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Intimate metabolic host–microbiome crosstalk regulates immune, metabolic, and neuronal response in health and disease, yet remains untapped for biomarkers or intervention for disease. Our recent study identified an altered microbiome in patients with pre-onset amnestic mild cognitive impairment (aMCI) and dementia Alzheimer’s disease (AD). Thus, we aimed to characterize the gut microbial metabolites among AD, aMCI, and healthy controls (HC). Here, a cohort of 77 individuals (22 aMCI, 27 AD, and 28 HC) was recruited. With the use of liquid-chromatography/gas chromatography mass spectrometry metabolomics profiling, we identified significant differences between AD and HC for tryptophan metabolites, short-chain fatty acids (SCFAs), and lithocholic acid, the majority of which correlated with altered microbiota and cognitive impairment. Notably, tryptophan disorders presented in aMCI and SCFAs decreased progressively from aMCI to AD. Importantly, indole-3-pyruvic acid, a metabolite from tryptophan, was identified as a signature for discrimination and prediction of AD, and five SCFAs for pre-onset and progression of AD. This study showed fecal-based gut microbial signatures were associated with the presence and progression of AD, providing a potential target for microbiota or dietary intervention in AD prevention and support for the host–microbe crosstalk signals in AD pathophysiology.

In beef cattle, production feedstuffs are the largest variable input cost. Beef cattle also have a large carbon footprint, raising concern about their environmental impact. Unfortunately, only a small proportion of dietary energy is directed toward protein deposition and muscle growth whereas the majority supports body maintenance. Improving feed efficiency would, therefore, have important consequences on productivity, profitability, and sustainability of the beef industry. Various measures of feed efficiency have been proposed to improve feed utilization, and currently, residual feed intake (RFI) is gaining popularity. However, the cost associated with measuring RFI and the limited knowledge of the biology underlying improved feed efficiency make its adoption prohibitive. Identifying molecular mechanisms explaining divergence in RFI in beef cattle would lead to the development of early detection methods for the selection of more efficient breeding stock. The objective of this study was to identify hepatic markers of metabolic feed efficiency in replacement beef heifers. A group of 87 heifers were tested for RFI adjusted for off-test backfat thickness (RFIfat). Preprandial liver biopsies were collected from 10 high- and 10 low-RFIfat heifers (7 Hereford–Aberdeen Angus and 3 Charolais–Red Angus–Main Anjou per group) and gene expression analysis was performed using RNA sequencing and quantitative real-time PCR. The heifers used in this study differed in RFIfat averaging 0.438 vs. –0.584 kg DM/d in high- and low-RFIfat groups, respectively. As expected, DMI was correlated with RFIfat and ADG did not differ between high- and low-RFIfat heifers. Through a combination of whole transcriptome and candidate gene analyses, we identified differentially expressed genes involved in inflammatory processes including hemoglobin β (HBB), myxovirus resistance 1 interferon-inducible protein p78 (MX1), ISG15 ubiquitin-like modifier (ISG15), hect domain and RLD 6 (HERC6), and interferon-induced protein 44 (IFI44) whose mRNA abundance was lower (HBB) or higher (MX1, ISG15, HERC6, and IFI44) in low-RFIfat heifers. These genes have been shown to be directly or indirectly modulated by interferon signaling and involved with innate immunity. Our results suggest that more efficient heifers respond differently to hepatic proinflammatory stimulus, potentially expending less energy toward combating systemic inflammation and redirecting nutrients toward growth and protein accretion.

Using effect directed analysis, the presence of estrogenic components in untreated and biologically treated oil sands process water (OSPW) was detected with the yeast estrogenic screening assay after fractionation with solid phase extraction followed by reversed phase high performance liquid chromatography. Comparison of the composition, as determined by electrospray ionization combined with high-resolution linear trap quadropole (LTQ)-Orbitrap Velos Pro hybrid mass spectrometry (negative ion) of selected estrogenic and nonestrogenic fractions identified compounds that were uniquely present in the estrogenic samples, biologically treated and untreated. Of the 30 most abundant compounds, there were 14 possible nonaromatic structures and 16 possible aromatic structures. Based on the published literature, the latter are the most likely to cause estrogenicity and were O2, O3 and O4 C17 to C20 compounds with double bond equivalents between 6 and 10 and chemical formulas similar to estrone- and estradiol-like compounds. This study shows exact formulas and masses of possible estrogenic compounds in OSPW. These findings will help to focus study on the most environmentally significant components in OSPW.

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