Many iron (Fe) redox processes that were previously assumed to be purely abiotic, such as photochemical Fe reactions, are now known to also be microbially mediated. Owing to this overlap, discerning ...whether biotic or abiotic processes control Fe redox chemistry is a major challenge for geomicrobiologists and biogeochemists alike. Therefore, to understand the network of reactions within the biogeochemical Fe cycle, it is necessary to determine which abiotic or microbially mediated reactions are dominant under various environmental conditions. In this Review, we discuss the major microbially mediated and abiotic reactions in the biogeochemical Fe cycle and provide an integrated overview of biotic and chemically mediated redox transformations.
The link between the gut microbiota and type 2 diabetes (T2D) warrants further investigation because of known confounding effects from antidiabetic treatment. Here, we profiled the gut microbiota in ...a discovery (n = 1,011) and validation (n = 484) cohort comprising Swedish subjects naive for diabetes treatment and grouped by glycemic status. We observed that overall gut microbiota composition was altered in groups with impaired glucose tolerance, combined glucose intolerance and T2D, but not in those with impaired fasting glucose. In addition, the abundance of several butyrate producers and functional potential for butyrate production were decreased both in prediabetes and T2D groups. Multivariate analyses and machine learning microbiome models indicated that insulin resistance was strongly associated with microbial variations. Therefore, our study indicates that the gut microbiota represents an important modifiable factor to consider when developing precision medicine approaches for the prevention and/or delay of T2D.
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•The overall gut microbiota shifts in parallel with glycemic status in humans•The shifts are observed in the absence of diabetes treatment•The variations strongly associate with insulin resistance, but not fasting glucose•Butyrate-producing bacteria are reduced in prediabetes and type 2 diabetes
Type 2 diabetes is associated with an altered gut microbiota, but the results may have been confounded by metformin medication. Wu et al. now use two populations encompassing almost 1,500 subjects to demonstrate that the gut microbiota is altered in prediabetes and diabetes independent of diabetes medication.
Neutrophilic microbial aerobic oxidation of ferrous iron (Fe(II)) is restricted to pH-circumneutral environments characterized by low oxygen where microaerophilic Fe(II)-oxidizing microorganisms ...successfully compete with abiotic Fe(II) oxidation. However, accumulation of ferric (bio)minerals increases competition by stimulating abiotic surface-catalyzed heterogeneous Fe(II) oxidation. Here, we present an experimental approach that allows quantification of microbial and abiotic contribution to Fe(II) oxidation in the presence or initial absence of ferric (bio)minerals. We found that at 20 μM O2 and the initial absence of Fe(III) minerals, an iron(II)-oxidizing enrichment culture (99.6% similarity to Sideroxydans spp.) contributed 40% to the overall Fe(II) oxidation within approximately 26 h and oxidized up to 3.6 × 10–15 mol Fe(II) cell–1 h–1. Optimum O2 concentrations at which enzymatic Fe(II) oxidation can compete with abiotic Fe(II) oxidation ranged from 5 to 20 μM. Lower O2 levels limited biotic Fe(II) oxidation, while at higher O2 levels abiotic Fe(II) oxidation dominated. The presence of ferric (bio)minerals induced surface-catalytic heterogeneous abiotic Fe(II) oxidation and reduced the microbial contribution to Fe(II) oxidation from 40% to 10% at 10 μM O2. The obtained results will help to better assess the impact of microaerophilic Fe(II) oxidation on the biogeochemical iron cycle in a variety of environmental natural and anthropogenic settings.
Interactions between the gut microbiota, diet, and the host potentially contribute to the development of metabolic diseases. Here, we identify imidazole propionate as a microbially produced ...histidine-derived metabolite that is present at higher concentrations in subjects with versus without type 2 diabetes. We show that imidazole propionate is produced from histidine in a gut simulator at higher concentrations when using fecal microbiota from subjects with versus without type 2 diabetes and that it impairs glucose tolerance when administered to mice. We further show that imidazole propionate impairs insulin signaling at the level of insulin receptor substrate through the activation of p38γ MAPK, which promotes p62 phosphorylation and, subsequently, activation of mechanistic target of rapamycin complex 1 (mTORC1). We also demonstrate increased activation of p62 and mTORC1 in liver from subjects with type 2 diabetes. Our findings indicate that the microbial metabolite imidazole propionate may contribute to the pathogenesis of type 2 diabetes.
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•Imidazole propionate levels are increased in subjects with type 2 diabetes (T2D)•Imidazole propionate is produced from histidine by T2D-associated bacteria•Imidazole propionate impairs glucose tolerance and insulin signaling•Imidazole propionate inhibits IRS via activation of p38γ/p62/mTORC1
Imidazole propionate, a metabolite produced by the gut microbiota, is elevated in type 2 diabetes and can directly impair glucose tolerance and insulin signaling.
Summary
Iron is the most abundant redox‐active metal in the Earth's crust. The one electron transfer between the two most common redox states, Fe(II) and Fe(III), plays a role in a huge range of ...environmental processes from mineral formation and dissolution to contaminant remediation and global biogeochemical cycling. It has been appreciated for more than a century that microorganisms can harness the energy of this Fe redox transformation for their metabolic benefit. However, this is most widely understood for anaerobic Fe(III)‐reducing or aerobic and microaerophilic Fe(II)‐oxidizing bacteria. Only in the past few decades have we come to appreciate that bacteria also play a role in the anaerobic oxidation of ferrous iron, Fe(II), and thus can act to form Fe(III) minerals in anoxic settings. Since this discovery, our understanding of the ecology of these organisms, their mechanisms of Fe(II) oxidation and their role in environmental processes has been increasing rapidly. In this article, we bring these new discoveries together to review the current knowledge on these environmentally important bacteria, and reveal knowledge gaps for future research.
The Danish Registry of Diabetic Retinopathy includes information from >200 000 patients who attends diabetic retinopathy (DR) screening in Denmark. Screening of patients with uncomplicated type 2 ...diabetes is often performed by practicing ophthalmologists, while patients with type 1 and complicated type 2 diabetes attends screening at hospitals. We performed a clinical reliability study of retinal images from Danish screening facilities to explore the inter-grader agreement between the primary screening ophthalmologist and a blinded, certified grader.
Invitations to participate were sent to screening facilities across Denmark. The primary grader uploaded fundus photographs with information on estimated level of DR (International Clinical Diabetic Retinopathy scale as 0 no DR, 1-3 mild, moderate or severe nonproliferative DR {NPDR}, or 4 proliferative DR {PDR}), region of screening, image style, and screening facility. Images were then regraded by a blinded, certified, secondary grader. Weighted kappa analysis was performed to evaluate agreement.
Fundus photographs from 230 patients (458 eyes) were received from practicing ophthalmologists (52.6%) and hospital-based grading centres (47.4%) from all Danish regions. Reported levels of DR by the primary graders were 66.8%, 12.2%, 13.1%, 1.3% and 5.5% for DR levels 0-4. The overall agreement between primary and secondary graders was 93% (κ = 0.83). Based on screening facility agreement was 96% (κ = 0.89) and 90% (κ = 0.76) for practicing ophthalmologists and hospital-based graders.
In this nationwide study, we observed a high overall inter-grader agreement and based on this, it is reasonable to assume that reported DR gradings in the screening programme in Denmark, accurately reflect the truth.
Purpose
A number of algorithms have been developed to calculate screening intervals for diabetic retinopathy on the basis of individual risk factors. However, these approaches have not considered ...proliferative diabetic retinopathy (PDR) and diabetic macular oedema (DME) as separate end points and death as competing risk.
Methods
A multi‐state survival model with death as competing risk was used to predict the screening interval for diabetic retinopathy based on information about all 2446 patients from a well‐defined population who had started treatment for either PDR or DME during 25 years. The performance of the model was tested on the existing database and at seven screening sites on patients who had not developed a treatment requiring condition.
Results
Testing on the existing database showed that at a risk level of 2% the algorithm could predict a screening interval with a success rate higher than 90% and a 1.75 times average prolongation of the screening interval without failing to detect the development of verified PDR og DME. The model was limited to a diabetes duration shorter than 40 years and depended on knowledge of relevant risk factors. At the other participating screening sites the algorithm predicted shorter intervals than the screener.
Conclusions
Algorithms for individualised screening for diabetic retinopathy can prolong screening intervals without losing patients who develop a vision threatening condition. The calculation of screening intervals requires access to relevant risk factors and should be developed on large data sets that reflect the population in which the algorithm should be used.
Nitrate-reducing iron(II)-oxidizing bacteria have been known for approximately 20 years. There has been much debate as to what extent the reduction of nitrate and the oxidation of ferrous iron are ...coupled via enzymatic pathways or via abiotic processes induced by nitrite formed by heterotrophic denitrification. The aim of the present study was to assess the coupling of nitrate reduction and iron(II) oxidation by monitoring changes in substrate concentrations, as well as in the activity of nitrate-reducing bacteria in natural littoral freshwater sediment, in response to stimulation with nitrate and iron(II). In substrate-amended microcosms, we found that the biotic oxidation of ferrous iron depended on the simultaneous microbial reduction of nitrate. Additionally, the abiotic oxidation of ferrous iron by nitrite in sterilized sediment was not fast enough to explain the iron oxidation rates observed in microbially active sediment. Furthermore, the expression levels of genes coding for enzymes crucial for nitrate reduction were in some setups stimulated by the presence of ferrous iron. These results indicate that there is a direct influence of ferrous iron on bacterial denitrification and support the hypothesis that microbial nitrate reduction is stimulated by biotic iron(II) oxidation.
The coupling of nitrate reduction and Fe(II) oxidation affects the environment at a local scale, e.g., by changing nutrient or heavy metal mobility in soils due to the formation of Fe(III) minerals, as well as at a global scale, e.g., by the formation of the primary greenhouse gas nitrous oxide. Although the coupling of nitrate reduction and Fe(II) oxidation was reported 20 years ago and has been studied intensively since then, the underlying mechanisms still remain unknown. One of the main knowledge gaps is the extent of enzymatic Fe(II) oxidation coupled to nitrate reduction, which has frequently been questioned in the literature. In the present study, we provide evidence for microbially mediated nitrate-reducing Fe(II) oxidation in freshwater sediments. This evidence is based on the rates of nitrate reduction and Fe(II) oxidation determined in microcosm incubations and on the effect of iron on the expression of genes required for denitrification.
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