| 1. |
- Kalin, Kenny, et al.
(författare)
-
The effect of saccharin consumption on microbiota composition and insulin sensitivity : a clinical, experimental open label pilot study
- 2020
-
Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 63:SUPPL 1, s. S223-S224
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background and aims: In a previous study it was suggested that consumption of saccharin, a non-caloric artificial sweetener (NAS), often consumed by individuals with type 2 diabetes mellitus, increases the risk of developing glucose intolerance in rodents and humans through microbiota alterations. However, the study was small and did not use insulin clamp, the gold standard for measuring insulin sensitivity in humans. Thus, our aim was to further investigate whether NAS affect insulin sensitivity and gut microbiota in humans.Materials and methods: We recruited 14 participants (8 women and 6 men) who were non-diabetic, 60.0 (IQR 56.8-64.0) years of age with a body mass index of 27.9 (IQR 27.1-28.5). The study was an open label study where participants acted as their own control. Their insulin sensitivity was measured before and after exposure of 240 mg saccharin/day for three months. Insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp and the ‘M value’ was calculated by dividing the glucose infusion rate during the last 60 minutes of the clamp by body weight (mg/kg/min). Stool samples were collected before and after saccharin consumption. Microbiota was analyzed by sequencing of the 16S rRNA gene.Results: Thirteen of the 14 participants completed the study. There was no change in insulin resistance after exposure to saccharin (mean M value difference (ΔM) 0.0 (SD 1.6). ΔM was not related to age or sex . Individual M values from the first and second insulin clamp are shown in Figure 1 and indicate some individual responses. During the study 6 participants reduced their HbA1c ≥ 3 mmol/mol. Overall, there was no change in composition or richness of the gut microbiota as a result of saccharin consumption. Furthermore, there was no change in microbiota at end of follow-up for participants with a HbA1c reduction compared to participants without a HbA1c reduction of 3 mmol/mol or more. However, there were small differences in gut microbiota between HbA1c reducers and non-reducers at baseline, with lower gut microbiota diversity in reducers. The reducer group was mainly men who tended to lose more weight than non-reducers; the weight loss was, however, not statistically significant. Statistical analyses of study data were performed by using Student’s t-test.Conclusion: In contrast to prior studies we did not find an effect of NAS on insulin sensitivity. Furthermore, NAS consumption did not alter microbiota composition in these overweight, middle aged adults without type 2 diabetes.
|
|
| 2. |
- Meijnikman, A. S., et al.
(författare)
-
Distinct differences in gut microbial composition and functional potential from lean to morbidly obese subjects.
- 2020
-
Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 288:6, s. 699-710
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction The gut microbiome may contribute to the development of obesity. So far, the extent of microbiome variation in people with obesity has not been determined in large cohorts and for a wide range of body mass index (BMI). Here, we aimed to investigate whether the faecal microbial metagenome can explain the variance in several clinical phenotypes associated with morbid obesity. Methods Caucasian subjects were recruited at our hospital. Blood pressure and anthropometric measurements were taken. Dietary intake was determined using questionnaires. Shotgun metagenomic sequencing was performed on faecal samples from 177 subjects. Results Subjects without obesity (n = 82, BMI 24.7 +/- 2.9 kg m(-2)) and subjects with obesity (n = 95, BMI 38.6 +/- 5.1 kg m(-2)) could be clearly distinguished based on microbial composition and microbial metabolic pathways. A total number of 52 bacterial species differed significantly in people with and without obesity. Independent of dietary intake, we found that microbial pathways involved in biosynthesis of amino acids were enriched in subjects with obesity, whereas pathways involved in the degradation of amino acids were depleted. Machine learning models showed that more than half of the variance in body fat composition followed by BMI could be explained by the gut microbiome composition and microbial metabolic pathways, compared to 6% of variation explained in triglycerides and 9% in HDL. Conclusion Based on the faecal microbiota composition, we were able to separate subjects with and without obesity. In addition, we found strong associations between gut microbial amino acid metabolism and specific microbial species in relation to clinical features of obesity.
|
|
| 3. |
- Vieira-Silva, S., et al.
(författare)
-
Statin therapy is associated with lower prevalence of gut microbiota dysbiosis
- 2020
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 581:7808, s. 310-315
-
Tidskriftsartikel (refereegranskat)abstract
- Microbiome community typing analyses have recently identified the Bacteroides2 (Bact2) enterotype, an intestinal microbiota configuration that is associated with systemic inflammation and has a high prevalence in loose stools in humans1,2. Bact2 is characterized by a high proportion of Bacteroides, a low proportion of Faecalibacterium and low microbial cell densities1,2, and its prevalence varies from 13% in a general population cohort to as high as 78% in patients with inflammatory bowel disease2. Reported changes in stool consistency3 and inflammation status4 during the progression towards obesity and metabolic comorbidities led us to propose that these developments might similarly correlate with an increased prevalence of the potentially dysbiotic Bact2 enterotype. Here, by exploring obesity-associated microbiota alterations in the quantitative faecal metagenomes of the cross-sectional MetaCardis Body Mass Index Spectrum cohort (n=888), we identify statin therapy as a key covariate of microbiome diversification. By focusing on a subcohort of participants that are not medicated with statins, we find that the prevalence of Bact2 correlates with body mass index, increasing from 3.90% in lean or overweight participants to 17.73% in obese participants. Systemic inflammation levels in Bact2-enterotyped individuals are higher than predicted on the basis of their obesity status, indicative of Bact2 as a dysbiotic microbiome constellation. We also observe that obesity-associated microbiota dysbiosis is negatively associated with statin treatment, resulting in a lower Bact2 prevalence of 5.88% in statin-medicated obese participants. This finding is validated in both the accompanying MetaCardis cardiovascular disease dataset (n = 282) and the independent Flemish Gut Flora Project population cohort (n=2,345). The potential benefits of statins in this context will require further evaluation in a prospective clinical trial to ascertain whether the effect is reproducible in a randomized population and before considering their application as microbiota-modulating therapeutics. © 2020, The Author(s), under exclusive licence to Springer Nature Limited.
|
|
