Pediococcus pentosaceus CECT 8330 protects DSS-induced colitis and regulates the intestinal microbiota and immune responses in mice.

Compelling evidences demonstrated that gut microbiota dysbiosis plays a critical role in the pathogenesis of inflammatory bowel diseases (IBD). Therapies for targeting the microbiota may provide alternative options for the treatment of IBD, such as probiotics. Here, we aimed to investigate the protective effect of a probiotic strain, Pediococcus pentosaceus (P. pentosaceus) CECT 8330, on dextran sulfate sodium (DSS)-induced colitis in mice. C57BL/6 mice were administered phosphate-buffered saline (PBS) or P. pentosaceus CECT 8330 (5 × 108 CFU/day) once daily by gavage for 5 days prior to or 2 days after colitis induction by DSS. Weight, fecal conditions, colon length and histopathological changes were examined. ELISA and flow cytometry were applied to determine the cytokines and regulatory T cells (Treg) ratio. Western blot was used to examine the tight junction proteins (TJP) in colonic tissues. Fecal short-chain fatty acids (SCFAs) levels and microbiota composition were analyzed by targeted metabolomics and 16S rRNA gene sequencing, respectively. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Cluster of orthologous groups of proteins (COG) pathway analysis were used to predict the microbial functional profiles. P. pentosaceus CECT 8330 treatment protected DSS-induced colitis in mice as evidenced by reducing the weight loss, disease activity index (DAI) score, histological damage, and colon length shortening. P. pentosaceus CECT 8330 decreased the serum levels of proinflammatory cytokines (TNF-α, IL-1β, and IL-6), and increased level of IL-10 in DSS treated mice. P. pentosaceus CECT 8330 upregulated the expression of ZO-1, Occludin and the ratio of Treg cells in colon tissue. P. pentosaceus CECT 8330 increased the fecal SCFAs level and relative abundances of several protective bacteria genera, including norank_f_Muribaculaceae, Lactobacillus, Bifidobacterium, and Dubosiella. Furthermore, the increased abundances of bacteria genera were positively correlated with IL-10 and SCFAs levels, and negatively associated with IL-6, IL-1β, and TNF-α, respectively. The KEGG and COG pathway analysis revealed that P. pentosaceus CECT 8330 could partially recover the metabolic pathways altered by DSS. P. pentosaceus CECT 8330 administration protects the DSS-induced colitis and modulates the gut microbial composition and function, immunological profiles, and the gut barrier function. Therefore, P. pentosaceus CECT 8330 may serve as a promising probiotic to ameliorate intestinal inflammation.

Dong F ，Xiao F ，Li X ，Li Y ，Wang X ，Yu G ，Zhang T ，Wang Y ... -  《Journal of Translational Medicine》

Bifidobacterium longum CECT 7894 Improves the Efficacy of Infliximab for DSS-Induced Colitis via Regulating the Gut Microbiota and Bile Acid Metabolism.

Background: Recent evidence suggests that the changes in gut microbiota and its metabolites could predict the clinical response of anti-tumor necrosis factor (TNF) agents, such as infliximab (IFX). However, whether manipulation of the gut microbiota can enhance the efficacy of anti-TNF agents remains unclear. Here, we aim to evaluate the effect of a probiotic strain, Bifidobacterium longum (B. longum) CECT 7894, on IFX efficacy for dextran sulfate sodium (DSS)-induced colitis in mice and attempt to explore the potential involved mechanisms. Methods: C57BL/6 mice were treated with phosphate-buffered saline (PBS) or B. longum CECT 7894 (5 × 108 CFU/day) once daily by gavage for 5 days and subsequently induced acute colitis by 3% (w/v) DSS in drinking water. The efficacies of IFX combined with or without B. longum CECT 7894 were assessed by weight loss, fecal consistency, colon length, and histopathological changes. Immunohistochemistry (IHC) was used to examine the expression of tight junction proteins (TJPs) in colonic tissues. The microbiota composition was characterized through 16 S rRNA gene sequencing. Fecal bile acids (BAs) levels were analyzed by targeted metabolomics. Results: B. longum CECT 7894 improved the efficacy of IFX for DSS-induced colitis as evidenced by decreased weight loss, disease activity index (DAI) scores, colon length shortening, histological damage, increased ZO-1, and Occludin expressions as compared with mice that received IFX only. B. longum CECT 7894 modified the composition and structure of the gut microbiota community in DSS-induced colitis mice. B. longum CECT 7894 increased the relative abundances of genera Bifidobacterium, Blautia, Butyricicoccus, Clostridium, Coprococcus, Gemmiger, and Parabacterioides, and reduced the relative abundances of bacteria genera Enterococcus and Pseudomonas. Furthermore, B. longum CECT 7894 changed the BAs metabolism by increasing the abundance of secondary BAs, such as a-MCA, ß-MCA, LCA, CDCA, UDCA, HCA, isoLCA, isoalloLCA. The covariance analysis revealed the upregulated secondary BAs were positively associated with the increased abundance of bacteria that contained bile salt hydrolases (BSH) and 7α-dehydroxylases genes. Conclusion: B. longum CECT 7894 improved the efficacy of IFX for DSS-induced colitis via regulating the gut microbiota composition and bile acid metabolism. Probiotics supplementation may provide a possibility to improve the clinical response of anti-TNF agents in IBD management.

Xiao F ，Dong F ，Li X ，Li Y ，Yu G ，Liu Z ，Wang Y ，Zhang T ... -  《-》

Pediococcus pentosaceus LI05 alleviates DSS-induced colitis by modulating immunological profiles, the gut microbiota and short-chain fatty acid levels in a mouse model.

The gut microbiota is considered a key factor in pathogenesis and progression of inflammatory bowel disease (IBD). The bacterium Pediococcus pentosaceus LI05 alleviated host inflammation by maintaining the gut epithelial integrity, modulating the host immunity, gut microbiota and metabolism, but its effect on IBD remains unclear. The present study aimed to investigate the role and mechanisms of P. pentosaceus LI05. Mice were administered P. pentosaceus LI05 or phosphate-buffered saline once daily by oral gavage for 14 days, and colitis was induced by providing mice 2% DSS-containing drinking water for 7 days. P. pentosaceus LI05 ameliorated colitis in mice and reduced the body weight loss, disease activity index (DAI) scores, colon length shortening, intestinal permeability and the proinflammatory cytokine levels. Furthermore, a significantly altered gut microbiota composition with increased diversity and short-chain fatty acid (SCFA) production was observed in mice treated with P. pentosaceus LI05. Several genera, including Akkermansia and Faecalibacterium, were differentially enriched in the P. pentosaceus LI05-treated mice and were negatively correlated with colitis indices and positively correlated with gut barrier markers and SCFA levels. The P. pentosaceus LI05 treatment alleviated intestinal inflammation by maintaining the intestinal epithelial integrity and modulating the immunological profiles, gut microbiome and metabolite composition. Based on our findings, P. pentosaceus LI05 might be applied as potential preparation to ameliorate colitis.

Bian X ，Yang L ，Wu W ，Lv L ，Jiang X ，Wang Q ，Wu J ，Li Y ，Ye J ，Fang D ，Shi D ，Wang K ，Wang Q ，Lu Y ，Xie J ，Xia J ，Li L ... -  《Microbial Biotechnology》

New strain of Pediococcus pentosaceus alleviates ethanol-induced liver injury by modulating the gut microbiota and short-chain fatty acid metabolism.

Intestinal dysbiosis has been shown to be associated with the pathogenesis of alcoholic liver disease (ALD), which includes changes in the microbiota composition and bacterial overgrowth, but an effective microbe-based therapy is lacking. Pediococcus pentosaceus (P. pentosaceus) CGMCC 7049 is a newly isolated strain of probiotic that has been shown to be resistant to ethanol and bile salts. However, further studies are needed to determine whether P. pentosaceus exerts a protective effect on ALD and to elucidate the potential mechanism. To evaluate the protective effect of the probiotic P. pentosaceus on ethanol-induced liver injury in mice. A new ethanol-resistant strain of P. pentosaceus CGMCC 7049 was isolated from healthy adults in our laboratory. The chronic plus binge model of experimental ALD was established to evaluate the protective effects. Twenty-eight C57BL/6 mice were randomly divided into three groups: The control group received a pair-fed control diet and oral gavage with sterile phosphate buffered saline, the EtOH group received a ten-day Lieber-DeCarli diet containing 5% ethanol and oral gavage with phosphate buffered saline, and the P. pentosaceus group received a 5% ethanol Lieber-DeCarli diet but was treated with P. pentosaceus. One dose of isocaloric maltose dextrin or ethanol was administered by oral gavage on day 11, and the mice were sacrificed nine hours later. Blood and tissue samples (liver and gut) were harvested to evaluate gut barrier function and liver injury-related parameters. Fresh cecal contents were collected, gas chromatography-mass spectrometry was used to measure short-chain fatty acid (SCFA) concentrations, and the microbiota composition was analyzed using 16S rRNA gene sequencing. The P. pentosaceus treatment improved ethanol-induced liver injury, with lower alanine aminotransferase, aspartate transaminase and triglyceride levels and decreased neutrophil infiltration. These changes were accompanied by decreased levels of endotoxin and inflammatory cytokines, including interleukin-5, tumor necrosis factor-α, granulocyte colony-stimulating factor, keratinocyte-derived protein chemokine, macrophage inflammatory protein-1α and monocyte chemoattractant protein-1. Ethanol feeding resulted in intestinal dysbiosis and gut barrier disruption, increased relative abundance of potentially pathogenic Escherichia and Staphylococcus, and the depletion of SCFA-producing bacteria, such as Prevotella, Faecalibacterium, and Clostridium. In contrast, P. pentosaceus administration increased the microbial diversity, restored the relative abundance of Lactobacillus, Pediococcus, Prevotella, Clostridium and Akkermansia and increased propionic acid and butyric acid production by modifying SCFA-producing bacteria. Furthermore, the levels of the tight junction protein ZO-1, mucin proteins (mucin [MUC]-1, MUC-2 and MUC-4) and the antimicrobial peptide Reg3β were increased after probiotic supplementation. Based on these results, the new strain of P. pentosaceus alleviated ethanol-induced liver injury by reversing gut microbiota dysbiosis, regulating intestinal SCFA metabolism, improving intestinal barrier function, and reducing circulating levels of endotoxin and proinflammatory cytokines and chemokines. Thus, this strain is a potential probiotic treatment for ALD.

Jiang XW ，Li YT ，Ye JZ ，Lv LX ，Yang LY ，Bian XY ，Wu WR ，Wu JJ ，Shi D ，Wang Q ，Fang DQ ，Wang KC ，Wang QQ ，Lu YM ，Xie JJ ，Li LJ ... -  《-》

Banxia Xiexin decoction modulates gut microbiota and gut microbiota metabolism to alleviate DSS-induced ulcerative colitis.

Banxia Xiexin decoction (BXD) is a classic traditional Chinese medicine prescription for treating ulcerative colitis (UC). However, its potential mechanism of action is still unclear. Reveal the correlation between the beneficial impacts of BXD on UC and the composition of the gut microbiota. The major constituents of BXD were identified using the HPLC-DAD technique. An experimental model of UC was induced in male C57BL/6 mice by administering dextran sodium sulfate (DSS). A total of 48 mice were divided into different groups, including control, model, high-dose BXD treatment, medium-dose BXD treatment, low-dose BXD treatment, and a group treated with 5-amino acid salicylic acid (5-ASA). Body weight changes and disease activity index (DAI) scores were documented; colon length, colon index, spleen index, and thymus index scores were determined; myeloperoxidase (MPO) and tumor necrosis factor-α (TNF-α) activities were assessed; and histological staining with hematoxylin-eosin and alcian blue/phosphate Schiff was performed. The immunofluorescence technique was employed to examine the presence of ZO-1 and occludin in the colon tissue. 16S rRNA sequencing was employed to assess the gut microbiota's diversity and metabolomics was utilized to examine alterations in metabolites within the gut microbiota. The impact of BXD on the gut microbiota was confirmed through fecal microbiota transplantation (FMT). BXD exhibited a positive impact on UC mice, particularly in the high-dose BXD treatment group. The BXD group experienced weight recovery, decreased DAI scores, improved colon length, and restored of spleen and thymus index scores compared to the DSS group. Additionally, BXD alleviated colon damage and the inflammatory response while restoring intestinal barrier function. FMT in BXD-treated mice also showed therapeutic effects in UC mice. At the phylum level, the relative abundance of Desulfobacterota, Deferribacterota and Actinobacteriota increased; at the genus level, g__norank__f__Muribaculaceae, Dubosiella, Akkermansia, and Lactobacillus increased, whereas Faecalibaculum, Alloprevotella, Turicibacter, and g_Paraprevotella decreased. g__norank_f__Muribaculaceae was positively correlated with body weight and colon length and negatively with colon index scores, splenic index scores, and MPO levels; Alloprevotella was positively correlated with splenic index scores, histological scores, and TNF-α levels and negatively with thymus index scores and thymus index scores. Faecalibaculum was positively correlated with colon index scores and MPO levels. Metabolic investigations revealed 58 potential indicators, primarily associated with the metabolism of amino acids, purines, and lipids. Alloprevotella, g_Paraprevotella, and Bifidobacterium were strongly associated with metabolic pathways. BXD showed beneficial therapeutic effects in UC mice. The mechanism may be by promoting the balance and variety of gut microbiota, as well as regulating the metabolism of amino acids, purines, and lipids.

Luo Y ，Fu S ，Liu Y ，Kong S ，Liao Q ，Lin L ，Li H ... -  《-》