation (FMT) from a 16 month old APP/PS1 mouse reconstituted the gut microbiota towards the donor and increased Aβ pathology in APP/PS1 mouse model. Metformin, peptides WN5 and PW5 all attenuated Aβ-plaque formation in APP/PS1 mouse model but each was associated with distinct gut microbiota status. No uniform gut microbiota pattern associated with Aβ pathology was found among different gut microbiota-targeted treatments. Conclusion: We found no uniform gut microbiota status associated with Aβ pathology suggesting gut microbiota status is not a suitable biomarker for AD diagnosis and treatment predictions. Alteration of gut microbiota in itself may not be sufficiently directly related to functional outcomes and might only be a shadow of deeper molecular mechanisms not fully understood. The findings here strongly suggested that the significance of gut microbiota alteration in disease pathology and treatment may have so far been over claimed and that interpretation of gut microbiota data should be done with utmost caution.

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“…For example, there was an increased abundance of Ruminococcus and Bacteroides and a decreased abundance of Bifidobacterium and Faecalibacterium in T1DM; the relative abundance of Prevotella was increased in MODY2, but Ruminococcus and Bacteroides were reduced. Moreover, intestinal permeability was increased in MODY2 and T1DM, accompanied by increased serum proinflammatory cytokines (e.g., IL-1β, IL-6, and TNF-α) and LPS in T1DM [115]. The inflammasome complexes NLRP3 is a multiprotein complex that recognizes microbial-associated molecular patterns and participates in proinflammatory pathways, and the mice lack these complexes show altered intestinal microbial composition and lead to NAFLD [116].…”

Section: Nlrp3 and The Microbiomementioning

confidence: 99%

Modulatory Mechanisms of the NLRP3 Inflammasomes in Diabetes

et al. 2019

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The inflammasome is a multiprotein complex that acts to enhance inflammatory responses by promoting the production and secretion of key cytokines. The best-known inflammasome is the NLRP3 (nucleotide-binding oligomerization domain-like receptor [NLR] family pyrin domain-containing 3) inflammasome. The evidence has shown that the NLRP3 inflammasome, IL-1β, thioredoxin-interacting protein (TXNIP), and pyroptosis play vital roles in the development of diabetes. This review summarizes the regulation of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) by NLRP3 via modulation of glucose tolerance, insulin resistance, inflammation, and apoptosis mediated by endoplasmic reticulum stress in adipose tissue. Moreover, NLRP3 participates in intestinal homeostasis and inflammatory conditions, and NLRP3-deficient mice experience intestinal lesions. The diversity of an individual’s gut microbiome and the resultant microbial metabolites determines the extent of their involvement in the physiological and pathological mechanisms within the gut. As such, further study of the interaction between the NLRP3 inflammasome and the complex intestinal environment in disease development is warranted to discover novel therapies for the treatment of diabetes.

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

Cited by 190 publications

References 43 publications

Evaluating the Causal Role of Gut Microbiota in Type 1 Diabetes and Its Possible Pathogenic Mechanisms

Evaluating the Causal Role of Gut Microbiota in Type 1 Diabetes and Its Possible Pathogenic Mechanisms

Non-uinform gut microbiota alteration patterns associated with therapeutic outcomes in an Alzheimer's disease animal model

Modulatory Mechanisms of the NLRP3 Inflammasomes in Diabetes

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