| 1. |
- Cowan, Theresa, et al.
(författare)
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Chronic coffee consumption in the diet-induced obese rat: impact on gut microbiota and serum metabolomics
- 2014
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Ingår i: Journal of Nutritional Biochemistry. - : Elsevier BV. - 0955-2863 .- 1873-4847. ; 25:4, s. 489-495
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Tidskriftsartikel (refereegranskat)abstract
- Epidemiological data confirms a strong negative association between regular coffee consumption and the prevalence of type 2 diabetes. Coffee is initially absorbed in the stomach and small intestine but is further fermented in the colon by gut microbiota. The bioavailability, production and biological activity of coffee polyphenols is modulated, in part, by gut microbiota. The purpose of this study was to determine if chronic coffee consumption could mitigate negative gut microbiota and metabolomic profile changes induced by a high-fat diet. Male Sprague-Dawley rats were randomized to chow (12% kcal fat) or high-fat (60% kcal fat) diet. Each group was further divided into water or caffeinated coffee for 10 weeks. Coffee consumption in high-fat-fed rats was associated with decreased body weight, adiposity, liver triglycerides and energy intake. Despite a more favorable body composition, rats displayed profound systemic insulin resistance, likely due to caffeine. Coffee consumption attenuated the increase in Firmicutes (F)-to-Bacteroidetes (B) ratio and Clostridium Cluster XI normally associated with high-fat feeding but also resulted in augmented levels of Enterobacteria. In the serum metabolome, coffee had a distinct impact, increasing levels of aromatic and circulating short-chain fatty acids while lowering levels of branched-chain amino acids. In summary, coffee consumption is able to alter gut microbiota in high-fat-fed rats although the role of these changes in reducing diabetes risk is unclear given the increased insulin resistance observed with coffee in this study.
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| 2. |
- Hamed, Samira A., et al.
(författare)
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Butyrate reduces adherent-invasive E. coli-evoked disruption of epithelial mitochondrial morphology and barrier function: involvement of free fatty acid receptor 3
- 2023
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Ingår i: Gut microbes. - : TAYLOR & FRANCIS INC. - 1949-0976 .- 1949-0984. ; 15:2
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Tidskriftsartikel (refereegranskat)abstract
- Gut bacteria provide benefits to the host and have been implicated in inflammatory bowel disease (IBD), where adherent-invasive E. coli (AIEC) pathobionts (e.g., strain LF82) are associated with Crohn's disease. E. coli-LF82 causes fragmentation of the epithelial mitochondrial network, leading to increased epithelial permeability. We hypothesized that butyrate would limit the epithelial mitochondrial disruption caused by E. coli-LF82. Human colonic organoids and the T84 epithelial cell line infected with E. coli-LF82 (MOI = 100, 4 h) showed a significant increase in mitochondrial network fission that was reduced by butyrate (10 mM) co-treatment. Butyrate reduced the loss of mitochondrial membrane potential caused by E. coli-LF82 and increased expression of PGC-1$\alpha $alpha mRNA, the master regulator of mitochondrial biogenesis. Metabolomics revealed that butyrate significantly altered E. coli-LF82 central carbon metabolism leading to diminished glucose uptake and increased succinate secretion. Correlating with preservation of mitochondrial network form/function, butyrate reduced E. coli-LF82 transcytosis across T84-cell monolayers. The use of the G-protein inhibitor, pertussis toxin, implicated GPCR signaling as critical to the effect of butyrate, and the free fatty acid receptor three (FFAR3, GPR41) agonist, AR420626, reproduced butyrate's effect in terms of ameliorating the loss of barrier function and reducing the mitochondrial fragmentation observed in E. coli-LF82 infected T84-cells and organoids. These data indicate that butyrate helps maintain epithelial mitochondrial form/function when challenged by E. coli-LF82 and that this occurs, at least in part, via FFAR3. Thus, loss of butyrate-producing bacteria in IBD in the context of pathobionts would contribute to loss of epithelial mitochondrial and barrier functions that could evoke disease and/or exaggerate a low-grade inflammation.
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| 3. |
- Mancini, Nicole L., et al.
(författare)
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Crohns Disease Pathobiont Adherent-Invasive E coli Disrupts Epithelial Mitochondrial Networks With Implications for Gut Permeability
- 2021
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Ingår i: Cellular and molecular gastroenterology and hepatology. - : American Gastroenterological Association. - 2352-345X. ; 11:2, s. 551-571
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Tidskriftsartikel (refereegranskat)abstract
- Background & aims: Adherent-invasive Escherichia coli are implicated in inflammatory bowel disease, and mitochondrial dysfunction has been observed in biopsy specimens from patients with inflammatory bowel disease. As a novel aspect of adherent-invasive E coli-epithelial interaction, we hypothesized that E coli (strain LF82) would elicit substantial disruption of epithelial mitochondrial form and function.Methods: Monolayers of human colon-derived epithelial cell lines were exposed to E coli-LF82 or commensal E coli and RNA sequence analysis, mitochondrial function (adenosine triphosphate synthesis) and dynamics (mitochondrial network imaging, immunoblotting for fission and fusion proteins), and epithelial permeability (transepithelial resistance, flux of fluorescein isothiocyanate-dextran and bacteria) were assessed.Results: E coli-LF82 significantly affected epithelial expression of ∼8600 genes, many relating to mitochondrial function. E coli-LF82-infected epithelia showed swollen mitochondria, reduced mitochondrial membrane potential and adenosine triphosphate, and fragmentation of the mitochondrial network: events not observed with dead E coli-LF82, medium from bacterial cultures, or control E coli. Treatment with Mitochondrial Division Inhibitor 1 (Mdivi1, inhibits dynamin-related peptide 1, guanosine triphosphatase principally responsible for mitochondrial fission) or P110 (prevents dynamin-related peptide 1 binding to mitochondrial fission 1 protein) partially reduced E coli-LF82-induced mitochondrial fragmentation in the short term. E coli-LF82-infected epithelia showed loss of the long isoform of optic atrophy factor 1, which mediates mitochondrial fusion. Mitochondrial Division Inhibitor 1 reduced the magnitude of E coli-LF82-induced increased transepithelial flux of fluorescein isothiocyanate dextran. By 8 hours after infection, increased cytosolic cytochrome C and DNA fragmentation were apparent without evidence of caspase-3 or apoptosis inducing factor activation.Conclusions: Epithelial mitochondrial fragmentation caused by E coli-LF82 could be targeted to maintain cellular homeostasis and mitigate infection-induced loss of epithelial barrier function. Data have been deposited in NCBI's Gene Expression Omnibus and are accessible through GEO series accession numbers GSE154121 and GSE154122 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE154121).
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| 4. |
- Palmnäs, Marie, 1988, et al.
(författare)
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Low-dose aspartame consumption differentially affects gut microbiota-host metabolic interactions in the diet-induced obese rat
- 2014
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203 .- 1932-6203. ; 9:10
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Tidskriftsartikel (refereegranskat)abstract
- Aspartame consumption is implicated in the development of obesity and metabolic disease despite the intention of limiting caloric intake. The mechanisms responsible for this association remain unclear, but may involve circulating metabolites and the gut microbiota. Aims were to examine the impact of chronic low-dose aspartame consumption on anthropometric, metabolic and microbial parameters in a diet-induced obese model. Male Sprague-Dawley rats were randomized into a standard chow diet (CH, 12% kcal fat) or high fat (HF, 60% kcal fat) and further into ad libitum water control (W) or low-dose aspartame (A, 5–7 mg/kg/d in drinking water) treatments for 8 week (n = 10–12 animals/treatment). Animals on aspartame consumed fewer calories, gained less weight and had a more favorable body composition when challenged with HF compared to animals consuming water. Despite this, aspartame elevated fasting glucose levels and an insulin tolerance test showed aspartame to impair insulin-stimulated glucose disposal in both CH and HF, independently of body composition. Fecal analysis of gut bacterial composition showed aspartame to increase total bacteria, the abundance of Enterobacteriaceae and Clostridium leptum. An interaction between HF and aspartame was also observed for Roseburia ssp wherein HF-A was higher than HF-W (P<0.05). Within HF, aspartame attenuated the typical HF-induced increase in the Firmicutes:Bacteroidetes ratio. Serum metabolomics analysis revealed aspartame to be rapidly metabolized and to be associated with elevations in the short chain fatty acid propionate, a bacterial end product and highly gluconeogenic substrate, potentially explaining its negative affects on insulin tolerance. How aspartame influences gut microbial composition and the implications of these changes on the development of metabolic disease require further investigation.
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