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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 -
Open Medicine (Warsaw, Poland) 2019Lower intraluminal colonic pH is an indication for the development of inflammatory bowel disease including active ulcerative colitis. Involvement of intestinal...
Lower intraluminal colonic pH is an indication for the development of inflammatory bowel disease including active ulcerative colitis. Involvement of intestinal sulfate-reducing bacteria in decreasing bowel pH by the production of HS and acetate as well as their sensitivity has never been reported before. The study of the relative pH and survival of Vib-7 by monitoring sulfate reduction parameters was the aim of this work. Monitoring was done through the measurement of bacterial growth (biomass), dissimilatory sulfate reduction parameters: sulfate consumption, lactate oxidation, hydrogen sulfide and acetate production. According to our results, we observed that lower pH (<5) significantly inhibited Vib-7 growth. This inhibition was also noticed when alkaline media (>9 pH) was used, though the reduction was not at the rate as in media with pH of 4. The research indicates that the growth of Vib-7 is inhibited at pH of 4 which is not as low as the pH found in people with severely developed inflammatory bowel diseases such as ulcerative colitis. Certainly the interaction (synergistic effect) between both hydrogen sulfide and acetate accumulation can also play an important etiological role in the development of bowel inflammation in humans and animals.
PubMed: 30775453
DOI: 10.1515/med-2019-0010 -
Nutrients Jan 2019Oral glucosamine sulfate (GS) and chondroitin sulfate (CS), while widely marketed as joint-protective supplements, have limited intestinal absorption and are...
Oral glucosamine sulfate (GS) and chondroitin sulfate (CS), while widely marketed as joint-protective supplements, have limited intestinal absorption and are predominantly utilized by gut microbiota. Hence the effects of these supplements on the gut microbiome are of great interest, and may clarify their mode of action, or explain heterogeneity in therapeutic responses. We conducted a systematic review of animal and human studies reporting the effects of GS or CS on gut microbial composition. We searched MEDLINE, EMBASE, and Scopus databases for journal articles in English from database inception until July 2018, using search terms microbiome, microflora, intestinal microbiota/flora, gut microbiota/flora and glucosamine or chondroitin. Eight original articles reported the effects of GS or CS on microbiome composition in adult humans (four articles) or animals (four articles). Studies varied significantly in design, supplementation protocols, and microbiome assessment methods. There was moderate-quality evidence for an association between CS exposure and increased abundance of genus in the murine and human gut, and low-quality evidence for an association between CS exposure and an increase in species, an increase in family, and a decrease in . We discuss the possible metabolic implications of these changes for the host. For GS, evidence of effects on gut microbiome was limited to one low-quality study. This review highlights the importance of considering the potential influence of oral CS supplements on gut microbiota when evaluating their effects and safety for the host.
Topics: Animals; Bacteria; Chondroitin Sulfates; Gastrointestinal Microbiome; Glucosamine; Humans
PubMed: 30704054
DOI: 10.3390/nu11020294 -
Journal of Immunology (Baltimore, Md. :... Mar 2018Commensal bacteria are critical for physiological functions in the gut, and dysbiosis in the gut may cause diseases. In this article, we report that mice deficient in...
Commensal bacteria are critical for physiological functions in the gut, and dysbiosis in the gut may cause diseases. In this article, we report that mice deficient in cathelin-related antimicrobial peptide (CRAMP) were defective in the development of colon mucosa and highly sensitive to dextran sulfate sodium (DSS)-elicited colitis, as well as azoxymethane-mediated carcinogenesis. Pretreatment of CRAMP mice with antibiotics markedly reduced the severity of DSS-induced colitis, suggesting CRAMP as a limiting factor on dysbiosis in the colon. This was supported by observations that wild-type (WT) mice cohoused with CRAMP mice became highly sensitive to DSS-induced colitis, and the composition of fecal microbiota was skewed by CRAMP deficiency. In particular, several bacterial species that are typically found in oral microbiota, such as , , and , were increased in feces of CRAMP mice and were transferred to WT mice during cohousing. When littermates of CRAMP parents were examined, the composition of the fecal microbiota of WT pups and heterozygous parents was similar. In contrast, although the difference in fecal microbiota between CRAMP and WT pups was small early on after weaning and single mouse housing, there was an increasing divergence with prolonged single housing. These results indicate that CRAMP is critical in maintaining colon microbiota balance and supports mucosal homeostasis, anti-inflammatory responses, and protection from carcinogenesis.
Topics: Animals; Antimicrobial Cationic Peptides; Colitis; Colon; Disease Models, Animal; Feces; Gastrointestinal Microbiome; Homeostasis; Intestinal Mucosa; Mice; Mice, Inbred C57BL; Microbiota; Proteins; Cathelicidins
PubMed: 29440355
DOI: 10.4049/jimmunol.1602073 -
Scientific Reports Sep 2017The aetiology of colic, a functional gastrointestinal disorder in infants, is not yet resolved. Different mechanisms have been suggested involving the gut microbiota and...
The aetiology of colic, a functional gastrointestinal disorder in infants, is not yet resolved. Different mechanisms have been suggested involving the gut microbiota and intermediate metabolites such as lactate. Lactate can be metabolized by lactate-utilizing bacteria (LUB) to form different end-products. Using a functional approach, we hypothesized that H production and accumulation by LUB is associated with the development of colic. The LUB communities in the feces of forty infants, including eight colicky infants, were characterized using a combination of culture- and molecular-based methods, and metabolite concentrations were measured by HPLC. Interactions among LUB strains isolated from feces were investigated with pure and mixed cultures using anaerobic techniques. We emphasized high prevalence of crying, flatulence, colic and positive correlations thereof in the first 3 months of life. Crying infants showed significantly higher ratio of LUB non-sulfate-reducing bacteria (LUB non-SRB) (H-producer), to LUB SRB (H-utilizer) at 3 months. Colicky infants had significantly higher number of H-producing Eubacterium hallii at 2 weeks compared to non-colicky infants. We revealed the function of Desulfovibrio piger and Eubacterium limosum to reduce H accumulation in co-cultures with H-producing Veillonella ratti. Our data suggest that the balance between H-producing and H-utilizing LUB might contribute to colic symptoms.
Topics: Bacteria; Chromatography, High Pressure Liquid; Colic; Dysbiosis; Feces; Female; Gastrointestinal Microbiome; Humans; Hydrogen; Infant; Infant, Newborn; Lactic Acid; Male; Metabolome
PubMed: 28894218
DOI: 10.1038/s41598-017-11509-1 -
Genome Announcements Feb 2017The complete genome sequence of FI11049 was determined. The genome consists of a single circular chromosome of 2,807,531 bp encoding seven rRNA operons, 76 tRNA genes,...
The complete genome sequence of FI11049 was determined. The genome consists of a single circular chromosome of 2,807,531 bp encoding seven rRNA operons, 76 tRNA genes, and 2,535 coding genes.
PubMed: 28209813
DOI: 10.1128/genomeA.01528-16 -
BMC Bioinformatics Sep 2016The explosive growth of microbiome research has yielded great quantities of data. These data provide us with many answers, but raise just as many questions. 16S rDNA-the...
BACKGROUND
The explosive growth of microbiome research has yielded great quantities of data. These data provide us with many answers, but raise just as many questions. 16S rDNA-the backbone of microbiome analyses-allows us to assess α-diversity, β-diversity, and microbe-microbe associations, which characterize the overall properties of an ecosystem. However, we are still unable to use 16S rDNA data to directly assess the microbe-microbe and microbe-environment interactions that determine the broader ecology of that system. Thus, properties such as competition, cooperation, and nutrient conditions remain insufficiently analyzed. Here, we apply predictive community metabolic models of microbes identified with 16S rDNA data to probe the ecology of microbial communities.
RESULTS
We developed a methodology for the large-scale assessment of microbial metabolic interactions (MMinte) from 16S rDNA data. MMinte assesses the relative growth rates of interacting pairs of organisms within a community metabolic network and whether that interaction has a positive or negative effect. Moreover, MMinte's simulations take into account the nutritional environment, which plays a strong role in determining the metabolism of individual microbes. We present two case studies that demonstrate the utility of this software. In the first, we show how diet influences the nature of the microbe-microbe interactions. In the second, we use MMinte's modular feature set to better understand how the growth of Desulfovibrio piger is affected by, and affects the growth of, other members in a simplified gut community under metabolic conditions suggested to be determinant for their dynamics.
CONCLUSION
By applying metabolic models to commonly available sequence data, MMinte grants the user insight into the metabolic relationships between microbes, highlighting important features that may relate to ecological stability, susceptibility, and cross-feeding. These relationships are at the foundation of a wide range of ecological questions that impact our ability to understand problems such as microbially-derived toxicity in colon cancer.
Topics: Bacteria; Metabolic Networks and Pathways; Metabolism; Microbiota; Models, Biological; Software; Species Specificity
PubMed: 27590448
DOI: 10.1186/s12859-016-1230-3