Dataset Information

Effect of Early Weaning on the Intestinal Microbiota and Expression of Genes Related to Barrier Function in Lambs.

ABSTRACT: Weaning stress has been reported to impair intestinal health. The gut microbiota plays a vital role in the long-term health of the host. However, our understanding of weaning stress on gut microbiota and barrier function is very limited in livestock species, especially lambs. We investigated the effects of early weaning stress on intestinal bacterial communities and intestinal barrier function in lambs. A total of 24 neonatal male Hu lambs were randomly allocated into two groups, one weaned on day 28 and the other weaned on day 56. At 42 and 84 days, six lambs from each group were randomly selected and sacrificed. Ileal tissue and ileal digesta were collected to compare the differences in ileal microbiota and the mRNA levels of Toll-like receptors (TLRs) and tight junction proteins between the early weaning group and the control group at day 42 when the early weaning group have been weaned for 14 days, and at day 84 when the 28 and 56 days weaning groups had been weaned for 56 and 28 days, respectively. 16S rRNA gene sequencing of ileal samples revealed that the ileal microbiota was very different between the two groups, even at 84 days of age. Early weaning significantly increased alpha diversity and altered the relative abundance of several bacterial taxa. The expression of genes related to intestinal barrier function was affected by early weaning. Early weaning significantly increased ileal mRNA levels of TLR1 on days 42 and 84; TLR2, TLR4, and TLR5 on day 84; claudin1 and claudin4 on day 42; and occludin on day 84. We demonstrate that early weaning not only altered the ileal microbiota on day 42 (compared with lambs that were not weaned), but also had lasting effects on the ileal microbiota at day 84; furthermore, early weaning impacts expression levels of genes related to intestinal barrier function.

SUBMITTER: Li C

PROVIDER: S-EPMC6036172 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Effect of Early Weaning on the Intestinal Microbiota and Expression of Genes Related to Barrier Function in Lambs.

Li Chong C Wang Weimin W Liu Ting T Zhang Qian Q Wang Guoxiu G Li Fadi F Li Fei F Yue Xiangpeng X Li Tingfu T

Frontiers in microbiology 20180702

Weaning stress has been reported to impair intestinal health. The gut microbiota plays a vital role in the long-term health of the host. However, our understanding of weaning stress on gut microbiota and barrier function is very limited in livestock species, especially lambs. We investigated the effects of early weaning stress on intestinal bacterial communities and intestinal barrier function in lambs. A total of 24 neonatal male Hu lambs were randomly allocated into two groups, one weaned on d ...[more]

PMID: 30013534

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Project description:BACKGROUND:Pre-weaning milk replacer (MR) feeding program is a key factor affecting the health and welfare of lambs during their weaning. Weaning stress is well known as an inducement that negatively impacts the immune system of young ruminants, whose physiological and immune state is closely linked to the community of microbiota in their intestines. This study had two objectives: 1) To evaluate the innate immune response to weaning stress at both the physiological and molecular level; 2) To investigate changes to the jejunal chyme and mucosal adhesive microbiota between the control and high plane of MR groups. RESULTS:In this experiment, the plasma concentrations of cortisol, norepinephrine (NE) and tumor necrosis factor-? (TNF?) were higher in the C than the H group (P?<?0.05), as was the expression of pro-inflammatory cytokines such as TNF? and CXCL8 (P?<?0.05) in plasma. In jejunal tissue, the expression of TLR4 and TNF? were also higher in the C group (P?<?0.01); histopathology showed the H group had lower lymphocyte infiltration. In the C group, however, major pathological changes were associated with extensive infiltration of lymphocytes, eosinophils, and neutrophils. Principal component analysis indicated the lamb immune response was influenced by weaning stress and modulated by the MR treatments. 16S-rRNA sequencing was used to evaluate jejunal mucosa and chyme bacterial diversity and composition. The C group's chyme had a greater alpha index (ACE: P?=?0.095; Chao1: P?=?0.085) than H group. In jejunal mucosa, the relative abundance of Plesiomonas was 4-fold higher (P?=?0.017) in the C than the H group. CONCLUSIONS:This study's results revealed that weaning stress induced alterations to the lambs' immune system that lasted beyond the 21 d measured, and that a long-term inflammatory response effect was evidenced by changes in their hematological and expressed pro-inflammatory cytokines. Pre-weaning with a differing MR allowance resulted in complicated biological responses and compositional changes to the lambs' jejunal microbiota. Clearly, an intensive MR feeding program induced a milder immunity response and lower relative abundance of pathogenic bacteria when compared with the traditional feeding program.

Project description:Early weaning induces intestinal injury, leading to a series of long-term symptoms such as inflammation, malabsorption and diarrhea. In this study, we hypothesized that microbes and their metabolites modulate the host's inflammatory response to early weaning stress in a goat model. A total of 18 female Tibetan goat kids (n = 9) were weaned from their mothers at 28 d (D28) and 60 d (D60) postpartum. D60 and D28 groups were fed the same solid diet ad libitum from weaning to 75 d of age. The colonic epithelium was subject to RNA-sequencing, the caecal digesta metabolomics were assessed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and the caecal microbiota composition was analysed by 16S ribosomal RNA gene sequencing. We found that early weaning substantially increased the colonic pro-apoptotic gene expression of B-cell lymphoma associated X (Bax), caspase-9, and caspase-3, and decreased the expression of zonula occludens-1 (ZO-1) and claudin-1 (P < 0.01). In addition, a significant Bacteroides acidifaciens enrichment was observed in the hindgut of early-weaned goats (P < 0.01), which negatively correlated with lysophosphatidylcholine products. Similarly, the chemokine signaling, IL-17 signaling, and peroxisome proliferators-activated receptor (PPAR) signaling pathways were upregulated in the colonic mucosa of the early-weaned goats. By applying caecal microbiota transplantation from goats to defaunated C57/6J mice, we confirmed that caecal microbiota of D28 goat kids increased the relative abundance of B. acidifaciens and significantly up-regulated the genes of Bax, G protein-coupled receptor (GPR) 109A, GPR 43, fatty acid binding protein 6, nuclear receptor subfamily 1 group H member 3, angiotensin converting enzyme 2, and IL-6 expression (P < 0.05), and decreased ZO-1, and claudin-1 protein expression in the mice jejunum and colon (P < 0.001). These results proposed that the hindgut microbiota and metabolites mediate the barrier function weakening during early weaning, and the relative abundance of B. acidifaciens was negatively correlated with the hindgut barrier gene expression. This study demonstrates how weaning stress can affect key host-microbe interaction regulators in the hindgut, in a lysophosphatidylcholine dependent and independent manner. Furthermore, based on our mice data, these results are transferable to other mammal species.

Project description:Intestinal health of broiler chickens is influenced by the concentration of dietary amino acids but data are limited on the role of dietary methionine (Met). Two experiments were conducted to investigate the implications of different Met sources for performance, gut barrier function, and intestinal microbiota in broilers. In the first experiment, Ross 308 off-sex birds (n = 900) were assigned to 10 dietary treatments each replicated 9 times in a 35-day study. Three sources of Met included DL-Met, L-Met, or Met hydroxy analog free acid (MHA-FA), each supplemented at suboptimal (SUB) at 80%, adequate (ADE) at 100% and over-requirement (OVR) at 120% of the specifications against a deficient (DEF) diet with no added Met. The second experiment used 96 Ross 308 broilers in a 2 × 4 factorial arrangement. Four diets included 3 sources of Met supplemented at ADE level plus the DEF treatment. On d 17, 19, and 23, half of the birds in each dietary treatment were injected with dexamethasone (DEX) to induce leaky gut. In the first experiment, without an interaction, from d 0 to 35, birds fed DL-Met and L-Met performed similarly for BWG, feed intake, and FCR but birds fed MHA-FA had less feed intake and BWG (P < 0.05). At d 23, mRNA expression of selected tight junction proteins was not affected except for claudin 2. Ileal microbiota of DEF treatment was different from DL-MET or L-MET supplemented birds (P < 0.05). However, microbiota of MHA-FA treatments was only different at OVR from the DEF group. The abundance of Peptostreptococcus increased in DEF treatment whereas Lactobacillus decreased. In the second experiment, DEX independently increased (P < 0.001) intestinal permeability assayed by fluorescein isothiocyanate dextran, but diet had no effect. DL-Met and L-Met fed birds had a higher level of claudin 3 only in DEX-injected birds (P < 0.05). In conclusion, unlike the level of supplementation, DL-Met, L-Met, and MHA-FA were largely similar in their limited impacts on intestinal barrier function and gut microbiota in broilers.

Project description:In the present study, we investigated the influence of weaning on antioxidant status, intestinal integrity, mitochondrial function, and the mitophagy level in piglets (weaned at 21 d) during the 1 wk after weaning. The redox status was measured by antioxidant enzymes activities, related genes expression, and malondialdehyde (MDA) content in jejunum. The intestinal barrier function was assessed by the Ussing chamber and expression of tight junction proteins in the jejunum. The function of intestine mitochondria was measured by mitochondrial DNA (mtDNA) content and activities of mitochondria oxidative phosphorylation complexes. The levels of light chain 3-1 (LC3-I), light chain 3-II (LC3-II), PTEN-induced putative kinase 1 (PINK1), and Parkin were determined to investigate whether mitophagy is involved in the weaning process. The results showed that, as compared with the preweaning phase (d 0), weaning suppressed (P < 0.05) the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) on d 3 and d 7 postweaning, decreased (P < 0.05) the expression of copper and zinc superoxide dismutase (Cu/Zn-SOD), manganese-containing superoxide dismutase (Mn-SOD) on d 3 postweaning, declined (P < 0.05) the level of glutathione peroxidase 1 (GPX-1) and glutathione peroxidase 4 (GPX-4) on d 3 and d 7 postweaning, and increased (P < 0.05) MDA content in jejunum on d 3 and d 7 postweaning. The jejunal transepithelial electrical resistance and levels of occludin, claudin-1, and zonula occludens-1 on d 3 and d 7 postweaning were reduced (P < 0.05), and paracellular flux of fluorescein isothiocyanatedextran (4 kDa) on d 3 and d 7 postweaning was increased (P < 0.05). Weaning induced mitochondrial dysfunction, as demonstrated by decreased (P < 0.05) content of mtDNA on d 3 and d 7 postweaning and declined (P < 0.05) activities of mitochondria complexes (I, II, III, IV) in jejunum on d 1, d 3, and d 7 postweaning. Weaning led to an increased (P < 0.05) expression level of mitophagy-related proteins, PINK1 and Parkin, in the intestinal mitochondria, as well as an enhancement (P < 0.05) of the ratio of LC3-II to LC3-I content in the jejunal mucosa on d 1, d 3, and d 7 postweaning. These results suggest that weaning disrupted intestinal oxidative balance, and this imbalance may impair intestinal barrier and mitochondrial function and trigger mitophagy in piglets.

Dataset Information

Effect of Early Weaning on the Intestinal Microbiota and Expression of Genes Related to Barrier Function in Lambs.

Publications

Effect of Early Weaning on the Intestinal Microbiota and Expression of Genes Related to Barrier Function in Lambs.

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