Search Results (120)

Pseudomonas aeruginosa is an important opportunistic pathogen associated with diverse healthcare-associated infections and increasing antimicrobial resistance. This systematic review evaluated antimicrobial treatment regimens, clinical outcomes, and pharmacokinetic/pharmacodynamic (PK/PD) considerations in P. aeruginosa infections. A systematic review was conducted according to PRISMA guidelines. PubMed/MEDLINE and the Cochrane Library were searched for studies published between January 2000 and March 2026. Data on antimicrobial therapies, clinical and microbiological outcomes, and PK/PD parameters were extracted. Study quality was assessed using the NHLBI quality assessment tool. Narrative synthesis was performed for all eligible studies, and a quantitative meta-analysis was conducted for studies with standardized outcome data. Of the 982 records identified, 249 studies met the inclusion criteria, and 34 were included in the quantitative meta-analysis. The evidence base was highly heterogeneous regarding study design, patient populations, infection types, and treatment regimens. Respiratory infections, particularly in cystic fibrosis patients, accounted for most studies. Quantitative synthesis showed no consistent superiority of any antimicrobial regimen (or combination of them), while treatment outcomes were influenced by infection characteristics, antimicrobial resistance patterns, and PK/PD factors. No universally superior antimicrobial regimen was identified for Pseudomonas aeruginosa infections. Some novel and promising treatment options have been identified, such as anti-Pseudomonas aeruginosa LPS monoclonal antibody panobacumab and inhaled Clostridium butyricum delivered via oxygen-driven nebulization. Two novel treatment modalities did not yield a clinically relevant effect, namely, the bispecific monoclonal antibody MEDI3902 (gremubamab) and the IC43 Pseudomonas aeruginosa vaccine. Treatment effectiveness appears to depend on clinical context, antimicrobial susceptibility, and PK/PD considerations, highlighting the need for further standardized research. Full article

Clostridioides difficile infection (CDI) remains a major healthcare-associated infection, and metronidazole (MNZ) is still used for selected patients with non-severe infection in Japan. Although Clostridium butyricum MIYAIRI 588 (CBM588) may be used as an adjunctive therapy, clinical evidence regarding its add-on value to MNZ in non-severe CDI remains limited. We conducted an exploratory single-center retrospective cohort study of adults with non-severe CDI treated with MNZ between April 2015 and March 2025. Of the 161 patients diagnosed with C. difficile infection, 53 patients met the eligibility criteria and were analyzed. Patients were categorized into MNZ monotherapy (n = 27) or MNZ plus CBM588 combination therapy groups (n = 26), and clinical outcomes were compared. Clinical cure was achieved in 51.9% of patients in the monotherapy group and 69.2% of patients in the combination therapy group; however, the difference was not statistically significant (p = 0.196). Recurrence was uncommon in both groups (3.7% vs. 0%), and exploratory multivariable analysis revealed that CBM588 use was not independently associated with clinical cure. These findings do not establish a definitive benefit of adjunctive CBM588 therapy and should be interpreted cautiously as hypothesis-generating given the limited sample size and non-significant result. Full article

This study induced obesity in mice through a high-fat diet (HFD) to investigate the regulatory effects of Clostridium butyricum WL-53 (C. butyricum WL-53) on lipid metabolism and intestinal inflammation. Thirty 6-week-old male C57 mice were randomly divided into three groups: the normal diet group (ND), the high-fat diet group (HFD), and the HFD supplemented with Clostridium butyricum (CB, C. butyricum) group (HFD-CB). The experiment lasted for five weeks. The results demonstrated that mice in the HFD-CB group exhibited significantly alleviated weight gain, reduced fat mass, and decreased hepatic lipid deposition. C. butyricum WL-53 treatment improved serum and hepatic lipid markers (TC, TG), decreased the levels of pro-inflammatory factors (TNF-α, IL-1β), and increased those of anti-inflammatory factors (IL-10, IL-4). Gut microbiota analysis indicated that HFD reduced microbial diversity and increased the abundance of Firmicutes. Meanwhile, C. butyricum WL-53 intervention reversed these changes and enriched beneficial genera. Metabolomics analysis revealed that C. butyricum WL-53 regulated glycerophospholipid metabolism, arachidonic acid metabolism, and cAMP signaling pathways, reversing metabolites to ameliorate lipid deposition and inflammation. In summary, C. butyricum WL-53 alleviates HFD-induced obesity and inflammation via gut microbiota modulation and metabolic reprogramming. Full article

Clostridium butyricum is a well-known Gram-positive, spore-forming, obligate anaerobic, and butyrate-producing bacterium with a few species of next-generation probiotic strains. By far, the most well-known strain is Clostridium butyricum CBM588 (also known as MIYAIRI 588). This strain has gained significant attention for its therapeutic potential across a variety of human health conditions. Preclinical studies have shown its ability to stabilize gut microbiota, enhance short-chain fatty acid (SCFA) production, and modulate immune responses, which contribute to its therapeutic effects in conditions such as ulcerative colitis, allergies, and cancer. We examined 28 interventional clinical trials and 7 observational studies investigating the effect of Clostridium butyricum strains. These studies have supported the findings of preclinical trials and demonstrated symptom improvement and immune modulation in diverse conditions. Clostridium butyricum CBM588 has shown efficacy in managing gastrointestinal diseases, such as acute gastroenteritis and inflammatory bowel disease, and has also proven beneficial in immune modulation, as evidenced by its positive effects in allergic rhinitis and cancer immunotherapy. Additionally, CBM588 has been reported to have a favorable safety and tolerability profile in various patient populations, including children, adults, and critically ill patients. Despite these promising results, clinical studies face limitations such as small sample sizes, varied protocols, and short study durations. Future well-designed, large-scale trials are necessary to further validate the long-term safety and efficacy of Clostridium butyricum in clinical practice. Full article

Background/Objectives: The gut–brain axis and its role in neurological disorders have garnered increasing attention in recent years. However, studies assessing the association between microbiota and Alzheimer’s disease in Japanese cohorts are scarce. This study investigated the potential role of the brain–gut axis in Japanese patients with Alzheimer’s disease (AD), focusing specifically on the role of microbiota composition in AD pathogenesis. Methods: Ten patients with AD and 21 healthy adults across three different age groups were enrolled. Fecal microbiota composition was assessed using 16S rRNA gene sequencing. Results: We found that some bacterial species, such as Ruminococcus inulinivorans and Ruminococcus torques, were more abundant in the AD group, whereas others—including Agathobacter rectalis, Bacteroides uniformis, and Clostridium butyricum—were relatively more abundant in healthy adults. However, individual taxa differences did not reach statistical significance. Conclusions: Although our preliminary findings suggest no significant differences in fecal microbiota compositions between patients with AD and healthy individuals, they suggest that microbiota can identify a potential risk for AD development. Future research may help elucidate the bacterial species associated with AD pathogenesis, potentially enabling the use of microbiota composition as a screening tool to identify healthy individuals and those with AD or preclinical AD—an increasingly critical goal amid rising global dementia rates and the urgent need for preventive strategies. Full article

Despite increasing interest in probiotics as antibiotic alternatives in swine production, few studies have directly compared the functional efficacy of different commercial probiotic formulations under controlled conditions. We conducted an in vitro study using porcine intestinal epithelial (IPEC-J2) and macrophage-like (3D4/21) cell models to compare the efficacy of three commercial probiotic consortia (C1: three strains of Bacillus velezensis; C2: B. licheniformis + B. subtilis; C3: Clostridium butyricum). Treatments were evaluated for their ability to inhibit pathogenic Escherichia coli, Clostridium perfringens, and Salmonella spp., enhance epithelial barrier integrity, and modulate immune responses. Experimental endpoints included pathogen inhibition assays, adhesion to IPEC-J2 cells, transepithelial electrical resistance (TEER), tight junction protein expression, and cytokine profiling via RT-qPCR and proteomics. Data were analyzed using the Kruskal–Wallis test with false discovery rate (FDR) control at 5%. C1 cell-free supernatant (CFS) strongly inhibited pathogen growth (84.8 ± 5.3% inhibition of ETEC F4⁺F18⁻ vs. medium control; p < 0.05), whereas C2 had no effect, and C3 inhibited only one isolate. The coculture of IPEC-J2 cells with C1 CFS increased the expression of TJ proteins ZO-1, MUC13, and MUC20 (+12.9–46.6% vs. control; p < 0.001) and anti-inflammatory TGF-β; reduced pro-inflammatory IL-6 in LPS-stimulated 3D4/21 cells. In comparison, C2 and C3 showed minimal impact on epithelial barrier integrity and immune modulation, as indicated by negligible changes in TEER values, tight junction protein expression (ZO-1, MUC13, MUC20), and cytokine profiles relative to the control. In conclusion, C1 demonstrated greater in vitro efficacy than C2 (B. licheniformis + B. subtilis) and C3 (Clostridium butyricum), including pathogen inhibition assays, epithelial adhesion, TEER measurements, and cytokine modulation, suggesting its potential as a leading candidate for functional probiotic applications. Full article

Most probiotics require separate administration from antibiotics due to sensitivity issues. Clostridium butyricum, however, exhibits intrinsic resistance, making it a promising candidate for combined therapy against diarrhea. In this study, a diarrhea model was established in mice induced by Escherichia coli, followed by treatment with azithromycin (AZM), C. butyricum (RH₂), or their combination (COM) to assess therapeutic efficacy. The results demonstrated that mice in RH₂ and COM groups achieved full body weight recovery and significant alleviation of diarrhea, accompanied by normalized fecal E. coli loads, preserved tissue integrity, reduced pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), and elevated anti-inflammatory IL-10. In contrast, AZM treatment led to sex-specific disparities in weight recovery and E. coli loads, and both sexes experienced relapse-prone diarrhea. Furthermore, the AZM group displayed shortened colons, sustained inflammatory infiltration, epithelial damage, and elevated IL-1β and male-specific IL-6. Gut microbiota analysis revealed that the COM group retained beneficial genera (e.g., Parabacteroides, Blautia) from the AZM group while uniquely enriching Lachnospiraceae taxa (e.g., NK4A136_group, FCS020_group). Untargeted metabolomics demonstrated the COM group activated GABA/arginine pathways, enhancing anti-inflammatory and barrier functions, whereas azithromycin disrupted butyrate synthesis and steroid metabolism. These findings highlight the advantage of combining C. butyricum with azithromycin for intestinal protection. Full article

Urban areas and suburbs are facing many environmental problems, one of which is the increasing pollution due to the accumulation of cellulosic waste. This article presents a laboratory study on the microbial biodegradation processes of paper as a cellulosic substrate under anaerobic and mesophilic cultivation conditions. A bacterial consortium with cellulose-degrading activity, as well as 4 individual strains originating from a methanogenic anaerobic bioreactor (BRA), was isolated, identified, and characterized. The results demonstrated that the consortium degraded 57.14% of the cellulose matrix within 20 days. Among the individual colonies, colonies 1 and 2 (identified as Clostridium tertium and Agromyces rhizospherae) exhibited lower activities (35.37% and 34.79%, respectively), while colony 3 (Clostridium paraputrificum) displayed the highest activity (83.74%). The mixture of all four colonies achieved lower degradation (21.22%). The performed metagenomic analysis of the microbial consortium revealed a wide variety of different bacterial genera, among which Clostridium, Bacteroides, and Ruminiclostridium dominate, and the species Bacteroides oleiciplenus, Clostridium butyricum, and Ruminiclostridium papyrosolvens. Scanning electron microscopy visualized the adhesion and morphological features of the degrading microbial population. Additional experiments on the development of a laboratory model for the anaerobic biodegradation of cellulose were carried out in BRAs by using different working volumes. A maximal level of cellulose decomposition was achieved in the BRA with a working volume of 1 L, reaching 71.0% cellulose decomposition on day 20. Long-term storage studies confirmed the survival and well-preserved activity of the consortium and individual isolates, demonstrating their potential for the development of bioconversion technologies. Full article

The restriction of antibiotics and therapeutic zinc oxide in piglet diets has increased challenges related to gut health and post-weaning performance. This study assessed the effects of a diet supplemented with organic acids and the probiotic Clostridium butyricum on intestinal integrity, fecal microbiota composition, and performance parameters in weaned piglets. Forty piglets were selected at weaning, and fecal samples were collected on day 0 and day 14 of supplementation. Gene expression of tight junction proteins (zonulin, occludin) and inflammatory markers (calprotectin, IFN-γ, TGF-β) was analyzed by PCR. Bacterial DNA quantification was used to evaluate microbiota changes. In addition, average daily gain (ADG), feed conversion ratio (FCR), and mortality were recorded across three feeding phases: CONTROL, TRANSITION, and 0M. No significant changes were found in tight junction protein expression post-weaning, but reductions in IFN-γ and TGF-β suggest improved immune modulation. Piglets in the TRANSITION and 0M groups showed higher ADG (CONTROL = 292.28 g/day; TRANSITION = 300.09 g/day; 0M = 307.45 g/day) and reduced mortality (CONTROL = 6.48%; TRANSITION = 5.10%; 0M = 5.08%) compared to CONTROL. These findings indicate that targeted dietary supplementation can support gut health and performance in weaned piglets, offering a promising alternative to medicated feed under current regulatory constraints. Further research is guaranteed to refine these strategies for broader application in sustainable pig production. Full article

Low-fishmeal feed is increasingly being adopted across the global aquaculture industry. This study evaluated dietary Clostridium butyricum and alanyl-glutamine (Ala-Gln) supplementation in juvenile triploid rainbow trout (Oncorhynchus mykiss) with a low-fishmeal diet. Four diets were tested: basal diet (SBM, 15% fishmeal and 21.6% soybean meal), SBM + 0.5% C. butyricum (CB), SBM + 1.0% Ala-Gln, and SBM + 0.5% C. butyricum + 1.0% Ala-Gln (CB-AG). Fish were fed in 500 L tanks in recirculating aquaculture systems for 8 weeks (62.52 ± 0.47 g). Each group comprised three tanks, with each tank housing 30 fish. Then 10 fish per tank were challenged with Aeromonas salmonicida. CB-AG showed significantly higher weight gain and specific growth rates than the SBM group (p < 0.05). Mortality was significantly lower in CB-AG and AG than in SBM after A. salmonicida challenge. Histomorphology revealed significant differences (p < 0.05) between CB-AG and SBM in muscularis thickness, villus width, and height. SBM sections showed inflammatory infiltration and border damage were attenuated in supplemented groups. Serum malondialdehyde (MDA) and dioxygenase (DAO) were significantly lower in CB-AG than SBM (p < 0.05), while serum and hepatic lysozyme (LZM) and hepatic superoxide dismutase (SOD) were higher. Digestive enzymes indicated significantly higher trypsin and lipase activities in CB-AG (p < 0.05). CB-AG upregulated intestinal tight junction proteins and PepT1 and downregulated pro-inflammatory mediators. Combined 0.5% C. butyricum and 1.0% Ala-Gln inclusion effectively preserved growth performance, antioxidant capacity, gut microbiome homeostasis, and intestinal health in rainbow trout on low-fishmeal diets. Full article

Background/Objectives: Calves have immature immune systems, hence immunization with vaccines is essential to protect them from infectious diseases. However, immune responses to vaccines vary widely among individuals. Therefore, strategies for enhancing vaccine efficacy are needed, particularly those targeting low responders to vaccines. Probiotics have attracted attention because of their beneficial immunomodulatory effects on the host. Although probiotics may improve calf immunity, their potential to enhance immune responses to vaccines in calves remains unclear. Thus, we investigated whether immune responses to vaccines, especially T-cell responses, are enhanced when calves receive a combination of probiotic supplementation and vaccination. Methods: Calves were divided into three feeding groups, as follows: negative control feed, live bacteria-mixed feed (Zeosapo KB), and Clostridium butyricum-only feed (CB). After weaning, all calves received two doses of a live attenuated hexavalent viral vaccine. T-cell responses to a vaccine antigen were evaluated by measuring the expression levels of lymphocyte activation markers CD25 and CD69, as well as Th1 cytokine production, in peripheral blood mononuclear cell culture assays. Results: CD25 expression significantly increased in CD4⁺ T cells four weeks after the booster vaccination in the Zeosapo KB- and CB-fed groups. In addition, the CD25⁺CD69⁺ cell ratio in CD4⁺ T cells was increased in these groups. The production of Th1 cytokines in the culture supernatant was also increased in the CB-fed group. Conclusions: This clinical study demonstrates that probiotics activate CD4⁺ T cells and enhance Th1 cytokine responses in vaccinated calves. Full article

A healthy gut microbiota in calves is necessary for optimal performance and development. Considering that probiotics have been shown to improve gut microbiota, the aim of this study was to investigate the effects of Clostridium butyricum on growth performance, blood parameters, and gut microbiota in Hanwoo calves. In total, 92 calves from two farms were randomly assigned to four groups: a control and three treatment groups that received increasing doses of C. butyricum (CB1, CB2, and CB3) during the first 5 days after birth. Independent experiments were conducted at each farm with different measurements, where body weight was monitored and blood, rumen, and fecal samples were collected to assess physiological responses and microbial profiles. Notably, significant differences were observed in blood amylase and acid–base parameters, suggesting that C. butyricum supplementation may enhance metabolic stability and buffering capacity. Microbial profiling revealed preserved alpha diversity and compositional shifts in both the rumen and fecal microbiota. Particularly, there was an increase in the relative abundances of Prevotella and Muribaculaceae and a decrease in the abundances of the pathogenic genera Escherichia and Shigella in calves fed C. butyricum-supplemented diets. These changes, along with a trend toward a reduced frequency and severity of diarrhea, suggest that C. butyricum supplementation may support gut health and promote stable early growth in neonatal calves. Full article

This study investigated the effects of dietary supplementation with varying doses of Clostridium butyricum (C. butyricum) on growth performance, diarrhea incidence, serum biochemical parameters, fecal short-chain fatty acids (SCFAs), and fecal microbiota in preweaning Holstein calves. Forty healthy newborn Holstein heifer calves with comparable birth weights were randomly assigned to four groups (control, 1 g/d supplementation, 3 g/d supplementation, and 5 g/d supplementation) for a 60-day trial. Growth parameters, diarrhea incidence, serum immunoglobulins (IgA, IgG, IgM), cytokines (IL-1β, TNF-α), antioxidant indicators (T-AOC, MDA), fecal short-chain fatty acids (SCFAs), and microbial composition were measured to evaluate the effects of C. butyricum. The results indicated that calves in the 5 g/d group exhibited a significantly higher average daily gain (ADG) compared with the control group (804.67 vs. 701.67 g/d, p < 0.05), with no significant differences in feed intake observed among groups (p > 0.05). During Days 22–42, the diarrhea incidence in the 5 g/d group was 7.74% lower than that in the control group (p < 0.05). This group exhibited significantly elevated serum IgM levels (Day 42, p < 0.05) and reduced IL-1β concentrations (Day 42, p < 0.05). Additionally, total antioxidant capacity (T-AOC) was significantly enhanced (Days 42 and 60, p < 0.05), while malondialdehyde (MDA) content was significantly decreased (Days 21 and 42, p < 0.05). At Day 42, fecal propionate and butyrate concentrations were significantly elevated in the 5 g/d group (p < 0.05), while the relative abundances of Bacteroides, Acidaminococcus, Bifidobacterium, Olsenella, Faecalitalea, and Ruminococcus were significantly increased (p < 0.05). The increase in these short-chain fatty acids and beneficial bacteria contributes to improved intestinal health and thus helps alleviate diarrhea. These findings indicate that supplementing preweaning calves’ milk with 5 g/d of C. butyricum significantly enhances growth performance and intestinal health. This provides evidence for the use of C. butyricum as a natural alternative to antibiotics in calf rearing. Full article

This study investigated the effects of Clostridium butyricum (C. butyricum) supplementation on the bacterial community composition and fermentation characteristics of the digestive system, assessed blood antioxidant capacity, and evaluated growth performance and digestibility in pre-weaning Angus calves. Sixteen male Angus calves were randomly divided into two groups (n = 8). The control group was fed a basal diet, while the other group was supplemented with 2 × 10⁷ colony-forming unit/d C. butyricum in the basal diet. After 8 weeks of feeding, body growth and nutrient intake were measured. Rumen fluid samples, blood samples, and fecal samples were collected and analyzed. Fecal scores were recorded daily, and the frequency of diarrhea treatments was documented. The results showed C. butyricum supplementation improved the digestibility of neutral detergent fiber, crude protein, and ether extract in calves, as well as the growth hormone content in the blood. Furthermore, supplementation elevated isovaleric acid concentrations in the rumen, modulated the microbiome, and increased pre-weaning body weight and average daily gain of calves. Meanwhile, C. butyricum supplementation reduced myeloperoxidase and superoxide dismutase levels while increasing total antioxidant capacity in the blood, alleviating oxidative stress, and enhancing the antioxidant capacity of the body. Intestinal health was also improved, as evidenced by an increase in butyrate content, a reduction in enterotoxigenic Escherichia coli, lower fecal scores, and a decreased need for diarrhea treatments. In summary, dietary C. butyricum supplementation may support digestive system development, enhance antioxidant capacity, and improve growth performance and health status in pre-weaning Angus calves. Full article

Despite being recognized as toxic in anaerobic systems, sulfide’s potential to enhance hydrogen fermentation via microbial modulation remains underexplored. This study evaluated the combined effects of sulfide concentration (0–800 mg S/L) and heat pretreatment on hydrogen production during dark fermentation (DF). Without pretreatment, hydrogen yield reached 83 ± 2 mL/g COD at 0 mg S/L but declined with increasing sulfide, becoming negligible at 800 mg S/L. In contrast, heat-pretreated inocula showed markedly improved performance: peak cumulative production (4628 ± 17 mL) and yield (231 ± 1 mL/g COD) were attained at 200 mg S/L, while the maximum production rate (1462 ± 64 mL/h) occurred at 400 mg S/L. These enhancements coincided with elevated acetic and butyric acids, indicating a metabolic shift toward hydrogen-producing pathways. The microbial analysis of heat-pretreated samples revealed an enrichment of Clostridium butyricum (from 73.1% to 87.5%) and Clostridium perfringens, which peaked at 13.5% at 400 mg S/L. This species contributed to butyric acid synthesis. At 800 mg S/L, Clostridium perfringens declined sharply to 0.6%, while non-hydrogenogenic Levilinea saccharolytica proliferated, correlating with reduced butyric acid and hydrogen output. These findings indicate that sulfide supplementation, when combined with heat pretreatment, selectively restructures microbial communities and metabolic pathways, enhancing DF performance. Full article