Multicomponent Pathogen-Mimicking Nanoparticles Induce Intestinal Immune Responses against Paratuberculosis.

Given the worldwide problem posed by enteric pathogens, the discovery of safe and efficient intestinal adjuvants combined with novel antigen delivery techniques is essential to the design of mucosal vaccines. In this work, we designed poly (lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) to codeliver all-trans retinoic acid (atRA), novel antigens, and CpG. To address the insolubility of the intestinal adjuvant atRA, we utilized PLGA to encapsulate atRA and form a "nanocapsid" with polydopamine. By leveraging polydopamine, we adsorbed the water-soluble antigens and the TLR9 agonist CpG onto the NPs' surface, resulting in the pathogen-mimicking PLPCa NPs. In this study, the novel fusion protein (HBf), consisting of the Mycobacterium avium subspecies paratuberculosis antigens HBHA, Ag85B, and Bfra, was coloaded onto the NPs. In vitro, PLPCa NPs were shown to promote the activation and maturation of bone marrow-derived dendritic cells. Additionally, we found that PLPCa NPs created an immune-rich microenvironment at the injection site following intramuscular administration. From the results, the PLPCa NPs induced strong IgA levels in the gut in addition to enhancing powerful systemic immune responses. Consequently, significant declines in the bacterial burden and inflammatory score were noted in PLPCa NPs-treated mice. In summary, PLPCa can serve as a novel and safe vaccine delivery platform against gut pathogens, such as paratuberculosis, capable of activating both systemic and intestinal immunity.

Multi-omics approach to study the dual effects of novel proteins on the intestinal health of juvenile largemouth bass (Micropterus salmoides) under an alternate feeding strategy.

Introduction: In an effort to minimize the usage of fishmeal in aquaculture, novel protein diets, including Tenebrio molitor, cottonseed protein concentrate, Clostridium autoethanogenum, and Chlorella vulgaris were evaluated for their potential to replace fishmeal. Nevertheless, comprehensive examinations on the gut health of aquatic animals under an alternate feeding strategy when fed novel protein diets are vacant. Methods: Five isonitrogenous and isolipidic diets containing various proteins were manufactured, with a diet consisting of whole fishmeal serving as the control and diets containing novel proteins serving as the experimental diets. Largemouth bass (Micropterus salmoides) with an initial body weight of 4.73 ± 0.04g employed as an experimental animal and given these five diets for the first 29 days followed by a fishmeal diet for the next 29 days. Results: The results of this study demonstrated that the growth performance of novel protein diets in the second stage was better than in the first stage, even though only the C. vulgaris diet increased antioxidant capacity and the cottonseed protein concentrate diet decreased it. Concerning the intestinal barriers, the C. autoethanogenum diet lowered intestinal permeability and plasma IL-1ß/TNF-α. In addition, the contents of intestinal immunological factors, namely LYS and sIgA-like, were greater in C. vulgaris than in fishmeal. From the data analysis of microbiome and metabolome, the levels of short chain fatty acids (SCFAs), anaerobic bacteria, Lactococcus, and Firmicutes were significantly higher in the C. autoethanogenum diet than in the whole fishmeal diet, while the abundance of Pseudomonas, aerobic bacteria, Streptococcus, and Proteobacteria was lowest. However, no extremely large differences in microbiota or short chain fatty acids were observed between the other novel protein diets and the whole fishmeal diet. In addition, the microbiota were strongly connected with intestinal SCFAs, lipase activity, and tight junctions, as shown by the Mantel test and Pearson's correlation. Discussion: Taken together, according to Z-score, the ranking of advantageous functions among these protein diets was C. autoethanogenum diet > C. vulgaris diet > whole fishmeal diet > cottonseed protein concentrate > T. molitor diet. This study provides comprehensive data illustrating a mixed blessing effect of novel protein diets on the gut health of juvenile largemouth bass under an alternate feeding strategy.

Influence of vitamin D metabolites on vitamin D status, immunity and gut health of piglets.

Immediately post-weaning, piglets are prone to gastrointestinal infectious diseases. The active metabolite of vitamin D 1,25-dihydroxyvitamin D has direct impact on immune cell function and responses. Thus, a low vitamin D status may compromise the immune responses during infectious diseases. The aim of this study was to examine the effect of supplementation of different forms of vitamin D (25-OH-D3 and vitamin D3) to suckling piglets' vitamin D status at weaning. In addition, to determine whether the vitamin D status could affect the immune development in piglets and their robustness against E. coli challenge. Genetically E. coli F4 susceptible litters of piglets were divided into two treatment groups: group 1 (n = 16) provided milk formula supplemented with vitamin D3 (CON), and group 2 (n = 16) provided milk formula supplemented with 25-OH-D3 (TREAT). Piglets were offered the experimental milk formulas from day 3 after farrowing until weaning (at day 28 of age). A commercial weaner diet with high protein content were provided to induce weaning stress. Milk formulas, sow and weaner diets as well as plasma and milk samples obtained from sows (n = 8) were analysed for vitamin D metabolites. Vitamin D status in piglets was investigated by collection of plasma samples on day 3, 15, 28 and 35 of age. Eight piglets randomly selected from each dietary group (in total 16 pigs) were inoculated with E. coli F4 O149 on day 2 and 3 post-weaning. Blood samples collected on day 2 and 9 post-weaning (pre- and post E. coli inoculation, respectively) were analysed for haematological and immunological parameters including immunoglobulins, antibodies specific to E. coli O149 K88, cytokines and C-reactive protein. In addition, intestinal samples were obtained one week after E. coli inoculation to study the influence of infection and vitamin D status on immune responses at different sites of the intestine. This was accomplished by gene expression of various cytokines and tight junction proteins. In general, vitamin D status of the piglets were low. However, piglets provided TREAT during the suckling period had increased vitamin D status at weaning compared to piglets provided CON. Vitamin D was used during activation of the immune system as pigs inoculated with E. coli had lower plasma concentrations of 25-OH-D3 than non-inoculated pigs possibly due to mobilising of vitamin D in the liver. Hence, increased vitamin D status at weaning might improve piglets' resistance to E. coli infection.

Fermented rice bran supplementation attenuates chronic colitis-associated extraintestinal manifestations in female C57BL/6N mice.

Patients with inflammatory bowel disease (IBD) have higher incidence of extraintestinal manifestations (EIM), including liver disorders, sarcopenia, and neuroinflammation. Fermented rice bran (FRB), generated from rice bran (RB), is rich in bioactive compounds, and exhibits anti-colitis activity. However, its role in EIM prevention is still unclear. Here, for the first time, we investigated whether EIM in female C57Bl/6N mice is attenuated by FRB supplementation. EIM was induced by repeated administration of 1.5% dextran sulfate sodium (DSS) in drinking water (4 d) followed by drinking water (12 d). Mice were divided into 3 groups-control (AIN93M), 10% RB, and 10% FRB. FRB ameliorated relapsing colitis and inflammation in muscle by significantly lowering proinflammatory cytokines Tnf-α and Il-6 in serum and advanced glycation end product-specific receptor (Ager) in serum and muscle when compared with the RB and control groups. As FRB reduced aspartate aminotransferase levels and oxidative stress, it might prevent liver disorders. FRB downregulated proinflammatory cytokine and chemokine transcripts responsible for neuroinflammation in the hippocampus and upregulated mRNA expression of G protein coupled receptors (GPRs), Gpr41 and Gpr43, in small and large intestines, which may explain the FRB-mediated protective mechanism. Hence, FRB can be used as a supplement to prevent IBD-associated EIM.

Rhamnolipids enhance growth performance by improving the immunity, intestinal barrier function, and metabolome composition in broilers.

BACKGROUND: Rhamnolipids (RLS), well known as glycolipid biosurfactants, display low toxicity, high biodegradability, and strong antibacterial properties. This study was carried out to evaluate the use of RLS supplementation as a substitute for antibiotics, and particularly to evaluate its effects on growth performance, immunity, intestinal barrier function, and metabolome composition in broilers. RESULTS: The RLS treatment improved the growth performance, immunity, and intestinal barrier function in broilers. The 16S rRNA sequencing revealed that the genus Alistipes was the dominant genus in broilers treated by RLS. An ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS)-based metabolomic analysis indicated that the sphingolipid metabolism, glycine, serine, and threonine metabolism, the gycerophospholipid metabolism, and the tryptophan metabolism were changed in broilers that were treated with RLS. CONCLUSION: l-Tryptophan may be the medium for RLS to regulate the growth and physiological metabolism. Rhamnolipids can be used as a potential alternative to antibiotics, with similar functions to antibiotics in the diet of broilers. The optimal level of supplemented RLS in the diet was 1000 mg kg-1 . © 2021 Society of Chemical Industry.

Term Infant Formulas Influencing Gut Microbiota: An Overview.

Intestinal colonization of the neonate is highly dependent on the term of pregnancy, the mode of delivery, the type of feeding [breast feeding or formula feeding]. Postnatal immune maturation is dependent on the intestinal microbiome implementation and composition and type of feeding is a key issue in the human gut development, the diversity of microbiome, and the intestinal function. It is well established that exclusive breastfeeding for 6 months or more has several benefits with respect to formula feeding. The composition of the new generation of infant formulas aims in mimicking HM by reproducing its beneficial effects on intestinal microbiome and on the gut associated immune system (GAIS). Several approaches have been developed currently for designing new infant formulas by the addition of bioactive ingredients such as human milk oligosaccharides (HMOs), probiotics, prebiotics [fructo-oligosaccharides (FOSs) and galacto-oligosaccharides (GOSs)], or by obtaining the so-called post-biotics also known as milk fermentation products. The aim of this article is to guide the practitioner in the understanding of these different types of Microbiota Influencing Formulas by listing and summarizing the main concepts and characteristics of these different models of enriched IFs with bioactive ingredients.

Camel milk ameliorates inflammatory mechanisms in an alcohol-induced liver injury mouse model.

Camel milk (CM) is considered to protect the liver in the practice of traditional medicine in nomadic areas. The purpose of the present study was to investigate the effects of CM on the hepatic biochemical and multiple omics alterations induced by chronic alcoholic liver disease (ALD). An intragastric gavage mice Lieber DeCarli + Gao binge model (NIAAA model) was employed to investigate the inflammatory mechanism of camel milk on the liver tissue of mice. A gut microbiota of the feces of mice and transcriptomic and proteomic analyses of the liver of mice were performed. Analysis of serum and liver biochemical indexes revealed that camel milk not only prevents alcohol-induced colonic dysfunction and lipid accumulation, but also regulates oxidative stress and inflammatory cytokine production to protect against chronic ALD in mouse. The gut microbial community of mice treated with camel milk was more similar to the untreated control group than to the model group, indicating that the intake of camel milk pre- and post-alcohol gavage effectively prevents and alleviates the intestinal microbial disorder caused by chronic alcoholism in mice. Furthermore, the results of the transcriptomic and proteomic analyses of the liver tissue showed that camel milk can improve alcoholic liver injury in mice by regulating inflammatory factors and immune system disruptions. This study provides insights into the molecular mechanism by which camel milk can be developed as a potential functional food with no side effects and against liver injury.

Berberine Attenuates Neonatal Sepsis in Mice By Inhibiting FOXA1 and NF-κB Signal Transduction Via the Induction of MiR-132-3p.

Neonatal sepsis (NS) is a severe syndrome in newborns that is induced by infections, and the initiation and development of NS are closely associated with the function of miRs. In the current study, the effects of berberine, which is a functional component in traditional Chinese medicine (TCM), against NS were assessed by focusing on the interaction of berberine with miR-132-3p-mediated signaling. An NS model was induced using cecal slurry (CS) in vivo and LPS in vitro, and berberine treatment was applies. The changes in survival rate, intestinal structure, and systemic inflammation in mice and the viability, apoptosis, and inflammatory response in intestinal cells were measured. At the molecular level, miR-132-3p levels and the activities of the FOXA1 and NF-κB pathways were analyzed. The data showed that berberine increased the survival rates of CS-induced mice. The intestinal injuries induced by CS were also attenuated by berberine, which was associated with inhibition of the production of systemic IL-6, IL-1ß, and TNF-α. At the molecular level, the expression of miR-132-3p was upregulated, suppressing the expression of FOXA1, p-IκBα, and p65 while inducing the expression of IκBα. The effects of berberine on NS-induced impairments were blocked by the injection of the miR-132-3p antagomir, which exacerbated intestinal injuries, induced systemic inflammation, and reactivated the FOXA1 and NF-κB pathways. The findings in the in vivo model were validated with in vitro assays. Collectively, the findings outlined in the current study indicated that berberine had solid protective effects against NS-induced symptoms in newborn mice, and the effects depended on the upregulation of miR-132-3p.

Gut immune-related gene expression, histomorphometry and hematoimmunological assays in Nile tilapia (Oreochromis niloticus) fed Aspergillus oryzae fermented olive cake.

Fermentation strategy is well documented to improve the nutritional value of agricultural waste by-products such olive cake (OC), which, in turn, provides healthy, safe, and affordable feedstuff. This study assessed the combined impact of Aspergillus oryzae-fermented OC (AFOC) on the growth performance, intestinal morphometry, blood biochemistry, lysozyme activity, gut immune-related genes, and flesh quality of Nile tilapia. We divided 225 fish into five groups and further subdivided into three replicates (n = 15 each) and fed them five diets (Control, AFOC5, AFOC10, AFOC15, AFOC20) to determine AFOC nutritional value and its optimized incorporation level in the diet. The trial continued for 3 months. The crude protein content of OC improved by 7.77% after A. oryzae fermentation, while lipid content decreased by 14.19%. In addition, growth and feed utilization significantly improved at (10.8-11.2) % AFOC dietary level. High-density lipoprotein (HDL) significantly improved, and the serum lysozyme level was significantly higher in the AFOC10 group compared to other groups. Interestingly, gut-related inflammatory cytokines tumor necrosis factor alpha (TNF- α) and interleukin 1 beta (IL-1ß) revealed higher relative mRNA expression in the AFOC10 group compared to other groups. The histomorphometric parameters was greatly influenced by the AFOC incorporation level (10%-20%). These findings suggested that A. orzae fermentation modifies the nutritional quality of OC, as seen through its positive impact on the growth performance, local and systemic immunity, and intestinal absorptive capacity of Nile tilapia. The recommended dose for dietary AFOC was around 11.

Polysaccharides from Premna microphylla turcz ameliorate inflammation via the enhancement of intestinal resistance in host.

ETHNOPHARMACOLOGICAL RELEVANCE: Premna microphylla turcz is traditionally used as a folk remedy. Its roots, stems and leaves can be invoked as medicines, which have the functions of detoxification, swelling and hemostasis. It belongs to the Premna in the Verbenaceae and is mainly distributed in the mountains of southeastern China. However, there are few reports of in-depth studies on the anti-inflammatory effects of polysaccharide, which was the main component in Premna microphylla turcz. MATERIALS AND METHODS: The flies were fed with standard corn flour-yeast medium to cause inflammation by sodium lauryl sulfate (SDS). The treatment group contained Premna microphylla turcz polysaccharide (pPMTLs) extract. The survival rate was obtained by feeding a vial containing five layers of filter paper, which was infiltrated with the 5% sucrose solution contaminated with SDS or SDS polysaccharide. The microvilli and nucleus of the midgut epithelial cells of different treatments were observed by transmission electron microscope, and the expression of inflammation-related genes was detected by real-time quantitative PCR (qRT-PCR). Finally, 16S rDNA analysis was conducted on the differences in the composition of the intestinal microbes of Drosophila. RESULTS: In the current study, we showed that pPMTLs significantly prolonged the life span of SDS-inflamed flies from 5 days to 6 days. And pPMTLs reduced the rupture of microvilli in the midgut and restored the nuclear structure. In addition, pPMTLs significantly improved expression level of immune-related genes in Inflammation Drosophila especially the defensin (4.32 ± 0.75 vs 9.97 ± 0.52 SDS-polysaccharide group: SDS group, p < 0.001). The analysis of intestinal microbiota showed that pPMTLs decreased the relative abundance of Raoultella while Wolbachia increased (p < 0.05). CONCLUSIONS: Collectively, our results revealed the potential application of pPMTLs in enhancing inflammation defense, which would be enormous significance for the inflammation-related disorders treatment.

Effects of Scrophularia striata hydroalcoholic extract in comparison to salinomycin on growth performance, intestinal health and immunity in broiler chickens following a mixed-species Eimeria challenge.

Poultry coccidiosis is an important disease affecting performance which is characterized by intestinal epithelium damageand increased mortality and is caused by the protozoa parasites of the genus Eimeria. This study evaluated the growth-promoting (experiment 1), protective, and immunostimulatory effects (experiment 2) of salinomycin and Scrophularia striata hydroalcoholic extract (SSE) against coccidiosis in broilers. Two experiments were conducted with 300 1-day-old broiler chickens, which were randomly assigned to 5 treatments with 6 replicate pens of 10 birds (experiment 1) or 10 replicate cages of 6 birds (experiment 2). In both experiments, treatments were: negative control (NC: untreated, and uninfected); positive control (PC: untreated, infected); or PC supplemented with salinomycin (Sal); 200 mg/kg of SSE (SSE200); or 400 mg/kg of SSE (SSE400). All these groups (except NC) were challenged via oral gavage with of sporulated oocysts of Eimeria species (Eimeria acervulina, Eimeria maxima, and Eimeria tenella) on d 10 (experiment 1) or d 14 (experiment 2). In the first trial, all treatments improved growth and feed conversion compared with the PC group, where the best values were noticed in the NC, SAL, and SSE400 groups throughout the entire experimental period (d 1-42). Further, a lower mortality rate (P < 0.05) was observed in the NC, Sal, and SSE400 groups as compared to that in the PC group. In the second trial, intestinal lesion scores and total oocyst numbers were reduced in the Sal and SSE400 groups compared to the PC group, although all coccidiosis-challenged groups had higher intestinal lesion scores (P < 0.05) compared to NC group. Immune responses revealed that among challenged birds, those fed diets Sal and SSE400 had significantly higher Eimeria-specific cecum IgG and IgM levels, but lower serum IFN-γ concentration than the PC group. Among the experimental treatments, broiler chickens fed diet SSE400 had greater (P < 0.05) Eimeria-specific serum IgG and TGF-ß levels, but lower (P < 0.05) serum IL-6 concentration than those fed the PC diet at d 24. Considering the results, dietary SSE, especially at high levels of inclusion in broiler diet (400 mg/kg), could result in a comparable growth performance and a better immune response, compared to a salinomycin supplement under coccidiosis challenge.

Diet, Immunity, and Microbiota Interactions: An Integrative Analysis of the Intestine Transcriptional Response and Microbiota Modulation in Gilthead Seabream (Sparus aurata) Fed an Essential Oils-Based Functional Diet.

Essential oils (EOs) are promising alternatives to chemotherapeutics in animal production due to their immunostimulant, antimicrobial, and antioxidant properties, without associated environmental or hazardous side effects. In the present study, the modulation of the transcriptional immune response (microarray analysis) and microbiota [16S Ribosomal RNA (rRNA) sequencing] in the intestine of the euryhaline fish gilthead seabream (Sparus aurata) fed a dietary supplementation of garlic, carvacrol, and thymol EOs was evaluated. The transcriptomic functional analysis showed the regulation of genes related to processes of proteolysis and inflammatory modulation, immunity, transport and secretion, response to cyclic compounds, symbiosis, and RNA metabolism in fish fed the EOs-supplemented diet. Particularly, the activation of leukocytes, such as acidophilic granulocytes, was suggested to be the primary actors of the innate immune response promoted by the tested functional feed additive in the gut. Fish growth performance and gut microbiota alpha diversity indices were not affected, while dietary EOs promoted alterations in bacterial abundances in terms of phylum, class, and genus. Subtle, but significant alterations in microbiota composition, such as the decrease in Bacteroidia and Clostridia classes, were suggested to participate in the modulation of the intestine transcriptional immune profile observed in fish fed the EOs diet. Moreover, regarding microbiota functionality, increased bacterial sequences associated with glutathione and lipid metabolisms, among others, detected in fish fed the EOs supported the metabolic alterations suggested to potentially affect the observed immune-related transcriptional response. The overall results indicated that the tested dietary EOs may promote intestinal local immunity through the impact of the EOs on the host-microbial co-metabolism and consequent regulation of significant biological processes, evidencing the crosstalk between gut and microbiota in the inflammatory regulation upon administration of immunostimulant feed additives.

Selenomethionine ameliorates LPS-induced intestinal immune dysfunction in chicken jejunum.

Selenomethionine (SeMet) is a widely used food supplement. However, the research on the effect of SeMet on intestinal immune function is not enough. Therefore, in this experiment, SeMet was added to the diet of chickens, and lipopolysaccharide (LPS) was used as harmful stimulation to study the effect of SeMet on intestinal immune function in chickens. We chose chicken jejunum as the research object. The results showed that LPS treatment decreased the expressions of selenoproteins and induced inflammatory reaction, cytokine disorder, decreases of immunoglobulin levels, heat shock protein expression disorder, and decreases of defensin expression levels in jejunum. However, dietary SeMet can effectively alleviate the above injury caused by LPS. Our results showed that SeMet could improve the intestinal immunity in chickens, and feeding SeMet could alleviate the intestinal immune dysfunction caused by LPS. The application range of SeMet in feed can be roughly given through our experiment; i.e. 0.35-0.5 mg/kg SeMet was effective. We speculated that dietary SeMet could effectively alleviate the intestinal immune dysfunction caused by harmful stimulation and help to resist the further damage caused by harmful stimulation.

Dietary Chitosan Nanoparticles: Potential Role in Modulation of Rainbow Trout (Oncorhynchus mykiss) Antibacterial Defense and Intestinal Immunity against Enteric Redmouth Disease.

Bio-nanotechnology employing bio-sourced nanomaterial is an emerging avenue serving the field of fish medicine. Marine-sourced chitosan nanoparticles (CSNPs) is a well-known antimicrobial and immunomodulatory reagent with low or no harm side effects on fish or their human consumers. In this study, in vitro skin mucus and serum antibacterial activity assays along with intestinal histology, histochemical, and gene expression analyses were performed to evaluate the impact of dietary CSNPs (5 g kg-1 dry feed) on rainbow trout resistance against 'enteric redmouth' disease. Two treatment conditions were included; short-term prophylactic-regimen for 21 days before the bacterial challenge, and long-term therapeutic-regimen for 21 days before the challenge and extended for 28 days after the challenge. Our results revealed higher antibacterial defense ability and positive intestinal histochemical and molecular traits of rainbow trout after dietary CSNPs. The prophylactic-regimen improved trout health while the therapeutic regimen improved their disease resistance and lowered their morbidity. Therefore, it is anticipated that CSNPs is an effective antibacterial and immunomodulatory fish feed supplement against the infectious threats. However, the CSNPs seem to be more effective in the therapeutic application rather than being used for short-term prophylactic applications.

Early immune response in large yellow croaker (Larimichthys crocea) after immunization with oral vaccine.

Mesoporous silica nanoparticles (MSNs) have been used in the field of biomedicine as antigen carriers and adjuvants for protective antigens. In the present study, an oral nanovaccine against Vibrio alginolyticus was prepared employing MSNs as carriers. The uptake of the dihydrolipoamide dehydrogenase (DLDH) antigens in the intestine of large yellow croaker was evaluated using an immunohistochemistry assay. Additionally, the effects of the nanovaccine on the early immune response in large yellow croaker were investigated via oral vaccination. The presence of the antigens was detected in the mucosa and lamina propria of the foregut, midgut, and hindgut of large yellow croaker at 3 h following oral immunization. The expression levels of cytokines (i.e., lysozyme, IFN-γ, IFITM, TNF-α, IL-1ß, IL-2, IL-4, IL-10, and IL-13) in the intestine, spleen, and head kidney tissues of large yellow croaker before and after the immune challenge were determined via RT-qPCR assay. The obtained results revealed that the expression levels of lysozyme, IFN-γ, IFITM, TNF-α, IL-1ß, IL-2, IL-4, IL-10, and IL-13 in the intestine and head kidney of the vaccinated large yellow croaker, as well as the expression of lysozyme, IL-1ß, and IL-10 in the spleen, exhibited time-dependent oscillation regulation patterns. Notably, the nanovaccine immunization could induce early (6 h) and high expression of IFN-γ in the spleen and kidney tissues after the bacterial infection. The current study supplements the available data on the early immune response to fish nanovaccines. It also provides a valuable theoretical basis for the future development of large yellow croaker oral vaccines.

Gut priming with bovine colostrum and T regulatory cells in preterm neonates: a randomized controlled trial.

BACKGROUND: Necrotizing enterocolitis (NEC) and neonatal sepsis are still considered major problems, especially in formula-fed preterm neonates. This study aimed to investigate the effect of bovine colostrum on T regulatory cells, NEC, and late-onset sepsis in preterm neonates ≤34 weeks. METHODS: This prospective double-blind randomized controlled trial was conducted on 80 preterm infants who were randomly assigned to either the bovine colostrum group (n = 32) or control group (n = 48). T lymphocytes and their subsets, necrotizing enterocolitis, late-onset sepsis (LOS) and its severity, feeding tolerance, growth, length of hospital stay, and mortality were documented. RESULTS: The bovine colostrum group showed higher follow-up levels of CD4+CD25+ FOXP3+ T lymphocyte % (FOXP3 Tregs). FOXP3 Tregs and its difference in change levels between baseline and follow-up were considered as the most related factors to the bovine colostrum. Bovine colostrum group showed positive trends for reduction of sepsis severity and mortality with no significant difference in the incidence of NEC, LOS, and length of hospital stay. CONCLUSIONS: Preterm neonates who received bovine colostrum showed a higher FOXP3 Treg level. IMPACT: Bovine colostrum has no significant effect on the incidence of necrotizing enterocolitis. FOXP3 T regulatory cells and their increased level between baseline and follow-up is considered as the most influencing factors related to the bovine colostrum. Positive trends were noted for reduction of sepsis severity and concomitant mortality, but the study lacked the power to assess these outcomes.

Associations among Dietary Omega-3 Polyunsaturated Fatty Acids, the Gut Microbiota, and Intestinal Immunity.

Omega-3 polyunsaturated fatty acids (omega-3 PUFAs), which are essential fatty acids that humans should obtain from diet, have potential benefits for human health. In addition to altering the structure and function of cell membranes, omega-3 PUFAs (docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), alpha-linolenic acid (ALA), and docosapentaenoic acid (DPA)) exert different effects on intestinal immune tolerance and gut microbiota maintenance. Firstly, we review the effect of omega-3 PUFAs on gut microbiota. And the effects of omega-3 PUFAs on intestinal immunity and inflammation were described. Furthermore, the important roles of omega-3 PUFAs in maintaining the balance between gut immunity and the gut microbiota were discussed. Additional factors, such as obesity and diseases (NAFLD, gastrointestinal malignancies or cancer, bacterial and viral infections), which are associated with variability in omega-3 PUFA metabolism, can influence omega-3 PUFAs-microbiome-immune system interactions in the intestinal tract and also play roles in regulating gut immunity. This review identifies several pathways by which the microbiota modulates the gut immune system through omega-3 PUFAs. Omega-3 supplementation can be targeted to specific pathways to prevent and alleviate intestinal diseases, which may help researchers identify innovative diagnostic methods.

Gut microbiota as a target to limit toxic effects of traditional Chinese medicine: Implications for therapy.

Traditional Chinese medicines (TCMs) are medicines that are widely used in oriental countries under the guidance of ancient Chinese medicinal philosophies. With thousands of years of experiences in fighting against diseases, TCMs are gaining increasing importance in the world. Although the efficacy of TCMs is well recognized in clinic, the toxicity of TCMs has become a serious issue around the world in recent years. In general, the toxicity of TCMs is caused by the toxic medicinal compounds and contaminants in TCMs such as pesticides, herbicides, and heavy metals. Recent studies have demonstrated that gut microbiota can interact with TCMs and thus influence the toxicity of TCMs. However, there is no focused review on gut microbiota and the toxicity of TCMs. Here, we summarized the influences of the gut microbiota on the toxicity of medicinal compounds in TCMs and the corresponding mechanisms were offered. Then, we discussed the relationships between gut microbiota and the TCM contaminants. In addition, we discussed the methods of manipulating gut microbiota to reduce the toxicity of TCMs. At the end of this review, the perspectives on gut microbiota and the toxicity of TCMs were also discussed.

Effects of Astragalus polysaccharides on intestinal morphology and intestinal immune cells of Muscovy ducklings infected with Muscovy duck reovirus.

Muscovy duck reovirus (MDRV) infection induces serious immunosuppression and intestinal injury in Muscovy ducklings with a high morbidity and mortality, and Astragalus polysaccharide (APS) pretreatment could efficiently protect ducklings from MDRV infection, although the underlying immunoregulatory mechanisms remain unclear. Thus, the objective of this study was to investigate effects of APS on the intestinal mucosal immunity in MDRV-infected Muscovy ducklings. A total of 190 1-day-old healthy Muscovy ducklings were randomly assigned to 3 groups (n = 50): normal control group, APS pretreatment for MDRV-infected group, and cohabitation infection group, then pretreated with 0.6 g/L APS or only drinking water followed by MDRV cohabitation infection with the remaining 40 artificially infected ducklings, respectively. At the 2, 3, 4, 6, 9 and 15 d after cohabitation infection, the intestinal samples were prepared to measure intestinal parameters including villus length, villus length/crypt depth (V/C) ratio, and wall thickness, together with counts of intraepithelial lymphocyte (IEL) and goblet cell (GC) by hematoxylin-eosin staining. Meanwhile, ileal secretory IgA (sIgA) and duodenal cytokine levels of IL-4, IL-6, IL-15, tumor necrosis factor-alpha, and interferon gamma were detected by the ELISA and radioimmunoassay, respectively. The results showed that APS significantly improved intestinal injuries of villi length, V/C ratio, and wall thickness of the small intestine infected with MDRV, effectively inhibited the reduction of IEL and GC caused by MDRV infection, subsequently increased sIgA and all the cytokine secretions at most time points, suggesting that APS pretreatment can effectively stimulate mucosal immune function by improving intestinal morphology and repair MDRV caused injures of small intestinal mucosal immune barrier in infected ducklings. Our findings lay the foundation for further application of APS in prevention and treatment of MDRV infection.

Electroacupuncture alleviates intestinal inflammation and barrier dysfunction by activating dopamine in a rat model of intestinal ischaemia.

BACKGROUND: To investigate whether the mechanism underlying the anti-inflammatory effects of electroacupuncture (EA) at ST36 involves dopamine (DA) and its receptor and whether it is mediated by the vagus nerve in a rat model of intestinal ischaemia-reperfusion (I/R) injury. METHODS: Rats were subjected to gut ischaemia for 30 min and then received EA for 30 min with or without abdominal vagotomy or intraperitoneal administration of butaclamol (D1 receptor antagonist) or spiperone (D2 receptor antagonist). Plasma levels of DA and tumour necrosis factor (TNF)-α were assessed 1 or 4 h after reperfusion. Myeloperoxidase (MPO) activity and malondialdehyde (MDA) content in intestinal tissues were assessed using enzyme-linked immunosorbent assay (ELISA) kits. Intestinal tissue injury was assessed by observation of the pathological lesions and permeability to 4 kDa fluorescein isothiocyanate (FITC)-dextran. RESULTS: EA significantly increased levels of DA and lowered levels of TNF-α. EA also inhibited intestinal levels of MPO and MDA and intestinal tissue injury and decreased intestinal permeability to FITC-dextran. Abdominal vagotomy and intraperitoneal administration of butaclamol (but not spiperone) inhibited the effects of EA. CONCLUSION: These findings suggest that EA at ST36 could attenuate intestinal I/R-induced inflammatory injury and that the underlying mechanism may involve EA-induced increases in levels of DA, mediated by the vagus nerve and D1 receptors.