Effects of Early Intervention with Sodium Butyrate on Gut Microbiota and the Expression of Inflammatory Cytokines in Neonatal Piglets

Abstract

Butyrate in the gut of animals has potential properties including regulating the innate immune, modulating the lipid metabolism, and protecting gut healthy. So far, only limited information on the impact of butyrate on the neonatal is available. This study aimed to investigate effects of oral administration of sodium butyrate (SB) on gut microbiota and the expression of inflammatory cytokine in neonatal piglets. Ten litters of crossbred newborn piglets were randomly allocated to the SB and control (CO) groups, each group consisted of five litters (replicates). Piglets in the SB group were orally administrated with 7 to 13 ml sodium butyrate solution (150 mmol/l) per day from the age of 1 to 7 days, respectively; piglets in the CO group were treated with the same dose of physiological saline. On days 8 and 21 (of age), gut digesta and tissues were collected for the analysis of microbiota, butyrate concentration and gene expression of inflammatory cytokine. Results showed that there was no difference in the butyrate concentration in the gut of piglets on days 8 and 21 between two groups. Real-time PCR assay showed that SB had no effect on the numbers of total bacteria in the stomach, ileum, and colon. MiSeq sequencing of the V3-V4 region of the 16S rRNA gene revealed that SB increased the richness in the stomach and colon, and the diversity of colonic microbiota on day 8 (P < 0.05). Genera Acinetobacter, Actinobacillus, Facklamia, Globicatella, Kocuria, Rothia, unclassified Leptotrichiaceae, unclassified Neisseriaceae, and unclassified Prevotellaceae in the stomach were increased in relative abundance by SB treatment, whereas the abundances of Lactobacillus decreased on day 8 (P < 0.05). At the genus and operational taxonomic unit (OTU) levels, SB had low impact on bacterial community in the ileum and colon on days 8 and 21. SB treatment decreased the expression of IL-6, IL-8, IFN-γ, IL-10, TGF-β, and histone deacetylase 1 (HDAC1) in the ileum of piglets on day 8 (P < 0.05). SB treatment down-regulated the expression of IL-8, IFN-γ, and IL-1β on day 21 (P < 0.05). Correlation analysis on the combined datasets revealed some potential relationships between gut microbiota and the expression of inflammatory cytokines. The results show that early intervention with sodium butyrate can modulate the ileum inflammatory cytokine in neonatal piglets with low impact on intestinal microbial structure, which suggests oral administration of SB may have a benefit role in the health of neonatal piglets.

Sodium Butyrate Attenuates Diarrhea in Weaned Piglets and Promotes Tight Junction Protein Expression in Colon in a GPR109A-Dependent Manner

“…In patients with Crohn's disease, butyrate decreases the expression of pro-inflammatory cytokines [24]. As shown in the study by Xu et al, early intervention with sodium butyrate modulates the inflammatory cytokine profile in the ileum of neonatal piglets [25]; notably, sodium butyrate effectively suppressed the expression of mRNA encoding the pro-inflammatory cytokine TNF-α in piglet colon tissue. Thus, sodium butyrate exerts positive effects on alleviating diarrhea and reducing inflammation.…”

Caecal infusion of the short‐chain fatty acid propionate affects the microbiota and expression of inflammatory cytokines in the colon in a fistula pig model

“…Butyrate, modulates inflammatory processes by inhibiting the activity of NF‐κB and HDAC1, and affects gene expression in colonic epithelial cells (Xu et al ., ). We also previously showed that butyrate downregulates HDAC1 and proinflammatory cytokines, and upregulates the expression of anti‐inflammatory cytokines in the gut (Xu et al ., ). Compared to butyrate, propionate exerts an equipotent effect, at suppressing the NF‐κB reporter activity, immune‐related gene expression and cytokine release in vitro (Tedelind et al ., ).…”

“…Anti‐inflammatory functions of SCFAs have been extensively investigated, particularly butyrate, which has been shown to have an important role in inhibiting inflammatory process. Maslowski and colleagues () and Xu and colleagues () have shown that butyrate upregulated the expression of anti‐inflammatory cytokines and downregulated proinflammatory agents in the intestinal epithelium. In addition to acting as signalling molecules, SCFAs also maintain the balance of intestine microbial ecosystem, which contributes to gut immune development (Lee and Mazmanian, ; Chung et al ., ; Kamada et al ., ).…”

“…In addition to acting as signalling molecules, SCFAs also maintain the balance of intestine microbial ecosystem, which contributes to gut immune development (Lee and Mazmanian, 2010;Chung et al, 2012;Kamada et al, 2013). Several studies have demonstrated that butyrate regulates the microbial composition (Xu et al, 2016a), and affects the ecological structure and metabolic activity of the gut microbiota (Castillo et al, 2006;Biagi et al, 2007). Collectively, this evidence suggests that SCFAs indirectly affect the development of intestinal immune system by modulating the homeostasis of microbiota.…”

“…Nuclear factor-jB (NF-jB) is a nuclear transcription factor that regulates gene expression of apoptosis, inflammation and autoimmune disease. Histone deacetylase (HDAC), a class of protease, modifies chromosome structure to regulate the expression of cytokines, including IL-6, IL-8 and IL-18 (Xu et al, 2016a). The activation of NF-jB or HDAC is thought to promote proinflammatory cytokine transcription and induce the inflammatory responses (Saleh and Trinchieri, 2011;Guo et al, 2013).…”