Restoration of gut dysbiosis through Clostridium butyricum and magnesium possibly balance blood glucose levels: an experimental study.

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by an elevated level of blood glucose due to the absence of insulin secretion, ineffectiveness, or lack of uptake of secreted insulin in the body. The improperly diagnosed and poorly managed DM can cause severe damage to organs in the body like the nerves, eyes, heart, and kidneys. This study was aimed at investigating the effect of Clostridium butyricum (probiotic) with magnesium supplementation to evaluate the effect on gut microbial dysbiosis and blood glucose levels. In the laboratory, 6-8 weeks old 24 male albino rats weighing 200-250 g were given free access to water and food. Diabetes was induced using streptozotocin (60 mg/kg) in overnight fasted rats. Diabetic rats were randomly divided into four groups (n = 6, 6 replicates in each group). Metformin (100 mg/kg/day) with a standard basal diet was provided to control group (G0), Clostridium butyricum (1.5 × 105 CFU/day) with standard basal diet was provided to treatment group (G1), magnesium (500 mg/kg/day) was provided to group (G2). Clostridium butyricum (1.5 × 105 CFU/day) and magnesium (300 mg/kg/day) in combination with a standard basal diet was provided to group (G3). Blood Glucose, Magnesium blood test and microbial assay were done. Random blood glucose levels were monitored twice a week for 21 days and were represented as mean of each week. The results conclude that Clostridium butyricum (1.5 × 105 CFU) is very effective in balancing random blood glucose levels from 206.6 ± 67.7 to 85.1 ± 3.8 (p = 0.006) compared to other groups (p > 0.005). The results of stool analysis showed that Clostridium butyricum as probiotic restores microbial dysbiosis as evident by the 105 CFU Clostridium butyricum load in G1, which was higher than G0, G2 and G3 which were 103 and 104 CFU respectively. The findings of this study conclude that Clostridium butyricum supplementation improved blood glucose levels and intestinal bacterial load in type II diabetes mellitus.

Novel mechanism of Clostridium butyricum alleviated coprophagy prevention-induced intestinal inflammation in rabbit.

As bacteria synthesize nutrients primarily in the cecum, coprophagy is indispensable for supplying rabbits with essential nutrients. Recent research has demonstrated its pivotal role in maintaining intestinal microbiota homeostasis and immune regulation in rabbits, although the specific mechanism remains unknown. Here, we used coprophagy prevention (CP) to investigate the effects of coprophagy on the cecum homeostasis and microbiota in New Zealand white rabbits. Furthermore, whether supplementation of Clostridium butyricum (C. butyricum) may alleviate the cecum inflammation and apoptosis caused by CP was also explored. Four groups were randomly assigned: control (Con), sham-coprophagy prevention (SCP), coprophagy prevention (CP), and CP and C. butyricum addition (CPCB). Compared to Con and SCP, CP augmented cecum inflammation and apoptosis, as well as bacterial adhesion to the cecal epithelial mucosa, while decreasing the expression of tight junction proteins (ZO-1, occluding, and claudin-1). The relative abundance of short-chain fatty acids (SCFAs)-producing bacteria was significantly decreased in the CP group. Inversely, there was an increase in the Firmicutes/Bacteroidetes ratio and the relative abundance of Christensenellaceae_R-7_group. Additionally, CP increased the levels of Flagellin, IFN-γ, TNF-a, and IL-1ß in cecum contents and promoted the expression of TLR5/MyD88/NF-κB pathway in cecum tissues. However, the CPCB group showed significant improvements in all parameters compared to the CP group. Dietary C. butyricum supplementation significantly increased the production of SCFAs, particularly butyric acid, triggering anti-inflammatory, tissue repairing, and barrier-protective responses. Notably, CPCB effectively mitigated CP-induced apoptosis and inflammation. In summary, CP disrupts the cecum epithelial barrier and induces inflammation in New Zealand white rabbits, but these effects can be alleviated by C. butyricum supplementation. This process appears to be largely associated with the TLR5/MyD88/NF-κB signaling pathway.

Clostridium butyricum inhibits the inflammation in children with primary nephrotic syndrome by regulating Th17/Tregs balance via gut-kidney axis.

BACKGROUND: Primary nephrotic syndrome (PNS) is a common glomerular disease in children. Clostridium butyricum (C. butyricum), a probiotic producing butyric acid, exerts effective in regulating inflammation. This study was designed to elucidate the effect of C. butyricum on PNS inflammation through the gut-kidney axis. METHOD: BALB/c mice were randomly divided into 4 groups: normal control group (CON), C. butyricum control group (CON+C. butyricum), PNS model group (PNS), and PNS with C. butyricum group (PNS+C. butyricum). The PNS model was established by a single injection of doxorubicin hydrochloride (DOX) through the tail vein. After 1 week of modeling, the mice were treated with C. butyricum for 6 weeks. At the end of the experiment, the mice were euthanized and associated indications were investigated. RESULTS: Since the successful modeling of the PNS, the 24 h urine protein, blood urea nitrogen (BUN), serum creatinine (SCr), urine urea nitrogen (UUN), urine creatinine (UCr), lipopolysaccharides (LPS), pro-inflammatory interleukin (IL)-6, IL-17A were increased, the kidney pathological damage was aggravated, while a reduction of body weights of the mice and the anti-inflammatory IL-10 significantly reduced. However, these abnormalities could be dramatically reversed by C. butyricum treatment. The crucial Th17/Tregs axis in PNS inflammation also was proved to be effectively regulated by C. butyricum treatment. This probiotic intervention notably affected the expression levels of signal transducer and activator of transcription 3 (STAT3), Heme oxygenase-1 (HO-1) protein, and retinoic acid-related orphan receptor gamma t (RORγt). 16S rRNA sequencing showed that C. butyricum could regulate the composition of the intestinal microbial community and found Proteobacteria was more abundant in urine microorganisms in mice with PNS. Short-chain fatty acids (SCFAs) were measured and showed that C. butyricum treatment increased the contents of acetic acid, propionic acid, butyric acid in feces, acetic acid, and valeric acid in urine. Correlation analysis showed that there was a closely complicated correlation among inflammatory indicators, metabolic indicators, microbiota, and associated metabolic SCFAs in the gut-kidney axis. CONCLUSION: C. butyricum regulates Th17/Tregs balance via the gut-kidney axis to suppress the immune inflammatory response in mice with PNS, which may potentially contribute to a safe and inexpensive therapeutic agent for PNS.

Gut microbiota dynamics and fecal SCFAs after colonoscopy: accelerating microbiome stabilization by Clostridium butyricum.

BACKGROUND: Colonoscopy is a classic diagnostic method with possible complications including abdominal pain and diarrhoea. In this study, gut microbiota dynamics and related metabolic products during and after colonoscopy were explored to accelerate gut microbiome balance through probiotics. METHODS: The gut microbiota and fecal short-chain fatty acids (SCFAs) were analyzed in four healthy subjects before and after colonoscopy, along with seven individuals supplemented with Clostridium butyricum. We employed 16S rRNA sequencing and GC-MS to investigate these changes. We also conducted bioinformatic analysis to explore the buk gene, encoding butyrate kinase, across C. butyricum strains from the human gut. RESULTS: The gut microbiota and fecal short-chain fatty acids (SCFAs) of four healthy subjects were recovered on the 7th day after colonoscopy. We found that Clostridium and other bacteria might have efficient butyric acid production through bioinformatic analysis of the buk and assessment of the transcriptional level of the buk. Supplementation of seven healthy subjects with Clostridium butyricum after colonoscopy resulted in a quicker recovery and stabilization of gut microbiota and fecal SCFAs on the third day. CONCLUSION: We suggest that supplementation of Clostridium butyricum after colonoscopy should be considered in future routine clinical practice.

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.

The biotherapeutic Clostridium butyricum MIYAIRI 588 strain potentiates enterotropism of Rorγt+Treg and PD-1 blockade efficacy.

Immune checkpoint inhibitors (ICI) have been positioned as a standard of care for patients with advanced non-small-cell lung carcinomas (NSCLC). A pilot clinical trial has reflected optimistic association between supplementation with Clostridium butyricum MIYAIRI 588 (CBM588) and ICI efficacy in NSCLC. However, it remains to be established whether this biotherapeutic strain may be sufficient to heighten the immunogenicity of the tumor draining lymph nodes to overcome resistance to ICI. Herein, we report that supplementation with CBM588 led to an improved responsiveness to antibody targeting programmed cell death protein 1 (aPD-1). This was statistically associated with a significant decrease in α-diversity of gut microbiota from CBM588-treated mice upon PD-1 blockade. At the level of the tumor-draining lymph node, such combination of treatment significantly lowered the frequency of microbiota-modulated subset of regulatory T cells that express Retinoic Orphan Receptor gamma t (Rorγt+ Treg). Specifically, this strongly immunosuppressive was negatively correlated with the abundance of bacteria that belong to the family of Ruminococcaceae. Accordingly, the colonic expression of both indoleamine 2,3-Dioxygenase 1 (IDO-1) and interleukin-10 (IL-10) were heightened in mice with greater PD-1 blockade efficacy. The CBM588-induced ability to secrete Interleukin-10 of lamina propria mononuclear cells was heightened in tumor bearers when compared with cancer-free mice. Conversely, blockade of interleukin-10 signaling preferentially enhanced the capacity of CD8+ T cells to secrete Interferon gamma when being cocultured with CBM588-primed lamina propria mononuclear cells of tumor-bearing mice. Our results demonstrate that CBM588-centered intervention can adequately improve intestinal homeostasis and efficiently overcome resistance to PD-1 blockade in mice.

Effect of the Combination of Clostridium butyricum and Mycelium of Phellinus igniarius on Intestinal Microbiota and Serum Metabolites in DSS-Induced Colitis.

Clostridium butyricum (CB) and Phellinus igniarius (PI) have anti-inflammatory, immune regulation, anti-tumor, and other functions. This study aimed to explore the therapeutic effect of CB and mycelium of PI (MPI) alone and in combination on colitis mice induced by dextran sodium sulfate (DSS). Mice were randomly assigned to five groups: (1) control (CTRL), (2) DSS, (3) CB, (4) MPI, and (5) CB + MPI (CON). The weight of the mice was recorded daily during the experiment, and the length of the colon was measured on the last day of the experiment. The colons were collected for hematoxylin and eosin staining, colon contents were collected for intestinal flora analysis, and serum was collected for metabolite analysis. The results showed that compared with the DSS group, CB, MPI, and CON treatments inhibited the weight loss and colon length shortening caused by DSS, significantly increased the concentrations of interleukin (IL)-4, IL-10, and superoxide dismutase, and significantly decreased the concentrations of IL-6, tumor necrosis factor-α, and myeloperoxidase. Gene sequence analysis of 16S rRNA showed that CB, MPI, and CON treatments changed the composition and structure of intestinal microorganisms. Metabolome results showed that CB, MPI, and CON treatments changed serum metabolites in DSS-treated mice, including dodecenoylcarnitine, L-urobilinogen, and citric acid. In conclusion, CB, MPI, and CON treatments alleviated DSS-induced colitis in mice by regulating intestinal flora and metabolites, with the CON group having the best effect.

The antioxidant strain Lactiplantibacillus plantarum AS21 and Clostridium butyricum ameliorate DSS-induced colitis in mice by remodeling the assembly of intestinal microbiota and improving gut functions.

Probiotics are known for their beneficial effects on improving intestinal function by alleviating the gut microbial diversity. However, the influences of antioxidant lactic acid bacteria (LAB) and anti-inflammatory Clostridium butyricum (CB) on ameliorating enteritis remain unclear. In this study, we investigated the effects of the antioxidant strain Lactiplantibacillus plantarum AS21 and CB alone, or in combination on intestinal microbiota, barrier function, oxidative stress and inflammation in mice with DSS-induced colitis. All probiotic treatments relieved the pathological development of colitis by improving the integrity of the intestinal mucosal barrier and the length of the colon. The probiotics also suppressed inflammation and oxidative stress by improving gut short-chain fatty acids and inhibiting the p38-MAPK/NF-κB pathway in colon tissues. According to the meta-network analysis, three distinct modules containing sensitive OTUs of the gut bacterial community specific to the control, DSS and DSS + probiotics groups were observed, and unlike the other two modules, Lachnospiraceae and Clostridia dominated the sensitive OTUs in the DSS + probiotics group. In addition, administration of the present probiotics particularly increased antioxidant and anti-inflammatory microbes Muribaculaceae, Bifidobacterium, Prevotellaceae and Alloprevotella. Furthermore, combined probiotic strain treatment showed a more stable anti-colitis effect than a single probiotic strain. Collectively, the present probiotics exhibited protective effects against colitis by suppressing the inflammation and oxidative damage in the colon, improving the gut microbiota and their functions, and consequently preventing the gut leak. The results indicate that the combination of the antioxidant properties of LAB and the anti-inflammatory properties of CB as nutritional intervention and adjuvant therapy could be an effective strategy to prevent and alleviate colitis.

Effects of probiotics in children with acute gastroenteritis: A systematic review and meta-analysis focusing on probiotics utilized in Japan.

BACKGROUND: Many randomized controlled trials and systematic reviews have evaluated the use of probiotics to treat acute infectious gastroenteritis. However, most probiotic species evaluated in previous large randomized controlled trials are unavailable in Japan. Our objective was to investigate the efficacy of probiotics utilized in Japan for acute gastroenteritis. METHODS: The inclusion criterion was a randomized controlled study that compared probiotics with a placebo to treat children younger than 18 years with acute infectious gastroenteritis. We excluded studies that did not contain the following species available in Japan: Bifidobacterium spp., Lactobacillus acidophilus, Enterococcus faecium, Clostridium butyricum, and Bacillus subtilis and studies in low- or lower-middle-income countries. We searched PubMed, CENTRAL, and Igaku Chuo Zasshi from their inception to November 27, 2022. After the risk of bias assessment, data on diarrhea duration, number of hospitalizations, length of hospital stay, and adverse effects were extracted. RESULTS: Fourteen studies were included in this meta-analysis. Diarrhea lasting longer than 48 h (7 articles, n = 878) was significantly lower in the probiotic group (risk ratio (RR) 0.70, 95 % confidence interval (CI) 0.59-0.83). The duration of diarrhea (14 articles; n = 1761) was 23.45 h (95 % CI 18.22-26.69) shorter in the probiotic group. Duration of hospitalization (6 articles; n = 971) was 17.73 h (95 % CI 6.9-28.56) shorter in the probiotic group. CONCLUSIONS: Although the certainty of evidence is very low, the use of probiotics for acute gastroenteritis in children may improve diarrhea approximately one day earlier. This study was registered with PROSPERO (CRD 42023405559).

Enhancing and monitoring spore production in Clostridium butyricum using pH-based regulation strategy and a robust soft sensor based on back-propagation neural networks.

Clostridium butyricum is a probiotic that forms anaerobic spores and plays a crucial role in regulating gut microbiota. However, the total viable cell count and spore yield of C. butyricum in industrial production are comparatively low. To this end, we investigated the metabolic characteristics of the strain and proposed three distinct pH regulation strategies for enhancing spore production. In addition, precise measurement of fermentation parameters such as substrate concentration, total viable cell count, and spore concentration is crucial for successful industrial probiotics production. Nevertheless, online measurement of these intricate parameters in the fermentation of C. butyricum poses a considerable challenge owing to the complex, nonlinear, multivariate, and strongly coupled characteristics of the production process. Therefore, we analyzed the capacitance and conductivity acquired from a viable cell sensor as the core parameters for the fermentation process. Subsequently, a robust soft sensor was developed using a seven-input back-propagation neural network model with input variables of fermentation time, capacitance, conductivity, pH, initial total sugar concentration, ammonium ion concentration, and calcium ion concentration. The model enables the online monitoring of total viable biomass count, substrate concentrations, and spore yield, and can be extended to similar fermentation processes with pH changes as a characteristic feature.

Dynamic flux balance analysis of 1,3-propanediol production by clostridium butyricum fermentation.

To study the relationship between the yield of 1,3-propanediol (1,3-PDO) and the flux change of the Clostridium butyricum metabolic pathway, an optimized calculation method based on dynamic flux balance analysis was used by combining genome-scale flux balance analysis with a kinetic model. A more comprehensive and extensive metabolic pathway was obtained by optimization calculations. The primary extended branches include: the dihydroxyacetone node, which enters the pentose phosphate pathway; the α-oxoglutarate node, which has synthetic metabolic pathways for glutamic acid and amino acids; and the serine and homocysteine nodes, which produce cystathionine before homocysteine enters the methionine cycle pathway. According to the expanded metabolic network, the flux distribution of key nodes in the metabolic pathway and the relationship between the flux distribution ratio of nodes and the yield of 1,3-PDO were analyzed. At the dihydroxyacetone node, the flux of dihydroxyacetone converted to dihydroxyacetone phosphate was positively correlated with the yield of 1,3-PDO. As an important intermediate product, the flux change in the metabolic pathway of α-oxoglutarate reacting with amino acids to produce glutamic acid is positively correlated with the yield. When pyruvate was used as the central node to convert into lactic acid and α-oxoglutarate, the proportion of branch flux was negatively correlated with the yield of 1,3-PDO. These studies provide a theoretical basis for the optimization and further study of the metabolic pathway of C. butyricum.

Clostridium butyricum Prazmowski can degrade and utilize resistant starch via a set of synergistically acting enzymes.

Resistant starch is a prebiotic fiber that is best known for its ability to increase butyrate production by the gut microbiota. This butyrate then plays an important role in modulating the immune system and inflammation. However, the ability to use this resistant starch appears to be a rare trait within the gut microbiota, with only a few species such as Ruminococcus bromii and Bifidobacterium adolescentis having been demonstrated to possess this ability. Furthermore, these bacteria do not directly produce butyrate themselves, rather they rely on cross-feeding interactions with other gut bacteria for its production. Here, we demonstrate that the often-used probiotic organism Clostridium butyricum also possesses the ability to utilize resistant starch from a number of sources, with direct production of butyrate. We further explore the enzymes responsible for this trait, demonstrating that they exhibit significant synergy, though with different enzymes exhibiting more or less importance depending on the source of the resistant starch. Thus, the co-administration of Clostridium butyricum may have the ability to improve the beneficial effects of resistant starch.IMPORTANCEClostridium butyricum is seeing increased use as a probiotic, due to potential health benefits tied to its ability to produce butyrate. Here, we demonstrate that this organism can use a variety of resistant starch sources and characterize the enzymes it uses to accomplish this. Given the relative rarity of resistant starch utilizing ability within the gut and the health benefits tied to resistant starch, the combined use of this organism with resistant starch in synbiotic formulations may prove beneficial.

Probiotic Clostridium butyricum ameliorates cognitive impairment in obesity via the microbiota-gut-brain axis.

Obesity is a risk factor for cognitive dysfunction and neurodegenerative disease, including Alzheimer's disease (AD). The gut microbiota-brain axis is altered in obesity and linked to cognitive impairment and neurodegenerative disorders. Here, we targeted obesity-induced cognitive impairment by testing the impact of the probiotic Clostridium butyricum, which has previously shown beneficial effects on gut homeostasis and brain function. Firstly, we characterized and analyzed the gut microbial profiles of participants with obesity and the correlation between gut microbiota and cognitive scores. Then, using an obese mouse model induced by a Western-style diet (high-fat and fiber-deficient diet), the effects of Clostridium butyricum on the microbiota-gut-brain axis and hippocampal cognitive function were evaluated. Finally, fecal microbiota transplantation was performed to assess the functional link between Clostridium butyricum remodeling gut microbiota and hippocampal synaptic protein and cognitive behaviors. Our results showed that participants with obesity had gut microbiota dysbiosis characterized by an increase in phylum Proteobacteria and a decrease in Clostridium butyricum, which were closely associated with cognitive decline. In diet-induced obese mice, oral Clostridium butyricum supplementation significantly alleviated cognitive impairment, attenuated the deficit of hippocampal neurite outgrowth and synaptic ultrastructure, improved hippocampal transcriptome related to synapses and dendrites; a comparison of the effects of Clostridium butyricum in mice against human AD datasets revealed that many of the genes changes in AD were reversed by Clostridium butyricum; concurrently, Clostridium butyricum also prevented gut microbiota dysbiosis, colonic barrier impairment and inflammation, and attenuated endotoxemia. Importantly, fecal microbiota transplantation from donor-obese mice with Clostridium butyricum supplementation facilitated cognitive variables and colonic integrity compared with from donor obese mice, highlighting that Clostridium butyricum's impact on cognitive function is largely due to its ability to remodel gut microbiota. Our findings provide the first insights into the neuroprotective effects of Clostridium butyricum on obesity-associated cognitive impairments and neurodegeneration via the gut microbiota-gut-brain axis.

Clostridium butyricum Ameliorates the Effect of Coprophagy Prevention on Hepatic Lipid Synthesis in Rabbits via the Gut-Liver Axis.

Coprophagy prevention (CP) affects the growth performance, hepatic lipid synthesis, and gut microbiota in rabbits. Supplementation with Clostridium butyricum (C. butyricum, Strain number: CCTCC M 2019962) has been found to improve growth performance in rabbits. However, it remains unknown whether C. butyricum can ameliorate the effects of CP on hepatic lipid synthesis and the underlying mechanisms are yet to be elucidated. Therefore, this study aimed to investigate the impact of CP on hepatic lipid synthesis and the underlying mechanism based on the gut-liver axis. The findings revealed that supplementation with C. butyricum could reverse CP-related growth performance, lipid accumulation, bile acid synthesis, and inflammation. Furthermore, C. butyricum exerted protective effects on the gut by preserving intestinal barrier integrity and modulating gut microbiota composition; these factors may represent potential mechanisms through which C. butyricum improves CP-related outcomes. Specifically, C. butyricum reshaped the microbiota by increasing butyric acid levels, thereby maintaining secondary bile acid (deoxycholic acid, chenodeoxycholic acid) balance and attenuating the inhibitory effects of the FXR/SHP pathway on lipid synthesis (SREBP1c/ApoA1). Moreover, the activation of butyrate/GPR43pathway by C. butyricum reduced damage to the intestinal barrier (ZO-1/Occludin/Claudin1) and restored the gut immune microenvironment in CP rabbits. In summary, supplementation with C. butyricum can alleviate the adverse effects of CP on growth performance and hepatic lipid synthesis by modulating the gut-liver axis.

The metagenomic and metabolomic profile of the gut microbes in Chinese full-term and late preterm infants treated with Clostridium butyricum.

The present study investigated the composition, abundance, and diversity of gut microbes in full-term and late-preterm infants from a medical center in eastern China. A total of 144 genomes of stool samples were captured for 16S rRNA metagenomic analyses. A high abundance of commensal intestinal bacteria was detected in these samples such as Phocaeicola vulgatus, Escherichia coli, and Faecalibacterium prausnitzii, indicating a relatively consistent diversity of gut microbes in the present full-term infants aged 38-40 weeks. However, late preterm infants (n = 50) with mandatory antimicrobials feeding exhibited lower diversity but a higher composition of opportunistic pathogens such as Enterococcus species. Centralized on the situation, we explored the regulatory effect of Clostridium butyricum as probiotics on these late preterm infants. The consumption of C. butyricum did not restore the composition of gut microbes altered by antimicrobials to normal levels, although several opportunistic pathogens decreased significantly after probiotic therapy including Staphylococcus aureus, Sphingomonas echinoides, and Pseudomonas putida. We also compared the effects of day-fed versus night-fed probiotics. Intriguingly, the nighttime feeding showed a higher proportion of C. butyricum compared with probiotic day-feeding. Finally, fecal metabolome and metabolites were analyzed in late preterm infants with (n = 20) or without probiotic therapy (n = 20). The KEGG enrichment analysis demonstrated that vitamin digestion and absorption, synaptic vesicle cycle, and biotin metabolism were significantly increased in the probiotic-treated group, while MSEA indicated that a series of metabolism were significantly enriched in probiotic-treated infants including glycerolipid, biotin, and lysine, indicating the complex effects of probiotic therapy on glutathione metabolism and nutrients digestion and absorption in late preterm infants. Overall, this study provided metagenomic and metabolomic profile of the gut microbes in full-term newborns and late preterm infants in eastern China. Further studies are needed to support and elucidate the role of probiotic feeding in late preterm infants with mandatory antimicrobial treatment.

Clostridium butyricum Alleviates DEHP Plasticizer-Induced Learning and Memory Impairment in Mice via Gut-Brain Axis.

Di-(2-ethylhexyl) phthalate (DEHP) plasticizer, a well-known environmental and food pollutant, has neurotoxicity. However, it is unknown whether DEHP leads to learning and memory impairment through gut-brain axis and whether Clostridium butyricum can alleviate this impairment. Here, C57BL/6 mice were exposed to DEHP and treated with C. butyricum. Learning and memory abilities were evaluated through the Morris water maze. The levels of synaptic proteins, inflammatory cytokines, and 5-hydroxytryptamine (5-HT) were detected by immunohistochemistry or ELISA. Gut microbiota were analyzed through 16S rRNA sequencing. C. butyricum alleviated DEHP-induced learning and memory impairment and restored synaptic proteins. It significantly relieved DEHP-induced inflammation and recovered 5-HT levels. C. butyricum recovered the richness of the gut microbiota decreased by DEHP, with the Bifidobacterium genus increasing the most. Overall, C. butyricum alleviated DEHP-induced learning and memory impairment due to reduced inflammation and increased 5-HT secretion, which was partly attributed to the recovery of gut microbiota.

Clostridium butyricum and Clostridium tyrobutyricum: angel or devil for necrotizing enterocolitis?

IMPORTANCE: This study sheds light on that treatment with Clostridium tyrobutyricum but not Clostridium butyricum is entitled to protect against necrotizing enterocolitis (NEC) development potentially. The mechanisms behind the opposite effect on NEC may result in different modulation on the level of Akkermansia muciniphila, which is deeply associated with intestinal homoeostasis. Briefly, through improving the abundance of A. muciniphila to alleviate intestinal inflammation and enhance intestinal barrier integrity, C. tyrobutyricum supplement may become a promising therapy for NEC.

Clostridium butyricum Strain CCFM1299 Reduces Obesity via Increasing Energy Expenditure and Modulating Host Bile Acid Metabolism.

Clostridium butyricum is a butyrate-producing microorganism which has beneficial effects on various diseases, including obesity. In our previous study, the anti-obesity Clostridium butyricum strain CCFM1299 (C20_1_1) was selected, but its anti-obesity mechanism was not clarified. Herein, CCFM1299 was orally administrated to high-fat-diet-treated C57BL/6J mice for 12 weeks to uncover the way the strain alleviates obesity. The results indicated that CCFM1299 alleviated obesity through increasing the energy expenditure and increasing the expression of genes related to thermogenesis in brown adipose tissue (BAT). Moreover, strain CCFM1299 could also affect the expression of immune-related genes in epididymal white adipose tissue (eWAT). This immunomodulatory effect might be achieved through its influence on the complement system, as the expression of the complement factor D (CFD) gene decreased significantly. From the view of metabolites, CCFM1299 administration increased the levels of ursodeoxycholic acid (UDCA) in feces and taurohyodeoxycholic acid (THDCA) in serum. Together, the anti-obesity potential of CCFM1299 might be attributed to the increase in energy consumption, the regulation of immune-related gene expression in eWAT, and the alteration of bile acid metabolism in the host. These provided new insights into the potential application of anti-obesity microbial preparations and postbiotics.

The novel immunobiotic Clostridium butyricum S-45-5 displays broad-spectrum antiviral activity in vitro and in vivo by inducing immune modulation.

Clostridium butyricum is known as a probiotic butyric acid bacterium that can improve the intestinal environment. In this study, we isolated a new strain of C. butyricum from infant feces and evaluated its physiological characteristics and antiviral efficacy by modulating the innate immune responses in vitro and in vivo. The isolated C. butyricum S-45-5 showed typical characteristics of C. butyricum including bile acid resistance, antibacterial ability, and growth promotion of various lactic acid bacteria. As an antiviral effect, C. butyricum S-45-5 markedly reduced the replication of influenza A virus (PR8), Newcastle Disease Virus (NDV), and Herpes Simplex Virus (HSV) in RAW264.7 cells in vitro. This suppression can be explained by the induction of antiviral state in cells by the induction of antiviral, IFN-related genes and secretion of IFNs and pro-inflammatory cytokines. In vivo, oral administration of C. butyricum S-45-5 exhibited prophylactic effects on BALB/c mice against fatal doses of highly pathogenic mouse-adapted influenza A subtypes (H1N1, H3N2, and H9N2). Before challenge with influenza virus, C. butyricum S-45-5-treated BALB/c mice showed increased levels of IFN-ß, IFN-γ, IL-6, and IL-12 in serum, the small intestine, and bronchoalveolar lavage fluid (BALF), which correlated with observed prophylactic effects. Interestingly, after challenge with influenza virus, C. butyricum S-45-5-treated BALB/c mice showed reduced levels of pro-inflammatory cytokines and relatively higher levels of anti-inflammatory cytokines at day 7 post-infection. Taken together, these findings suggest that C. butyricum S-45-5 plays an antiviral role in vitro and in vivo by inducing an antiviral state and affects immune modulation to alleviate local and systemic inflammatory responses caused by influenza virus infection. Our study provides the beneficial effects of the new C. butyricum S-45-5 with antiviral effects as a probiotic.

Dietary supplementation with Clostridium butyricum and its ferment substance improves the egg quality and ovarian function in laying hens from 50 to 58 weeks of age.

The current study was conducted to explore the effects of dietary Clostridium butyricum (C. butyricum) and fermented calcium (Ca) butyrate produced by C. butyricum on the performance and egg quality of post-peak laying. A total of 384 50-week-old hens were fed a basal diet, the basal diet with 300 mg/kg of fermented Ca butyrate or 1 × 109 CFU/kg C. butyricum for 8 weeks. Hens received a C. butyricum exhibited higher yolk properties, albumen height, and Haugh unit. A diet with fermented Ca butyrate or C. butyricum increased the egg mass and the pre-grade yellow follicle number. RNA-sequencing (RNA-seq) data showed that these observations were associated with cytokine-cytokine receptor interaction and intestinal immune status. Accordingly, when compared with the basal diet group, Ca butyrate and C. butyricum addition decreased serum pro-inflammatory cytokine levels and increased the concentration of immunoglobulin A, along with improved intestinal barrier. In addition, dietary C. butyricum inclusion induced a higher abundance of Ruminococcaceae and Lachnospiraceae at the family level. In summary, dietary fermented Ca butyrate or C. butyricum supplementation improved egg quality and ovarian function, which might be related to the enhanced intestinal barrier and immunity in post-peak laying hens.