Effect of Niacin on Growth Performance, Intestinal Morphology, Mucosal Immunity and Microbiota Composition in Weaned Piglets.

This study aimed to investigate the effects of niacin on growth performance, intestinal morphology, intestinal mucosal immunity, and colonic microbiota in weaned piglets. A total of 96 weaned piglets (Duroc × (Landrace × Yorkshire), 21-d old, 6.65 ± 0.02 kg body weight (BW)) were randomly allocated into 3 treatment groups (8 replicate pens per treatment, each pen containing 4 males; n = 32/treatment) for 14 d. Piglets were fed a control diet (CON) or the CON diet supplemented with 20.4 mg/kg niacin (NA) or an antagonist for the niacin receptor GPR109A (MPN). The results showed that NA or MPN had no effect on ADG, ADFI, G/F or diarrhea incidence compared with the CON diet. However, compared with piglets in the NA group, piglets in the MPN group had lower ADG (p = 0.042) and G/F (p = 0.055). In comparison with the control and MPN group, niacin supplementation increased the villus height and the ratio of villus height to crypt depth (p < 0.05), while decreasing the crypt depth in the duodenum (p < 0.05). Proteomics analysis of cytokines showed that niacin supplementation increased the expression of duodenal transforming growth factor-ß (TGF-ß), jejunal interleukin-10 (IL-10) and ileal interleukin-6 (IL-6) (p < 0.05), and reduced the expression of ileal interleukin-8 (IL-8) (p < 0.05) compared with the control diet. Piglets in the MPN group had significantly increased expression of ileal IL-6, and jejunal IL-8 and interleukin-1ß (IL-1ß) (p < 0.05) compared with those in the control group. Piglets in the MPN group had lower jejunal IL-10 level and higher jejunal IL-8 level than those in the NA group (p < 0.05). The mRNA abundance of duodenal IL-8 and ileal granulocyte-macrophage colony-stimulating factor (GM-CSF) genes were increased (p < 0.05), and that of ileal IL-10 transcript was decreased (p < 0.05) in the MPN group compared with both the control and NA groups. Additionally, niacin increased the relative abundance of Dorea in the colon as compared with the control and MPN group (p < 0.05), while decreasing that of Peptococcus compared with the control group (p < 0.05) and increasing that of Lactobacillus compared with MPN supplementation (p < 0.05). Collectively, the results indicated that niacin supplementation efficiently ensured intestinal morphology and attenuated intestinal inflammation of weaned piglets. The protective effects of niacin on gut health may be associated with increased Lactobacillus and Dorea abundance and butyrate content and decreased abundances of Peptococcus.

Polysaccharides from Pinus massoniana pollen improve intestinal mucosal immunity in chickens.

Intestinal mucosa is the largest immune organ in animals, and its immune function is directly related to the resistance against various diseases. Taishan Pinus massoniana pollen polysaccharides (TPPPS) have been recognized as an effective vaccine adjuvant and potential immune enhancer against viral infections. However, little is known about their direct immune-enhancing activity on intestinal mucosa. In this study, we extracted the polysaccharides from Taishan masson pine pollen to investigate its promotive effect on intestinal mucosal immunity. A total of 120 1-day-old chickens were divided into 4 groups and inoculated with PBS or 3 different doses of TPPPS (10 mg/mL, 20 mg/mL, and 40 mg/mL), respectively. Feces, intestinal specimens, and serum samples were collected from the chickens at 7, 14, and 21 d after inoculation. The antibodies in serum, mucosal secretion of IgA, structure of intestinal villi, and expressions of cytokine genes and mucosal immune-related genes in the chickens were all significantly improved by TPPPS treatments. At 21 d after inoculation following the challenge of Newcastle disease virus, the chickens inoculated with 20 and 40 mg/mL TPPPS exhibited decreased weight loss and reduced intestinal pathologic damage and viral loads in the intestine. In summary, our results demonstrate that TPPPS can enhance mucosal immunity and promote intestinal villi development. This study has established the foundation for the development of novel immune-enhancing agent with immune-regulatory effects on intestinal mucosa.

Self-assembled aggregations in Coptidis Rhizoma decoction dynamically regulate intestinal tissue permeability through Peyer's patch-associated immunity / 中草药·英文版

Objective: To investigate the dynamic regulation of self-assembled aggregations (SAA) in Coptidis Rhizoma decoction on the permeability of intestinal tissue and the mechanism underlying. Methods: The effects of SAA on berberine (Ber) absorption were respectively analyzed in an in situ intestinal perfusion model and in an Ussing Chamber jejunum model with or without Peyer's patches (PPs). The expression levels of ZO-1, Occludin and Claudin-1 were detected by immunofluorescence to evaluate the tight junction (TJ) between intestinal epithelium cells. The expression levels of T-box-containing protein expressed in T cells, signal transducers and activators of tranion-6, retinoic acid receptor-related orphan receptor γt and forkhead box P3 in PPs were detected by the reverse transcription-polymerase chain reaction and the secretions of interferon-γ (IFN-γ), interleukin-4 (IL-4), interleukin-17 (IL-17) and transforming growth factor-β (TGF-β) in PPs were evaluated by immunohistochemistry, to reflect the differentiation of T lymphocyte in PPs to helper T (Th) cell 1, Th2, Th17 and regulatory T (Treg) cell. To confirm the correlation between SAA in Coptidis Rhizoma decoction, PPs-associated immunity and intestinal epithelium permeability, SAA were administrated on an Ussing Chamber jejunum model with immunosuppressed PPs and evaluated its influences on intestinal tissue permeability and TJ proteins expression. Results: SAA in Coptidis Rhizoma decoction could dose-dependently promote Ber absorption in jejunum segment, with the participation of PPs. The dose-dependent and dynamical regulations of SAA on permeability of intestinal tissue and TJ proteins expression level between intestinal epithelium cells occurred along with the dynamically changed T lymphocyte differentiation and immune effectors secretion in PPs. The administration of SAA on immunosuppressed PPs exhibited dose-dependent PPs activation, inducing dynamic promotion on intestinal tissue permeability and inhibition on TJ proteins expression. Conclusion: SAA can improve the Ber absorption in small intestine, through the PPs-associated immunity induced dynamic regulation on intestinal tissue permeability and TJ proteins expression. These findings might enlighten the research of traditional Chinese medicine decoction.

Self-assembled aggregations in Coptidis Rhizoma decoction dynamically regulate intestinal tissue permeability through Peyer's patch-associated immunity.

Objective: To investigate the dynamic regulation of self-assembled aggregations (SAA) in Coptidis Rhizoma decoction on the permeability of intestinal tissue and the mechanism underlying. Methods: The effects of SAA on berberine (Ber) absorption were respectively analyzed in an in situ intestinal perfusion model and in an Ussing Chamber jejunum model with or without Peyer's patches (PPs). The expression levels of ZO-1, Occludin and Claudin-1 were detected by immunofluorescence to evaluate the tight junction (TJ) between intestinal epithelium cells. The expression levels of T-box-containing protein expressed in T cells, signal transducers and activators of tranion-6, retinoic acid receptor-related orphan receptor γt and forkhead box P3 in PPs were detected by the reverse transcription-polymerase chain reaction and the secretions of interferon-γ (IFN-γ), interleukin-4 (IL-4), interleukin-17 (IL-17) and transforming growth factor-ß (TGF-ß) in PPs were evaluated by immunohistochemistry, to reflect the differentiation of T lymphocyte in PPs to helper T (Th) cell 1, Th2, Th17 and regulatory T (Treg) cell. To confirm the correlation between SAA in Coptidis Rhizoma decoction, PPs-associated immunity and intestinal epithelium permeability, SAA were administrated on an Ussing Chamber jejunum model with immunosuppressed PPs and evaluated its influences on intestinal tissue permeability and TJ proteins expression. Results: SAA in Coptidis Rhizoma decoction could dose-dependently promote Ber absorption in jejunum segment, with the participation of PPs. The dose-dependent and dynamical regulations of SAA on permeability of intestinal tissue and TJ proteins expression level between intestinal epithelium cells occurred along with the dynamically changed T lymphocyte differentiation and immune effectors secretion in PPs. The administration of SAA on immunosuppressed PPs exhibited dose-dependent PPs activation, inducing dynamic promotion on intestinal tissue permeability and inhibition on TJ proteins expression. Conclusion: SAA can improve the Ber absorption in small intestine, through the PPs-associated immunity induced dynamic regulation on intestinal tissue permeability and TJ proteins expression. These findings might enlighten the research of traditional Chinese medicine decoction.

Coptis chinensis Franch polysaccharides provide a dynamically regulation on intestinal microenvironment, based on the intestinal flora and mucosal immunity.

ETHNOPHARMACOLOGICAL RELEVANCE: Coptis chinensis Franch is one of the most widely used traditional Chinese herbs in China and was firstly recorded in "Shennong's Classic of Materia Medica" in the Han Dynasty. The medical records in past thousands years have fully confirmed the clinical efficacies of Coptis chinensis Franch against intestinal diseases. The polysaccharides in herbal medicines can be digested by the flora and uptaken by the Peyer's patches (PPs) in intestine. It can be reasonably presumed that the polysaccharides in Coptis chinensis Franch (CCP) should be one of the critical element in the regulation of intestinal microenvironment. AIM OF THE STUDY: This study intended to explore the dynamic regulation of CCP on intestinal microenvironment from the perspective of the intestinal mucosal immunity and the intestinal flora, in order to provide a new research perspective for the pharmacological mechanism of Coptis chinensis Franch. MATERIALS AND METHODS: The absorption and distribution of CCP in intestinal tissues were observed after the perfusion of FITC labeled CCP. The influences of CCP on intestinal flora were evaluated by the 16sRNA gene illumina-miseq sequencing after gavage. The regulations of CCP on intestinal mucosal immunity were evaluated by the immunohistochemical analysis of the interferon-γ (IFN-γ), interleukin-4 (IL-4), interleukin-17 (IL-17) and transforming growth factor-ß (TGF-ß) secretion in PPs and intestinal epithelial tissue. RESULTS: With the self-aggregation into particles morphology, CCP can be up-taken by PPs and promote the IFN-γ, IL-4, IL-17 and TGF-ß secretion in PPs in a dose-dependent manner. The CCP can also be utilized by the intestinal flora and dynamically regulate the diversity, composition and distribution of the intestinal flora. The temporal regulations of CCP on IFN-γ, IL-4, IL-17 and TGF-ß secretions in intestinal epithelial tissues are consistent with the variation tendency of intestinal flora. CONCLUSION: CCP can provide effective, dynamical and dose-dependent regulations on intestinal microenvironment, not only the intestinal flora but also the PPs and intestinal epithelium related immune response. These may be involved in the multiple biological activities of Coptis chinensis Franch.

Clematichinenoside AR ameliorated spontaneous colitis in Il-10-/- mice associated with improving the intestinal barrier function and abnormal immune responses.

OBJECTIVES: Clematichinenoside AR (AR) is a saponin extracted for traditional Chinese medicine with the effects of improving the expression of tight junction (TJ) proteins and mediating anti-inflammatory activities. However, its effect on Crohn's disease (CD) is still unknown. We aimed to investigate the impact of AR on CD-like colitis and determine the mechanism underlying its effects. METHODS: Interleukin-10 gene knockout (Il-10-/-) mice (male, fifteen weeks old) with spontaneous colitis were allocated to the positive control and AR-treated (32 mg/kg AR administered every other day by gavage for 4 weeks) groups. Wild-type (WT) mice (male, fifteen weeks old) composed the negative control group. The effects of AR on intestinal barrier function and structure and T cell responses as well as the potential mechanisms underlying these effects were investigated. RESULTS: AR treatment significantly improved spontaneous colitis in Il-10-/- mice as demonstrated by reductions in the inflammatory score, disease activity index (DAI) and levels of inflammatory factors. The effects of AR on colitis in Il-10-/- mice were related to protecting intestinal barrier function and maintaining immune system homeostasis (regulatory T cell (Treg)/T helper 17 (Th17) cell balance). The anticolitis effect of AR may partly act by downregulating PI3K/Akt signaling. CONCLUSIONS: AR may have therapeutic potential for treating CD in humans.

Protective effects of γ-irradiated Astragalus polysaccharides on intestinal development and mucosal immune function of immunosuppressed broilers.

This study was aimed to assess the protective effects of γ-irradiated Astragalus polysaccharides (IAPS) on the development of small intestine and intestinal mucosal immunity of immunosuppressed broilers induced by cyclophosphamide (CPM). A total of 384 one-day-old broiler chicks with similar initial weight were randomly assigned into 6 groups: non-treated group (control), and CPM-treated groups fed either a basal diet or the diets containing 900 mg/kg APS, or 900, 600, 300 mg/kg IAPS, respectively. On days 16, 18, and 20, all broilers except for control group were intramuscularly injected with 0.5 mL CPM (40 mg/kg of BW). Broilers in the control group were intramuscularly injected with 0.5 mL sterilized saline (0.75%, wt/vol). This trial was lasted for 21 d. The results revealed that both APS and IAPS treatment elevated the duodenal IgA-producing cells number and the jejunal mRNA expression of interleukin-2 (IL-2), interleukin-10 (IL-10), and interferon γ of CPM-injected broilers (P < 0.05). The decreased jejunal villus height (VH), the ratio of VH to crypt depth (V/C), as well as the intestinal intraepithelial lymphocytes (IELs) and goblet cells number in CPM-injected broilers were elevated by dietary supplementation with 900 mg/kg APS or 900, 600 mg/kg IAPS (P < 0.05). The CPM-induced decrease in jejunum index, the duodenal VH and the jejunal IgA-producing cells number were only improved in the 900 mg/kg IAPS group (P < 0.05). Furthermore, the number of IELs and IgA-producing cells in duodenum, VH, V/C, the number of goblet cells, and mRNA expression of IL-2 and IL-10 in jejunum were higher in the 900 mg/kg IAPS group than those in the 900 mg/kg APS group (P < 0.05). In summary, IAPS possessed stronger immunomodulatory effect than APS at the same supplementation level. Therefore, gamma irradiation can be used as an alternative treatment to enhance the immunomodulatory activity of APS.