Clostridium Butyricum Research Articles

Time restricted eating (TRE) and immunotherapy outcomes in head and neck squamous cell carcinoma (HNSCC) via modulation of microbial butyrate and tryptophan metabolic pathways.

e18028 Background: Metastatic HNSCC continues to have very poor prognosis. Only a fraction of patients respond to immune checkpoint blocker therapy (ICB), with no effective treatment options for non-responders. Gut microbial composition and diversity have been associated with response to ICB in many cancers including HNSCC. We have previously demonstrated that TRE significantly improved progression free survival via modulation of gut microbiota. We herein report our mechanistic data demonstrating critical role of microbially mediated butyric and tryptophan metabolic pathways in augmenting antitumor immune response to ICB. Methods: Paired blood and stool samples, at baseline and at first response assessment, from 43 HNSCC patients enrolled in the TRE study (NCT05083416) was collected and analyzed using untargeted and targeted metabolomics, focusing on tryptophan and short chain fatty acid pathway. Further shot gun metagenomic sequencing was conducted on stool samples. Finally, we performed an in vitro luciferase cytotoxicity assay using SCC-4 human cancer cells to demonstrate TRE mediated antitumor immune response. We co-cultured MHC-I and NY-ESO-1, and NY-ESO-1-specific TCR-transduced T cells. tumor cells and the T cells under different conditions of butyrate concentration and T cell-to-tumor cell ratio (1:5, 1:10) and evaluated T cell mediated tumors killing. Results: We noted significantly higher abundance of clostridium butyricum (OR-1004, p-0.0002) with corresponding higher expression of butyrate kinase enzyme in stool of patients who observed TRE (OR-1.9, p-0.0003) vs those who did not, leading to higher concentration of fecal butyric acid and hydroxy indole acetic acid (HIAA) (OR-4.2, p-0.003), both of which were independently associated with longer progression free survival (HR-0.9, p<0.01). Higher abundance of butyric acid in gut is known to enhance the gut barrier function with consequent decrease in plasma butyrate and HIAA, lower systemic levels of which, was found to be associated with longer progression free survival in our cohort (OR-0.9, p-0.05). Both butyrate and 5HIAA are known activators of immunosuppressive aryl hydrocarbon receptor (AhR) expressed on cytotoxic CD8T cells, inhibiting CD8 mediated antitumor response. In line with our hypothesis, we observed that butyrate and 5HIAA impaired CD8 T mediated T cell killing of tumor cells in a dose-dependent manner. Conclusions: These results suggest that TRE favorably modulates ICB response via enrichment of gut microbiota with butyrate producing microbial organism, leading to increased abundance of gut butyrate and microbial tryptophan metabolites and their consequent reduction in systemic circulation, ultimately enhancing antitumor immune response.

Bound Polyphenols of Oat Bran Released by Gut Microbiota Mitigate High Fat Diet-Induced Oxidative Stress and Strengthen the Gut Barrier via the Colonic ROS/Akt/Nrf2 Pathway.

Whole-grain foods are rich in bound polyphenols (BPs) whose health benefits were largely underestimated compared with free polyphenols. We first found that DFBP (dietary fiber with BPs from oat bran) exhibited stronger colonic antioxidant activities than DF. 16S rRNA sequencing showed that DFBP selectively changed gut microbial composition, which reciprocally released BPs from DFBP. Released polyphenols from DFBP reduced excessive colonic ROS and exhibited colonic antioxidant activities via the ROS/Akt/Nrf2 pathway revealed by transcriptome and western blot analysis. Colonic antioxidant activities of DFBP mediated by gut microbiota were next proven by treating mice with broad-spectrum antibiotics. Next, Clostridium butyricum, as a distinguished bacterium after DFBP intervention, improved colonic antioxidant capacities synergistically with DFBP in HFD-fed mice. This was explained by the upregulated mRNA expression of esterase, and cellulase of Clostridium butyricum participated in releasing BPs. Our results would provide a solid basis for explaining the health benefits of whole grains.

Bacillus coagulans and Clostridium butyricum synergistically alleviate depression in a chronic unpredictable mild stress mouse model through altering gut microbiota and prefrontal cortex gene expression

Introduction: The prevalence of major depressive disorder (MDD) has gradually increased and has attracted widespread attention. The aim of this study was to investigate the effect of a probiotic compound consisting of Bacillus coagulans and Clostridium butyricum, on a mouse depression model.Methods: Mice were subjected to chronic unpredictable mild stress (CUMS) and then treated with the probiotics at different concentrations. And mice received behavior test such as forced swimming test and tail suspension test. After that, all mice were sacrificed and the samples were collected for analysis. Moreover, prefrontal cortex (PFC) gene expression and the gut microbiota among different groups were also analyzed.Results: Probiotics improved depressive-like behavior in CUMS mice, as indicated by decreased immobility time (p < 0.05) in the forced swimming test and tail suspension test. probiotics intervention also increased the level of 5-hydroxytryptamine (5-HT) in the prefrontal cortex and decreased the adrenocorticotropic hormone (ACTH) level in serum. In addition, by comparing the PFC gene expression among different groups, we found that the genes upregulated by probiotics were enriched in the PI3K-Akt signaling pathway in the prefrontal cortex. Moreover, we found that downregulated genes in prefrontal cortex of CUMS group such as Sfrp5 and Angpt2, which were correlated with depression, were reversed by the probiotics. Furthermore, the probiotics altered the structure of the gut microbiota, and reversed the reduction of cob(II)yrinate a,c-diamide biosynthesis I pathway in CUMS group. Several species like Bacteroides caecimuris and Parabacteroides distasoni, whose abundance was significantly decreased in the CUMS group but reversed after the probiotics intervention, showed significantly positive correlation with depression associated genes such as Tbxas1 and Cldn2.Discussion: These findings suggested that CUMS-induced depression-like behavior can be alleviated by the probiotics, possibly through alterations in the PFC gene expression and gut microbiota.

#2696 The effect of laxatives on reducing serum phosphate levels of probiotics in hemodialysis patients: a subanalysis of RCT

Abstract Background and Aims Dysbiosis of the intestinal microbiota in chronic kidney disease increases uremic toxin, which damage the epithelial tight junctions and increase the permeability of the intestinal wall via endotoxemia and systemic inflammation. Some articles reported that probiotics reduced the uremic toxin and decreased inflammation biomarkers in CKD patients. Meanwhile, we have already reported that oral administration of Bifidobacterium longum in a gastro-resistant seamless capsule decreases serum phosphate levels in patients receiving hemodialysis (Clin Kidney J, 5:373-374, 2012). In addition, in this congress, we reported that three-combination probiotics decreased serum phosphate levels. Meanwhile, some articles reported the relationship hypophosphatemia and laxative abuse. The aim of this subanalysis study is to evaluate the efficacy of laxatives on reducing serum phosphate levels of three-combination probiotic in patients receiving hemodialysis. Method A 6-month prospective, randomized, double-blind, placebo-controlled study was conducted at three hemodialysis centers. As probiotic therapy, of three-combination probiotics (Bio-Three) tablets, each containing 2 mg of lactomin (Streptococcus faecalis T-110), 10 mg of Clostridium butyricum TO-A, and 10 mg of Bacillus mesentericus TO-A, were used. The patients receiving hemodialysis were randomly assigned to the Bio-Three group (n = 37) and the placebo group (n = 36). In both the Bio-Three group and the placebo group, patients orally received 6 tablets 3 times daily. We evaluated the effect of probiotic on serum phosphate level and gut microbiome before and 6 months after the start of treatment. The gut microbiome composition was analyzed by a 16s rRNA gene-based sequencing protocol. In addition, in patients with laxative (n = 24), we evaluate the effect of probiotic on serum phosphate levels and gut microbiome. Results The serum phosphate levels in the Bio-Three group significantly decreased after 6-month treatment, while did not change in the placebo group. Furthermore, the serum phosphate level in patients with Bio-Three and laxative additionally decreased. In a 16s rRNA gene-based sequencing protocol analysis, serum phosphate levels were positively correlated with the occupancy ratio of Erysipelotrichaceae, Lachnospiraceae, Oscillospiraceae, Ruminococcaceae, and Sutterellaceae and were negatively correlated with the occupancy ratio of Leuconostocaceae and Lachnospiraceae in patients with Bio-Three and laxatives. Conclusion In this subanalysis study, the effect of reducing serum phosphate levels on three-combination probiotic might be augmented by laxatives and the specific bacteria in the gut microbiome might contribute to the decrease of serum phosphate levels.

Clostridium butyricum upregulates GPR109A/AMPK/PGC-1α and ameliorates acute pancreatitis-associated intestinal barrier injury in mice.

Acute pancreatitis frequently causes intestinal barrier damage, which aggravates pancreatitis. Although Clostridium butyricum exerts anti-inflammatory and protective effects on the intestinal barrier during acute pancreatitis, the underlying mechanism is unclear. The G protein-coupled receptors 109A (GPR109A) and adenosine monophosphate-activated protein kinase (AMPK)/ peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α) signaling pathways can potentially influence the integrity of the intestinal barrier. Our study generated acute pancreatitis mouse models via intraperitoneal injection of cerulein and lipopolysaccharides. After intervention with Clostridium butyricum, the model mice showed reduced small intestinal and colonic intestinal barrier damage, dysbiosis amelioration, and increased GPR109A/AMPK/PGC-1α expression. In conclusion, Clostridium butyricum could improve pancreatic and intestinal inflammation and pancreatic injury, and relieve acute pancreatitis-induced intestinal barrier damage in the small intestine and colon, which may be associated with GPR109A/AMPK/PGC-1α.

Enhancing Growth and Intestinal Health in Triploid Rainbow Trout Fed a Low-Fish-Meal Diet through Supplementation with Clostridium butyricum

Enhancing Growth and Intestinal Health in Triploid Rainbow Trout Fed a Low-Fish-Meal Diet through Supplementation with Clostridium butyricum

Fermenting kale (Brassica oleracea L.) enhances its functional food properties by increasing accessibility of key phytochemicals and reducing antinutritional factors.

The properties of kale as a functional food are well established. We sought to determine how fermentation further enhances these properties. We tested different fermentation conditions: (i) spontaneous fermentation with naturally occurring bacteria, (ii) spontaneous fermentation with 2% salt, (iii) Lactococcus lactis, (iv) Lactobacillus acidophilus, (v) mixture of L. lactis and L. acidophilus, (vi) mixture of L. lactis, L. acidophilus, and Clostridium butyricum. We quantified selected bioactive components using high-performance liquid chromatography (HPLC) and antinutritional factors using a gravimetric method and spectrophotometry. We then determined (i) the antioxidant capacity of the vegetable, (ii) anti-inflammation capacity, and (iii) the surface microbiota composition by 16S sequencing. All fermentation methods imparted some benefits. However, fermentation with mixed culture of L. lactis and L. acidophilus was most effective in increasing polyphenols and sulforaphane accessibility, increasing antioxidant activity, and reducing antinutritional factors. Specifically, fermentation with L. lactis and L. acidophilus increased total polyphenols from 8.5 to 10.7 mgGAE/g (milligrams of gallium acid equivalent per gram) and sulforaphane from 960.8 to 1777 μg/g (microgram per gram) but decreased the antinutritional factors oxalate and tannin. Total oxalate was reduced by 49%, while tannin was reduced by 55%-65%. The antioxidant capacity was enhanced but not the anti-inflammation potential. Both unfermented and fermented kale protected equally against lipopolysaccharide (LPS)-induced inflammation in RAW 264.7 macrophages and prevented increases in inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 messenger RNA (IL-6 mRNA) expression by 84.3%, 62%, 68%, and 85.5%, respectively. Unfermented and naturally fermented kale had high proportions of sulfur reducing Desulfubrio and Proteobacteria usually associated with inflammation. Fermenting with L. lactis and/or L. acidophilus changed the bacterial proportions, reducing the Proteobacteria while increasing the genera Lactobacilli and Lactococcus. In summary, fermentation enhances the well-known beneficial impacts of kale. Fermentation with mixed cultures of L. lactis and L. acidophilus imparts higher benefits compared to the single cultures or fermentation with native bacteria present in the vegetable.

Preparation of valine-curcumin conjugate and its in vitro antibacterial and antitumor activity and in vivo biological effects on American eels (Anguilla rostrata)

Curcumin (Cur) exhibits diverse natural pharmacological activities, despite its limited water solubility (hydrophobicity) and low bioavailability. In this investigation, a valine-curcumin conjugate (Val-Cur) was synthesized through amino acid side chain modification, and its solubility increased to 1.78 mg/mL. In vitro experimental findings demonstrated that the antibacterial activity of Val-Cur against Escherichia coli, Staphylococcus aureus, Aeromonas hydrophila, and Vibrio parahaemolyticus was significantly superior to that of Cur. The inhibition rate of Val-Cur against HepG2 (human hepatocellular carcinoma) cells was higher than that of Cur at low concentrations (below 25 μmol/L), although the IC50 value of Val-Cur did not differ significantly from that of Cur. In vivo biological effects of Val-Cur were assessed by adding it into the feed (150 mg/kg) of American eels (Anguilla rostrata). Val-Cur significantly improved the growth performance (↑weight gain rate, ↑specific growth rate, and ↓feed conversion rate) and activities of intestinal digestive enzymes (amylase and lipase) and antioxidant enzymes (superoxide dismutase) in American eels. Additionally, Val-Cur significantly improved serum biochemical indices (↑high-density lipoprotein cholesterol, ↓low-density lipoprotein cholesterol, ↓aspartate and alanine aminotransferases). Furthermore, Val-Cur increased intestinal microbial diversity, reduced the abundance of potentially pathogenic bacteria (Spiroplasma, Clostridium, and Pseudomonas), and elevated the abundance of beneficial digestion-promoting bacteria (Romboutsia, Phyllobacterium, Romboutsia sedimentorum, and Clostridium butyricum) conducive to glucose metabolism (P < 0.05). To the best of our knowledge, this study is the first to explore water-soluble curcumin in aquaculture, and the findings will lay the groundwork for the potential application of water-soluble curcumin in the field of aquaculture.

Pangenome analyses of Clostridium butyricum provide insights into its genetic characteristics and industrial application

Clostridium butyricum is a Gram-positive anaerobic bacterium known for its ability to produce butyate. In this study, we conducted whole-genome sequencing and assembly of 14C. butyricum industrial strains collected from various parts of China. We performed a pan-genome comparative analysis of the 14 assembled strains and 139 strains downloaded from NCBI. We found that the genes related to critical industrial production pathways were primarily present in the core and soft-core gene categories. The phylogenetic analysis revealed that strains from the same clade of the phylogenetic tree possessed similar antibiotic resistance and virulence factors, with most of these genes present in the shell and cloud gene categories. Finally, we predicted the genes producing bacteriocins and botulinum toxins as well as CRISPR systems responsible for host defense. In conclusion, our research provides a desirable pan-genome database for the industrial production, food application, and genetic research of C. butyricum.

The Effect of Clostridium butyricum on Gut Microbial Changes and Functional Profiles of Metabolism in High-fat Diet-fed Rats Depending on Age and Sex.

A high-fat diet (HFD) causes dysbiosis and promotes inflammatory responses in the colon. This study aims to evaluate the effects of Clostridium butyricum on HFD-induced gut microbial changes in rats. Six-week-old Fischer-344 rats with both sexes were given a control or HFD during 8 weeks, and 1-to-100-fold diluted Clostridium butyricum were administered by gavage. Fecal microbiota analyses were conducted using 16S ribosomal RNA metagenomic sequencing and predictive functional profiling of microbial communities in metabolism. A significant increase in Ruminococcaceae and Lachnospiraceae, which are butyric acid-producing bacterial families, was observed in the probiotics groups depending on sex. In contrast, Akkermansia muciniphila, which increased through a HFD regardless of sex, and decreased in the probiotics groups. A. muciniphila positively correlated with Claudin-1 expression in males (P < 0.001) and negatively correlated with the expression of Claudin-2 (P = 0.042), IL-1β (P = 0.037), and IL-6 (P = 0.044) in females. In terms of functional analyses, a HFD decreased the relative abundances of M00131 (carbohydrate metabolism module), M00579, and M00608 (energy metabolism), and increased those of M00307 (carbohydrate metabolism), regardless of sex. However, these changes recovered especially in male C. butyricum groups. Furthermore, M00131, M00579, and M00608 showed a positive correlation and M00307 showed a negative correlation with the relative abundance of A. muciniphila (P < 0.001). The beneficial effects of C. butyricum on HFD-induced gut dysbiosis in young male rats originate from the functional profiles of carbohydrate and energy metabolism.

Influence of Dietary Probiotic and Alpha-Monolaurin on Performance, Egg Quality, Blood Constituents, and Egg Fatty Acids' Profile in Laying Hens.

This work was designed to evaluate the advantages of using multi-strain probiotics feed (Bacillus subtilis, Bacillus licheniformis and Clostridium butyricum) (PRO) and alpha-monolaurin (AML) on laying performance, criteria of egg quality, blood parameters, and yolk fatty acids' profile in laying hens. One hundred forty of Bovans brown laying hens at 45 weeks old (25th week of egg production) were randomly allocated into four groups, with seven replicates of five birds each in a complete randomized design. The first group was fed a basal diet without feed additives (0g/kg diet), and the second, third, and fourth groups received diets containing 1g PRO, 1g AML, and 1g PRO + 1g AML/kg diet, respectively. No significant impacts of PRO, AML, or their mixture on body weight (BW), body weight gain (BWG), feed intake (FI), or egg weight. Egg production, egg mass, and feed conversion ratio (FCR) were enhanced by 1g PRO/kg and /or 1g AML/kg supplementation in laying hen diets. Furthermore, egg shape index, eggshell thickness, and yolk color were statistically higher by PRO and AML supplementation at 55 weeks. However, oviduct, infundibulum, and uterus weights were significantly decreased by 1g PRO or/and 1g AML. Additionally, total cholesterol, triglycerides, low density lipoprotein (LDL), glucose, and glutamate pyruvate transaminase (GPT) levels were decreased by PRO and AML supplementation. In conclusion, it seems that dietary inclusion with 1g PRO/kg, 1g of AML/kg, and 1g PRO + 1g AML improved egg production, egg mass, FCR, and yolk fatty acids profile and lowered total cholesterol and malondialdehyde (MDA) contents in laying hens.

Multiplex genetic manipulations in Clostridium butyricum and Clostridium sporogenes to secrete recombinant antigen proteins for oral-spore vaccination

BackgroundClostridium spp. has demonstrated therapeutic potential in cancer treatment through intravenous or intratumoral administration. This approach has expanded to include non-pathogenic clostridia for the treatment of various diseases, underscoring the innovative concept of oral-spore vaccination using clostridia. Recent advancements in the field of synthetic biology have significantly enhanced the development of Clostridium-based bio-therapeutics. These advancements are particularly notable in the areas of efficient protein overexpression and secretion, which are crucial for the feasibility of oral vaccination strategies. Here, we present two examples of genetically engineered Clostridium candidates: one as an oral cancer vaccine and the other as an antiviral oral vaccine against SARS-CoV-2.ResultsUsing five validated promoters and a signal peptide derived from Clostridium sporogenes, a series of full-length NY-ESO-1/CTAG1, a promising cancer vaccine candidate, expression vectors were constructed and transformed into C. sporogenes and Clostridium butyricum. Western blotting analysis confirmed efficient expression and secretion of NY-ESO-1 in clostridia, with specific promoters leading to enhanced detection signals. Additionally, the fusion of a reported bacterial adjuvant to NY-ESO-1 for improved immune recognition led to the cloning difficulties in E. coli. The use of an AUU start codon successfully mitigated potential toxicity issues in E. coli, enabling the secretion of recombinant proteins in C. sporogenes and C. butyricum. We further demonstrate the successful replacement of PyrE loci with high-expression cassettes carrying NY-ESO-1 and adjuvant-fused NY-ESO-1, achieving plasmid-free clostridia capable of secreting the antigens. Lastly, the study successfully extends its multiplex genetic manipulations to engineer clostridia for the secretion of SARS-CoV-2-related Spike_S1 antigens.ConclusionsThis study successfully demonstrated that C. butyricum and C. sporogenes can produce the two recombinant antigen proteins (NY-ESO-1 and SARS-CoV-2-related Spike_S1 antigens) through genetic manipulations, utilizing the AUU start codon. This approach overcomes challenges in cloning difficult proteins in E. coli. These findings underscore the feasibility of harnessing commensal clostridia for antigen protein secretion, emphasizing the applicability of non-canonical translation initiation across diverse species with broad implications for medical or industrial biotechnology.

Complete genome sequence of Clostridium butyricum DKU-11, isolated from healthy infant feces.

Clostridium butyricum DKU-11, a bacterium has been isolated from the stools of breastfed infants near Cheonan-Asan city, Republic of Korea, and has a genome sequence of 4,630,814 bp. The GC content is 28.7% and a total of 4,137 coding sequences in two contigs.

Exploring the effect of Clostridium butyricum on lung injury associated with acute pancreatitis in mice by combined 16S rRNA and metabolomics analysis

ObjectivesAcute lung injury is a critical complication of severe acute pancreatitis (SAP). The gut microbiota and its metabolites play an important role in SAP development and may provide new targets for AP-associated lung injury. Based on the ability to reverse AP injury, we proposed that Clostridium butyricum may reduce the potential for AP-associated lung injury by modulating with intestinal microbiota and related metabolic pathways. MethodsAn AP disease model was established in mice and treated with C. butyricum. The structure and composition of the intestinal microbiota in mouse feces were analyzed by 16 S rRNA gene sequencing. Non-targeted metabolite analysis was used to quantify the microbiota derivatives. The histopathology of mouse pancreas and lung tissues was examined using hematoxylin–eosin staining. Pancreatic and lung tissues from mice were stained with immunohistochemistry and protein immunoblotting to detect inflammatory factors IL-6, IL-1β, and MCP-1. ResultsC. butyricum ameliorated the dysregulation of microbiota diversity in a model of AP combined with lung injury and affected fatty acid metabolism by lowering triglyceride levels, which were closely related to the alteration in the relative abundance of Erysipelatoclostridium and Akkermansia. In addition, C. butyricum treatment attenuated pathological damage in the pancreatic and lung tissues and significantly suppressed the expression of inflammatory factors in mice. ConclusionsC. butyricum may alleviate lung injury associated with AP by interfering with the relevant intestinal microbiota and modulating relevant metabolic pathways.

Physiological and biochemical characteristics of the carbon ion beam irradiation-generated mutant strain Clostridium butyricum FZM 240 in vitro and in vivo

Clostridium butyricum (C. butyricum) represents a new generation of probiotics, which is beneficial because of its good tolerance and ability to produce beneficial metabolites, such as short-chain fatty acids and enzymes; however, its low enzyme activity limits its probiotic efficacy. In this study, a mutant strain, C. butyricum FZM 240 was obtained using carbon ion beam irradiation, which exhibited greatly improved enzyme production and tolerance. The highest filter paper, endoglucanase, and amylase activities produced by C. butyricum FZM 240 were 125.69 U/mL, 225.82 U/ mL, and 252.28 U/mL, which were 2.58, 1.95, and 2.21-fold higher, respectively, than those of the original strain. The survival rate of the strain increased by 11.40 % and 5.60 % after incubation at 90 °C for 5 min and with simulated gastric fluid at pH 2.5 for 2 h, respectively, compared with that of the original strain. Whole-genome resequencing and quantitative real-time PCR(qRT-PCR) analysis showed that the expression of genes related to enzyme synthesis (GE000348, GE001963 and GE003123) and tolerance (GE001114) was significantly up-regulated, while that of genes related to acid metabolism (GE003450) was significantly down-regulated. On this basis, homology modeling and functional prediction of the proteins encoded by the mutated genes were performed. According to the results, the properties related to the efficacy of C. butyricum as a probiotic were significantly enhanced by carbon ion beam irradiation, which is a novel strategy for the application of Clostridium spp. as feed additives.

Immunoregulatory role of the gut microbiota in inflammatory depression

Inflammatory depression is a treatment-resistant subtype of depression. A causal role of the gut microbiota as a source of low-grade inflammation remains unclear. Here, as part of an observational trial, we first analyze the gut microbiota composition in the stool, inflammatory factors and short-chain fatty acids (SCFAs) in plasma, and inflammatory and permeability markers in the intestinal mucosa of patients with inflammatory depression (ChiCTR1900025175). Gut microbiota of patients with inflammatory depression exhibits higher Bacteroides and lower Clostridium, with an increase in SCFA-producing species with abnormal butanoate metabolism. We then perform fecal microbiota transplantation (FMT) and probiotic supplementation in animal experiments to determine the causal role of the gut microbiota in inflammatory depression. After FMT, the gut microbiota of the inflammatory depression group shows increased peripheral and central inflammatory factors and intestinal mucosal permeability in recipient mice with depressive and anxiety-like behaviors. Clostridium butyricum administration normalizes the gut microbiota, decreases inflammatory factors, and displays antidepressant-like effects in a mouse model of inflammatory depression. These findings suggest that inflammatory processes derived from the gut microbiota can be involved in neuroinflammation of inflammatory depression.

Clostridium butyricum isolated from giant panda can attenuate dextran sodium sulfate-induced colitis in mice.

Probiotics are beneficial to the intestinal barrier, but few studies have investigated probiotics from giant pandas. This study aims to explore the preventive effects of giant panda-derived Clostridium butyricum on dextran sodium sulfate (DSS)-induced colitis in mice. Clostridium butyricum was administered to mice 14 days before administering DSS treatment to induce enteritis. Clostridium butyricum B14 could more effectively prevent colitis in mice than C. butyricum B13. C. butyricum B14 protected the mouse colon by decreasing the histology index and serum interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) levels, which improved intestinal inflammation-related symptoms. In addition, the treatment led to the regulation of the expression of Tifa, Igkv12-89, and Nr1d1, which in turn inhibited immune pathways. The expression of Muc4, Lama3, Cldn4, Cldn3, Ocln, Zo1, Zo2, and Snai is related the intestinal mucosal barrier. 16S sequencing shows that the C. butyricum B14 significantly increased the abundance of certain intestinal probiotics. Overall, C. butyricum B14 exerted a preventive effect on colitis in mice by inhibiting immune responses, enhancing the intestinal barrier and increasing the abundance of probiotic species. Thus, C. butyricum B14 administration helps regulate the balance of the intestinal microecology. It can suppress immune pathways and enhance barrier-protective proteins.

Effects of Clostridium butyricum on Production Performance and Bone Development of Laying Hens.

Probiotics are safe, inexpensive, and effective feed additives, and Clostridium butyricum (CB) has been reported to regulate bone health in addition to having conventional probiotic effects. The bone health of laying hens is closely related to their production performance. Here, we investigated the effects of CB supplementation on the bone health and performance of laying hens. We added CB to the feed of green-shell laying hens, Luhua laying hens, and Hy-line Brown laying hens and examined changes in body weight, feed intake, egg production performance, and egg quality to determine the impact of CB on production performance. The impact of CB on the bones of laying hens was determined by analyzing the bone index, bone bending strength, bone calcium and phosphorus content, and bone mineral density. The study found that CB had little effect on the body weight and feed intake of laying hens. Feed additions of 108 and 109 CFU/kg CB can significantly increase the tibia index and bone mineral density of four-week-old green-shell laying hens. Feed additions of 107 and 108 CFU/kg CB can significantly increase the average egg weight, eggshell weight, and tibia index of 26-week-old Luhua laying hens, but 107 CFU/kg CB will reduce the egg production rate. Adding 108 CFU/kg CB to feed can significantly increase the average egg weight, eggshell weight, and tibia bending strength of 40-week-old Hy-line Brown laying hens. In summary, adding 108 CFU/kg CB is beneficial to the bone and production health of laying hens.

Clostridium butyricum Bacteremia Associated with Probiotic Use, Japan.

Clostridium butyricum, a probiotic commonly prescribed in Asia, most notably as MIYA-BM (Miyarisan Pharmaceutical Co., Ltd.; https://www.miyarisan.com), occasionally leads to bacteremia. The prevalence and characteristics of C. butyricum bacteremia and its bacteriologic and genetic underpinnings remain unknown. We retrospectively investigated patients admitted to Osaka University Hospital during September 2011-February 2023. Whole-genome sequencing revealed 5 (0.08%) cases of C. butyricum bacteremia among 6,576 case-patients who had blood cultures positive for any bacteria. Four patients consumed MIYA-BM, and 1 patient consumed a different C. butyricum-containing probiotic. Most patients had compromised immune systems, and common symptoms included fever and abdominal distress. One patient died of nonocclusive mesenteric ischemia. Sequencing results confirmed that all identified C. butyricum bacteremia strains were probiotic derivatives. Our findings underscore the risk for bacteremia resulting from probiotic use, especially in hospitalized patients, necessitating judicious prescription practices.

Probiotic Roles of Clostridium butyricum in Piglets: Considering Aspects of Intestinal Barrier Function.

China, as the global leader in pork production and consumption, is faced with challenges in ensuring sustainable and wholesome growth of the pig industry while also guaranteeing meat food safety amidst the ban on antibiotics usage in animal feed. The focus of the pig industry lies in guaranteeing piglet health and enhancing overall production performance through nutrition regulation. Clostridium butyricum (C. butyricum), a new type of probiotic, possesses characteristics such as heat resistance, acid resistance, and bile-salt tolerance, meaning it has potential as a feed additive. Previous studies have demonstrated that C. butyricum has a probiotic effect on piglets and can serve as a substitute for antibiotics. The objective of this study was to review the probiotic role of C. butyricum in the production of piglets, specifically focusing on intestinal barrier function. Through this review, we explored the probiotic effects of C. butyricum on piglets from the perspective of intestinal health. That is, C. butyricum promotes intestinal health by regulating the functions of the mechanical barrier, chemical barrier, immune barrier, and microbial barrier of piglets, thereby improving the growth of piglets. This review can provide a reference for the rational utilization and application of C. butyricum in swine production.