Recent analyses of ribosomal RNA sequence diversity have demonstrated the extent of bacterial diversity in the human colon, and have provided new tools for monitoring changes in the composition of ...the gut microbial community. There is now an excellent opportunity to correlate ecological niches and metabolic activities with particular phylogenetic groups among the microbiota of the human gut. Bacteria that associate closely with particulate material and surfaces in the gut include specialized primary degraders of insoluble substrates, including resistant starch, plant structural polysaccharides and mucin. Butyrate-producing bacteria found in human faeces belong mainly to the clostridial clusters IV and XIVa. In vitro and in vivo evidence indicates that a group related to Roseburia and Eubacterium rectale plays a major role in mediating the butyrogenic effect of fermentable dietary carbohydrates. Additional cluster XIVa species can convert lactate to butyrate, while some members of the clostridial cluster IX convert lactate to propionate. The metabolic outputs of the gut microbial community depend not only on available substrate, but also on the gut environment, with pH playing a major role. Better understanding of the colonic microbial ecosystem will help to explain and predict the effects of dietary additives, including nondigestible carbohydrates, probiotics and prebiotics.
Background: It has been proposed that the development of obesity in humans is influenced by the relative proportions of the two major phyla of bacteria (Bacteroidetes and Firmicutes) present in the ...large intestine. Objective: To examine the relationships between body mass index, weight loss and the major bacterial groups detected in fecal samples. Design: Major groups of fecal bacteria were monitored using fluorescent in situ hybridization (FISH) in obese and non-obese subjects under conditions of weight maintenance, and in obese male volunteers undergoing weight loss on two different reduced carbohydrate weight-loss diets given successively for 4 weeks each. Results: We detected no difference between obese and non-obese individuals in the proportion of Bacteroidetes measured in fecal samples, and no significant change in the percentage of Bacteroidetes in feces from obese subjects on weight loss diets. Significant diet-dependent reductions in a group of butyrate-producing Firmicutes were, however, detected in fecal samples from obese subjects on weight loss diets. Conclusions: Diets designed to achieve weight loss in obese subjects can significantly alter the species composition of the gut microbiota, but we find no evidence that the proportions of Bacteroidetes and Firmicutes among fecal bacteria have a function in human obesity.
Summary
Background
The role of the gut microbiota in patho‐physiology of irritable bowel syndrome (IBS) is suggested by several studies. However, standard cultural and molecular methods used to date ...have not revealed specific and consistent IBS‐related groups of microbes.
Aim
To explore the constipated‐IBS (C‐IBS) gut microbiota using a function‐based approach.
Methods
The faecal microbiota from 14 C‐IBS women and 12 sex‐match healthy subjects were examined through a combined strictly anaerobic cultural evaluation of functional groups of microbes and fluorescent in situ hybridisation (16S rDNA gene targeting probes) to quantify main groups of bacteria. Starch fermentation by C‐IBS and healthy faecal samples was evaluated in vitro.
Results
In C‐IBS, the numbers of lactate‐producing and lactate‐utilising bacteria and the number of H2‐consuming populations, methanogens and reductive acetogens, were at least 10‐fold lower (P < 0.05) compared with control subjects. Concomitantly, the number of lactate‐ and H2‐utilising sulphate‐reducing population was 10 to 100 fold increased in C‐IBS compared with healthy subjects. The butyrate‐producing Roseburia – E. rectale group was in lower number (0.01 < P < 0.05) in C‐IBS than in control. C‐IBS faecal microbiota produced more sulphides and H2 and less butyrate from starch fermentation than healthy ones.
Conclusions
A major functional dysbiosis was observed in constipated‐irritable bowel syndrome gut microbiota, reflecting altered intestinal fermentation. Sulphate‐reducing population increased in the gut of C‐IBS and were accompanied by alterations in other microbial groups. This could be responsible for changes in the metabolic output and enhancement in toxic sulphide production which could in turn influence gut physiology and contribute to IBS pathogenesis.
Knowledge of the composition of the colonic microbiota is important for our understanding of how the balance of these microbes is influenced by diet and the environment, and which bacterial groups ...are important in maintaining gut health or promoting disease. Molecular methodologies have advanced our understanding of the composition and diversity of the colonic microbiota. Importantly, however, it is the continued isolation of bacterial representatives of key groups that offers the best opportunity to conduct detailed metabolic and functional studies. This also permits bacterial genome sequencing which will accelerate the linkage to functionality. Obtaining new human colonic bacterial isolates can be challenging, because most of these are strict anaerobes and many have rather exact nutritional and physical requirements. Despite this many new species are being isolated and described that occupy distinct niches in the colonic microbial community. This review focuses on these under-studied yet important gut anaerobes.
Minimal phenotyping refers to the reliance on the use of a small number of self-reported items for disease case identification, increasingly used in genome-wide association studies (GWAS). Here we ...report differences in genetic architecture between depression defined by minimal phenotyping and strictly defined major depressive disorder (MDD): the former has a lower genotype-derived heritability that cannot be explained by inclusion of milder cases and a higher proportion of the genome contributing to this shared genetic liability with other conditions than for strictly defined MDD. GWAS based on minimal phenotyping definitions preferentially identifies loci that are not specific to MDD, and, although it generates highly predictive polygenic risk scores, the predictive power can be explained entirely by large sample sizes rather than by specificity for MDD. Our results show that reliance on results from minimal phenotyping may bias views of the genetic architecture of MDD and impede the ability to identify pathways specific to MDD.
In 2000, the thematic network ENTRANSFOOD was launched to assess four different topics that are all related to the testing or assessment of food containing or produced from genetically modified ...organisms (GMOs). Each of the topics was linked to a European Commission (EC)-funded large shared cost action (see
http://www.entransfood.com). Since the exchange of genetic information through horizontal (lateral) gene transfer (HGT) might play a more important role, in quantity and quality, than hitherto imagined, a working group dealing with HGT in the context of food and feed safety was established. This working group was linked to the GMOBILITY project (GMOBILITY, 2003) and the results of the deliberations are laid down in this review paper. HGT is reviewed in relation to the potential risks of consuming food or feed derived from transgenic crops. First, the mechanisms for obtaining transgenic crops are described. Next, HGT mechanisms and its possible evolutionary role are described. The use of marker genes is presented in detail as a special case for genes that may pose a risk. Furthermore, the exposure to GMOs and in particular to genetically modified (GM) deoxyribonucleic acid (DNA) is discussed as part of the total risk assessment. The review finishes off with a number of conclusions related to GM food and feed safety. The aim of this paper is to provide a comprehensive overview to assist risk assessors as well as regulators and the general public in understanding the safety issues related to these mechanisms.
Current temperatures in microrefugia may persist longer than in nearby areas as temperatures warm. However, locating and measuring the contribution of microrefugia to thermal inertia in a landscape ...is challenging. We measured the thermal buffering capacity of microrefugia across a 40,000 km2 region of complex mountain topography by quantifying environmental lapse rate and solar radiation effects on air temperature in 0.1 km2 hexagons, a resource management‐relevant scale for climate adaptation. The greatest buffering capacity is −1.62°C, and only 2.8% of the region can buffer 1°C or greater. Historical loss of local cooling capacity is low, but by 2069 only 6.9%–11% of the region retains baseline temperature conditions. This thermal buffer index can find the most climate change‐buffered areas in lands identified as high priority for habitat conservation, wildlife corridors, and forest preservation. Other processes such as cold air pooling can complement our approach but depend on additional factors.
Plain Language Summary
Microrefugia are areas where local climate conditions may persist longer as temperatures warm because of their topographic features, which include the level of solar radiation and the elevation range they contain. Such areas are of conservation interest because their potential to retain current climate conditions longer, as global warming continues may be of particular importance for species with low dispersal capabilities. We modeled these features across a large mountainous region using 10 ha (25 acre) hexagons. The use of a standard size permitted inter‐comparison of 404,700 units to identify their relative capacity to retain their climate conditions from a temporal baseline of 1981–2010. We found that warming between the 1951–1980 and the baseline only affected about 14% of the region. However, by 2069, only 6.9%–11% of the hexagons still retained the conditions from baseline period, and by 2100 less than 1% of the landscape retains the baseline temperature conditions. The identification of hexagons with the most temperature buffering capacity can inform a number of land management and conservation strategies. We illustrate their use in frameworks for preserving vegetation types, landscape connectivity protection, and late seral forest preservation.
Key Points
Species with low dispersal capacity may depend on local microrefugia to persist as temperatures warm
Over a 40,250 km2 area, we found that microrefugia buffering capacity at 10 ha scale is only retained in ∼6.9%–11% of the region by 2069
Quantifying local capacity to retain baseline temperatures can be used in a variety of natural resource strategies for climate adaptation
Aims
Whether and when glomerular filtration rate (GFR) in preterms catches up with term peers is unknown. This study aims to develop a GFR maturation model for (pre)term-born individuals from birth ...to 18 years of age. Secondarily, the function is applied to data of different renally excreted drugs.
Methods
We combined published inulin clearance values and serum creatinine (Scr) concentrations in (pre)term born individuals throughout childhood. Inulin clearance was assumed to be equal to GFR, and Scr to reflect creatinine synthesis rate/GFR. We developed a GFR function consisting of GFR
birth
(GFR at birth), and an Emax model dependent on PNA (with GFR
max
, PNA
50
(PNA at which half of
GFR
max
is reached) and Hill coefficient). The final GFR model was applied to predict gentamicin, tobramycin and vancomycin concentrations.
Result
In the GFR model, GFR
birth
varied with birthweight linearly while in the PNA-based Emax equation, GA was the best covariate for PNA
50
, and current weight for GFR
max
. The final model showed that for a child born at 26 weeks GA, absolute GFR is 18%, 63%, 80%, 92% and 96% of the GFR of a child born at 40 weeks GA at 1 month, 6 months, 1 year, 3 years and 12 years, respectively. PopPK models with the GFR maturation equations predicted concentrations of renally cleared antibiotics across (pre)term-born neonates until 18 years well.
Conclusions
GFR of preterm individuals catches up with term peers at around three years of age, implying reduced dosages of renally cleared drugs should be considered below this age.
Purpose
Despite being off-label, intravenous paracetamol (PCM) is increasingly used to control mild-to-moderate pain in preterm neonates. Here we aim to quantify the maturation of paracetamol ...elimination pathways in preterm neonates born below 32 weeks of gestation.
Methods
Datasets after single dose (rich data) or multiple doses (sparse data) of intravenous PCM dose (median (range)) 9 (3–25) mg/kg were pooled, containing 534 plasma and 44 urine samples of PCM and metabolites (PCM–glucuronide, PCM–sulfate, PCM–cysteine, and PCM–mercapturate) from 143 preterm neonates (gestational age 27.7 (24.0–31.9) weeks, birthweight 985 (462–1,925) g, postnatal age (PNA) 5 (0–30) days, current weight 1,012 (462–1,959) g. Population pharmacokinetic analysis was performed using NONMEM® 7.4.
Results
For a typical preterm neonate (birthweight 985 g; PNA 5 days), PCM clearance was 0.137 L/h, with glucuronidation, sulfation, oxidation and unchanged renal clearance accounting for 5.3%, 73.7%, 16.3% and 4.6%, respectively. Maturational changes in total PCM clearance and its elimination pathways were best described by birthweight and PNA. Between 500–1,500 g birthweight, total PCM clearance increases by 169%, with glucuronidation, sulfation and oxidation clearance increasing by 347%, 164% and 164%. From 1–30 days PNA for 985 g birthweight neonate, total PCM clearance increases by 167%, with clearance via glucuronidation and oxidation increasing by 551%, and sulfation by 69%.
Conclusion
Birthweight and PNA are the most important predictors for maturational changes in paracetamol clearance and its glucuronidation, sulfation and oxidation. As a result, dosing based on bodyweight alone will not lead to consistent paracetamol concentrations among preterm neonates.
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