A Case of Ocular Infection with Clostridium tertium Caused by a Salute Gun Explosion.

BACKGROUND: In February 2024, our hospital confirmed a case of ocular infection with Clostridium tertium caused by a salute gun explosion. The patient sought medical attention at our hospital due to a salute gun explosion injury in the right eye. Two days ago, a patient mistakenly believed that the fuse was not ignited when firing a salute gun. When observing, the salute gun exploded and injured his right eye. The patient immediately went to the local hos-pital for treatment. The CT scan of the local hospital showed rupture of the right eyeball. For additional diagnosis and treatment, the patient came to our hospital. The patient in this case has an acute onset, severe condition, no additional systemic diseases, and no history of drug or food allergies. METHODS: Intraocular exploration, cranial CT, local and systemic anti infection treatment. Pathogen examination items: bacterial smear, bacterial culture and identification. Venous blood test items: blood routine, liver function, kidney function, and coagulation function. RESULTS: Intraocular exploration showed conjunctival congestion and edema in the right eye, corneal haze and ede-ma, shallow anterior chamber, anterior chamber hemorrhage, and unclear intraocular structure. Clinical treatment: debridement and suturing of right eye rupture + repair of eyeball rupture + removal of intraocular foreign body + repair of superior rectus muscle detachment + anterior chamber flushing + anterior chamber shaping + suture of eyelid laceration. Pathogen examination item: Eye secretion bacterial smear (Gram staining): A large number of gram-positive bacilli were found, and the secretion bacterial culture and identification (MALDI-TOF MS): Clostridium tertium. Auxiliary examination: Blood routine (venous blood): White blood cells 10.89 x 109/L, neutrophil count 9.65 x 109/L, whole blood hypersensitive C-reactive protein 20.28 mg/L, renal function: urea 9.15 mmol/L, uric acid 428.5 µmol/L, fasting glucose 6.48 mmol/L, no further abnormalities observed. Clinical drug treatment plan: Tetanus human immunoglobulin 250 IU im, tobramycin eye drops 0.1 g ext qd, vancomycin 0.5 g ih qd, levofloxacin 0.5g ivgtt qd, aluminum magnesium suspension 15 mL po bid, potassium chloride sustained-release tablets 0.5 g po qd. After 7 days of treatment, the patient's body temperature returned to normal, conjunctival congestion and edema decreased, anterior chamber hemorrhage decreased, corneal incision closed properly, and the patient improved and was discharged. CONCLUSIONS: This article reports a case of ocular infection caused by a salute gun explosion with Clostridium tertium. Clostridium tertium was quickly and accurately identified by a mass spectrometer, and reasonable treatment measures were adopted clinically. The patient improved and was discharged. I hope that in the future, this study can provide assistance for the clinical diagnosis and treatment of special site infections caused by Clostridium tertium.

Elucidating human gut microbiota interactions that robustly inhibit diverse Clostridioides difficile strains across different nutrient landscapes.

The human gut pathogen Clostridioides difficile displays substantial inter-strain genetic variability and confronts a changeable nutrient landscape in the gut. We examined how human gut microbiota inter-species interactions influence the growth and toxin production of various C. difficile strains across different nutrient environments. Negative interactions influencing C. difficile growth are prevalent in an environment containing a single highly accessible resource and sparse in an environment containing C. difficile-preferred carbohydrates. C. difficile toxin production displays significant community-context dependent variation and does not trend with growth-mediated inter-species interactions. C. difficile strains exhibit differences in interactions with Clostridium scindens and the ability to compete for proline. Further, C. difficile shows substantial differences in transcriptional profiles in co-culture with C. scindens or Clostridium hiranonis. C. difficile exhibits massive alterations in metabolism and other cellular processes in co-culture with C. hiranonis, reflecting their similar metabolic niches. C. hiranonis uniquely inhibits the growth and toxin production of diverse C. difficile strains across different nutrient environments and robustly ameliorates disease severity in mice. In sum, understanding the impact of C. difficile strain variability and nutrient environments on inter-species interactions could help improve the effectiveness of anti-C. difficile strategies.

Evaluation of individual and combined effect of lactic acid-consuming bacteria on mesophilic hydrogen production from lactic acid effluent from food waste treatment.

Lactic acid has been applied as a precursor for hydrogen (H2) production from substrates rich in lactic acid bacteria (LAB), focusing on microbial interactions between producing and consuming LAB tested with model substrates. Therefore, this study evaluated the effect of single and combined lactic acid-consuming bacteria on mesophilic H2 production in batch tests from lactic acid from fermented food waste (FW). Megasphaera elsdenii, Clostridium beijerinckii, and Clostridium butyricum were inoculated at different ratios (v/v). Additionally, thermal pretreated sludge (TPS) was added to the strain mixtures. The highest production was obtained with M. elsdenii, C. beijerinckii, and C. butyricum (17:66:17 ratio), obtaining 1629.0 mL/Lreactor. The optimal mixture (68:32:0 of M. elsdenii and C. beijerinckii) enriched with TPS reached 1739.3 ± 98.6 mL H2/Lreactor, consuming 98 % of lactic acid added. M. elsdenii and Clostridium strains enhance H2 production from lactic acid as they persist in a microbial community initially dominated by LAB.

One-pot synthesis of cellobiose from sucrose using sucrose phosphorylase and cellobiose phosphorylase co-displaying Pichia pastoris as a reusable whole-cell biocatalyst.

Cellobiose has received increasing attention in various industrial sectors, ranging from food and feed to cosmetics. The development of large-scale cellobiose applications requires a cost-effective production technology as currently used methods based on cellulose hydrolysis are costly. Here, a one-pot synthesis of cellobiose from sucrose was conducted using a recombinant Pichia pastoris strain as a reusable whole-cell biocatalyst. Thermophilic sucrose phosphorylase from Bifidobacterium longum (BlSP) and cellobiose phosphorylase from Clostridium stercorarium (CsCBP) were co-displayed on the cell surface of P. pastoris via a glycosylphosphatidylinositol-anchoring system. Cells of the BlSP and CsCBP co-displaying P. pastoris strain were used as whole-cell biocatalysts to convert sucrose to cellobiose with commercial thermophilic xylose isomerase. Cellobiose productivity significantly improved with yeast cells grown on glycerol compared to glucose-grown cells. In one-pot bioconversion using glycerol-grown yeast cells, approximately 81.2 g/L of cellobiose was produced from 100 g/L of sucrose, corresponding to 81.2% of the theoretical maximum yield, within 24 h at 60 °C. Moreover, recombinant yeast cells maintained a cellobiose titer > 80 g/L, even after three consecutive cell-recycling one-pot bioconversion cycles. These results indicated that one-pot bioconversion using yeast cells displaying two phosphorylases as whole-cell catalysts is a promising approach for cost-effective cellobiose production.

Clinical and microbiological characteristics of anaerobic bacteremia during 1994-2019: A Danish population-based cohort study.

OBJECTIVES: Bacteremia with anaerobic bacteria is generally a marker of severe prognosis. However, population-based data is lacking. Our aim was to describe the epidemiology and the 30-day mortality rate of anaerobic bacteremia in a Danish population-based setting. METHODS: In this population-based cohort study, all first-time episodes of anaerobic bacteremia from the North Denmark Bacteremia Research Database during 1994-2019 were identified. Information on comorbidities, discharge diagnoses, and mortality was retrieved. 30-day mortality rates were calculated and a multivariate logistic regression analysis to identify risk factors for death was performed. RESULTS: 1750 episodes with anaerobic bacteremia were identified, corresponding to an incidence rate of 12.5 per 100,000 inhabitants (increasing from 11.2 in 1994-2014 to 17.7 in 2015-2019). Of these episodes, a third were polymicrobial, and the majority (70 %) of patients had one or more comorbid conditions. Abdominal infection was the source of bacteremia in 61 % of patients, while it was unknown for 15 %. The most frequently isolated genera were Bacteroides (45 %), Clostridium (20 %) and Fusobacterium (6 %). The overall crude 30-day mortality rate was 27 %, but rates were even higher for patients of high age, with liver disease, and solid tumors. The odds ratio (OR) for 30-day mortality was 1.32 for Clostridium species, and 1.27 for polymicrobial bacteremia with aerobic bacteria. CONCLUSIONS: The incidence rate of anaerobic bacteremia increased, and the 30-day mortality rate remained high during the study period. Multiple factors influence 30-day mortality rates, including high age, liver disease, solid tumor, polymicrobial bacteremia, and bacteremia with Clostridium species.

BCAA-producing Clostridium symbiosum promotes colorectal tumorigenesis through the modulation of host cholesterol metabolism.

Identification of potential bacterial players in colorectal tumorigenesis has been a focus of intense research. Herein, we find that Clostridium symbiosum (C. symbiosum) is selectively enriched in tumor tissues of patients with colorectal cancer (CRC) and associated with higher colorectal adenoma recurrence after endoscopic polypectomy. The tumorigenic effect of C. symbiosum is observed in multiple murine models. Single-cell transcriptome profiling along with functional assays demonstrates that C. symbiosum promotes the proliferation of colonic stem cells and enhances cancer stemness. Mechanistically, C. symbiosum intensifies cellular cholesterol synthesis by producing branched-chain amino acids (BCAAs), which sequentially activates Sonic hedgehog signaling. Low dietary BCAA intake or blockade of cholesterol synthesis by statins could partially abrogate the C. symbiosum-induced cell proliferation in vivo and in vitro. Collectively, we reveal C. symbiosum as a bacterial driver of colorectal tumorigenesis, thus identifying a potential target in CRC prediction, prevention, and treatment.

An acid-tolerant Clostridium sp. BLY-1 strain with high biohydrogen production rate.

Screening and isolating acid-tolerant bacteria capable of efficient hydrogen production can mitigate the inhibitory effects on microbial activity caused by rapid pH drops during fermentation. In this study, we isolated an acid-tolerant and highly efficient hydrogen-producing bacterium, named Clostridium sp. BLY-1, from acidic soil. Compared to the model strain Clostridium pasteurianum DSM 525, BLY-1 demonstrates a faster growth rate and superior hydrogen production capabilities. At an initial pH of 4.0, BLY-1's hydrogen production is 7.5 times greater than that of DSM 525, and under optimal conditions (pH=5.0), BLY-1's hydrogen production rate is 42.13% higher than DSM 525. Genomic analysis revealed that BLY-1 possesses a complete CiaRH two-component system and several stress-resistance components absent in DSM 525, which enhance its growth and hydrogen production in acidic environments. These findings provide a novel avenue for boosting the hydrogen production capabilities of Clostridium strains, offering new resources for advancing the green hydrogen industry.

Genomic characterization of prophage elements in Clostridium clostridioforme: an understudied component of the intestinal microbiome.

Genome sequencing of Clostridium clostridioforme strain LM41 revealed the presence of an atypically high proportion of mobile genetic elements for this species, with a particularly high abundance of prophages. Bioinformatic analysis of prophage sequences sought to characterize these elements and identify prophage-linked genes contributing to enhanced fitness of the host bacteria in the dysbiotic gut. Using PHASTER, PhageScope and manual curation, this work has identified 15 prophages: 4 predicted to be intact, 2 predicted to be defective and 9 which are unclassified. Quantitative PCR (qPCR) analysis revealed spontaneous release of four of the LM41 prophages (φ1, φ2, φ4 and φ10) into the culture supernatant, with virion-like particles visualized using transmission electron microscopy. The majority (12/14) of these particles had morphology akin to podoviruses, which is consistent with morphology predictions for φ1 and φ4. We observed diversity in the lysogeny mechanisms utilized by the prophages, with examples of the classical λ-like CI/Cro system, the ICEBs1 ImmR/ImmA-like system and the Mu-like C/Ner system. Classical morons, such as toxins or immune evasion factors, were not observed. We did, however, identify a variety of genes with roles in mediating restriction modification and genetic diversity, as well as some candidate genes with potential roles in host adaptation. Despite being the most abundant entities in the intestine, there is a dearth of information about phages associated with members of the microbiome. This work begins to shed light on the contribution of these elements to the lifestyle of C. clostridioforme LM41.

Pseudocin 196, a novel lantibiotic produced by Bifidobacterium pseudocatenulatum elicits antimicrobial activity against clinically relevant pathogens.

Bacteriocins are broad or narrow-spectrum antimicrobial compounds that have received significant scientific attention due to their potential to treat infections caused by antibiotic-resistant pathogenic bacteria. The genome of Bifidobacterium pseudocatenulatum MM0196, an antimicrobial-producing, fecal isolate from a healthy pregnant woman, was shown to contain a gene cluster predicted to encode Pseudocin 196, a novel lantibiotic, in addition to proteins involved in its processing, transport and immunity. Following antimicrobial assessment against various indicator strains, protease-sensitive Pseudocin 196 was purified to homogeneity from cell-free supernatant. MALDI TOF mass spectrometry confirmed that the purified antimicrobial compound corresponds to a molecular mass of 2679 Da, which is consistent with that deduced from its genetic origin. Pseudocin 196 is classified as a lantibiotic based on its similarity to lacticin 481, a lanthionine ring-containing lantibiotic produced by Lactococcus lactis. Pseudocin 196, the first reported bacteriocin produced by a B. pseudocatenulatum species of human origin, was shown to inhibit clinically relevant pathogens, such as Clostridium spp. and Streptococcus spp. thereby highlighting the potential application of this strain as a probiotic to treat and prevent bacterial infections.

Strain-dependent induction of primary bile acid 7-dehydroxylation by cholic acid.

BACKGROUND: Bile acids (BAs) are steroid-derived molecules with important roles in digestion, the maintenance of host metabolism, and immunomodulation. Primary BAs are synthesized by the host, while secondary BAs are produced by the gut microbiome through transformation of the former. The regulation of microbial production of secondary BAs is not well understood, particularly the production of 7-dehydroxylated BAs, which are the most potent agonists for host BA receptors. The 7-dehydroxylation of cholic acid (CA) is well established and is linked to the expression of a bile acid-inducible (bai) operon responsible for this process. However, little to no 7-dehydroxylation has been reported for other host-derived BAs (e.g., chenodeoxycholic acid, CDCA or ursodeoxycholic acid, UDCA). RESULTS: Here, we demonstrate that the 7-dehydroxylation of CDCA and UDCA by the human isolate Clostridium scindens is induced when CA is present, suggesting that CA-dependent transcriptional regulation is required for substantial 7-dehydroxylation of these primary BAs. This is supported by the finding that UDCA alone does not promote expression of bai genes. CDCA upregulates expression of the bai genes but the expression is greater when CA is present. In contrast, the murine isolate Extibacter muris exhibits a distinct response; CA did not induce significant 7-dehydroxylation of primary BAs, whereas BA 7-dehydroxylation was promoted upon addition of germ-free mouse cecal content in vitro. However, E. muris was found to 7-dehydroxylate in vivo. CONCLUSIONS: The distinct expression responses amongst strains indicate that bai genes are regulated differently. CA promoted bai operon gene expression and the 7-dehydroxylating activity in C. scindens strains. Conversely, the in vitro activity of E. muris was promoted only after the addition of cecal content and the isolate did not alter bai gene expression in response to CA. The accessory gene baiJ was only upregulated in the C. scindens ATCC 35704 strain, implying mechanistic differences amongst isolates. Interestingly, the human-derived C. scindens strains were also capable of 7-dehydroxylating murine bile acids (muricholic acids) to a limited extent. This study shows novel 7-dehydroxylation activity in vitro resulting from the presence of CA and suggests distinct bai gene expression across bacterial species.

The first isolation of Clostridium massiliodielmoense from a dead beef cow in Japan and pitfalls to be aware of in identifying the Clostridium species.

Clostridium sp. was detected in the organs of a cow with black watery diarrhea in Japan. Results identifying this species were inconsistent; Clostridium novyi type A infection was suggested by PCR assay targeting Clostridium fliC region (fliC-multiplex PCR), while 16S rRNA gene sequencing identified the isolated bacteria as Clostridium massiliodielmoense. Sequencing of fliC-multiplex PCR products from the isolates revealed the presence of fliC region in C. massiliodielmoense, which had 92.7% nucleotide similarity to that of C. novyi type A JCM 1406T, leading to the false positive detection of C. novyi by the PCR. This is the first C. massiliodielmoense isolation from clinical specimens, suggesting the need for further research on its pathogenicity and improvement in fliC-multiplex PCR.

Identification of volatile metabolites produced from levodopa metabolism by different bacteria strains of the gut microbiome.

Interspecies pathways in the gut microbiome have been shown to metabolize levodopa, the primary treatment for Parkinson's disease, and reduce its bioavailability. While the enzymatic reactions have been identified, the ability to establish the resulting macromolecules as biomarkers of microbial metabolism remains technically challenging. In this study, we leveraged an untargeted mass spectrometry-based approach to investigate volatile organic compounds (VOCs) produced during levodopa metabolism by Enterococcus faecalis, Clostridium sporogenes, and Eggerthella lenta. We cultured these organisms with and without their respective bioactive metabolites and detected levodopa-induced shifts in VOC profiles. We then utilized bioinformatics to identify significant differences in 2,6-dimethylpyrazine, 4,6-dimethylpyrimidine, and 4,5-dimethylpyrimidine associated with its biotransformation. Supplementing cultures with inhibitors of levodopa-metabolizing enzymes revealed specific modulation of levodopa-associated diazines, verifying their relationship to its metabolism. Furthermore, functional group analysis depicts strain-specific VOC profiles that reflect interspecies differences in metabolic activity that can be leveraged to assess microbiome functionality in individual patients. Collectively, this work identifies previously uncharacterized metabolites of microbe-mediated levodopa metabolism to determine potential indicators of this activity and further elucidate the metabolic capabilities of different gut bacteria.

Two glycosyl transferase 2 genes from the gram-positive bacterium Clostridium ventriculi encode (1,3;1,4)-ß-D-glucan synthases.

The exopolysaccharides of the Gram-positive bacterium Romboutsia ilealis have recently been shown to include (1,3;1,4)-ß-D-glucans. In the present study, we examined another Clostridia bacterium Clostridium ventriculi that has long been considered to contain abundant amounts of cellulose in its exopolysaccharides. We treated alcohol insoluble residues of C. ventriculi that include the exopolysaccharides with the enzyme lichenase that specifically hydrolyses (1,3;1,4)-ß-D-glucans, and examined the oligosaccharides released. This showed the presence of (1,3;1,4)-ß-D-glucans, which may have previously been mistaken for cellulose. Through genomic analysis, we identified the two family 2 glycosyltransferase genes CvGT2-1 and CvGT2-2 as possible genes encoding (1,3;1,4)-ß-D-glucan synthases. Gain-of-function experiments in the yeast Saccharomyces cerevisiae demonstrated that both of these genes do indeed encode (1,3;1,4)-ß-D-glucan synthases.

Dietary Clostridium autoethanogenum protein has dose-dependent influence on the gut microbiota, immunity, inflammation and disease resistance of abalone Haliotis discus hannai.

Clostridium autoethanogenum protein (CAP) is an eco-friendly protein source and has great application potential in aquafeeds. The present study aimed to investigate the effects of dietary CAP inclusion on the anti-oxidation, immunity, inflammation, disease resistance and gut microbiota of abalone Haliotis discus hannai after a 110-day feeding trial. Three isonitrogenous and isolipidic diets were formulated by adding 0 % (control), 4.10 % (CAP4.10) and 16.25 % (CAP16.25) of CAP, respectively. A total of 540 abalones with an initial mean body weight of 22.05 ± 0.19 g were randomly distributed in three groups with three replicates per group and 60 abalones per replicate. Results showed that the activities of superoxide dismutase and glutathione peroxidase in the cell-free hemolymph (CFH) were significantly decreased and the content of malondialdehyde in CFH was significantly increased in the CAP16.25 group. The diet with 4.1 % of CAP significantly increased the activities of lysozyme and acid phosphatase in CFH. The expressions of pro-inflammatory genes such as tumor necrosis factor-α (tnf-α), nuclear factor-κb (nf-κb) and toll-like receptor 4 (tlr4) in digestive gland were downregulated, and the expressions of anti-inflammatory genes such as ß-defensin and mytimacin 6 in digestive gland were upregulated in the CAP4.10 group. Dietary CAP inclusion significantly decreased the cumulative mortality of abalone after the challenge test with Vibrio parahaemolyticus for 7 days. Dietary CAP inclusion changed the composition of gut microbiota of abalone. Besides, the balance of the ecological interaction network of bacterial genera in the intestine of abalone was enhanced by dietary CAP. The association analysis showed that two bacterial genera Ruegeria and Bacteroides were closely correlated with the inflammatory genes. In conclusion, the 4.10 % of dietary CAP enhanced the immunity and disease resistance as well as inhibited the inflammation of abalone. The 16.25 % of dietary CAP decreased the anti-oxidative capacity of abalone. The structure of the gut microbiota of abalone changed with dietary CAP levels.

Maternal gestational diabetes mellitus associates with altered gut microbiome composition and head circumference abnormalities in male offspring.

The impact of gestational diabetes mellitus (GDM) on maternal or infant microbiome trajectory remains poorly understood. Utilizing large-scale longitudinal fecal samples from 264 mother-baby dyads, we present the gut microbiome trajectory of the mothers throughout pregnancy and infants during the first year of life. GDM mothers had a distinct microbiome diversity and composition during the gestation period. GDM leaves fingerprints on the infant's gut microbiome, which are confounded by delivery mode. Further, Clostridium species positively correlate with a larger head circumference at month 12 in male offspring but not females. The gut microbiome of GDM mothers with male fetuses displays depleted gut-brain modules, including acetate synthesis I and degradation and glutamate synthesis II. The gut microbiome of female infants of GDM mothers has higher histamine degradation and dopamine degradation. Together, our integrative analysis indicates that GDM affects maternal and infant gut composition, which is associated with sexually dimorphic infant head growth.

Lactate-mediated mixotrophic co-cultivation of Clostridium drakei and recombinant Acetobacterium woodii for autotrophic production of volatile fatty acids.

BACKGROUND: Acetogens, a diverse group of anaerobic autotrophic bacteria, are promising whole-cell biocatalysts that fix CO2 during their growth. However, because of energetic constraints, acetogens exhibit slow growth and the product spectrum is often limited to acetate. Enabling acetogens to form more valuable products such as volatile fatty acids during autotrophic growth is imperative for cementing their place in the future carbon neutral industry. Co-cultivation of strains with different capabilities has the potential to ease the limiting energetic constraints. The lactate-mediated co-culture of an Acetobacterium woodii mutant strain, capable of lactate production, with the Clostridium drakei SL1 type strain can produce butyrate and hexanoate. In this study, the preceding co-culture is characterized by comparison of monocultures and different co-culture approaches. RESULTS: C. drakei grew with H2 + CO2 as main carbon and energy source and thrived when further supplemented with D-lactate. Gas phase components and lactate were consumed in a mixotrophic manner with acetate and butyrate as main products and slight accumulation of hexanoate. Formate was periodically produced and eventually consumed by C. drakei. A lactate-mediated co-culture of the A. woodii [PbgaL_ldhD_NFP] strain, engineered for autotrophic lactate production, and C. drakei produced up to 4 ± 1.7 mM hexanoate and 18.5 ± 5.8 mM butyrate, quadrupling and doubling the respective titers compared to a non-lactate-mediated co-culture. Further co-cultivation experiments revealed the possible advantage of sequential co-culture over concurrent approaches, where both strains are inoculated simultaneously. Scanning electron microscopy of the strains revealed cell-to-cell contact between the co-culture partners. Finally, a combined pathway of A. woodii [PbgaL_ldhD_NFP] and C. drakei for chain-elongation with positive ATP yield is proposed. CONCLUSION: Lactate was proven to be a well-suited intermediate to combine the high gas uptake capabilities of A. woodii with the chain-elongation potential of C. drakei. The cell-to-cell contact observed here remains to be further characterized in its nature but hints towards diffusive processes being involved in the co-culture. Furthermore, the metabolic pathways involved are still speculatory for C. drakei and do not fully explain the consumption of formate while H2 + CO2 is available. This study exemplifies the potential of combining metabolically engineered and native bacterial strains in a synthetic co-culture.

Synbiotic therapy with Clostridium sporogenes and xylan promotes gut-derived indole-3-propionic acid and improves cognitive impairments in an Alzheimer's disease mouse model.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized primarily by cognitive impairment. Recent investigations have highlighted the potential of nutritional interventions that target the gut-brain axis, such as probiotics and prebiotics, in forestalling the onset of AD. In this study, whole-genome sequencing was employed to identify xylan as the optimal carbon source for the tryptophan metabolism regulating probiotic Clostridium sporogenes (C. sporogenes). Subsequent in vivo studies demonstrated that administration of a synbiotic formulation comprising C. sporogenes (1 × 1010 CFU per day) and xylan (1%, w/w) over a duration of 30 days markedly enhanced cognitive performance and spatial memory faculties in the 5xFAD transgenic AD mouse model. The synbiotic treatment significantly reduced amyloid-ß (Aß) accumulation in the cortex and hippocampus of the brain. Importantly, synbiotic therapy substantially restored the synaptic ultrastructure in AD mice and suppressed neuroinflammatory responses. Moreover, the intervention escalated levels of the microbial metabolite indole-3-propionic acid (IPA) and augmented the relative prevalence of IPA-synthesizing bacteria, Lachnospira and Clostridium, while reducing the dominant bacteria in AD, such as Aquabacterium, Corynebacterium, and Romboutsia. Notably, synbiotic treatment also prevented the disruption of gut barrier integrity. Correlation analysis indicated a strong positive association between gut microbiota-generated IPA levels and behavioral changes. In conclusion, this study demonstrates that synbiotic supplementation significantly improves cognitive and intellectual deficits in 5xFAD mice, which could be partly attributed to enhanced IPA production by gut microbiota. These findings provide a theoretical basis for considering synbiotic therapy as a novel microbiota-targeted approach for the treatment of metabolic and neurodegenerative diseases.

Trauma-Induced Clostridium cadaveris Septic Arthritis of the Knee in an Immunocompetent Young Patient: A Case Report.

BACKGROUND Clostridium cadaveris is a motile, anaerobic, gram-positive, spore-forming bacillus usually found in soil. However, rare cases of opportunistic infections have been documented in immunosuppressed individuals. This report details the case of an immunocompetent young patient who developed septic arthritis of the knee after a traumatic injury involving a rusty nail. The aim of this paper is to provide a comprehensive literature review, shed light on the potential occurrence of Clostridium cadaveris septic arthritis, and explore its management. CASE REPORT A young patient with no medical history presented a traumatic inoculation leading to septic arthritis on a native knee by Clostridium cadaveris. The patient underwent 2 surgical debridements after an initial bad evolution under probabilistic antibiotic therapy. Bacteriological long-growing cultures and antibiotic testing were employed to guide antibiotic therapy selection. The patient had a favorable clinical outcome with no residual knee complications, with laboratory results showed good evolution. A review of the literature showed that Clostridium cadaveris septic arthritis in immunocompetent patients is very rare. The management and subsequent results emphasize the potential impact of the initial emergency room treatment on patient outcomes, especially concerning seemingly benign traumas. CONCLUSIONS This case report highlights the necessity of rapid diagnosis of the cause of septic arthritis, particularly in children, to prevent joint and tissue damage, and the rare diagnosis of knee arthritis with Clostridium cadaveris. This report expands understanding of osteoarticular infections and enhances the need for rapid diagnosis and early treatment, when managing cases with atypical presentations.

Dietary fibre directs microbial tryptophan metabolism via metabolic interactions in the gut microbiota.

Tryptophan is catabolized by gut microorganisms resulting in a wide range of metabolites implicated in both beneficial and adverse host effects. How gut microbial tryptophan metabolism is directed towards indole, associated with chronic kidney disease, or towards protective indolelactic acid (ILA) and indolepropionic acid (IPA) is unclear. Here we used in vitro culturing and animal experiments to assess gut microbial competition for tryptophan and the resulting metabolites in a controlled three-species defined community and in complex undefined human faecal communities. The generation of specific tryptophan-derived metabolites was not predominantly determined by the abundance of tryptophan-metabolizing bacteria, but rather by substrate-dependent regulation of specific metabolic pathways. Indole-producing Escherichia coli and ILA- and IPA-producing Clostridium sporogenes competed for tryptophan within the three-species community in vitro and in vivo. Importantly, fibre-degrading Bacteroides thetaiotaomicron affected this competition by cross-feeding monosaccharides to E. coli. This inhibited indole production through catabolite repression, thus making more tryptophan available to C. sporogenes, resulting in increased ILA and IPA production. The fibre-dependent reduction in indole was confirmed using human faecal cultures and faecal-microbiota-transplanted gnotobiotic mice. Our findings explain why consumption of fermentable fibres suppresses indole production but promotes the generation of other tryptophan metabolites associated with health benefits.

Evaluation of long-term supplementation of a Bacillus subtilis direct-fed microbial and enzymatically hydrolyzed yeast cell culture product used alone or in combination on Clostridia, Clostridium perfringens, Escherichia coli, and Salmonella prevalence in beef steers.

The objective was to determine the influence of long-term supplementation (258 d) of a direct-fed microbial (DFM) and/or yeast cell wall (YCW) product on bacterial populations in beef steers. Single-sourced Charolais × Red Angus steers (n = 256; body weight = 246 ±â€…1.68 kg) were used in a randomized complete block design and blocked by location into one of four treatments: 1) fed no DFM and no YCW (Control); 2) fed only the DFM (DFM; Certillus CP B1801 Dry, 28 g/steer d-1 ); 3) fed only the YCW (YCW; Celmanax; 18 g/steer d-1 ); and 4) fed the DFM and the YCW (DFM+YCW). Steers were vaccinated for respiratory and clostridial diseases and treated for internal and external parasites at processing and individually weighed on days 1, 14, 42, 77, 105, 133, 161, 182, 230, and 258. To determine bacterial prevalence, fecal samples were collected on days 1, 14, 77, 133, 182, and 230 and environmental (pen area, feed, and water) samples were collected at the beginning of the week when cattle were weighed. No treatment × day interactions or treatment effects (P > 0.05) were observed between treatment groups at any sampling days for the bacterial populations. Samples on days 1, 133, and 182 had greater (P < 0.05) Clostridia levels compared to the other sampling points but were not different from each other. Clostridia levels were also greater (P < 0.05) on day 77 compared to days 14 and 230. Samples on days 77 and 230 had greater (P < 0.05) Clostridium perfringens levels compared to the other sampling points but were not different (P > 0.05) from each other. Samples on days 1 and 14 had lower (P < 0.05) total Escherichia coli levels compared to the other sampling points but were not different (P > 0.05) from each other. Escherichia coli levels on day 77 were higher (P < 0.05) compared to days 133, 182, and 230. Little Salmonella prevalence (1.5%) was observed throughout the study. This study had greater levels of Clostridia compared to small and large commercial feedlots in the Church and Dwight research database, but C. perfringens, total and pathogenic E. coli, and Salmonella prevalence were notably lower. Collectively, there were no appreciable treatment influences on bacterial populations. These data further indicate a low pathogenic bacterial challenge at the trial site, which could partially explain the lack of differences with DFM or YCW supplementation. The DFM and YCW used alone or in combination cannot be expected to show additional benefits when animals are relatively unstressed with a low pathogenic bacterial challenge.

The objective of this research was to determine the influence of long-term supplementation (258 d) of a direct-fed microbial (DFM) and/or yeast cell wall (YCW) product on bacterial populations in beef steers. Collectively, there were no appreciable treatment influences on bacterial populations. These data further indicate a low pathogenic bacterial challenge at the trial site, which could further explain the reasons for little differences. The DFM and YCW used alone or in combination cannot be expected to show productive benefits when animals are relatively unstressed with a low pathogenic bacterial challenge.