The Fecal Microbiota Is Already Altered in Normoglycemic Individuals Who Go on to Have Type 2 Diabetes

Wang, Li; Yu, Xuefeng; Xu, Xiaoqiang; Ming, Jie; Wang, Zhifeng; Gao, Bin; Xing, Ying; Zhou, Jie; Fu, Jianfang; Liu, Tao; Li, Xiangyang; Garstka, Malgorzata; Wang, Xiaokai; Ji, Qiuhe

doi:10.3389/fcimb.2021.598672

Cited by 33 publications

(44 citation statements)

References 43 publications

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“…This of course would need to be explored more deeply, for example by evaluating subjects’ feces metabolome. Changes in methane metabolism, glycosaminoglycan degradation and carbon fixation pathways in procaryotes were all found to be increased in T2D patients and in patients who later developed T2D in the study by Wang et al ., 47 which concordant with our current findings.…”

Section: Discussionsupporting

confidence: 94%

The human gut microbiota contributes to type-2 diabetes non-resolution 5-years after Roux-en-Y gastric bypass

et al. 2022

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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.

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Section: Discussionsupporting

confidence: 94%

The human gut microbiota contributes to type-2 diabetes non-resolution 5-years after Roux-en-Y gastric bypass

et al. 2022

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“…However, the causality between gut dysbiosis and T2D remains enigmatic. A recent study showed that subjects that went on to develop T2D already presented a distinct GM composition prior to the dysregulation in glucose homeostasis [ 12 ]. Besides, another study reported that GM composition changes during the course of the T2D, since subjects with PreD presented microbiota features different from those observed in healthy individuals or those with T2D [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Antidiabetic Effects of Pediococcus acidilactici pA1c on HFD-Induced Mice

Cabello-Olmo

Oneca²,

Pajares

et al. 2022

Nutrients

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Prediabetes (PreD), which is associated with impaired glucose tolerance and fasting blood glucose, is a potential risk factor for type 2 diabetes mellitus (T2D). Growing evidence suggests the role of the gastrointestinal microbiota in both PreD and T2D, which opens the possibility for a novel nutritional approach, based on probiotics, for improving glucose regulation and delaying disease progression of PreD to T2D. In this light, the present study aimed to assess the antidiabetic properties of Pediococcus acidilactici (pA1c) in a murine model of high-fat diet (HFD)-induced T2D. For that purpose, C57BL/6 mice were given HFD enriched with either probiotic (1 × 1010 CFU/day) or placebo for 12 weeks. We determined body weight, fasting blood glucose, glucose tolerance, HOMA-IR and HOMA-β index, C-peptide, GLP-1, leptin, and lipid profile. We also measured hepatic gene expression (G6P, PEPCK, GCK, IL-1β, and IL-6) and examined pancreatic and intestinal histology (% of GLP-1+ cells, % of goblet cells and villus length). We found that pA1c supplementation significantly attenuated body weight gain, mitigated glucose dysregulation by reducing fasting blood glucose levels, glucose tolerance test, leptin levels, and insulin resistance, increased C-peptide and GLP-1 levels, enhanced pancreatic function, and improved intestinal histology. These findings indicate that pA1c improved HFD-induced T2D derived insulin resistance and intestinal histology, as well as protected from body weight increase. Together, our study proposes that pA1c may be a promising new dietary management strategy to improve metabolic disorders in PreD and T2D.

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“…In a prospective study in the same year, 341 samples were assessed. Lower abundances of Bifidobacterium longum, Coprobacillus unclassified , and Veillonella dispar and higher abundances of Roseburia hominis, Porphyromonas bennonis , and Paraprevotella unclassified were found in diabetic patients [ 14 ]. Although many studies have been reported, most studies have reported only the intestinal flora associated with diabetes and did not clarify the importance of intestinal microbes in the occurrence and development of diabetes.…”

Section: Introductionmentioning

confidence: 99%

Gut Microbiome-Based Diagnostic Model to Predict Diabetes Mellitus

et al. 2021

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The aim of this study was to determine the diversity of intestinal microflora and its correlation with clinical parameters in diabetic patients and healthy subjects and to assess the importance of intestinal flora in patients with diabetes. Forty-four patients with diabetes were included. The control group included 47 healthy people. Their data, biochemical indicators and results from 16S rRNA sequencing of their fecal samples were collected. Compared with the healthy population, the intestinal flora of the diabetic patients was obviously abnormal. Within the diabetes group, the abundances of the genera Faecalibacterium, Prevotella, and Roseburia were higher, and the abundances of the genera Shigella and Bifidobacterium were lower. In the correlation analysis between bacteria and clinical indicators, it was found that the genera Veillonella and unclassified_Enterobacteriaceae were negatively related to blood glucose, while the genera Phascolarctobacterium, unidentified_Bacteroidales and Prevotella were significantly positively correlated with fasting blood glucose. Twelve microbial markers were detected in the random forest model, and the area under the curve (AUC) was 84.1%. This index was greater than the diagnostic effect of fasting blood glucose. This was also supported by the joint diagnostic model of microorganisms and clinical indicators. In addition, the intestinal flora significantly improved the diagnosis of diabetes. In conclusion, it can be concluded from these results that intestinal flora is essential for the occurrence and development of diabetes, which seems to be as important as blood glucose itself. Abbreviations: PCoA: principal coordinate analysis; NMDS: non econometric multidimensional scaling analysis; LEfSe: linear discriminant analysis effect size; LDA: linear discriminant analysis; POD: probability of disease; BMI: body mass index; DCA: decision curve analysis

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The Fecal Microbiota Is Already Altered in Normoglycemic Individuals Who Go on to Have Type 2 Diabetes

Cited by 33 publications

References 43 publications

The human gut microbiota contributes to type-2 diabetes non-resolution 5-years after Roux-en-Y gastric bypass

The human gut microbiota contributes to type-2 diabetes non-resolution 5-years after Roux-en-Y gastric bypass

Antidiabetic Effects of Pediococcus acidilactici pA1c on HFD-Induced Mice

Gut Microbiome-Based Diagnostic Model to Predict Diabetes Mellitus

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