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Gut Jan 2021Type 1 diabetes (T1D) is characterised by islet autoimmunity and beta cell destruction. A gut microbiota-immunological interplay is involved in the pathophysiology of... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Type 1 diabetes (T1D) is characterised by islet autoimmunity and beta cell destruction. A gut microbiota-immunological interplay is involved in the pathophysiology of T1D. We studied microbiota-mediated effects on disease progression in patients with type 1 diabetes using faecal microbiota transplantation (FMT).
DESIGN
Patients with recent-onset (<6 weeks) T1D (18-30 years of age) were randomised into two groups to receive three autologous or allogenic (healthy donor) FMTs over a period of 4 months. Our primary endpoint was preservation of stimulated C peptide release assessed by mixed-meal tests during 12 months. Secondary outcome parameters were changes in glycaemic control, fasting plasma metabolites, T cell autoimmunity, small intestinal gene expression profile and intestinal microbiota composition.
RESULTS
Stimulated C peptide levels were significantly preserved in the autologous FMT group (n=10 subjects) compared with healthy donor FMT group (n=10 subjects) at 12 months. Small intestinal was inversely related to residual beta cell function (r=-0.55, p=0.02), whereas plasma metabolites 1-arachidonoyl-GPC and 1-myristoyl-2-arachidonoyl-GPC levels linearly correlated with residual beta cell preservation (rho=0.56, p=0.01 and rho=0.46, p=0.042, respectively). Finally, baseline CD4 +CXCR3+T cell counts, levels of small intestinal and CCL22 and CCL5 gene expression in duodenal biopsies predicted preserved beta cell function following FMT irrespective of donor characteristics.
CONCLUSION
FMT halts decline in endogenous insulin production in recently diagnosed patients with T1D in 12 months after disease onset. Several microbiota-derived plasma metabolites and bacterial strains were linked to preserved residual beta cell function. This study provides insight into the role of the intestinal gut microbiome in T1D.
TRIAL REGISTRATION NUMBER
NTR3697.
Topics: Adolescent; Adult; C-Peptide; Diabetes Mellitus, Type 1; Duodenum; Fecal Microbiota Transplantation; Female; Gastrointestinal Microbiome; Humans; Insulin-Secreting Cells; Male; Transplantation, Autologous; Young Adult
PubMed: 33106354
DOI: 10.1136/gutjnl-2020-322630 -
Biomolecules Jun 2020A comparative study of the kinetic characteristics (specific activity, initial and maximum rate, and affinity for substrates) of key enzymes of assimilatory sulfate...
A comparative study of the kinetic characteristics (specific activity, initial and maximum rate, and affinity for substrates) of key enzymes of assimilatory sulfate reduction (APS reductase and dissimilatory sulfite reductase) in cell-free extracts of sulphate-reducing bacteria (SRB) from various biotopes was performed. The material for the study represented different strains of SRB from various ecotopes. Microbiological (isolation and cultivation), biochemical (free cell extract preparation) and chemical (enzyme activity determination) methods served in defining kinetic characteristics of SRB enzymes. The determined affinity data for substrates (i.e., sulfite) were 10 times higher for SRB strains isolated from environmental (soil) ecotopes than for strains from the human intestine. The maximum rate of APS reductase reached 0.282-0.862 µmol/min×mg of protein that is only 10 to 28% higher than similar initial values. The maximum rate of sulfite reductase for corrosive relevant collection strains and SRB strains isolated from heating systems were increased by 3 to 10 times. A completely different picture was found for the intestinal SRB V in the strains Desulfovibrio piger Vib-7 (0.67 µmol/min × mg protein) and Desulfomicrobium orale Rod-9 (0.45 µmol/min × mg protein). The determinant in the cluster distribution of SRB strains is the activity of the terminal enzyme of dissimilatory sulfate reduction-sulfite reductase, but not APS reductase. The data obtained from the activity of sulfate reduction enzymes indicated the adaptive plasticity of SRB strains that is manifested in the change in enzymatic activity.
Topics: Adenosine Phosphosulfate; Biodegradation, Environmental; Desulfovibrio desulfuricans; Desulfovibrio vulgaris; Hydrogen Sulfide; Oxidoreductases Acting on Sulfur Group Donors
PubMed: 32560561
DOI: 10.3390/biom10060921 -
Frontiers in Cellular and Infection... 2020Gut dysbiosis has been associated with several disease outcomes including diabetes in human populations. Currently, there are no studies of the gut microbiome...
Gut dysbiosis has been associated with several disease outcomes including diabetes in human populations. Currently, there are no studies of the gut microbiome composition in relation to type 2 diabetes (T2D) in Africans. Here, we describe the profile of the gut microbiome in non-diabetic adults (controls) and investigate the association between gut microbiota and T2D in urban West Africans. Gut microbiota composition was determined in 291 Nigerians (98 cases, 193 controls) using fecal 16S V4 rRNA gene sequencing done on the Illumina MiSeq platform. Data analysis of operational taxonomic units (OTU) was conducted to describe microbiome composition and identify differences between T2D and controls. The most abundant phyla were , and . , and were significantly lower in cases than controls ( < 0.001). Feature selection analysis identified a panel of 18 OTUs enriched in cases that included . A panel of 17 OTUs that was enriched in the controls included , and . OTUs with strain-level annotation showing the largest fold-change included (logFC = -3.1; = 4.2 × 10), (logFC = -2.5; = 0.005), (logFC = -1.76; = 0.01), all lower in cases. These findings are notable because supplementation with and has been shown to improve hyperglycemia and reduce insulin resistance in murine models. This first investigation of gut microbiome and diabetes in urban Africans shows that T2D is associated with compositional changes in gut microbiota highlighting the possibility of developing strategies to improve glucose control by modifying bacterial composition in the gut.
Topics: Actinobacteria; Bacteroidetes; Black People; Case-Control Studies; Diabetes Mellitus, Type 2; Dysbiosis; Female; Firmicutes; Gastrointestinal Microbiome; Humans; Hypoglycemic Agents; Male; Metformin; Middle Aged; Nigeria; Urban Health
PubMed: 32158702
DOI: 10.3389/fcimb.2020.00063 -
Journal of Clinical Medicine Jul 2019The small-large intestine axis in hydrogen sulfide accumulation and testing of sulfate and lactate in the gut-gut axis of the intestinal environment has not been well...
UNLABELLED
The small-large intestine axis in hydrogen sulfide accumulation and testing of sulfate and lactate in the gut-gut axis of the intestinal environment has not been well described. Sulfate reducing bacteria (SRB) of the genus reduce sulfate to hydrogen sulfide and can be involved in ulcerative colitis development. The background of the research was to find correlations between hydrogen sulfide production under the effect of an electron acceptor (sulfate) and donor (lactate) at different concentrations and Vib-7 growth, as well as their dissimilatory sulfate reduction in the intestinal small-large intestinal environment.
METHODS
Microbiological, biochemical, and biophysical methods, and statistical processing of the results (principal component and cross-correlation analyses) were used.
RESULTS
Vib-7 showed increased intensity of bacterial growth and hydrogen sulfide production under the following concentrations of sulfate and lactate: 17.4 mM and 35.6 mM, respectively. The study showed in what kind of intestinal environment Vib-7 grows at the highest level and produces the highest amount of hydrogen sulfide.
CONCLUSIONS
The optimum intestinal environment of Vib-7 can serve as a good indicator of the occurrence of inflammatory bowel diseases; meaning that these findings can be broadly used in medicine practice dealing with the monitoring and diagnosis of intestinal ailments.
PubMed: 31330956
DOI: 10.3390/jcm8071054