Microbial−mammalian cometabolites dominate the age-associated urinary metabolic phenotype in Taiwanese and American populations

Understanding the metabolic processes associated with aging is key to developing effective management and treatment strategies for age-related diseases. We investigated the metabolic profiles associated with age in a Taiwanese and an American population. 1H NMR spectral profiles were generated for urine specimens collected from the Taiwanese Social Environment and Biomarkers of Aging Study (SEBAS; n = 857; age 54–91 years) and the Mid-Life in the USA study (MIDUS II; n = 1148; age 35–86 years). Multivariate and univariate linear projection methods revealed some common age-related characteristics in urinary metabolite profiles in the American and Taiwanese populations, as well as some distinctive features. In both cases, two metabolites—4-cresyl sulfate (4CS) and phenylacetylglutamine (PAG)—were positively associated with age. In addition, creatine and β-hydroxy-β-methylbutyrate (HMB) were negatively correlated with age in both populations (p < 4 × 10–6). These age-associated gradients in creatine and HMB reflect decreasing muscle mass with age. The systematic increase in PAG and 4CS was confirmed using ultraperformance liquid chromatography–mass spectrometry (UPLC–MS). Both are products of concerted microbial–mammalian host cometabolism and indicate an age-related association with the balance of host–microbiome metabolism.

Environmentally-acquired bacteria influence microbial diversity and natural innate immune responses at gut surfaces

Background: Early microbial colonization of the gut reduces the incidence of infectious, inflammatory and autoimmune diseases. Recent population studies reveal that childhood hygiene is a significant risk factor for development of inflammatory bowel disease, thereby reinforcing the hygiene hypothesis and the potential importance of microbial colonization during early life. The extent to which early-life environment impacts on microbial diversity of the adult gut and subsequent immune processes has not been comprehensively investigated thus far. We addressed this important question using the pig as a model to evaluate the impact of early-life environment on microbe/host gut interactions during development. Results: Genetically-related piglets were housed in either indoor or outdoor environments or in experimental isolators. Analysis of over 3,000 16S rRNA sequences revealed major differences in mucosa-adherent microbial diversity in the ileum of adult pigs attributable to differences in earlylife environment. Pigs housed in a natural outdoor environment showed a dominance of Firmicutes, in particular Lactobacillus, whereas animals housed in a hygienic indoor environment had reduced Lactobacillus and higher numbers of potentially pathogenic phylotypes. Our analysis revealed a strong negative correlation between the abundance of Firmicutes and pathogenic bacterial populations in the gut. These differences were exaggerated in animals housed in experimental isolators. Affymetrix microarray technology and Real-time Polymerase Chain Reaction revealed significant gut-specific gene responses also related to early-life environment. Significantly, indoorhoused pigs displayed increased expression of Type 1 interferon genes, Major Histocompatibility Complex class I and several chemokines. Gene Ontology and pathway analysis further confirmed these results.

Selected wheat seed defense proteins exhibit competitive binding to model microbial lipid interfaces

Puroindolines (Pins) and purothionins (Pths) are basic, amphiphilic, cysteine-rich wheat proteins that play a role in plant defense against microbial pathogens. We have examined the co-adsorption and sequential addition of Pins (Pin-a, Pin-b and a mutant form of Pin-b with Trp-44 to Arg-44 substitution) and β-purothionin (β-Pth) model anionic lipid layers, using a combination of surface pressure measurements, external reflection FTIR spectroscopy and neutron reflectometry. Results highlighted differences in the protein binding mechanisms, and in the competitive binding and penetration of lipid layers between respective Pins and β-Pth. Pin-a formed a blanket-like layer of protein below the lipid surface that resulted in the reduction or inhibition of β-Pth penetration of the lipid layer. Wild-type Pin-b participated in co-operative binding with β-Pth, whereas the mutant Pin-b did not bind to the lipid layer in the presence of β-Pth. The results provide further insight into the role of hydrophobic and cationic amino acid residues in antimicrobial activity.

The role of soil microbes in the global carbon cycle: tracking the below-ground microbial processing of plant-derived carbon for manipulating carbon dynamics in agricultural systems.

It is well known that atmospheric concentrations of carbon dioxide (CO2) (and other greenhouse gases) have increased markedly as a result of human activity since the industrial revolution. It is perhaps less appreciated that natural and managed soils are an important source and sink for atmospheric CO2 and that, primarily as a result of the activities of soil microorganisms, there is a soil-derived respiratory flux of CO2 to the atmosphere that overshadows by tenfold the annual CO2 flux from fossil fuel emissions. Therefore small changes in the soil carbon cycle could have large impacts on atmospheric CO2 concentrations. Here we discuss the role of soil microbes in the global carbon cycle and review the main methods that have been used to identify the microorganisms responsible for the processing of plant photosynthetic carbon inputs to soil. We discuss whether application of these techniques can provide the information required to underpin the management of agro-ecosystems for carbon sequestration and increased agricultural sustainability. We conclude that, although crucial in enabling the identification of plant-derived carbon-utilising microbes, current technologies lack the high-throughput ability to quantitatively apportion carbon use by phylogentic groups and its use efficiency and destination within the microbial metabolome. It is this information that is required to inform rational manipulation of the plant–soil system to favour organisms or physiologies most important for promoting soil carbon storage in agricultural soil.

Long-term cultivation-independent microbial diversity analysis demonstrates that bacterial communities infecting the adult cystic fibrosis lung show stability and resilience.

Whilst not true in all cases, the microbial communities that chronically infect the airways of patients with CF can vary little over a year despite antibiotic perturbation. The species present tended to vary more between than within subjects, suggesting that each CF airway infection is unique, with relatively stable and resilient bacterial communities. The inverse relationship between community richness and disease severity is similar to findings reported in other mucosal infections.

Mammalian-microbial cometabolism of L-Carnitine in the context of atherosclerosis

g-butyrobetaine has long been known as the precursor of endogenous L-carnitine synthesis. In this issue, Koeth et al. (2014) demonstrate that it is also a major metabolite of L-carnitine degradation by gut bacteria that precedes the enteric production of trimethylamine and trimethylamine-N-oxide.

Intra-tumor heterogeneity: lessons from microbial evolution and clinical implications

Multiple subclonal populations of tumor cells can coexist within the same tumor. This intra-tumor heterogeneity will have clinical implications and it is therefore important to identify factors that drive or suppress such heterogeneous tumor progression. Evolutionary biology can provide important insights into this process. In particular, experimental evolution studies of microbial populations, which exist as clonal populations that can diversify into multiple subclones, have revealed important evolutionary processes driving heterogeneity within a population. There are transferrable lessons that can be learnt from these studies that will help us to understand the process of intra-tumor heterogeneity in the clinical setting. In this review, we summarize drivers of microbial diversity that have been identified, such as mutation rate and environmental influences, and discuss how knowledge gained from microbial experimental evolution studies may guide us to identify and understand important selective factors that promote intra-tumor heterogeneity. Furthermore, we discuss how these factors could be used to direct and optimize research efforts to improve patient care, focusing on therapeutic resistance. Finally, we emphasize the need for longitudinal studies to address the impact of these potential tumor heterogeneity-promoting factors on drug resistance, metastatic potential and clinical outcome.

Microbial community dynamics in the forefield of glaciers

Retreating ice fronts (as a result of a warming climate) expose large expanses of deglaciated forefield, which become colonized by microbes and plants. There has been increasing interest in characterizing the biogeochemical development of these ecosystems using a chronosequence approach. Prior to the establishment of plants, microbes use autochthonously produced and allochthonously delivered nutrients for growth. The microbial community composition is largely made up of heterotrophic microbes (both bacteria and fungi), autotrophic microbes and nitrogen-fixing diazotrophs. Microbial activity is thought to be responsible for the initial build-up of labile nutrient pools, facilitating the growth of higher order plant life in developed soils. However, it is unclear to what extent these ecosystems rely on external sources of nutrients such as ancient carbon pools and periodic nitrogen deposition. Furthermore, the seasonal variation of chronosequence dynamics and the effect of winter are largely unexplored. Modelling this ecosystem will provide a quantitative evaluation of the key processes and could guide the focus of future research. Year-round datasets combined with novel metagenomic techniques will help answer some of the pressing questions in this relatively new but rapidly expanding field, which is of growing interest in the context of future large-scale ice retreat.

Prebiotics modulate the effects of antibiotics on gut microbial diversity and functioning in vitro

Intestinal bacteria carry out many fundamental roles, such as the fermentation of non-digestible dietary carbohydrates to produce short chain fatty acids (SCFAs), which can affect host energy levels and gut hormone regulation. Understanding how to manage this ecosystem to improve human health is an important but challenging goal. Antibiotics are the front line of defence against pathogens, but in turn they have adverse effects on indigenous microbial diversity and function. Here, we have investigated whether dietary supplementation—another method used to modulate gut composition and function—could be used to ameliorate the side effects of antibiotics. We perturbed gut bacterial communities with gentamicin and ampicillin in anaerobic batch cultures in vitro. Cultures were supplemented with either pectin (a non-fermentable fibre), inulin (a commonly used prebiotic that promotes the growth of beneficial bacteria) or neither. Although antibiotics often negated the beneficial effects of dietary supplementation, in some treatment combinations, notably ampicillin and inulin, dietary supplementation ameliorated the effects of antibiotics. There is therefore potential for using supplements to lessen the adverse effects of antibiotics. Further knowledge of such mechanisms could lead to better therapeutic manipulation of the human gut microbiota.

The impact of date palm fruits and their component polyphenols, on gut microbial ecology, bacterial metabolites and colon cancer cell proliferation

The fruit of the date palm (Phoenix dactylifera L.) is a rich source of dietary fibre and polyphenols. We have investigated gut bacterial changes induced by the whole date fruit extract (digested date extract; DDE) and its polyphenol-rich extract (date polyphenol extract; DPE) using faecal, pH-controlled, mixed batch cultures mimicking the distal part of the human large intestine, and utilising an array of microbial group-specific 16S rRNA oligonucleotide probes. Fluorescence microscopic enumeration indicated that there was a significant increase in the growth of bifidobacteria in response to both treatments, whilst whole dates also increased bacteroides at 24 h and the total bacterial counts at later fermentation time points when compared with DPE alone. Bacterial metabolism of whole date fruit led to the production of SCFA, with acetate significantly increasing following bacterial incubation with DDE. In addition, the production of flavonoid aglycones (myricetin, luteolin, quercetin and apigenin) and the anthocyanidin petunidin in less than 1 h was also observed. Lastly, the potential of DDE, DPE and metabolites to inhibit Caco-2 cell growth was investigated, indicating that both were capable of potentially acting as antiproliferative agents in vitro, following a 48 h exposure. This potential to inhibit growth was reduced following fermentation. Together these data suggest that consumption of date fruits may enhance colon health by increasing beneficial bacterial growth and inhibiting the proliferation of colon cancer cells. This is an early suggestion that date intake by humans may aid in the maintenance of bowel health and even the reduction of colorectal cancer development.

Terrestrial exposure of oilfield flowline additives diminish soil structural stability and remediative microbial function

Onshore oil production pipelines are major installations in the petroleum industry, stretching many thousands of kilometres worldwide which also contain flowline additives. The current study focuses on the effect of the flowline additives on soil physico-chemical and biological properties and quantified the impact using resilience and resistance indices. Our findings are the first to highlight deleterious effect of flowline additives by altering some fundamental soil properties, including a complete loss of structural integrity of the impacted soil and a reduced capacity to degrade hydrocarbons mainly due to: (i) phosphonate salts (in scale inhibitor) prevented accumulation of scale in pipelines but also disrupted soil physical structure; (ii) glutaraldehyde (in biocides) which repressed microbial activity in the pipeline and reduced hydrocarbon degradation in soil upon environmental exposure; (iii) the combinatory effects of these two chemicals synergistically caused severe soil structural collapse and disruption of microbial degradation of petroleum hydrocarbons.