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Human exposure to persistent, nonbiological nanoparticles and microparticles via the oral route is continuous and large scale (10 12 -10 13 particles per day per adult in Europe). Whether this matters or not is unknown but confirmed health risks with airborne particle exposure warns against complacency. Murine models of oral exposure will help to identify risk but, to date, lack validation or relevance to humans. This work addresses that gap. It reports i) on a murine diet, modified with differing concentrations of the common dietary particle, food grade titanium dioxide (fgTiO 2 ), an additive of polydisperse form that contains micro- and nano-particles, ii) that these diets deliver particles to basal cells of intestinal lymphoid follicles, exactly as is reported as a "normal occurrence" in humans, iii) that confocal reflectance microscopy is the method of analytical choice to determine this, and iv) that food intake, weight gain, and Peyer's patch immune cell profiles, up to 18 weeks of feeding, do not differ between fgTiO 2 -fed groups or controls. These findings afford a human-relevant and validated oral dosing protocol for fgTiO 2 risk assessment as well as provide a generalized platform for application to oral exposure studies with nano- and micro-particles., (© 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Pigment-grade titanium dioxide (TiO 2 ) particles are an additive to some foods (E171 on ingredients lists), toothpastes, and pharma-/nutraceuticals and are absorbed, to some extent, in the human intestinal tract. TiO 2 can act as a modest adjuvant in the secretion of the pro-inflammatory cytokine interleukin 1β (IL-1β) when triggered by common intestinal bacterial fragments, such as lipopolysaccharide (LPS) and/or peptidoglycan. Given the variance in human genotypes, which includes variance in genes related to IL-1β secretion, we investigated whether TiO 2 particles might, in fact, be more potent pro-inflammatory adjuvants in cells that are genetically susceptible to IL-1β-related inflammation., Methods: We studied bone marrow-derived macrophages from mice with a mutation in the nucleotide-binding oligomerisation domain-containing 2 gene (Nod2 m/m ), which exhibit heightened secretion of IL-1β in response to the peptidoglycan fragment muramyl dipeptide (MDP). To ensure relevance to human exposure, TiO 2 was food-grade anatase (119 ± 45 nm mean diameter ± standard deviation). We used a short 'pulse and chase' format: pulsing with LPS and chasing with TiO 2 +/- MDP or peptidoglycan., Results: IL-1β secretion was not stimulated in LPS-pulsed bone marrow-derived macrophages, or by chasing with MDP, and only very modestly so by chasing with peptidoglycan. In all cases, however, IL-1β secretion was augmented by chasing with TiO 2 in a dose-dependent fashion (5-100 μg/mL). When co-administered with MDP or peptidoglycan, IL-1β secretion was further enhanced for the Nod2 m/m genotype. Tumour necrosis factor α was triggered by LPS priming, and more so for the Nod2 m/m genotype. This was enhanced by chasing with TiO 2 , MDP, or peptidoglycan, but there was no additive effect between the bacterial fragments and TiO 2 ., Conclusion: Here, the doses of TiO 2 that augmented bacterial fragment-induced IL-1β secretion were relatively high. In vivo, however, selected intestinal cells appear to be loaded with TiO 2 , so such high concentrations may be 'exposure-relevant' for localised regions of the intestine where both TiO 2 and bacterial fragment uptake occurs. Moreover, this effect is enhanced in cells from Nod2 m/m mice indicating that genotype can dictate inflammatory signalling in response to (nano)particle exposure. In vivo studies are now merited.

Perceptions of production methods for organic and conventional milk are changing, with consumers prepared to pay premium prices for milk from either certified organic or conventional grass-fed cows. Our study investigated whether chemical composition differed between milk produced by these two farming systems. Sampling was conducted on two farms sets, each comprised of one organic and one conventional farm. All farms applied year-round pasture grazing. Milk samples were collected throughout the milking season and analysed for free oligosaccharides, fatty acids, major casein and whey proteins, and milk fat volatiles. Fatty acids were influenced by breed and fertilizer application. Oligosaccharides differed between farming systems, with causes presently unknown, while farm set was the dominant influence factor on protein composition. Factors identified in this study influencing milk composition are not exclusive to either farming system, and pasture feeding conventional cows will remove differences previously reported for organic and conventionally produced milk., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

A bovine milk oligosaccharide (BMO) library, prepared from cow colostrum, with 34 structures was generated and used to rapidly screen oligosaccharides in domestic animal milks and a whey permeate powder. The novel library was entered into a custom Personal Compound Database and Library (PCDL) and included accurate mass, retention time, and tandem mass spectra. Oligosaccharides in minute-sized samples were separated using nanoliquid chromatography (nanoLC) coupled to a high resolution and sensitive quadrupole-Time of Flight (Q-ToF) MS system. Using the PCDL, 18 oligosaccharides were found in a BMO-enriched product obtained from whey permeate processing. The usefulness of the analytical system and BMO library was further validated using milks from domestic sheep and buffaloes. Through BMO PCDL searching, 15 and 13 oligosaccharides in the BMO library were assigned in sheep and buffalo milks, respectively, thus demonstrating significant overlap between oligosaccharides in bovine (cow and buffalo) and ovine (sheep) milks. This method was shown to be an efficient, reliable, and rapid tool to identify oligosaccharide structures using automated spectral matching.

Ruminant animals contribute significantly to the global value of agriculture and rely on a complex microbial community for efficient digestion. However, little is known of how this microbial-host relationship develops and is maintained. To begin to address this, we have determined the ability of three Bifidobacterium species isolated from the faeces of newborn calves to grow on carbohydrates typical of a newborn ruminant diet. Genome sequences have been determined for these bacteria with analysis of the genomes providing insights into the host association and identification of several genes that may mediate interactions with the ruminant gastrointestinal tract. The present study provides a starting point from which we can define the role of potential beneficial microbes in the nutrition of young ruminants and begin to influence the interactions between the microbiota and the host. The differences observed in genomic content hint at niche partitioning among the bifidobacterial species analysed and the different strategies they employ to successfully adapt to this habitat.

Differing amounts of fresh forage and concentrates fed, and level of input contributes to the differences reported in fatty acid (FA) composition of organic and conventionally produced cow milk. In many previous studies designed to investigate this phenomenon, comparisons were made between grazed organic cows and housed conventional cows. In the present study, we have investigated differences between organic and conventional milk produced using year-round pasture grazing, as practiced in New Zealand. The FA composition was determined in milk sampled at morning and evening milking in both spring and autumn. Samples were taken from 45 cows from the Massey University organic herd and compared with 50 cows from the corresponding conventional herd grazed and managed similarly at the same location. Forty-three out of 51 analyzed FA were influenced by season, whereas 28 were different between production systems. In addition, one-half were also different due to time of milking. Levels of linoleic acid and α-linolenic acid were higher in organic milk, whereas conjugated linoleic acid (CLA) and vaccenic acid were higher in conventional milk. The first 3 FA (linoleic acid, α-linolenic acid, and CLA) were more abundant in milk harvested during autumn, and the CLA concentration was also significantly influenced by time of milking. Our results confirm reports that the FA profile is affected by season and time of milking, and we also showed an effect due to the production system, when both sets of cows were kept continuously on pasture, even after taking milking time and seasonal effect into account., (Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Consumer perception of organic cow milk is associated with the assumption that organic milk differs from conventionally produced milk. The value associated with this difference justifies the premium retail price for organic milk. It includes the perceptions that organic dairy farming is kinder to the environment, animals, and people; that organic milk products are produced without the use of antibiotics, added hormones, synthetic chemicals, and genetic modification; and that they may have potential benefits for human health. Controlled studies investigating whether differences exist between organic and conventionally produced milk have so far been largely equivocal due principally to the complexity of the research question and the number of factors that can influence milk composition. A main complication is that farming practices and their effects differ depending on country, region, year, and season between and within organic and conventional systems. Factors influencing milk composition (e.g., diet, breed, and stage of lactation) have been studied individually, whereas interactions between multiple factors have been largely ignored. Studies that fail to consider that factors other than the farming system (organic vs. conventional) could have caused or contributed to the reported differences in milk composition make it impossible to determine whether a system-related difference exists between organic and conventional milk. Milk fatty acid composition has been a central research area when comparing organic and conventional milk largely because the milk fatty acid profile responds rapidly and is very sensitive to changes in diet. Consequently, the effect of farming practices (high input vs. low input) rather than farming system (organic vs. conventional) determines milk fatty acid profile, and similar results are seen between low-input organic and low-input conventional milks. This confounds our ability to develop an analytical method to distinguish organic from conventionally produced milk and provide product verification. Lack of research on interactions between several influential factors and differences in trial complexity and consistency between studies (e.g., sampling period, sample size, reporting of experimental conditions) complicate data interpretation and prevent us from making unequivocal conclusions. The first part of this review provides a detailed summary of individual factors known to influence milk composition. The second part presents an overview of studies that have compared organic and conventional milk and discusses their findings within the framework of the various factors presented in part one., (Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

This study was conducted to investigate the catabolism and fermentation of caprine milk oligosaccharides (CMO) by selected bifidobacteria isolated from 4 breast-fed infants. Seventeen bifidobacterial isolates consisting of 3 different species (Bifidobacterium breve, Bifidobacterium longum subsp. longum and Bifidobacterium bifidum) were investigated. A CMO-enriched fraction (CMOF) (50% oligosaccharides, 10% galacto-oligosaccharides (GOS), 20% lactose, 10% glucose and 10% galactose) from caprine cheese whey was added to a growth medium as a sole source of fermentable carbohydrate. The inclusion of the CMOF was associated with increased bifidobacterial growth for all strains compared to glucose, lactose, GOS, inulin, oligofructose, 3'-sialyl-lactose and 6'-sialyl-lactose. Only one B. bifidum strain (AGR2166) was able to utilize the sialyl-CMO, 3'-sialyl-lactose and 6'-sialyl-lactose, as carbohydrate sources. The inclusion of CMOF increased the production of acetic and lactic acid (P < 0.001) after 36 h of anaerobic fermentation at 37 °C, when compared to other fermentable substrates. Two B. bifidum strains (AGR2166 and AGR2168) utilised CMO, contained in the CMOF, to a greater extent than B. breve or B. longum subsp longum isolates, and this increased CMO utilization was associated with enhanced sialidase activity. CMOF stimulated bifidobacterial growth when compared to other tested fermentable carbohydrates and also increased the consumption of mono- and disaccharides, such as galactose and lactose present in the CMOF. These findings indicate that the dietary consumption of CMO may stimulate the growth and metabolism of intestinal Bifidobacteria spp. including B. bifidum typically found in the large intestine of breast-fed infants.