Dataset Information

Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults.

ABSTRACT:

Background

Recent evidence suggests that there is a link between metabolic diseases and bacterial populations in the gut. The aim of this study was to assess the differences between the composition of the intestinal microbiota in humans with type 2 diabetes and non-diabetic persons as control.

Methods and findings

The study included 36 male adults with a broad range of age and body-mass indices (BMIs), among which 18 subjects were diagnosed with diabetes type 2. The fecal bacterial composition was investigated by real-time quantitative PCR (qPCR) and in a subgroup of subjects (N = 20) by tag-encoded amplicon pyrosequencing of the V4 region of the 16S rRNA gene. The proportions of phylum Firmicutes and class Clostridia were significantly reduced in the diabetic group compared to the control group (P = 0.03). Furthermore, the ratios of Bacteroidetes to Firmicutes as well as the ratios of Bacteroides-Prevotella group to C. coccoides-E. rectale group correlated positively and significantly with plasma glucose concentration (P = 0.04) but not with BMIs. Similarly, class Betaproteobacteria was highly enriched in diabetic compared to non-diabetic persons (P = 0.02) and positively correlated with plasma glucose (P = 0.04).

Conclusions

The results of this study indicate that type 2 diabetes in humans is associated with compositional changes in intestinal microbiota. The level of glucose tolerance should be considered when linking microbiota with metabolic diseases such as obesity and developing strategies to control metabolic diseases by modifying the gut microbiota.

SUBMITTER: Larsen N

PROVIDER: S-EPMC2816710 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults.

Larsen Nadja N Vogensen Finn K FK van den Berg Frans W J FW Nielsen Dennis Sandris DS Andreasen Anne Sofie AS Pedersen Bente K BK Al-Soud Waleed Abu WA Sørensen Søren J SJ Hansen Lars H LH Jakobsen Mogens M

PloS one 20100205 2

<h4>Background</h4>Recent evidence suggests that there is a link between metabolic diseases and bacterial populations in the gut. The aim of this study was to assess the differences between the composition of the intestinal microbiota in humans with type 2 diabetes and non-diabetic persons as control.<h4>Methods and findings</h4>The study included 36 male adults with a broad range of age and body-mass indices (BMIs), among which 18 subjects were diagnosed with diabetes type 2. The fecal bacteria ...[more]

PMID: 20140211

Similar Datasets

Project description:Type 2 diabetes (T2D) is a prevalent non-communicable disease among the world's growing elderly population. The contribution of the gut microbiota to T2D in several Westernized countries has been established. However, there is little information on the role of the gut microbiota in T2D from the African continent where lifestyle and life expectancy are different. Aims:This study sought to investigate gut microbiota variation in relation to elderly people living with T2D. in Nigeria. Methods:Whole microbial community DNA were derived from the stool samples of healthy urban-dwelling elderly individuals and urban-dwelling elderly individuals with T2D. The V4 region of the 16S rRNA gene was Illumina-sequenced and analyzed using QIIME2. Results:Beta taxonomic diversity was significantly different between healthy elderly individuals and elderly individuals with T2D. However, no difference in the alpha taxonomic diversity and predicted functional alpha diversity of the gut microbiota was observed. The genus Ruminococcus (T2D versus Healthy: 2.89% vs 2.21%), families Coriobacteriaceae (Collinsella, T2D versus Healthy: 2.62 % vs 1.25%) and Bifidobacteriaceae were enriched in elderly individuals with T2D, while members of Clostridiaceae (Clostridium, Healthy versus T2D: 5.6% vs 3.2%) and Peptostreptococcaceae (Healthy versus T2D: 3.45% vs 1.99%) were enriched in healthy volunteers. Pathways involved in amino acid biosynthesis were enriched in elderly individuals with T2D, while pathways involved in respiration and the biosynthesis of vital building blocks were enriched in healthy volunteers. Conclusions:The study demonstrated for the first time in an African elderly population that the abundance of Bifidobacteriaceae, Collinsella, and Ruminococcus within the gut varies in relation to T2D. Findings from this study suggest that the restoration of features associated with healthiness via the way of gut microbiota modification could be one step needed to improve elderly patient care.

Project description:Intestinal homeostasis underpins the development of type 1 diabetes (T1D), and dietary manipulations to enhance intestinal homeostasis have been proposed to prevent T1D. The current study aimed to investigate the efficacy of supplementing a novel specific low-methoxyl pectin (LMP) dietary fiber in preventing T1D development. Female NOD mice were weaned onto control or 5% (wt/wt) LMP supplemented diets for up to 40 weeks of age, overt diabetes incidence and blood glucose were monitored. Then broad-spectrum antibiotics (ABX) treatment per os for 7 days followed by gut microbiota transfer was performed to demonstrate gut microbiota-dependent effects. Next-generation sequencing was used for analyzing the composition of microbiota in caecum. Concentration of short chain fatty acids were determined by GC-MS. The barrier reinforcing tight junction proteins zonula occludens-2 (ZO-2), claudin-1 and NOD like receptor protein 3 (NLRP3) inflammasome activation were determined by Western blot. The proportion of CD25+Foxp3+CD4+ regulatory T cell (Foxp3+ Treg) in the pancreas, pancreatic and mesenteric lymph nodes was analyzed by flow cytometry. We found that LMP supplementation ameliorated T1D development in non-obese diabetic (NOD) mice, as evidenced by decreasing diabetes incidence and fasting glucose levels in LMP fed NOD mice. Further microbiota analysis revealed that LMP supplementation prevented T1D-associated caecal dysbiosis and selectively enriched caecal bacterial species to produce more SCFAs. The LMP-mediated microbial balance further enhanced caecal barrier function and shaped gut-pancreatic immune environment, as characterized by higher expression of tight junction proteins claudin-1, ZO-2 in caecum, increased Foxp3+ Treg population and decreased NLRP3 inflammasome activation in both caecum and pancreas. The microbiota-dependent beneficial effect of LMP on T1D was further proven by the fact that aberration of caecal microbiota by ABX treatment worsened T1D autoimmunity and could be restored with transfer of feces of LMP-fed NOD mice. These data demonstrate that this novel LMP limits T1D development by inducing caecal homeostasis to shape pancreatic immune environment. This finding opens a realistic option for gut microbiota manipulation and prevention of T1D in humans.

Project description:The incidence of type 1 diabetes (T1D) is determined by both genetic and environmental factors. In recent years, the gut microbiota have been identified to be an important environmental factor that could modify diabetes susceptibility. We have previously shown that Myeloid differentiation primary response gene 88 (MyD88), a major adaptor protein downstream of most innate immune Toll-like receptor (TLR) signaling, is important for mediating diabetes susceptibility in the non-obese diabetic (NOD) mouse model of human T1D. Here we report the role of TIR-domain-containing adapter-inducing interferon-β (TRIF) in T1D development, as TRIF is an important adaptor protein downstream of TLR3 and TLR4 signaling. We found that TRIF-deficient (TRIF-/-) NOD mice were protected from development of diabetes, but only when housed with TRIF-deficient (TRIF-/-) NOD mice. When housed with TRIF-sufficient wild type (WT, i.e., TRIF+/+) NOD mice, the mice developed diabetes. We further investigated the gut microbiota as a potential cause for the altered diabetes development. Interestingly, TRIF-/-NOD mice had a different microbiota composition compared to WT NOD mice, only if they were housed with TRIF-/-NOD mice. However, the composition of gut microbiota in the TRIF-/-NOD mice was indistinguishable from WT NOD mice, if they were housed with WT NOD mice. The difference in the gut microbiota in TRIF-/-NOD mice, due to cohousing, accorded with the diabetes development in TRIF-/-NOD mice. Comparing the gut microbiota in TRIF-/- and WT NOD mice, we identified changes in percentage of Sutterella, Rikenella and Turicibacter species. Moreover, bacteria from WT NOD mice induced significantly stronger inflammatory immune responses in vitro compared to those from TRIF-/-NOD mice. Further immunological analysis revealed impaired function of dendritic cells and reduced T cell activation and proliferation in TRIF-/-NOD mice. Our data show that TRIF-deficiency protects NOD mice from diabetes development through alteration of the gut microbiota and reduced immune cell activation; however, that protection is over-ridden upon exposure to WT NOD bacteria. Therefore exposure to different microbiota can modify disease susceptibility determined by genetic factors related to innate immunity.

Project description:Despite improved understanding of the pathophysiology of type 2 diabetes mellitus, explanations for individual variability in disease progression and response to treatment are incomplete. The gut microbiota has been linked to the pathophysiology of type 2 diabetes mellitus and may account for this variability. We conducted a systematic review to assess the effectiveness of dietary and physical activity/exercise interventions in modulating the gut microbiota and improving glucose control in adults with type 2 diabetes mellitus.A systematic search was conducted to identify studies reporting on the effect of dietary and physical activity/exercise interventions on the gut microbiota and glucose control in individuals with a confirmed diagnosis of type 2 diabetes mellitus. Study characteristics, methodological quality and details relating to interventions were captured using a data-extraction form. Meta-analyses were conducted where sufficient data were available, and other results were reported narratively.Eight studies met the eligibility criteria of the systematic review. No studies were found that reported on the effects of physical activity/exercise on the gut microbiota and glucose control. However, studies reporting on dietary interventions showed that such interventions were associated with modifications to the composition and diversity of the gut microbiota. There was a statistically significant improvement in HbA1c (standardised mean difference [SMD] -2.31 mmol/mol [95% CI -2.76, -1.85] [0.21%; 95% CI -0.26, -0.16]; I2?=?0%, p?<?0.01), but not in fasting blood glucose (SMD -0.25 mmol/l [95% CI -0.85, 0.35], I2?=?87%, p?>?0.05), fasting insulin (SMD -1.82 pmol/l [95% CI -7.23, 3.60], I2?=?54%, p?>?0.05) or HOMA-IR (SMD -0.15 [95% CI -0.63, 0.32], I2?=?69%, p?>?0.05) when comparing dietary interventions with comparator groups. There were no significant changes in the relative abundance of bacteria in the genera Bifidobacterium (SMD 1.29% [95% CI -4.45, 7.03], I2?=?33%, p?>?0.05), Roseburia (SMD -0.85% [95% CI -2.91, 1.21], I2?=?79%, p?>?0.05) or Lactobacillus (SMD 0.04% [95% CI -0.01, 0.09], I2?=?0%, p?>?0.05) when comparing dietary interventions with comparator groups. There were, however, other significant changes in the gut microbiota, including changes at various taxonomic levels, including phylum, family, genus and species, Firmicutes:Bacteroidetes ratios and changes in diversity matrices (? and ?). Dietary intervention had minimal or no effect on inflammation, short-chain fatty acids or anthropometrics.Dietary intervention was found to modulate the gut microbiota and improve glucose control in individuals with type 2 diabetes. Although the results of the included studies are encouraging, this review highlights the need for further well-conducted interventional studies to inform the clinical use of dietary interventions targeting the gut microbiota.

Project description:Roux-en-Y gastric bypass (RYGB) is efficient at inducing drastic albeit variable weight loss and type-2 diabetes (T2D) improvements in patients with severe obesity and T2D. We hypothesized a causal implication of the gut microbiota (GM) in these metabolic benefits, as RYGB is known to deeply impact its composition. In a cohort of 100 patients with baseline T2D who underwent RYGB and were followed for 5-years, we used a hierarchical clustering approach to stratify subjects based on the severity of their T2D (Severe vs Mild) throughout the follow-up. We identified via nanopore-based GM sequencing that the more severe cases of unresolved T2D were associated with a major increase of the class Bacteroidia, including 12 species comprising Phocaeicola dorei, Bacteroides fragilis, and Bacteroides caecimuris. A key observation is that patients who underwent major metabolic improvements do not harbor this enrichment in Bacteroidia, as those who presented mild cases of T2D at all times. In a separate group of 36 patients with similar baseline clinical characteristics and preoperative GM sequencing, we showed that this increase in Bacteroidia was already present at baseline in the most severe cases of T2D. To explore the causal relationship linking this enrichment in Bacteroidia and metabolic alterations, we selected 13 patients across T2D severity clusters at 5-years and performed fecal matter transplants in mice. Our results show that 14 weeks after the transplantations, mice colonized with the GM of Severe donors have impaired glucose tolerance and insulin sensitivity as compared to Mild-recipients, all in the absence of any difference in body weight and composition. GM sequencing of the recipient animals revealed that the hallmark T2D-severity associated bacterial features were transferred and were associated with the animals' metabolic alterations. Therefore, our results further establish the GM as a key contributor to long-term glucose metabolism improvements (or lack thereof) after RYGB.

Dataset Information

Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults.

Background

Methods and findings

Conclusions

Publications

Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets