Integrated microbiota-host-metabolome approaches reveal adaptive ruminal changes to prolonged high-grain feeding and phytogenic supplementation in cattle.

Diets rich in readily fermentable carbohydrates primarily impact microbial composition and activity, but can also impair the ruminal epithelium barrier function. By combining microbiota, metabolome, and gene expression analysis, we evaluated the impact of feeding a 65% concentrate diet for 4 weeks, with or without a phytogenic feed additive (PFA), on the rumen ecosystem of cattle. The breaking point for rumen health seemed to be the second week of high grain (HG) diet, with a dysbiosis characterized by reduced alpha diversity. While we did not find changes in histological evaluations, genes related with epithelial proliferation (IGF-1, IGF-1R, EGFR, and TBP) and ZO-1 were affected by the HG feeding. Integrative analyses allowed us to define the main drivers of difference for the rumen ecosystem in response to a HG diet, identified as ZO-1, MyD88, and genus Prevotella 1. PFA supplementation reduced the concentration of potentially harmful compounds in the rumen (e.g. dopamine and 5-aminovaleric acid) and increased the tolerance of the epithelium toward the microbiota by altering the expression of TLR-2, IL-6, and IL-10. The particle-associated rumen liquid microbiota showed a quicker adaptation potential to prolonged HG feeding compared to the other microenvironments investigated, especially by the end of the experiment.

Growing and laying performance of two different-plumage color Japanese quail varieties supplemented with corn silk in their diet.

The current study aimed to investigate the dietary supplementation effect of corn silk (CS) on performance and blood chemistry of brown and white-feathered quails during the grower and layer periods. Japanese quails of brown and white-feathered color (180 birds/variety at 2 wks old) were randomly allotted into three groups with 3 replicates each (n = 20 birds/replicate). Corn silk powder (CS) was supplemented to the basal diet at 0, 1, and 2% of the diet for each quail variety for 1-month growing period, then continued for another 6-wk laying period to assess the egg production and egg quality characteristics. CS supplementation at 1% and 2% for brown and white-feathered quails respectively improved their growth performance (body weight and weight gain), carcass yield, and intestinal villi length with increasing feed consumption but without changes in feed conversion ratio. In both quail varieties, CS addition had a hypolipidemic effect, confirmed by lowering serum triglyceride (TG), cholesterol (CHO), and low density lipoprotein (LDL) while increased high density lipoprotein (HDL) concentrations (P < 0.05) with a clear response observed in white quails than the brown ones. Besides, CS supplementation increased (P = 0.002) hen day egg production in brown feathered quails, while reducing it in the white-feathered quails compared with the CS-free diet. The increased egg production was not significantly (P > 0.05) correlated with lower content of TG and CHO, while significantly increased the antioxidant content in both quail varieties (P < 0.05). Moreover, CS dietary supplementation significantly enhanced (P = 0.003) the yolk color, especially in brown-feathered quail. In conclusion, CS can be safely supplemented to the Japanese quail diet (1% and 2% for brown-feathered and white-feathered quails respectively) to improve growth performance, and egg quality characteristics.

Supplementation of mixed doses of glutamate and glutamine can improve the growth and gut health of piglets during the first 2 weeks post-weaning.

The aim of this study was to test the effect of mixing doses of glutamate (Glu) and glutamine (Gln) on the growth, health and gut health of post-weaning piglets. One hundred twenty weaned piglets (24 ± 2 days of age) were assigned to 6 dietary groups: (1) standard diet (CO); (2) CO plus Glu (6 kg/Ton): 100Glu; (3) CO plus 75Glu + 25Gln; (4) CO plus 50Glu + 50Gln; (5) CO plus 25Glu + 75Gln and (6) CO plus 100Gln. At days 8 and 21, blood was collected for haematological and reactive oxygen metabolite analysis, intestinal mucosa for morphological and gene expression analysis, and caecal content for microbial analysis. Data were fitted using a Generalised Linear Model (GLM). Piglet growth increased linearly with an increase in Gln from d7 to d14. The Glu:Gln ratio had a quadratic effect on faecal consistency and days of diarrhoea, neutrophil% and lymphocyte%, and a positive linear effect on monocyte% in the blood at d8. The amino acids (AAs) reduced the intraepithelial lymphocytes in the jejunum, and 100Gln improved intestinal barrier integrity at d8. The caecal microbiota did not differ. Overall, this study suggested a favourable effect of mixing Glu and Gln (25 + 75-50 + 50) as a dietary supplementation in post-weaning piglets to benefit the immune and barrier function of the gut, resulting in an increase in faecal consistency and improvement of growth during the first 2 weeks post-weaning.

A new byciclic monoterpene glucoside and a new biflavone from the male reproduction organs of Wollemia nobilis.

In this work, the fifth part of an ongoing phytochemical study on Wollemia nobilis was reported. The attention was now focused on the male reproduction organs of which the content in both primary and secondary metabolites was analyzed. Twenty compounds, belonging to seven different classes of natural compounds, were identified from the ethanolic extract by means of Column Chromatography and NMR and MS Spectroscopy. They all represent new compounds for the studied organ whereas some of them are also new constituents of the genus or even previously undescribed phytochemicals. Their presence was able to display a general overview of these organs from the phytochemical standpoint and to provide more elements in confirmation with the current botanical classification of the species. Moreover, they add a further experimental evidence of the tendency of this species to accumulate different metabolites in different organs. This characteristic as well as the occurrence of several compounds with added value, make this plant a possible candidate for large scale cultivation with extractive purposes to obtain useful phytochemicals for botanicals and pharmaceutical fields. Moreover, they offer the opportunity to develop an additional method of conservation and protection for this endangered and very rare species.

Probiotic supplementation affects the glycan composition of mucins secreted by Brunner's glands of the pig duodenum.

The effect of a dietary probiotic blend on the carbohydrate composition of mucins secreted by the Brunner's glands in the duodenum of growing-finishing pigs was investigated by means of conventional (periodic acid-Schiff, Alcian Blue pH 2.5, high iron diamine staining) and lectin (15 lectins) histochemistry. Pigs were assigned to two dietary treatments: a control basal diet without the probiotic blend (No-Pro) and a test diet that included the probiotic blend (Pro). Duodenal tissue fragments were fixed in 4% phosphate-buffered-saline-buffered paraformaldehyde, dehydrated through a graded alcohol series, and embedded in paraffin wax. The secretory cells of the Brunner's glands from No-Pro pigs primarily produced neutral glycoproteins and a small amount of acidic non-sulphated mucins. This glycan pattern was opposite that of the Brunner's glands from Pro animals. A comparison of lectin-binding profiles of the secretory cells of Brunner's glands in these two groups showed that in Pro pigs, there was (i) a decrease in N-linked glycans containing α1,2-linked fucose (Con A, UEA I); (ii) a loss of complex types of N-glycans (PHA-L, PHA-E) terminating with lactosamine (RCA120), α1,6- and α1,3-linked fucose (LTA), and α-galactose (GSA I-B4), as well as of O-glycans with terminal Galß1,3GalNAc (PNA); and (iii) an increase in O-glycans containing GalNAc HPA. No-Pro and Pro samples showed no change in the expression of α2,6 sialoglycans and terminal GlcNAc residues and no affinity for MAL II, DBA, and SBA. These results indicate that probiotic supplementation affects the glycan composition of mucins produced in the Brunner's glands of growing-finishing pigs. These changes could effectively act on the gastrointestinal function and health status of these animals because the probiotic blend induced higher growth performance and meat quality in the test probiotic group than it did in the control basal diet group (Tufarelli et al., 2017).

Probiotic supplementation in trained trotter horses: effect on blood clinical pathology data and urine metabolomic assessed in field.

The attention of sports community toward probiotic supplementation as a way to promote exercise and training performance, together with good health, has increased in recent years. This has applied also to horses, with promising results. Here, for the first time, we tested a probiotic mix of several strains of live bacteria typically employed for humans to improve the training performance of Standardbred horses in athletic activity. To evaluate its effects on the horse performance, we measured lactate concentration in blood, a translational outcome largely employed for the purpose, combined with the study of hematological and biochemical parameters, together with urine from a metabolomics perspective. The results showed that the probiotic supplementation significantly reduced postexercise blood lactate concentration. The hematological and biochemical parameters, together with urine molecular profile, suggested that a likely mechanism underlying this positive effect was connected to a switch of energy source in muscle from carbohydrates to short-chain fatty acids. Three sulfur-containing molecules differently concentrated in urines in connection to probiotics administration suggested that such switch was linked to sulfur metabolism. NEW & NOTEWORTHY Probiotic supplementation could reduce postexercise blood lactate concentration in Standardbred horses in athletic activity. Blood parameters, together with urine molecular profile, suggest the mechanism underlying this positive effect is connected to a switch of energy source in muscle from carbohydrates to short-chain fatty acids. Sulfur-containing molecules found in urines in connection to probiotics administration suggested that such switch was linked to sulfur metabolism.

SLAB51 Probiotic Formulation Activates SIRT1 Pathway Promoting Antioxidant and Neuroprotective Effects in an AD Mouse Model.

The gut-brain axis is a bidirectional communication network functionally linking the gut and the central nervous system (CNS). Based on this, the rational manipulation of intestinal microbiota represents a novel attractive therapeutic strategy for the treatment of CNS-associated disorders. In this study, we explored the properties of a probiotic formulation (namely SLAB51) in counteracting brain oxidative damages associated with Alzheimer's disease (AD). Specifically, transgenic AD mice (3xTg-AD) were treated with SLAB51 and the effects on protein oxidation, neuronal antioxidant defence and repair systems were monitored, with the particular focus on the role of SIRT1-related pathways. We demonstrated that SLAB51 markedly reduced oxidative stress in AD mice brain by activating SIRT1-dependent mechanisms, thus representing a promising therapeutic adjuvant in AD treatment.

Wild type and mutant amyloid precursor proteins influence downstream effects of proteasome and autophagy inhibition.

Cells rely on complementary proteolytic pathways including the ubiquitin-proteasome system and autophagy to maintain proper protein degradation. There is known to be considerable interplay between them, whereby the loss of one clearance system results in compensatory changes in other proteolytic pathways of the cell. Disturbances in proteolysis are known to occur in Alzheimer's disease, and potentially contribute to neurophysiological and neurodegenerative processes. Currently, few data are available on how the presence of wild type and mutant amyloid precursor protein (APPwt and APPmut) potentially alters the reciprocal interplay between the different intracellular proteolytic pathways. This study used human SH-SY5Y neuronal cell lines, and SH-SY5Y transfected with either APPwt or APPmut (valine-to-glycine substitution at position 717), in order to explore if the presence of APPwt or APPmut altered the downstream effects of pharmacological proteasome or autophagy inhibition. The occurrence of APPwt or APPmut was observed to disturb proteasome or autophagy activities upon treatment with proteasome inhibitors or authophagy inhibitors. Interestingly, APPwt and APPmut expression was observed to significantly and robustly enhance the induction in cathepsin B following the administration of an established proteasome inhibitor. The presence of APPwt and APPmut also significantly reduced the elevation in ubiquitinated proteins following proteasome inhibitor treatments. Our data strongly suggest that APP is able to affect the downstream effects of protease inhibition in neural cells including enhancement of cathepsin B activity, with these changes in cathepsin B significantly and inversely related to the levels of ubiquitinated protein.

Potential of a Khaya ivorensis -Alstonia boonei extract combination as antimalarial prophylactic remedy.

ETHNOPHARMACOLOGICAL RELEVANCE: The decoction of the combined stem barks of Khaya ivorensis A. Chev. (Meliaceae) and Alstonia boonei De Wild (Apocynaceae) has a history of use in traditional medicine of central Cameroon for malaria treatment but also for the prevention of the disease. AIM OF THE STUDY: The purpose of this investigation was to determine the antiplasmodial activity of Khaya ivorensis (K) and Alstonia boonei (A) preparations in the murine malaria model Plasmodium berghei/Anopheles stephensi, to estimate their prophylactic potential and to assess acute and sub-acute toxicity of the formulations prepared according to the traditional recipes. MATERIALS AND METHODS: Aqueous extracts from the stem-bark of the two plants were prepared and tested separately and in combination. BALB/c mice were treated for 9 days and challenged on day 3 by exposure to mosquitoes infected with Plasmodium berghei. Treatment doses ranged between 200 and 400mg/kg/day, corresponding approximately to the dosage applied by traditional healers to cure malaria patients or prevent the disease. Parasitemia reduction in treated animals was calculated from Giemsa smear counts, of two replicate experiments. To estimate acute toxicity in terms of median lethal dose (LD50), geometrically increasing doses were administered to mice. Sub-acute toxicity of the herbal combination (KA) was investigated by administering the same doses as in the antiplasmodial activity test for a period of 14 days, followed by 14 days of recovery observation. Locomotor activity (Open Field Test), body weight, liver and kidney morphology were monitored. RESULTS: The combination KA was found to exhibit antiplasmodial activity in the murine malaria model. In mice treated with the combination remedy at a dosage of 200mg/kg/day, parasitemia values of 6.2% ± 1.7 and 6.5% ± 0.8 were recorded, compared to 10.8% ± 1.3 and 12.0% ± 4.0 in controls (p<0.01). Doubling the dosage of the extracts did not significantly increase parasite suppression. When extracts of K and A were administered separately at a dosage of 400mg/kg, a reduction in parasitemia was still obtained, but it did not reach statistical significance. Toxicity studies yielded comforting results: the LD50 was estimated to be greater than 2779.5mg/kg. Moreover, mice exposed to the fourteen-day repeated-dose toxicity test (sub-acute toxicity test) did not display weight loss, liver or kidney morphological modifications, significant alterations in locomotor activity or any other sign of illness. CONCLUSION: The antiplasmodial activity and the wide dose interval between the therapeutic dosage and the toxic dosage exhibited by the KA herbal combination in the murine malaria model argue in favor of its use as an antimalarial prophylactic remedy. It remains to be demonstrated by human clinical trials whether the combination remedy, when taken by inhabitants during malaria transmission season, can reduce parasite density and lead to a reduction of malaria episodes in the community.

Red wine and green tea reduce H pylori- or VacA-induced gastritis in a mouse model.

AIM: To investigate whether red wine and green tea could exert anti-H pylori or anti-VacA activity in vivo in a mouse model of experimental infection. METHODS: Ethanol-free red wine and green tea concentrates were administered orally as a mixture of the two beverages to H pylori infected mice, or separately to VacA-treated mice. Gastric colonization and gastric inflammation were quantified by microbiological, histopathological, and immunohistochemical analyses. RESULTS: In H pylori-infected mice, the red wine and green tea mixture significantly prevented gastritis and limited the localization of bacteria and VacA to the surface of the gastric epithelium. Similarly, both beverages significantly prevented gastric epithelium damage in VacA-treated mice; green tea, but not red wine, also altered the VacA localization in the gastric epithelium. CONCLUSION: Red wine and green tea are able to prevent H pylori-induced gastric epithelium damage, possibly involving VacA inhibition. This observation supports the possible relevance of diet on the pathological outcome of H pylori infection.