The importance of organic aerosol particles in the environment has been long established, influencing cloud formation and lifetime, absorbing and scattering sunlight, affecting atmospheric ...composition and impacting on human health. Conventionally, ambient organic particles were considered to exist as liquids. Recent observations in field measurements and studies in the laboratory suggest that they may instead exist as highly viscous semi-solids or amorphous glassy solids under certain conditions, with important implications for atmospheric chemistry, climate and air quality. This review explores our understanding of aerosol particle phase, particularly as identified by measurements of the viscosity of organic particles, and the atmospheric implications of phase state.
Propolis has abundant polyphenolic constituents and is used widely as a health/functional food. Here, we investigated the effects of polyphenol-rich propolis extracts (PPE) on intestinal barrier ...function in human intestinal epithelial Caco-2 cells, as well as in rats. In Caco-2 cells, PPE increased transepithelial electrical resistance and decreased lucifer yellow flux. PPE-treated cells showed increased expression of the tight junction (TJ) loci occludin and zona occludens (ZO)-1. Confocal microscopy showed organized expressions in proteins related to TJ assembly, i.e., occludin and ZO-1, in response to PPE. Furthermore, PPE led to the activation of AMPK, ERK1/2, p38, and Akt. Using selective inhibitors, we found that the positive effects of PPE on barrier function were abolished in cells in which AMPK and ERK1/2 signaling were inhibited. Moreover, rats fed a diet supplemented with PPE (0.3% in the diet) exhibited increased colonic epithelium ZO-1 expression. Overall, these data suggest that PPE strengthens intestinal barrier function by activating AMPK and ERK signaling and provide novel insights into the potential application of propolis for human gut health.
Colorectal cancer (CRC) is a leading cause of preventable cancer deaths worldwide, with dietary factors being recognised as key risk modifiers. Foods containing dietary fibre are protective to a ...degree that the World Cancer Research Fund classifies the evidence supporting their consumption as 'convincing'. The mechanisms by which fibre components protect against CRC remain poorly understood, especially their interactions with the gut microbiome. Fibre is a composite of indigestible plant polysaccharides and it is emerging that fermentable fibres, including resistant starch (RS), are particularly important. RS fermentation induces SCFA production, in particular, relatively high butyrate levels, and in vitro studies have shown that this acid has strong anti-tumorigenic properties. Butyrate inhibits proliferation and induces apoptosis of CRC cell lines at physiological concentrations. These effects are attributed to butyrate's ability to alter gene transcription by inhibiting histone deacetylase activity. However, the more recent discovery of G-protein coupled receptors that bind butyrate and other SCFA and data obtained from proteomic and genomic experiments suggest that alternative pathways are involved. Here, we review the mechanisms involved in butyrate-induced apoptosis in CRC cells and, additionally, the potential role this SCFA may play in mediating key processes in tumorigenesis including genomic instability, inflammation and cell energy metabolism. This discussion may help to inform the development of strategies to lower CRC risk at the individual and population levels.
The human gut is colonized with a wide variety of microorganisms, including species, such as those belonging to the bacterial genus Bifidobacterium, that have beneficial effects on human physiology ...and pathology. Among the most distinctive benefits of bifidobacteria are modulation of host defence responses and protection against infectious diseases. Nevertheless, the molecular mechanisms underlying these effects have barely been elucidated. To investigate these mechanisms, we used mice associated with certain bifidobacterial strains and a simplified model of lethal infection with enterohaemorrhagic Escherichia coli O157:H7, together with an integrated 'omics' approach. Here we show that genes encoding an ATP-binding-cassette-type carbohydrate transporter present in certain bifidobacteria contribute to protecting mice against death induced by E. coli O157:H7. We found that this effect can be attributed, at least in part, to increased production of acetate and that translocation of the E. coli O157:H7 Shiga toxin from the gut lumen to the blood was inhibited. We propose that acetate produced by protective bifidobacteria improves intestinal defence mediated by epithelial cells and thereby protects the host against lethal infection.
Gut commensal microbes shape the mucosal immune system by regulating the differentiation and expansion of several types of T cell. Clostridia, a dominant class of commensal microbe, can induce ...colonic regulatory T (Treg) cells, which have a central role in the suppression of inflammatory and allergic responses. However, the molecular mechanisms by which commensal microbes induce colonic Treg cells have been unclear. Here we show that a large bowel microbial fermentation product, butyrate, induces the differentiation of colonic Treg cells in mice. A comparative NMR-based metabolome analysis suggests that the luminal concentrations of short-chain fatty acids positively correlates with the number of Treg cells in the colon. Among short-chain fatty acids, butyrate induced the differentiation of Treg cells in vitro and in vivo, and ameliorated the development of colitis induced by adoptive transfer of CD4(+) CD45RB(hi) T cells in Rag1(-/-) mice. Treatment of naive T cells under the Treg-cell-polarizing conditions with butyrate enhanced histone H3 acetylation in the promoter and conserved non-coding sequence regions of the Foxp3 locus, suggesting a possible mechanism for how microbial-derived butyrate regulates the differentiation of Treg cells. Our findings provide new insight into the mechanisms by which host-microbe interactions establish immunological homeostasis in the gut.
The viscosity of primary and secondary organic aerosol (SOA) has important implications for the processing of aqueous organic aerosol phases in the atmosphere, their involvement in climate forcing, ...and transboundary pollution. Here we introduce a new thermodynamics-based group-contribution model, which is capable of accurately predicting the dynamic viscosity of a mixture over several orders of magnitude (∼10-3 to >1012 Pa s) as a function of temperature and mixture composition, accounting for the effect of relative humidity on aerosol water content. The mixture viscosity modelling framework builds on the thermodynamic activity coefficient model AIOMFAC (Aerosol Inorganic–Organic Mixtures Functional groups Activity Coefficients) for predictions of liquid mixture non-ideality, including liquid–liquid phase separation, and the calorimetric glass transition temperature model by DeRieux et al. (2018) for pure-component viscosity values of organic components. Comparing this new model with simplified modelling approaches reveals that the group-contribution method is the most accurate in predicting mixture viscosity, although accurate pure-component viscosity predictions (and associated experimental data) are key and one of the main sources of uncertainties in current models, including the model presented here. Nonetheless, we find excellent agreement between the viscosity predictions and measurements for systems in which mixture constituents have a molar mass below 350 g mol−1. As such, we demonstrate the validity of the model in quantifying mixture viscosity for aqueous binary mixtures (glycerol, citric acid, sucrose, and trehalose), aqueous multicomponent mixtures (citric acid plus sucrose and a mixture of nine dicarboxylic acids), and aqueous SOA surrogate mixtures derived from the oxidation of α-pinene, toluene, or isoprene. We also use the model to assess the expected change in SOA particle viscosity during idealized adiabatic air parcel transport from the surface to higher altitudes within the troposphere. This work demonstrates the capability and flexibility of our model in predicting the viscosity for organic mixtures of varying degrees of complexity and its applicability for modelling SOA viscosity over a wide range of temperatures and relative humidities.
Gut dysbiosis might underlie the pathogenesis of type 1 diabetes. In mice of the non-obese diabetic (NOD) strain, we found that key features of disease correlated inversely with blood and fecal ...concentrations of the microbial metabolites acetate and butyrate. We therefore fed NOD mice specialized diets designed to release large amounts of acetate or butyrate after bacterial fermentation in the colon. Each diet provided a high degree of protection from diabetes, even when administered after breakdown of immunotolerance. Feeding mice a combined acetate- and butyrate-yielding diet provided complete protection, which suggested that acetate and butyrate might operate through distinct mechanisms. Acetate markedly decreased the frequency of autoreactive T cells in lymphoid tissues, through effects on B cells and their ability to expand populations of autoreactive T cells. A diet containing butyrate boosted the number and function of regulatory T cells, whereas acetate- and butyrate-yielding diets enhanced gut integrity and decreased serum concentration of diabetogenic cytokines such as IL-21. Medicinal foods or metabolites might represent an effective and natural approach for countering the numerous immunological defects that contribute to T cell-dependent autoimmune diseases.
Detection of bioaerosols, or primary biological aerosol particles (PBAPs), has become increasingly important for a wide variety of research communities and scientific questions. In particular, ...real-time (RT) techniques for autonomous, online detection and characterization of PBAP properties in both outdoor and indoor environments are becoming more commonplace and have opened avenues of research. With advances in technology, however, come challenges to standardize practices so that results are both reliable and comparable across technologies and users. Here, we present a critical review of major RT instrument classes that have been applied to PBAP research, especially with respect to environmental science, allergy monitoring, agriculture, public health, and national security. Eight major classes of RT techniques are covered, including the following: (i) fluorescence spectroscopy, (ii) elastic scattering, microscopy, and holography, (iii) Raman spectroscopy, (iv) mass spectrometry, (v) breakdown spectroscopy, (vi) remote sensing, (vii) microfluidic techniques, and (viii) paired aqueous techniques. For each class of technology we present technical limitations, misconceptions, and pitfalls, and also summarize best practices for operation, analysis, and reporting. The final section of the article presents pressing scientific questions and grand challenges for RT sensing of PBAP as well as recommendations for future work to encourage high-quality results and increased cross-community collaboration.
Commonwealth Scientific and Industrial Research Organization,
Health Sciences and Nutrition, Adelaide,
Australia
Topping, David L. and
Peter M. Clifton.
Short-Chain Fatty Acids and Human Colonic ...Function: Roles of
Resistant Starch and Nonstarch Polysaccharides. Physiol. Rev. 81: 1031-1064, 2001. Resistant starch (RS) is starch and products of its small
intestinal digestion that enter the large bowel. It occurs for various reasons including chemical structure, cooking of food, chemical modification, and food mastication. Human colonic bacteria ferment RS
and nonstarch polysaccharides (NSP; major components of dietary fiber)
to short-chain fatty acids (SCFA), mainly acetate, propionate, and
butyrate. SCFA stimulate colonic blood flow and fluid and electrolyte
uptake. Butyrate is a preferred substrate for colonocytes and appears
to promote a normal phenotype in these cells. Fermentation of some RS
types favors butyrate production. Measurement of colonic fermentation
in humans is difficult, and indirect measures (e.g., fecal samples) or
animal models have been used. Of the latter, rodents appear to be of
limited value, and pigs or dogs are preferable. RS is less effective
than NSP in stool bulking, but epidemiological data suggest that it is
more protective against colorectal cancer, possibly via butyrate. RS is
a prebiotic, but knowledge of its other interactions with the
microflora is limited. The contribution of RS to fermentation and
colonic physiology seems to be greater than that of NSP. However, the
lack of a generally accepted analytical procedure that accommodates the
major influences on RS means this is yet to be established.