Lentilactobacillus kefiri SGL 13 and Andrographis paniculata alleviate dextran sulfate sodium induced colitis in mice.

Introduction: Inflammatory bowel diseases (IBD) are chronic inflammatory conditions that typically involve diarrhea, abdominal pain, fatigue, and weight loss, with a dramatic impact on patients' quality of life. Standard medications are often associated with adverse side effects. Thus, alternative treatments such as probiotics are of great interest. The purpose of the present study was to evaluate the effects of oral administration of Lentilactobacillus kefiri (basonym: Lactobacillus kefiri) SGL 13 and Andrographis paniculata, namely, Paniculin 13™, on dextran sodium sulfate (DSS)- treated C57BL/6J mice. Methods: Colitis was induced by administering 1.5% DSS in drinking water for 9 days. Forty male mice were divided into four groups, receiving PBS (control), 1.5% DSS, Paniculin 13™ and 1.5% DSS + Paniculin 13™. Results: The results showed that body weight loss and Disease Activity Index (DAI) score were improved by Paniculin 13™. Moreover, Paniculin 13™ ameliorated DSS-induced dysbiosis, by modulating the gut microbiota composition. The gene expression of MPO, TNFα and iNOS in colon tissue was reduced and these data matched with the histological results, supporting the efficacy of Paniculin 13™ in reducing the inflammatory response. No adverse effects were associated to Paniculin 13™ administration. Discussion: In conclusion, Paniculin 13™ could be an effective add-on approach to conventional therapies for IBD.

Exploring the wound healing, anti-inflammatory, anti-pathogenic and proteomic effects of lactic acid bacteria on keratinocytes.

The topical application of lactic acid bacteria (LAB) is recognized as a useful approach to improve skin health. This work aims to characterize by a multidisciplinary approach, the wound healing, anti-inflammatory, anti-pathogens and proteomic effects of six LAB lysates, belonging to the genus Lactobacillus. Our results demonstrated that the lysates of tested LAB stimulated the proliferation of keratinocytes, and that L. plantarum SGL 07 and L. salivarius SGL 19 accelerated the re-epithelization by inducing keratinocyte migration. The bacterial lysates also reduced the secretion of specific pro-inflammatory mediators from keratinocytes. Furthermore, viable L. salivarius SGL 19 and L. fermentum SGL 10 had anti-pathogenic effects against S. aureus and S. pyogenes, while L. brevis SGL 12 and L. paracasei SGL 04 inhibited S. aureus and S. pyogenes, respectively. The tested lactobacilli lysates also induced specific proteome modulation of the exposed keratinocytes, involving dysregulation of proteins (such as interleukin enhancer-binding factor 2 and ATP-dependent RNA helicase) and pathways (such as cytokine, NF-kB, Hedgehog, and RUNX signaling) associated with their specific wound healing and anti-inflammatory effects. This study indicates the different potential of selected lactobacilli, suggesting that they may be successfully used in the future together with conventional therapies to bring relief from skin disorders.

Investigating the Proteomic Profile of HT-29 Colon Cancer Cells After Lactobacillus kefiri SGL 13 Exposure Using the SWATH Method.

Despite some studies revealed that kefir acts on different cancers, such as colorectal cancer, the proteomic changes that occur in the colon cancer cells remain to be explored. In this study, the proteomic analysis was combined with determination of kefir characteristics (e.g., adhesion capacity, gastrointestinal and antibiotic resistances), in order to confirm its use as a probiotic. Therefore, a label-free strategy based on SWATH-MS was applied to investigate the proteomic profile of HT-29 cells after exposure for 24 h to a specific strain of Lactobacillus kefiri named SGL 13. We identified a total of 60 differentially expressed proteins in HT-29 cells, among which most are located into the extracellular exosome, playing important/crucial roles in translation and cell adhesion, as indicated by the enrichment analysis. The eIF2 and retinoid X receptor activation pathways appeared to be correlated with the anti-tumoral effect of SGL 13. Immunoblot analysis showed an increase in Bax and a decrease in caspase 3 and mutant p53, and ELISA assay revealed inhibition of IL-8 secretion from HT-29 cells stimulated with LPS upon SGL 13 treatment, suggesting pro-apoptotic and anti-inflammatory properties of kefir. In conclusion, the results of this study, the first of its kind using co-culture of kefir and colon cancer cells, demonstrate that L. kefiri SGL 13 possesses probiotic potency and contribute to elucidate the molecular mechanisms involved in the L. kefiri-colon cancer cell interactions.

Draft Genome Sequence of Lactobacillus kefiri SGL 13, a Potential Probiotic Strain Isolated from Kefir Grains.

In this report, we present the draft genome sequence of a newly discovered potential probiotic strain of Lactobacillus kefiri, SGL 13, isolated from kefir grains. Antibiotic resistance analysis did not reveal evidence of interspecific horizontal gene transfer since the identified bacitracin resistance gene does not have mobile genetic elements.

Draft Genome Sequence of Lactobacillus salivarius SGL 03, a Novel Potential Probiotic Strain.

In this work, we report the draft genome sequence of Lactobacillus salivarius SGL 03, a novel potential probiotic strain isolated from healthy infant stools. Antibiotic resistance analysis revealed the presence of a tetracycline resistance gene without elements potentially responsible for interspecific horizontal gene transfer.

Round Spermatid Injection Rescues Female Lethality of a Paternally Inherited Xist Deletion in Mouse.

In mouse female preimplantation embryos, the paternal X chromosome (Xp) is silenced by imprinted X chromosome inactivation (iXCI). This requires production of the noncoding Xist RNA in cis, from the Xp. The Xist locus on the maternally inherited X chromosome (Xm) is refractory to activation due to the presence of an imprint. Paternal inheritance of an Xist deletion (XpΔXist) is embryonic lethal to female embryos, due to iXCI abolishment. Here, we circumvented the histone-to-protamine and protamine-to-histone transitions of the paternal genome, by fertilization of oocytes via injection of round spermatids (ROSI). This did not affect initiation of XCI in wild type female embryos. Surprisingly, ROSI using ΔXist round spermatids allowed survival of female embryos. This was accompanied by activation of the intact maternal Xist gene, initiated with delayed kinetics, around the morula stage, resulting in Xm silencing. Maternal Xist gene activation was not observed in ROSI-derived males. In addition, no Xist expression was detected in male and female morulas that developed from oocytes fertilized with mature ΔXist sperm. Finally, the expression of the X-encoded XCI-activator RNF12 was enhanced in both male (wild type) and female (wild type as well as XpΔXist) ROSI derived embryos, compared to in vivo fertilized embryos. Thus, high RNF12 levels may contribute to the specific activation of maternal Xist in XpΔXist female ROSI embryos, but upregulation of additional Xp derived factors and/or the specific epigenetic constitution of the round spermatid-derived Xp are expected to be more critical. These results illustrate the profound impact of a dysregulated paternal epigenome on embryo development, and we propose that mouse ROSI can be used as a model to study the effects of intergenerational inheritance of epigenetic marks.

Incomplete meiotic sex chromosome inactivation in the domestic dog.

BACKGROUND: In mammalian meiotic prophase, homologous chromosome recognition is aided by formation and repair of programmed DNA double-strand breaks (DSBs). Subsequently, stable associations form through homologous chromosome synapsis. In male mouse meiosis, the largely heterologous X and Y chromosomes synapse only in their short pseudoautosomal regions (PARs), and DSBs persist along the unsynapsed non-homologous arms of these sex chromosomes. Asynapsis of these arms and the persistent DSBs then trigger transcriptional silencing through meiotic sex chromosome inactivation (MSCI), resulting in formation of the XY body. This inactive state is partially maintained in post-meiotic haploid spermatids (postmeiotic sex chromatin repression, PSCR). For the human, establishment of MSCI and PSCR have also been reported, but X-linked gene silencing appears to be more variable compared to mouse. To gain more insight into the regulation and significance of MSCI and PSCR among different eutherian species, we have performed a global analysis of XY pairing dynamics, DSB repair, MSCI and PSCR in the domestic dog (Canis lupus familiaris), for which the complete genome sequence has recently become available, allowing a thorough comparative analyses. RESULTS: In addition to PAR synapsis between X and Y, we observed extensive self-synapsis of part of the dog X chromosome, and rapid loss of known markers of DSB repair from that part of the X. Sequencing of RNA from purified spermatocytes and spermatids revealed establishment of MSCI. However, the self-synapsing region of the X displayed higher X-linked gene expression compared to the unsynapsed area in spermatocytes, and was post-meiotically reactivated in spermatids. In contrast, genes in the PAR, which are expected to escape MSCI, were expressed at very low levels in both spermatocytes and spermatids. Our comparative analysis was then used to identify two X-linked genes that may escape MSCI in spermatocytes, and 21 that are specifically re-activated in spermatids of human, mouse and dog. CONCLUSIONS: Our data indicate that MSCI is incomplete in the dog. This may be partially explained by extensive, but transient, self-synapsis of the X chromosome, in association with rapid completion of meiotic DSB repair. In addition, our comparative analysis identifies novel candidate male fertility genes.

DNA-array of gene variants in venous leg ulcers: detection of prognostic indicators.

OBJECTIVE: Wound healing in venous leg ulcer (VLU) is a multi-step process involving complex pathways. Scanty knowledge at molecular level hinders clinical assessment and treatment. Anomalous handling of local iron overload, as well as unbalancing in matrix metalloproteinases (MMPs) and transglutaminase, has a recognized role in VLU establishment. We selected a number of single nucleotide polymorphisms (SNPs) in candidate genes (HFE, FPN1, MMP12, and FXIII) involved in VLU to identify potentially prognostic markers by means of DNA-array technology. METHODS AND RESULTS: The DNA-array-genotyping was assessed in 638 subjects for the following SNPs: HFE (C282Y, H63D), FPN1 (-8CG), MMP12 (-82AG) and FXIII (V34L). Of the subjects, 221 were affected by VLU (171 primary and 50 post-thrombosis), 112 by severe chronic venous disease (CVD) (CEAP, C3-C4), while 305 were matched healthy controls. The HFE and FXIII SNPs had been previously genotyped by conventional polymerase chain reaction (PCR)-methods on the same group of subjects (J Vasc Surg 2005;42:309; J Vasc Surg 2006;44:554; J Vasc Surg 2006;44:815). For the purpose of DNA-array, they were re-genotyped by means of array-techniques resulting in a 100% matching. Intergroup statistical comparisons were performed. In the risk computation, the FPN1 -8GG genotype had an overall CVD risk of 4.3 (95% CI, 1.6-12) and a VLU risk of 5.2 (95% CI, 1.9-15) virtually the same among primary VLU (4.98; 95% CI, 1.82-14.9). The MMP12-82AA genotype had a VLU risk of 1.96 (95% CI, 1.18-3.2) only in primary VLU (P = .01). In the genotype-ulcer size association studies, from a subgroup of 167 cases, we observed a smaller mean ulcer size in the MMP12 GG-genotype compared with the other genotypes (P = .001). Combining the present results with our previous published data on the same population, we suggest them to apply as tentative prognostic indicators in primary CVD. CONCLUSION: By analyzing simultaneously selected SNPs, it might be possible to glean precious information in predicting VLU onset or in stratifying patients according to their potential to heal. Although significant, our findings must be considered preliminary and the proposed prognostic indicators considered with caution, before ulterior more extensive studies in different populations can eventually confirm the present findings.

Coagulation gene predictors of photodynamic therapy for occult choroidal neovascularization in age-related macular degeneration.

PURPOSE: To determine whether different coagulation-balance genetic polymorphisms explain the variable clinical outcomes of photodynamic therapy with verteporfin (PDT-V) in Caucasian patients with occult subfoveal choroidal neovascularization (CNV) due to age-related macular degeneration (AMD). METHODS: The clinical records of consecutive patients with AMD-related occult CNV, treated with PDT-V for evidence of disease progression, were retrospectively examined. Eighty-four eligible subjects were subdivided into responders and nonresponders based on CNV responsiveness to the first PDT-V over a 3-month period. Six gene polymorphisms (i.e., factor V G1691A, prothrombin G20210A, factor XIII-A G185T, methylenetetrahydrofolate reductase C677T, methionine synthase A2756G, and methionine synthase reductase A66G) were genotyped in each patient. Logistic regression analyses were performed to explore the predictive role of phenotypic and genotypic variables for PDT-V effectiveness. RESULTS: Regression models documented that PDT-V nonresponders were more frequently patients with the hyperfibrinolytic G185T mutation of factor XIII-A (odds ratio [OR], 0.28; 95% confidence interval [CI], 0.11-0.73; P < 0.01). Univariate logistic regression was indicative of an overrepresentation of PDT-V responders among the combined carriers of thrombophilic factor V 1691A and prothrombin 20210A alleles (OR = 3.8; 95% CI: 0.94-15.6; P = 0.07). All the other predictors considered did not significantly influence the short-term CNV responsiveness to PDT-V. CONCLUSIONS: These data provide evidence of the presence of a pharmacogenetic relationship between peculiar coagulation-balance genetic backgrounds and different levels of PDT-V effectiveness in patients with AMD with occult CNV.

Predictive role of coagulation-balance gene polymorphisms in the efficacy of photodynamic therapy with verteporfin for classic choroidal neovascularization secondary to age-related macular degeneration.

OBJECTIVES: Age-related macular degeneration (AMD) represents the leading cause of blindness in Western populations. The majority of severe vision loss occurs in the exudative form of AMD, characterized by the development of choroidal neovascularization (CNV) beneath the fovea. Photodynamic therapy with verteporfin (PDT-V) represents one of the most largely employed modality that maybe achieves the subfoveal CNV inactivation in AMD patients. Although several ocular factors have been hitherto investigated as predictors, these researches have weakly contributed to PDT-V optimization. As PDT-V benefit is determined by CNV photothrombosis, we have retrospectively studied several coagulation-balance gene polymorphisms as predictors of PDT-V efficacy. METHODS: Ninety Caucasian patients with neovascular AMD were subdivided in responder and nonresponder, on the basis of CNV responsiveness to PDT-V application. Six gene polymorphisms, that is factor V G1691A, prothrombin G20210A, factor XIII-A G185T, methylenetetrahydrofolate reductase C677T, methionine synthase A2756G, and methionine synthase reductase A66G, were genotyped in the entire cohort. RESULTS: Logistic regression models showed that PDT-V responders were more prevalent within patients with prothrombin G20210A mutation [odds ratio (OR)=5.6, 95% confidence interval (CI) (1.2, 27.2), P=0.03], and within methylenetetrahydrofolate reductase 677T carriers [OR=6.9, 95% CI (2.7, 18.1), P<0.001]. Conversely, PDT-V nonresponders were overrepresented in carriers for factor XIII-A 185T [OR=0.13, 95% CI (0.05, 0.36), P<0.001]. CONCLUSION: These results provide evidences for the presence of pharmacogenetic relationship between peculiar coagulation-balance gene polymorphisms and different levels of PDT-V effectiveness in patients with AMD-related CNV.

Poor responsiveness to clopidogrel: drug-specific or class-effect mechanism? Evidence from a clopidogrel-to-ticlopidine crossover study.

OBJECTIVES: This study was designed to investigate whether poor responders to thienopyridines after clopidogrel remain so even after ticlopidine administration (class effect) or whether a drug-specific effect exists between currently available thienopyridines. BACKGROUND: Whether clopidogrel poor responders also display inadequate platelet inhibition after ticlopidine administration remains undefined. METHODS: Platelet aggregation (PA) was measured in 143 patients, while they were taking aspirin, with light transmission aggregometry using adenosine diphosphate as an agonist at baseline (T0) and at clopidogrel steady state (T1). After T1) clopidogrel was stopped and substituted with ticlopidine. Then PA was assessed at ticlopidine steady state (T2). Resistance was defined as an absolute difference between T0 and after-treatment (T1 or T2) PA < or =10%. RESULTS: Clopidogrel and ticlopidine responsiveness was normally distributed; PA at T1 did not differ compared with T2. Thirty (21%) and 28 (19%) patients were clopidogrel and ticlopidine nonresponders, respectively. Only 5 patients (3.5%) were nonresponders to both clopidogrel and ticlopidine (class effect), whereas 25 patients (83%) who were clopidogrel nonresponders at T1 were responsive to ticlopidine, reaching a higher level of platelet inhibition at T2 (PA 69 +/- 15 vs. 44 +/- 18, p < 0.01) (drug-specific response). On the other hand, 23 patients who were responsive to clopidogrel showed resistance to ticlopidine at T2 (PA 46 +/- 15 vs. 70 +/- 15, p < 0.01) (drug-specific response). CONCLUSIONS: Poor responsiveness to either clopidogrel or ticlopidine at steady state was common, whereas nonresponders to both drugs were relatively infrequent (3.5%, 95% confidence interval 1.5% to 7.9%), suggesting that poor response to thienopyridines may frequently be a drug-specific mechanism.

Methylenetetrahydrofolate reductase C677T and A1298C gene variants in adult non-Hodgkin's lymphoma patients: association with toxicity and survival.

BACKGROUND AND OBJECTIVES: Common methylenetetrahydrofolate reductase gene variants (MTHFR C677T and A1298C) have been described to have opposite effects on cancer patients. They may reduce cancer susceptibility and increase drug-related toxicity when folate antagonists (e.g. methotrexate) are utilized. We analyzed 110 patients with high-grade non-Hodgkin's lymphoma (NHL), 68 of whom were eligible for a chemotherapy combination containing methotrexate (MACOP-B) and 42 for chemotherapy without methotrexate (CHOP). DESIGN AND METHODS: Patients were genotyped by polymerase chain reaction and stratified by MTHFR variants. These data were related to the toxicity (WHO grade GO-4) that the patients suffered and their survival. Overall 64 cases (58.2%) developed some form of toxicity and 23 (20.9%) had grade 3/4 toxicity. RESULTS: When considering toxicity of any grade (grade 1-4), the 677TT genotype was significantly over-represented among cases with mucositis (OR=4.85; 95% CI, 1.47-15.97; p=0.009) and those with hepatic toxicity (OR=3.43; 95% CI, 0.99-11.86; p=0.052). Sub-analyses in the group treated with MACOP-B showed a slight increase in the risk of developing mucositis (OR=5.22; 95% CI, 1.20-27.27; p=0.03), and a strong increase in the risk of hepatic toxicity (OR=7.08; 95% CI, 1.38-36.2; p=0.019) and thrombocytopenia (OR=7.69, 95% CI 1.0-58.94; p=0.05). Interestingly, compared to the risk of developing toxicity of any grade, the risk of developing severe (grade 3/4) mucositis was almost doubled in the whole group of cases with 677TT (OR=8.13; 95% CI 1.61-41.04; p=0.011) and dramatically increased in the MACOP-B-treated cases with this gene variant (OR=24.6; 95% CI 2.49-87.41; p=0.001). There were significant results for 1298CC cases exclusively for mucositis (any grade, OR=5.33; 95% CI, 1.25-22.70; p=0.023 and OR=9.15; 95% CI, 1.14-73.41; p=0.037; for the whole group and the MACOP-B-treated group, respectively). Similarly, the risk of 1298CC patients developing severe mucositis increased (OR=9.24; 95% CI, 1.47-58.0; p=0.017 and OR=11.53; 0.93-143.18; p=0.057; in the whole group and in the MACOP-B-treated group, respectively). Event-free survival analysis revealed a lower probability of event-free survival at 5 years for 677T-carriers (log-ranks, p=0.05 and p=0.07 in the whole group and in the MACOP-B-treated group, respectively). More significant results were obtained when 1298CC cases were excluded from the reference group (log-ranks, p=0.03 and p=0.04, respectively). No significant associations were found in the CHOP-treated group. INTERPRETATION AND CONCLUSIONS: Our data suggest that MTHFR gene variants play a critical role in NHL outcome, possibly by interfering with the action of methotrexate with significant effects on toxicity and survival. Genotyping of folate pathway gene variants might be useful to enable reduction of chemotherapy toxicity and/or to improve survival by indicating when dose adjustments or alternative treatments are necessary.

Factor XIIIA-V34L and factor XIIIB-H95R gene variants: effects on survival in myocardial infarction patients.

It has been demonstrated recently that coagulation factor XIII (FXIII) plays an extraordinary role in myocardial healing after infarction, improving survival in a mouse model. Common FXIII gene variants (i.e. FXIIIA-V34L and FXIIIB-H95R) significantly influence the molecular activity. To evaluate whether there is a relationship between the two FXIII gene variants and survival in patients after myocardial infarction (MI), V34L and H95R were PCR-genotyped in a cohort of 560 MI cases and follow-up was monitored. Cases with ST-segment elevation MI (STEMI) were 416 (74.3%) and 374 of these were treated with primary percutaneous coronary intervention (PCI) (89.9%). The remaining 144 patients showed non-ST-segment elevation MI (NSTEMI) at enrollment. The combined endpoint was the occurrence of death, re-infarction, and heart failure. Kaplan-Meier analysis at one year yielded an overall rate for adverse events of 24.5% with a lower incidence in the L34-carriers (28.8% vs 17.1%; log-rank, P = 0.00025), similar to that of the 416 STEMI (23.8%) being (28.0% and 16.9%; VV34- and L34-carriers respectively; log-rank, P = 0.001). Primary PCI-group had a slight lower incidence (22.9%) of adverse events (26.8% and 17.1%; VV34- and L34-carriers respectively; log-rank, P = 0.009). During hospitalization, 506 patients received PCI (374 primary PCI and 132 elective PCI). Significance was conserved also in the overall PCI-group (28.6% and 17.8%; VV34- and L34-carriers respectively; log-rank, P = 0.001). Similar findings were observed at 30 days follow-up. Cases carrying both FXIII variants had improved survival rate (log-rank, P = 0.019). On the other hand, minor bleeding complications were found increased in L34-carriers (P = 0.0001) whereas major bleeding complications were not. Finally, more direct evidence on the role of FXIII molecule on survival might come from the fact that despite significant FXIII antigen reductions observed in cases after MI, regardless the FXIII genotype considered, L34-carriers kept almost normal FXIII activity (VV34- vs L34-carriers; P < 0.001). We conclude that FXIII L34-allele improves survival after MI in all the groups analyzed, possibly through its higher activity associated with assumable positive effects on myocardial healing and recovered functions. Genetically determined higher FXIII activity might influence post-MI outcome. This paves the way for using FXIII molecules to improve myocardial healing, recovery of functions, and survival after infarction.

Influence of gene polymorphisms in ulcer healing process after superficial venous surgery.

OBJECTIVE: Role of superficial venous surgery in reducing the time it takes for ulcers to heal is still controversial, although all studies confirm a significant reduction in ulcer recurrences. Recently, the HFE-C282Y and FXIII-V34L gene variants demonstrated a role in the risk of venous ulceration in primary chronic venous disorder (CVD) and in modulating lesion size in chronic venous ulcer (CVU), respectively. This study was conducted to investigate the role of HFE-C282Y and FXIII (V34L and P564L) gene variants in ulcer healing time after superficial venous surgery, by assessing the outcome of a cohort of homogeneous CVU patients. METHODS: The study selected 91 patients affected by primary CVU (CEAP C6, Ep, Asp, Pr), with the exclusion of any other comorbidity factor involved in delayed healing process, who underwent surgery. We assessed the ulcer area and the healing time. Patients were genotyped by polymerase chain reaction for FXIII (V34L and P564L) and for HFE-C282Y substitutions. RESULTS: Globally, CVU cases had a postoperative mean healing time of 8.5 +/- 5.7 weeks. For the subset of cases above and below the median value (M = 8.0 weeks), FXIII-V34L genotype distribution significantly differed (P < .0001). In addition, Kaplan-Meier analysis yielded specific healing time profiles for the different FXIII-V34L classes of genotype (P = .00001), with an increased risk of delayed healing for the FXIII-VV genotype (hazard ratio, 4.14; 95% confidence interval, 2.1 to 8.2; P = .00005). Although FXIII-P54L genotype distributions did not differ, homozygous 564LL cases (P = .005) and double carriers for both FXIII variants (P < .0001), had a significantly reduced healing time vs wild types. No differences in healing time were observed between carriers and noncarriers of the HFE-C282Y variant, whereas when these cases were stratified by FXIII-V34L genotypes, the L34 carriers had a significantly shorter healing time, irrespective of the HFE genotype. CONCLUSION: The FXIII-34L variant was significantly associated with shorter healing time after superficial venous surgery, suggesting a role in the healing and tissue regeneration phases. Conversely, HFE-C282Y, despite its role in ulcer establishment, did not affect the postoperative healing time. In perspective, the identification of patients with a poor prognosis may give clinicians the opportunity to modify management and to target tailored therapies in the view of a new and alternative concept of treatment based on pharmacogenomics.

Characterization and heterologous expression of the oxalyl coenzyme A decarboxylase gene from Bifidobacterium lactis.

Oxalyl coenzyme A (CoA) decarboxylase (Oxc) is a key enzyme in the catabolism of the highly toxic compound oxalate, catalyzing the decarboxylation of oxalyl-CoA to formyl-CoA. The gene encoding a novel oxalyl-CoA decarboxylase from Bifidobacterium lactis DSM 10140 (oxc) was identified and characterized. This strain, isolated from yogurt, showed the highest oxalate-degrading activity in a preliminary screening with 12 strains belonging to Bifidobacterium, an anaerobic intestinal bacterial group largely used in probiotic products. The oxc gene was isolated by probing a B. lactis genomic library with a probe obtained by amplification of the oxalyl-CoA decarboxylase gene from Oxalobacter formigenes, an anaerobic bacterium of the human intestinal microflora. The oxc DNA sequence analysis revealed an open reading frame of 1,773 bp encoding a deduced 590-amino-acid protein with a molecular mass of about 63 kDa. Analysis of amino acid sequence showed a significant homology (47%) with oxalyl-CoA decarboxylase of O. formigenes and a typical thiamine pyrophosphate-binding site that has been reported for several decarboxylase enzymes. Primer extension experiments with oxc performed by using RNA isolated from B. lactis identified the transcriptional start site 28 bp upstream of the ATG start codon, immediately adjacent to a presumed promoter region. The protein overexpressed in Escherichia coli cross-reacted with an anti-O. formigenes oxalyl-CoA decarboxylase antibody. Enzymatic activity, when evaluated by capillary electrophoresis analysis, demonstrated that the consumption substrate oxalyl-CoA was regulated by a product inhibition of the enzyme. These findings suggest a potential role for Bifidobacterium in the intestinal degradation of oxalate.