Comprehensive study on the effect of dietary leucine supplementation on intestinal physiology, TOR signaling and microbiota in juvenile turbot (Scophthalmus maximus L.).

Intestinal damage and inflammation are major health and welfare issues in aquaculture. Considerable efforts have been devoted to enhancing intestinal health, with a specific emphasis on dietary additives. Branch chain amino acids, particularly leucine, have been reported to enhance growth performance in various studies. However, few studies have focused on the effect of leucine on the intestinal function and its underlying molecular mechanism is far from fully illuminated. In the present study, we comprehensively evaluated the effect of dietary leucine supplementation on intestinal physiology, signaling transduction and microbiota in fish. Juvenile turbot (Scophthalmus maximus L.) (10.13 ± 0.01g) were fed with control diet (Con diet) and leucine supplementation diet (Leu diet) for 10 weeks. The findings revealed significant improvements in intestinal morphology and function in the turbot fed with Leu diet. Leucine supplementation also resulted in a significant increase in mRNA expression levels of mucosal barrier genes, indicating enhanced intestinal integrity. The transcriptional levels of pro-inflammatory factors il-1ß, tnf-α and irf-1 was decreased in response to leucine supplementation. Conversely, the level of anti-inflammatory factors tgf-ß, il-10 and nf-κb were up-regulated by leucine supplementation. Dietary leucine supplementation led to an increase in intestinal complement (C3 and C4) and immunoglobulin M (IgM) levels, along with elevated antioxidant activity. Moreover, dietary leucine supplementation significantly enhanced the postprandial phosphorylation level of the target of rapamycin (TOR) signaling pathway in the intestine. Finally, intestinal bacterial richness and diversity were modified and intestinal bacterial composition was re-shaped by leucine supplementation. Overall, these results provide new insights into the beneficial role of leucine supplementation in promoting intestinal health in turbot, offering potential implications for the use of leucine as a nutritional supplement in aquaculture practices.

A 90-day oral exposure to food-grade gold at relevant human doses impacts the gut microbiota and the local immune system in a sex-dependent manner in mice.

BACKGROUND: Edible gold (Au) is commonly used as a food additive (E175 in EU) for confectionery and cake decorations, coatings and in beverages. Food-grade gold is most often composed of thin Au sheets or flakes exhibiting micro- and nanometric dimensions in their thickness. Concerns about the impact of mineral particles used as food additives on human health are increasing with respect to the particular physico-chemical properties of nanosized particles, which enable them to cross biological barriers and interact with various body cell compartments. In this study, male and female mice were exposed daily to E175 or an Au nanomaterial (Ref-Au) incorporated into food at relevant human dose for 90 days in order to determine the potential toxicity of edible gold. RESULTS: E175 or Ref-Au exposure in mice did not induce any histomorphological damage of the liver, spleen or intestine, nor any genotoxic effects in the colon and liver despite an apparent higher intestinal absorption level of Au particles in mice exposed to Ref-Au compared to the E175 food additive. No changes in the intestinal microbiota were reported after treatment with Ref-Au, regardless of sex. In contrast, after E175 exposure, an increase in the Firmicutes/Bacteroidetes ratio and in the abundance of Proteobacteria were observed in females, while a decrease in the production of short-chain fatty acids occurred in both sexes. Moreover, increased production of IL-6, TNFα and IL-1ß was observed in the colon of female mice at the end of the 90-day exposure to E175, whereas, decreased IL-6, IL-1ß, IL-17 and TGFß levels were found in the male colon. CONCLUSIONS: These results revealed that a 90-day exposure to E175 added to the diet alters the gut microbiota and intestinal immune response in a sex-dependent manner in mice. Within the dose range of human exposure to E175, these alterations remained low in both sexes and mostly appeared to be nontoxic. However, at the higher dose, the observed gut dysbiosis and the intestinal low-grade inflammation in female mice could favour the occurrence of metabolic disorders supporting the establishment of toxic reference values for the safe use of gold as food additive.

Toxoplasma gondii Infection Decreases Intestinal 5-Lipoxygenase Expression, while Exogenous LTB4 Controls Parasite Growth.

5-Lipoxygenase (5-LO) is an enzyme required for the production of leukotrienes and lipoxins and interferes with parasitic infections. In vitro, Toxoplasma gondii inhibits leukotriene B4 (LTB4) production, and mice deficient in 5-LO are highly susceptible to infection. The aim of this study was to investigate the effects of the pharmacological inhibition of the 5-LO pathway and exogenous LTB4 supplementation during experimental toxoplasmosis. For this purpose, susceptible C57BL/6 mice were orally infected with T. gondii and treated with LTB4 or MK886 (a selective leukotriene inhibitor through inhibition of 5-LO-activating protein [FLAP]). The parasitism, histology, and immunological parameters were analyzed. The infection decreased 5-LO expression in the small intestine, and treatment with MK886 reinforced this reduction during infection; in addition, MK886-treated infected mice presented higher intestinal parasitism, which was associated with lower local interleukin-6 (IL-6), interferon gamma (IFN-γ), and tumor necrosis factor (TNF) production. In contrast, treatment with LTB4 controlled parasite replication in the small intestine, liver, and lung and decreased pulmonary pathology. Interestingly, treatment with LTB4 also preserved the number of Paneth cells and increased α-defensins expression and IgA levels in the small intestine of infected mice. Altogether, these data demonstrated that T. gondii infection is associated with a decrease in 5-LO expression, and on the other hand, treatment with the 5-LO pathway product LTB4 resulted in better control of parasite growth in the organs, adding to the knowledge about the pathogenesis of T. gondii infection.

Effects of fishmeal replacement by black soldier fly on growth performance, digestive enzyme activity, intestine morphology, intestinal flora and immune response of pearl gentian grouper (Epinephelus fuscoguttatus ♀ × Epinephelus lanceolatus ♂).

An 8-week feeding trial was conducted to investigate the influence of partial replacement of fishmeal (FM) by black soldier fly (BSF) (Hermetia illucens) on the growth, distal intestine morphology, intestinal flora, and intestinal immune response of pearl gentian grouper (Epinephelus fuscoguttatus ♀ × Epinephelus lanceolatus ♂). Four diets were formulated, 0% (0 g kg-1), 10% (50 g kg-1), 20% (100 g kg-1) and 30% (150 g kg-1) fishmeal were replaced with BSF, named as FM, BSF10, BSF20, BSF30, severally. The study found that, with the increasing dietary BSF levels, growth and feed conversion ratio of fish decreased significantly (P < 0.05). Chitinase and trypsin activities were significantly increased with increasing dietary BSF levels (P < 0.05). With the increasing dietary BSF levels, distal intestinal muscularis thickness and mucosal fold length decreased significantly (P < 0.05), as well as total abundance of intestinal flora. The relative abundance of four phyla and six genera among the top 20 genera were significantly affected by dietary BSF levels (P < 0.05). With the increasing dietary BSF levels, the mRNA levels of nf-κbem1, r-cel and il-10 up-regulated significantly (P < 0.05). For fish fed BSF30 diet, the mRNA levels of myd88 and tlr22 were significantly higher than fish fed FM diet (P < 0.05). In conclusion, replacement fishmeal with BSF increased activity of digestive enzymes, but negatively affected growth performance and intestinal health of pearl gentian grouper.

Dietary vitamin A deficiency reduces growth performance, immune function of intestine, and alters tight junction proteins of intestine for juvenile hybrid grouper (Epinephelus fuscoguttatus ♀ × Epinephelus lanceolatus ♂).

This study was carried out to investigate the effects of dietary vitamin A (VA) on growth performance, antioxidant capacity, digestion, intestinal immune response, and mRNA expression of intestinal tight junction proteins for juvenile hybrid grouper (Epinephelus fuscoguttatus ♀ × Epinephelus lanceolatus ♂). Six isonitrogenous and isolipidic experimental diets were formulated to obtain VA levels (317, 1136, 2038, 4142, 7715, 15204 IU/kg diet, respectively). The triplicate groups of fish (average weight of 9.01 ± 0.27 g) were fed twice daily (8:00 and 16:00) for 7 weeks. Based on the broken-line analysis model of WG and LYZ activity, the dietary VA requirement of hybrid grouper were estimated to be 2688.58 and 4096.36 IU/kg diet. The results showed that VA deficiency or excess could reduce Weight gain, specific growth rate, and protein efficiency ratio, and increase feed conversion ratio and hepatosomatic index (P < 0.05). In addition, VA deficiency could reduce the serum activities of acid phosphatase (ACP), superoxide dismutase, and total antioxidant capacity and increase the malondialdehyde content (P < 0.05). VA deficiency also could reduce intestinal activities of ACP, alkaline phosphatase, lysozyme, complement 3, complement 4 contents, and activities of alpha-amylase, lipase, and trypsin (P < 0.05). Meanwhile, VA deficiency could reduce villus height in proximal intestine (PI) and mid intestine (MI), as well as muscle thickness in PI and distal intestine (DI) (P < 0.05). Moreover, VA deficiency could down-regulated antimicrobial peptides (ß-defensin, Hepcidin [not in MI and DI], Epinecidin), anti-inflammatory cytokines (interleukin 10 and transforming growth factor ß1 [not in DI]), tight junction proteins (occluding and claudin3) mRNA levels in the PI, MI and DI, and up-regulated pro-inflammatory cytokines (tumor necrosis factor α [not in MI] and interleukin 1ß [not in MI]), signaling molecules c-Rel and p65 (P < 0.05). Collectively, VA deficiency could reduce growth performance because of a negative effect on intestinal health by depressing digestive abilities, intestinal morphology, immunity and tight junction function in the intestine.

Histological and ultrastructural study of Myxobolus mugchelo (Parenzan, 1966) with initial histopathology survey of the Liza ramada host intestine.

This paper provides histological and ultrastructural data on Myxobolus mugchelo (Myxozoa), a parasite of the intestinal wall of thinlip mullet Liza ramada from the Comacchio lagoons (Northern Adriatic Sea, Italy). About 80% of the examined mullets were infected with this myxozoan. In histological sections, the plasmodia appeared rounded to ovoid and spindle shaped, measured 181.61 ± 97 × 122.79 ± 53.16 µm (mean ± standard deviation, SD) in size. Early sporogenic plasmodia were located primarily in the muscle layer where no pronounced inflammatory response was detected. Plasmodia containing mature spores were situated closer to mucosal folds and were encircled by numerous immune cells, especially mast cells. Mature spores were generally oval and 6.06 ± 0.40 × 3.48 ± 0.92 µm in size. The spores showed symmetrical and smooth valves. The anterior end of the spores contained two equal pyriform polar capsules measuring 2.19 ± 0.47 × 1.59 ± 0.29 µm. Inside the polar capsules, an isofilar polar filament displayed 5-6 coils perpendicular or slightly oblique to the longitudinal axis. The wall of the polar capsule was filled with a hyaline substance contrasting with the very dense internal matrix. The mucus layer surrounded the spore surface. A thorough comparison with the Myxobolus species infecting intestine of fish is provided. This is the first report on occurrence of this myxozoan species in L. ramada population of the North Adriatic Sea.

Lactobacillus rhamnosus and L. plantarum Combination Treatment Ameliorated Colitis Symptoms in a Mouse Model by Altering Intestinal Microbial Composition and Suppressing Inflammatory Response.

SCOPE: Changes in composition of intestinal microbes may disrupt the balance of their interaction with a susceptible host, resulting in development of inflammatory bowel disease (IBD). METHODS AND RESULTS: The study applied in combination two Lactobacillus strains (L. rhamnosus BY-02, L. plantarum BY-05) ("LS treatment"), previously isolates from feces of healthy human infants, in a mouse model of dextran sodium sulfate (DSS)-induced colitis, and evaluates their ameliorative effect and its possible mechanism. LS treatment suppresses weight loss and colon shortening, and reduces disease activity index in the mice. It also has several additional beneficial effects: i) maintains goblet cell numbers and ameliorates intestinal barrier damage in colonic tissue; ii) alters intestinal microbial composition close to normal by increasing abundances of Muribaculaceae, Akkermansia, Clostridia, Oscillospiraceae, and Lachnospiraceae, and decreasing abundance of Escherichia-Shigella; iii) increases content of short-chain fatty acids; iv) reduces content of pro-inflammatory lipopolysaccharides; v) suppresses overactivation of TLR4/NF-κB inflammatory signaling pathway. CONCLUSION: Combination treatment with two Lactobacillus strains strongly ameliorates colitis symptoms in the mouse model by favorably altering intestinal microbial composition and suppressing inflammatory response.

Congenital diarrheal disorders: an updated diagnostic approach.

Congenital diarrheal disorders (CDDs) are a group of inherited enteropathies with a typical onset early in the life. Infants with these disorders have frequently chronic diarrhea of sufficient severity to require parenteral nutrition. For most CDDs the disease-gene is known and molecular analysis may contribute to an unequivocal diagnosis. We review CDDs on the basis of the genetic defect, focusing on the significant contribution of molecular analysis in the complex, multistep diagnostic work-up.

Term infant formula supplemented with milk-derived oligosaccharides shifts the gut microbiota closer to that of human milk-fed infants and improves intestinal immune defense: a randomized controlled trial.

BACKGROUND: Bovine milk-derived oligosaccharides (MOS) containing primarily galacto-oligosaccharides with inherent concentrations of sialylated oligosaccharides can be added to infant formula to enhance the oligosaccharide profile. OBJECTIVE: To investigate the effects of an MOS-supplemented infant formula on gut microbiota and intestinal immunity. METHODS: In a double-blind, randomized, controlled trial, healthy term formula-fed infants aged 21-26 d either received an intact protein cow milk-based formula (control group, CG, n = 112) or the same formula containing 7.2 g MOS/L (experimental group, EG, n = 114) until the age of 6 mo. Exclusively human milk-fed infants (HFI, n = 70) from an observational study served as the reference. Fecal samples collected at baseline, and the ages of 2.5 and 4 mo were assessed for microbiota (16S ribosomal RNA-based approaches), metabolites, and biomarkers of gut health and immune response. RESULTS: Aged 2.5 and 4 mo, redundancy analysis (P = 0.002) and average phylogenetic distance (P < 0.05) showed that the overall microbiota composition in EG was different from CG and closer to that of HFI. Similarly, EG caesarean-born infants were different from CG caesarean- or vaginally born infants and approaching HFI vaginally born infants. Relative bifidobacteria abundance was higher in EG compared with CG (P < 0.05) approaching HFI. At the age of 4 mo, counts of Clostridioides difficile and Clostridium perfringens were ∼90% (P < 0.001) and ∼65% (P < 0.01) lower in EG compared with CG, respectively. Geometric LS mean (95% CI) fecal secretory IgA in EG was twice that of CG [70 (57, 85) compared with 34 (28, 42) mg/g, P < 0.001] and closer to HFI. Fecal oral polio vaccine-specific IgA was ∼50% higher in EG compared with CG (P = 0.065). Compared with CG, EG and HFI had lower fecal calcium excretion (by ∼30%, P < 0.005) and fecal pH (P < 0.001), and higher lactate concentration (P < 0.001). CONCLUSIONS: Infant formula with MOS shifts the gut microbiota and metabolic signature closer to that of HFI, has a strong bifidogenic effect, reduces fecal pathogens, and improves the intestinal immune response.

Lactiplantibacillus plantarum Strains Modulate Intestinal Innate Immune Response and Increase Resistance to Enterotoxigenic Escherichia coli Infection.

Currently, probiotic bacteria with not transferable antibiotic resistance represent a sustainable strategy for the treatment and prevention of enterotoxigenic Escherichia coli (ETEC) in farm animals. Lactiplantibacillus plantarum is among the most versatile species used in the food industry, either as starter cultures or probiotics. In the present work, the immunobiotic potential of L. plantarum CRL681 and CRL1506 was studied to evaluate their capability to improve the resistance to ETEC infection. In vitro studies using porcine intestinal epithelial (PIE) cells and in vivo experiments in mice were undertaken. Expression analysis indicated that both strains were able to trigger IL-6 and IL-8 expression in PIE cells in steady-state conditions. Furthermore, mice orally treated with these strains had significantly improved levels of IFN-γ and TNF-α in the intestine as well as enhanced activity of peritoneal macrophages. The ability of CRL681 and CRL1506 to beneficially modulate intestinal immunity was further evidenced in ETEC-challenge experiments. In vitro, the CRL1506 and CRL681 strains modulated the expression of inflammatory cytokines (IL-6) and chemokines (IL-8, CCL2, CXCL5 and CXCL9) in ETEC-stimulated PIE cells. In vivo experiments demonstrated the ability of both strains to beneficially regulate the immune response against this pathogen. Moreover, the oral treatment of mice with lactic acid bacteria (LAB) strains significantly reduced ETEC counts in jejunum and ileum and prevented the spread of the pathogen to the spleen and liver. Additionally, LAB treated-mice had improved levels of intestinal IL-10 both at steady state and after the challenge with ETEC. The protective effect against ETEC infection was not observed for the non-immunomodulatory TL2677 strain. Furthermore, the study showed that L. plantarum CRL1506 was more efficient than the CRL681 strain to modulate mucosal immunity highlighting the strain specific character of this probiotic activity. Our results suggest that the improved intestinal epithelial defenses and innate immunity induced by L. plantarum CRL1506 and CRL681 would increase the clearance of ETEC and at the same time, protect the host against detrimental inflammation. These constitute valuable features for future probiotic products able to improve the resistance to ETEC infection.

Infant Formula With a Specific Blend of Five Human Milk Oligosaccharides Drives the Gut Microbiota Development and Improves Gut Maturation Markers: A Randomized Controlled Trial.

Background: Human milk oligosaccharides (HMOs) have important biological functions for a healthy development in early life. Objective: This study aimed to investigate gut maturation effects of an infant formula containing five HMOs (2'-fucosyllactose, 2',3-di-fucosyllactose, lacto-N-tetraose, 3'-sialyllactose, and 6'-sialyllactose). Methods: In a multicenter study, healthy infants (7-21 days old) were randomly assigned to a standard cow's milk-based infant formula (control group, CG); the same formula with 1.5 g/L HMOs (test group 1, TG1); or with 2.5 g/L HMOs (test group 2, TG2). A human milk-fed group (HMG) was enrolled as a reference. Fecal samples collected at baseline (n∼150/formula group; HMG n = 60), age 3 (n∼140/formula group; HMG n = 65) and 6 (n∼115/formula group; HMG n = 60) months were analyzed for microbiome (shotgun metagenomics), metabolism, and biomarkers. Results: At both post-baseline visits, weighted UniFrac analysis indicated different microbiota compositions in the two test groups (TGs) compared to CG (P < 0.01) with coordinates closer to that of HMG. The relative abundance of Bifidobacterium longum subsp. infantis (B. infantis) was higher in TGs vs. CG (P < 0.05; except at 6 months: TG2 vs. CG P = 0.083). Bifidobacterium abundance was higher by ∼45% in TGs vs. CG at 6-month approaching HMG. At both post-baseline visits, toxigenic Clostridioides difficile abundance was 75-85% lower in TGs vs. CG (P < 0.05) and comparable with HMG. Fecal pH was significantly lower in TGs vs. CG, and the overall organic acid profile was different in TGs vs. CG, approaching HMG. At 3 months, TGs (vs. CG) had higher secretory immunoglobulin A (sIgA) and lower alpha-1-antitrypsin (P < 0.05). At 6 months, sIgA in TG2 vs. CG remained higher (P < 0.05), and calprotectin was lower in TG1 (P < 0.05) vs. CG. Conclusion: Infant formula with a specific blend of five HMOs supports the development of the intestinal immune system and gut barrier function and shifts the gut microbiome closer to that of breastfed infants with higher bifidobacteria, particularly B. infantis, and lower toxigenic Clostridioides difficile. Clinical Trial Registration: [https://clinicaltrials.gov/ct2/show/], identifier [NCT03722550].

Integrated Analysis of mRNA-Seq and MiRNA-Seq Reveals the Molecular Mechanism of the Intestinal Immune Response in Marsupenaeus japonicus Under Decapod Iridescent Virus 1 Infection.

The intestine is not only an important digestive organ but also an important immune organ for shrimp; it plays a key role in maintaining homeostasis. Decapod iridescent virus 1 (DIV1) is a new type of shrimp-lethal virus that has received extensive attention in recent years. To date, most studies of the shrimp intestinal immune response under viral infections have relied on single omics analyses; there is a lack of systematic multi-omics research. In the current study, intestinal mRNA-seq and microRNA (miRNA)-seq analyses of Marsupenaeus japonicus under DIV1 infection were performed. A total of 1,976 differentially expressed genes (DEGs) and 32 differentially expressed miRNAs (DEMs) were identified. Among them, 21 DEMs were negatively correlated with 194 DEGs from a total of 223 correlations. Functional annotation analysis revealed that M. japonicus can regulate glycosaminoglycan biosynthesis (chondroitin sulfate, dermatan sulfate, and keratan sulfate), vitamin metabolism (retinol metabolism and ascorbate and aldarate metabolism), immune pathway activation (Toll and IMD signaling pathways, Wnt signaling pathway, IL-17 signaling pathway, and Hippo signaling pathway), immunity enzyme activity promotion (triose-phosphate isomerase), antimicrobial peptide (AMP) expression, reactive oxygen species (ROS) production, and cell apoptosis through miRNAs to participate in the host's antiviral immune response, while DIV1 can influence Warburg effect-related pathways (pyruvate metabolism, glycolysis/gluconeogenesis, and citrate cycle), glycosphingolipid biosynthesis-related pathways (glycosphingolipid biosynthesis-globo and isoglobo series and glycosphingolipid biosynthesis-lacto and neolacto series), and the tight junction and adhesion junction of the intestinal mucosal epithelium through the host's miRNAs and mRNA to promote its own invasion and replication. These results indicate that intestinal miRNAs play important roles in the shrimp immune response against DIV1 infection. This study provides a basis for further study of the shrimp intestinal antiviral immune response and for the formulation of effective new strategies for the prevention and treatment of DIV1 infection.

p38 mitogen-activated protein kinases (MAPKs) are involved in intestinal immune response to bacterial muramyl dipeptide challenge in Ctenopharyngodon idella.

The p38 mitogen-activated protein kinases (MAPKs) are essential cytoplasmic signal molecules of innate immune pathways that play a vital role in host immune defense responses to pathogenic challenges. In this study, two fish p38 genes (Cip38α and Cip38ß) were characterized for the first time from the grass carp Ctenopharyngodon idella. Similar to other reported p38MAPKs, both Cip38α and Cip38ß contained a conserved phosphorylation motif (Thr-Gly-Tyr, TGY) and a substrate binding site (Ala-Thr-Arg-Trp, ATRW) in the serine/threonine protein kinase (S_TKc) domain. Expression profile analysis showed that Cip38α and Cip38ß mRNAs were broadly expressed in all of the examined tissues and developmental stages of C. idella. In addition, in vivo injection experiments directly revealed that Cip38α and Cip38ß showed strong responsiveness to Aeromonas hydrophila and muramyl dipeptide (MDP) challenges, and their expression levels were significantly upregulated in the intestine of grass carp. Additionally, the MDP-induced expression levels of intestinal inflammatory cytokines (TNF-α and IL-15) and an antimicrobial peptide (ß-defensin) were significantly inhibited by the p38MAPK-specific inhibitor SB203580. Moreover, the nutritional dipeptide carnosine and Ala-Gln were found to significantly suppress the bacterial MDP-induced expression of p38MAPK pathway genes and inflammatory cytokines in the intestine of grass carp. Finally, overexpression analysis demonstrated that Cip38α and Cip38ß could act as efficient activators in the regulation of AP-1 signaling pathways through interaction with CiMKK6. Altogether, this study provided experimental evidence of the presence of a functional p38 pathway in grass carp, which revealed its involvement in the intestinal immune response to bacterial challenges in bony fish.

Effects of Lactobacillus rhamnosus GG and Escherichia coli Nissle 1917 Cell-Free Supernatants on Modulation of Mucin and Cytokine Secretion on Human Intestinal Epithelial HT29-MTX Cells.

This study examined modulation effects of cell-free supernatants of two commonly studied probiotic bacteria Lactobacillus rhamnosus GG (LGG) and Escherichia coli Nissle 1917 (EcN) on mucin and cytokine profiles of human intestinal epithelial HT29-MTX cells. It was found that LGG and EcN supernatants differentially modulated MUC5AC and MUC5B mRNA and protein, and total mucin-like glycoprotein secretion. Regarding modulation of cytokine profiles, LGG supernatants moderately influenced the secretion of anti-inflammatory cytokines such as interleukin (IL)-4, IL-5, and IL-10, while those of EcN exerted a broad proinflammatory effect to intestinal epithelial cells by inducing the secretion of proinflammatory cytokines such as IL-8, monocyte chemotactic protein-1, transforming growth factor α, tumor necrosis factor α, granulocyte macrophage colony-stimulating factor, and interferon γ. These results suggested that LGG and EcN might produce different bioactive products that display differential modulation of mucin and cytokines, which may contribute to intestinal health and/or defense against bacteria/pathogens. PRACTICAL APPLICATION: The results suggested that LGG and EcN might produce different bioactive products that display differential modulation of mucin and cytokines, which may contribute to intestinal health and/or defense against bacteria/pathogens.

Modulation of Intestinal Immune and Barrier Functions by Vitamin A: Implications for Current Understanding of Malnutrition and Enteric Infections in Children.

The micronutrient vitamin A refers to a group of compounds with pleiotropic effects on human health. These molecules can modulate biological functions, including development, vision, and regulation of the intestinal barrier. The consequences of vitamin A deficiency and supplementation in children from developing countries have been explored for several years. These children live in an environment that is highly contaminated by enteropathogens, which can, in turn, influence vitamin A status. Vitamin A has been described to modulate gene expression, differentiation and function of diverse immune cells; however, the underlying mechanisms are not fully elucidated. This review aims to summarize the most updated advances on elucidating the vitamin A effects targeting intestinal immune and barrier functions, which may help in further understanding the burdens of malnutrition and enteric infections in children. Specifically, by covering both clinical and in vivo/in vitro data, we describe the effects of vitamin A related to gut immune tolerance/homeostasis, intestinal barrier integrity, and responses to enteropathogens in the context of the environmental enteric dysfunction. Some of the gaps in the literature that require further research are also highlighted.

Susceptibility of Broiler Chickens to Coccidiosis When Fed Subclinical Doses of Deoxynivalenol and Fumonisins-Special Emphasis on the Immunological Response and the Mycotoxin Interaction.

Deoxynivalenol (DON) and fumonisins (FB) are the most frequently encountered mycotoxins produced by Fusarium species in livestock diets. The effect of subclinical doses of mycotoxins in chickens is largely unknown, and in particular the susceptibility of birds to pathogenic challenge when fed these fungal metabolites. Therefore, the present study reports the effects of DON and FB on chickens challenged with Eimeria spp, responsible for coccidiosis. Broilers were fed diets from hatch to day 20, containing no mycotoxins, 1.5 mg DON/kg, 20 mg FB/kg, or both toxins (12 pens/diet; 7 birds/pen). At day 14, six pens of birds per diet (half of the birds) were challenged with a 25×-recommended dose of coccidial vaccine, and all birds (challenged and unchallenged) were sampled 6 days later. As expected, performance of birds was strongly affected by the coccidial challenge. Ingestion of mycotoxins did not further affect the growth but repartitioned the rate of reduction (between the fraction due to the change in maintenance and feed efficiency), and reduced apparent nitrogen digestibility. Intestinal lesions and number of oocysts in the jejunal mucosa and feces of challenged birds were more frequent and intense in the birds fed mycotoxins than in birds fed control feed. The upregulation of cytokines (interleukin (IL) IL-1ß, IL-6, IL-8 and IL-10) following coccidial infection was higher in the jejunum of birds fed mycotoxins. Further, the higher intestinal immune response was associated with a higher percentage of T lymphocytes CD4⁺CD25⁺, also called Tregs, observed in the cecal tonsils of challenged birds fed mycotoxins. Interestingly, the increase in FB biomarker of exposure (sphinganine/sphingosine ratio in serum and liver) suggested a higher absorption and bioavailability of FB in challenged birds. The interaction of DON and FB was very dependent on the endpoint assessed, with three endpoints reporting antagonism, nine additivity, and two synergism. In conclusion, subclinical doses of DON and FB showed little effects in unchallenged chickens, but seem to result in metabolic and immunologic disturbances that amplify the severity of coccidiosis.

S-1-Propenylcysteine promotes the differentiation of B cells into IgA-producing cells by the induction of Erk1/2-dependent Xbp1 expression in Peyer's patches.

OBJECTIVES: S-Allylcysteine (SAC) and S-1-propenylcysteine (S1PC) are the characteristic sulfur-containing amino acids in aged garlic extract. In this study, we investigated the effect of SAC and S1PC on intestinal immunoglobulin (Ig)A production to gain insight into the immunomodulatory effect of aged garlic extract. METHODS: In vitro study: Mouse splenic lymphocytes were treated with S1PC (0.1 and 0.3 mM) or SAC (0.1 and 0.3 mM) for 3 d, and IgA concentration in the culture medium was examined. In vivo study: Mice were orally administrated S1PC (7.5, 15, and 30 mg/kg) for 5 d and the IgA level in the intestinal lavage fluids as well as the population of IgA-producing cells in Peyer's patches were measured using mouse IgA enzyme-linked immunosorbent assay quantification set and flow cytometer, respectively. RESULTS: S1PC enhanced IgA production in mouse splenic lymphocytes in culture. However, SAC was ineffective. In addition, oral administration of S1PC to mice increased the IgA level and number of IgA-producing cells in Peyer's Patches. Furthermore, S1PC induced the expression of X-box binding protein 1 (Xbp1) mRNA, an inducer of plasma cell differentiation, in Peyer's patches. This induction was accompanied by the degradation of paired box protein 5 and the activation of mitogen activated protein/extracellular signal-regulated kinase signaling pathway. CONCLUSION: These results suggest that S1PC increases IgA-producing cells via the enhancement of Erk1/2-mediated Xbp1 expression in the intestine.