Effect of Clostridium butyricum and Butyrate on Intestinal Barrier Functions: Study of a Rat Model of Severe Acute Pancreatitis With Intra-Abdominal Hypertension

Abstract

Background/Aims: Severe acute pancreatitis (SAP) is associated with intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS), but treatment of these conditions is difficult. We studied a rat model of SAP + IAH to determine the effect of oral administration of Clostridium butyricum and butyrate (its major metabolite) on intestinal barrier functions.Methods: A total of 48 rats were assigned to four groups, with 12 rats per group: Sham, SAP+IAH, SAP+IAH+C. butyricum, and SAP + IAH + butyrate. SAP was induced by sodium taurocholate infusion into the biliopancreatic duct, intra-abdominal pressure (IAP), mortality was measured 24 h later, and then rats were euthanized. The plasma levels of several markers [amylase, diamine oxidase (DAO), fluorescein isothiocyanate (FITC)-dextran, tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-1β, IL-12, lipopolysaccharide (LPS)] and fecal butyric acid level were determined. The pancreas and intestine were examined using histology, and RT-PCR and Western blotting of intestinal tissues were used to measure the expression of six markers {tight junction proteins [zonula occludens protein-1 (ZO-1), claudin-1, claudin-2, occluding], matrix metalloproteinase 9 [MMP9], and TNF-α}. The gut flora of the rats was examined by 16S rRNA sequencing.Results: Induction of SAP + IAH altered several functions of the intestinal barrier, and enhanced intestinal permeability, decreased the levels of ZO-1, claudin-1, occludin, the richness and diversity of the microflora community, the relative abundance (RA) of Firmicutes, and the number of probiotic organisms. However, induction of SAP+IAH increased the expression of claudin-2, MMP9, and TNF-α, and the RA of Proteobacteria

The Anti-Inflammatory Effect and Mucosal Barrier Protection of Clostridium butyricum RH2 in Ceftriaxone-Induced Intestinal Dysbacteriosis

“…It’s worth noting that administration of CB RH2 in high dose promoted the relative abundance of Lactobacillus (P = 0.052, Figure 2K ), which were thought to be beneficial to several digestive diseases including IBS and IBD. This result was consistent with other studies ( Liu et al., 2020b ; Zhao et al., 2020 ).…”

“…Our previous study showed that a probiotic-enriched dietary intervention could decrease the abundance of Desulfovibrio in high-fat diet-induced obesity in rats ( Li et al., 2020 ). It could be decreased by C. butyricum or butyrate in the study of Zhao et al. (2020) .…”

“…After the CB RH2 administration, especially in low dose, Bacteroidetes was significantly increased and F/B ratio was significantly decreased relative to the CS group. In a study of a rat model of severe acute pancreatitis with intra-abdominal hypertension, Zhao et al (2020) reported that C. butyricum or butyrate could increase the relative abundance of Bacteroidetes significantly compare with both of sham and model groups. It was also observed that the proportion of Deferribacteres was significantly decreased following high concentration of CB RH2 treatment compared with CS group.…”

“…Our previous study showed that a probiotic-enriched dietary intervention could decrease the abundance of Desulfovibrio in high-fat diet-induced obesity in rats . It could be decreased by C. butyricum or butyrate in the study of Zhao et al (2020). As part of the phylum Deferribacteres, Mucispirillum is a core member of murine gut microbiota, which can colonize the intestinal tract from the stomach to the colon (Xiao et al, 2019).…”

“…The exact functions of Claudin-1 and Claudin-4 remain debated, with contradicting findings suggesting context-dependent functions and potential roles both as seal and pore formers. As a pore former, Claudin-2 was detected overexpressed in the pathological response, which was reversed by C. butyricum or butyrate ( Zhao et al., 2020 ). Therefore, the pore-forming Claudin-1 and Claudin-4 proteins may also play the role in increasing paracellular permeability.…”