Alzheimer’s disease (AD) is a rapidly growing epidemic with a heavy social and economic burden. Evidence suggests that systemic inflammation, dysregulation of the immune response and the resulting neuroinflammation and neurodegeneration play a significant role in AD pathogenesis. Currently, given that there is no fully convincing cure for AD, the interest in lifestyle factors (such as diet), which potentially delay onset and reduce the severity of symptoms, is increasing. This review is aimed at summarizing the effects of dietary supplementation on cognitive decline, neuroinflammation and oxidative stress in AD-like animal models with a focus on neuroinflammation induced by lipopolysaccharide (LPS) injection, which mimics systemic inflammation in animals. The compounds reviewed include curcumin, krill oil, chicoric acid, plasmalogens, lycopene, tryptophan-related dipeptides, hesperetin and selenium peptides. Despite the heterogeneity of these compounds, there is a strong consensus on their counteracting action on LPS-induced cognitive deficits and neuroinflammatory responses in rodents by modulating cell-signaling processes, such as the NF-κB pathway. Overall, dietary interventions could represent an important resource to oppose AD due to their influence in neuroprotection and immune regulation.

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Dietary Protection against Cognitive Impairment, Neuroinflammation and Oxidative Stress in Alzheimer’s Disease Animal Models of Lipopolysaccharide-Induced Inflammation

Prebiotic mannooligosaccharides (MOS) are small chains of mannose that are known to confer health benefits to the consumers. At present, commercial MOS are derived by the degradation of yeast cell-wall mannans. MOS are also synthesized by the physicochemical or enzymatic treatment of naturally occurring mannans. Recently, these oligomers are being explored for their role in the modulation of beneficial gut microbiota of animals and their possible usage as functional food ingredients in humans. Experimental evidences strongly point out that dietary MOS impart numerous health benefits, including antineoplastic, immunomodulatory, and hypolipidemic effects, indicating that they have immense potential as a functional food ingredient. In this article, we present up-to-date developments related to the production and applications of MOS. 

Advances in Prebiotic Mannooligosaccharides

Echinacea purpurea (L.) Moench is one of the most economically important medicinal plants, cultivated worldwide for its high medicinal value and with several industrial applications in both pharmaceutical and food industries. Thanks to its various phytochemical contents, including caffeic acid derivatives (CADs), E. purpurea extracts have antioxidant, anti-inflammatory, and immuno-stimulating properties. Among CADs, chicoric acid is one of the most important compounds which have shown important pharmacological properties. The present research was aimed at optimizing the production of chicoric acid in E. purpurea cell culture. Methyl jasmonate (MeJa) at different concentrations and for different duration of treatments was utilized as elicitor, and the content of total polyphenols and chicoric acid was measured. Several genes involved in the chicoric acid biosynthetic pathway were selected, and their expression evaluated at different time points of cell culture growth. This was performed with the aim of identifying the most suitable putative molecular markers to be used as a proxy for the early prediction of chicoric acid contents, without the need of expensive quantification methods. A correlation between the production of chicoric acid in response to MeJa and an increased response to oxidative stress was also proposed.

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C3H Expression Is Crucial for Methyl Jasmonate Induction of Chicoric Acid Production by Echinacea purpurea (L.) Moench Cell Suspension Cultures

The use of the fermented total mixed ration (FTMR) is a promising approach for the preservation of feedstuff, but the effect of FTMR on the between growth performance and ruminal microflora of lambs are still limited. This study aimed to assess the effects of different roughage types in the FTMR on growth performance and rumen microbiota of lambs. Forty-five six-month-old Small tail Han sheep × Ujumqin male lambs were randomly allocated into three groups (three pens per treatment and five lambs per pen) with the initial body weight (BW) of 28.50 ± 1.50 kg. The three treatments were as follows: the low oat percentages group (LO) contained 200 g/kg oat hay + 400 g/kg alfalfa hay, the medium oat percentages group (MO) contained 300 g/kg oat hay + 300 g/kg alfalfa hay, and the high oat percentages group (HO) contained 400 g/kg oat hay + 200 g/kg alfalfa hay. The result revealed that the dry matter intake and average daily gain were markedly (p < 0.05) higher in the MO treatment than in the LO and HO treatments, whereas no significant difference (p > 0.05) was found in the final body weight. There were no significant (p > 0.05) differences on the Shannon and Simpson index among the three treatments. The PCoA score plot illustrated the individual separation in the LO, MO, and HO treatments. At the phylum level, the presence of Bacteroidetes and Firmicutes belonging to the dominant phyla is widely described in rumen communities among the three treatments. The relative abundances of Prevotella, Fibrobacter, and Succinivibrio in the level of the genes were remarkably higher (p < 0.05) in MO treatment than that in LO and HO treatments, while the relative abundance of Sediminispirochaeta was remarkably higher (p < 0.05) in LO treatment than that in MO and HO treatments. These results indicated that the MO treatments could more effectively improve growth performance than the LO and HO treatments, and also revealed that the different forage types in diets reshaped the compositions and function of the rumen microbiota. Consequently, the findings presented in this study provide a reference for the application of FTMR in animal production and the understanding of the interaction between diet, animal performance, and ruminal microbiota.

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Effects of Replacing Alfalfa Hay with Oat Hay in Fermented Total Mixed Ration on Growth Performance and Rumen Microbiota in Lambs

Transition milk (TRM) is a rich source of bioactive components that promotes intestinal development and growth, and reduces the susceptibility to diarrhoea in calves. The objective of this study was to characterise the effects of replacing pasteurised waste milk (none-saleable milk containing antibiotic and/or drug residues) with pasteurised TRM for 3 wk on blood metabolites of dairy calves at 21 d of age. A total of 84 healthy newborn female Holstein calves was blocked by birth order and assigned randomly to four treatment groups with partial replacement of pasteurised waste milk by TRM (second milking after parturition) at 0 (0 L/day TRM + 6 L/day milk), 0.5 (0.5 L/day TRM + 5.5 L/day milk), 1 (1 L/day TRM + 5 L/day milk), or 2 L (2 L/day TRM + 4 L/day milk) for a 21-day period. Serum metabolome was determined by liquid chromatography with tandem mass spectrometry-based metabolomics analysis on a subset of 26 randomly selected individuals from calves fed pasteurised waste milk (CON, 6 L/d milk; n = 13) or TRM (2 L/d TRM + 4 L/d milk; n = 13) at 21 d of age. The identified metabolites (194 out of 265) were categorised according to chemical class and the number of metabolites per class in the serum, amongst which glycerophospholipids 16% (n = 43), fatty acyls 7% (n = 19), organic acids 7% (n = 18), organic heterocyclic compounds 5% (n = 13), benzenoids 5% (n = 12), sphingolipids 5% (n = 12), organic oxygen compounds 4% (n = 11), and nucleic acids 3% (n = 9), were the predominant types. Significant differences in metabolites were determined by the volcano plot. Applying the volcano plot, only two metabolites (ceramide and phosphatidylserine) were significantly different between CON and TRM. Overall, our results suggested that prolonged TRM feeding for 3 wk had little effect on the serum metabolome of the dairy calves. We speculate that the potential effects of feeding TRM for 3 wk compared with waste milk were spatially limited to affect the composition of the local gut microbial community and the growth or function of the intestinal epithelium, not allowing detection of the likely effects in the serum through a metabolomic approach. 

Effects of extended transition milk feeding on blood metabolites of female Holstein dairy calves at 3 weeks of age: a liquid chromatography with tandem mass spectrometry-based metabolomics approach.

Successful establishment of passive immunity (PIT) and regulation of intestinal microbiota are crucial for ruminants to maintain body health and reduce the risk of disease during the neonatal period. Thus, the objective of this study was to investigate the effects of mannan oligosaccharide (MOS) supplementation on passive transfer of immunoglobulin G (IgG), serum inflammatory cytokines and antioxidant levels as well as bacteria composition in the ileal digesta. A total of 14 healthy neonatal Ganxi black goats with similar birth weight (BW: 2.35 ± 0.55 kg) were selected and allocated into two groups, only fed colostrum and milk replacer (CON, n = 7) and supplemented MOS (0.06% of birth BW) in the colostrum and milk replacer (MOS, n = 7). The results indicated that MOS supplementation significantly reduced (p < 0.05) serum IgG level at 3 and 6 h after colostrum feeding. Serum GLP-1 level of goats in the MOS group was significantly lower (p = 0.001) than that in the CON group. Goats in the MOS group had higher serum CAT and lower MDA level than those in the CON group (p < 0.05). Serum anti-inflammatory cytokine level of interleukin 4 (IL-4) was increased (p < 0.05), while pro-inflammatory cytokine IL-6 level was reduced (p < 0.05) in the MOS group when compared with the CON group. In addition, MOS supplementation remarkably increased (p < 0.05) the level of secretory IgA (sIgA) in the ileal digesta. Principal coordinate analysis of 16S rRNA sequence based on Brinary jaccard, Bray curtis, and weighted UniFrac distance of ileal microbiota showed a distinct microbial differentiation between the CON and MOS groups (p < 0.05). The relative abundance of Firmicutes in the MOS group was higher than that in the CON group, while the abundance of Verrucomicrobia was lower in the MOS group than that in the CON group at the phylum level (p < 0.05). The relative abundance of Proteobacteria tended to decrease (p = 0.078) in the MOS group at the phylum level. The results of LEfSe analysis showed that MOS group was characterized by a higher relative abundance of Lactobacillus, while the CON group was represented by a higher relative abundance of Akkermansia and Ruminiclostridium_5. Our findings demonstrated that MOS supplementation during the neonatal period increases antioxidant capacity and reduces the inflammatory response, and promotes IgA secretion and Lactobacillus colonization in the ileum. Thus, MOS induced positive effects are more pronounced in neonatal goats that might be an effective approach to maintain intestinal health and improve the surviving rate of neonatal ruminants.

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Supplementing Mannan Oligosaccharide Reduces the Passive Transfer of Immunoglobulin G and Improves Antioxidative Capacity, Immunity, and Intestinal Microbiota in Neonatal Goats

Chicoric acid has been widely used in food, medicine, animal husbandry, and other commercial products because of its significant pharmacological activities. However, the shortage of chicoric acid limits its further development and utilization. Currently, Echinacea purpurea (L.) Moench serves as the primary natural resource of chicoric acid, while other sources of it are poorly known. Extracting chicoric acid from plants is the most common approach. Meanwhile, chicoric acid levels vary in different plants as well as in the same plant from different areas and different medicinal parts, and different extraction methods. We comprehensively reviewed the information regarding the sources of chicoric acid from plant extracts, its chemical synthesis, biosynthesis, and bioactive effects.

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Chicoric Acid: Natural Occurrence, Chemical Synthesis, Biosynthesis, and Their Bioactive Effects

Silybum marianum meal is a by-product that remains silymarin complex and is perceived as a potential-protein source. The potential and its mechanism of silybum marianum meal as a protein supplement in ruminants were evaluated by testing the growth performance, biochemical parameters, cytokine levels, gut transcriptome and microbial community profiles. Forty-two male Hulunbeier growing lambs (aged about 3-month-old; averaged body weight of 21.55 kg) were randomly divided into the CON (with 10% soybean meal) and SIL groups (with 10% silybum marianum meal). There was no significant difference in growth performance, feed intakes, or serum biochemical parameters between CON and SIL. The serum levels of IL-1β, TNF-α, TGF-β, HGF, and VEGF were all increased (p < 0.05) in the SIL group as compared with the CON group. Transcriptome gene set enrichment analysis (GSEA) revealed that the core genes in the rumen from SIL group were enriched with fructose and mannose metabolism, while the core genes in the ileum were enriched for three biological process, including digestive tract development, positive regulation of MAPK cascade, and regulation of I-kappaB kinase/NF-kappaB signaling. The 16S rDNA results showed that the relative abundance of Bacteroidetes, Firmicutes, Synergistetes, and Verrucomicrobia in the rumen from SIL group was significantly higher than that in CON group (p < 0.05), whereas Proteobacteria was significantly lower than that in CON group (p < 0.05). The LEfSe analysis showed that the genera Pyramidobacter, Saccharofermentans, Anaerovibrio, Oscillibacter and Barnesiella were enriched in the rumen from SIL group, whereas Sharpea was enriched in the CON group (LDA > 2). In the ileum, there were no significant differences in the phylum-level classification of microbes observed. At the genus level, the relative abundances of Bifidobacterium and Ruminococcus in the ileum from SIL group were significantly higher than that in the CON group (p < 0.05), whereas the relative abundance of Clostridium_XI was lower (p < 0.05). Correlation analysis showed that Clostridium_XI was negatively correlated with VEGF, TGF-β, TNF-α and HGF (p < 0.05). Core genes BMP4 and CD4 were negatively correlated with Clostridium_XI (p < 0.05). Our results indicated that supplementing silybum marianum meal as a replacement for soybean meal resulted in increased cytokines production without affecting growth performance in growing lambs, and the enrichment of immune-related genes and altered microbial community in the ileum were contributed to the increased immune responses.

/pdf/an-integrated-transcriptome-and-microbial-community-analysis-12lj7z85.pdf

An integrated transcriptome and microbial community analysis reveals potential mechanisms for increased immune responses when replacing silybum marianum meal with soybean meal in growing lambs

Tianxi Zhang

Papers

Supplementing Mannan Oligosaccharide Reduces the Passive Transfer of Immunoglobulin G and Improves Antioxidative Capacity, Immunity, and Intestinal Microbiota in Neonatal Goats

Chicoric Acid: Natural Occurrence, Chemical Synthesis, Biosynthesis, and Their Bioactive Effects

An integrated transcriptome and microbial community analysis reveals potential mechanisms for increased immune responses when replacing silybum marianum meal with soybean meal in growing lambs