Oxalate degrading bacteria: new treatment option for patients with primary and secondary hyperoxaluria?

154

142

This study presents the complete genome sequence of Lactobacillus gasseri ATCC 33323, a neotype strain of human origin and a native species found commonly in the gastrointestinal tracts of neonates and adults. The plasmid-free genome was 1,894,360 bp in size and predicted to encode 1,810 genes. The GC content was 35.3%, similar to the GC content of its closest relatives, L. johnsonii NCC 533 (34%) and L. acidophilus NCFM (34%). Two identical copies of the prophage LgaI (40,086 bp), of the Sfi11-like Siphoviridae phage family, were integrated tandomly in the chromosome. A number of unique features were identified in the genome of L. gasseri that were likely acquired by horizontal gene transfer and may contribute to the survival of this bacterium in its ecological niche. L. gasseri encodes two restriction and modification systems, which may limit bacteriophage infection. L. gasseri also encodes an operon for production of heteropolysaccharides of high complexity. A unique alternative sigma factor was present similar to that of B. caccae ATCC 43185, a bacterial species isolated from human feces. In addition, L. gasseri encoded the highest number of putative mucusbinding proteins (14) among lactobacilli sequenced to date. Selected phenotypic characteristics that were compared between ATCC 33323 and other human L. gasseri strains included carbohydrate fermentation patterns, growth and survival in bile, oxalate degradation, and adhesion to intestinal epithelial cells, in vitro. The results from this study indicated high intraspecies variability from a genome encoding traits important for survival and retention in the gastrointestinal tract.

Section: Annotation For Functions Important In the Git (I) Sugar Tramentioning

confidence: 99%

Analysis of the Genome Sequence ofLactobacillus gasseriATCC 33323 Reveals the Molecular Basis of an Autochthonous Intestinal Organism

Azcarate‐Peril

Altermann

Goh

et al. 2008

154

142

“…The ability to recolonize individuals lacking O. formigenes was previously addressed in a study in which two healthy adults not colonized with O. formigenes became colonized following the ingestion of cultured O. formigenes (3) and remained colonized for 9 months. However, studies in which O. formigenes was provided in either a lyophilized form in enteric coated capsules or as a frozen paste to patients suffering from primary hyperoxaluria resulted in only a minority of the patients remaining colonized posttreatment (4,5). Therefore, although it seems quite possible that O. formigenes colonization of noncolonized stone formers may be an effective way to minimize the risk of recurrent calcium oxalate stone disease, a better understanding of the factors that influence colonization is required.…”

mentioning

confidence: 99%

Response of Germfree Mice to Colonization by Oxalobacter formigenes and Altered Schaedler Flora

Ellis

Dowell

et al. 2016

Colonization with Oxalobacter formigenes may reduce the risk of calcium oxalate kidney stone disease. To improve our limited understanding of host-O. formigenes and microbe-O. formigenes interactions, germfree mice and mice with altered Schaedler flora (ASF) were colonized with O. formigenes. Germfree mice were stably colonized with O. formigenes, which suggests that O. formigenes does not require other organisms to sustain its survival. Examination of intestinal material indicated no viable O. formigenes in the small intestine and ϳ4 ؋ 10 6 CFU O. formigenes per 100 mg contents in the cecum and proximal colon, with ϳ0.02% of total cecal O. formigenes cells being tightly associated with the mucosa. O. formigenes did not alter the overall microbial composition of ASF, and ASF did not affect the capacity of O. formigenes to degrade dietary oxalate in the cecum. Twentyfour-hour collections of urine and feces in metabolic cages in semirigid isolators demonstrated that the introduction of ASF into germfree mice significantly reduced urinary oxalate excretion. These experiments also showed that O. formigenes-monocolonized mice excreted significantly more urinary calcium than did germfree mice, which may be due to degradation of calcium oxalate crystals by O. formigenes and subsequent intestinal absorption of free calcium. In conclusion, the successful establishment of mouse models with defined flora and O. formigenes should improve our understanding of O. formigenes-host and O. formigenes-microbe interactions. These data support the use of O. formigenes as a probiotic that has limited impact on the composition of the resident microbiota but provides an efficient oxalate-degrading function. Oxalobacter formigenes is part of the bacterial flora in the large intestine of many humans and other mammalian species and is unique in that it is the only bacterium yet identified in the intestines of mammals that requires oxalate as both an energy source and a carbon source. Recent evidence suggests that a lack of colonization with this oxalate-degrading specialist is a risk factor for idiopathic recurrent calcium oxalate stone disease (1, 2). A review of worldwide data indicated that 38% to 77% of a normal population and only 17% of stone formers were colonized with O. formigenes (1). The ability to recolonize individuals lacking O. formigenes was previously addressed in a study in which two healthy adults not colonized with O. formigenes became colonized following the ingestion of cultured O. formigenes (3) and remained colonized for 9 months. However, studies in which O. formigenes was provided in either a lyophilized form in enteric coated capsules or as a frozen paste to patients suffering from primary hyperoxaluria resulted in only a minority of the patients remaining colonized posttreatment (4, 5). Therefore, although it seems quite possible that O. formigenes colonization of noncolonized stone formers may be an effective way to minimize the risk of recurrent calcium oxalate stone disease, a better understanding o...

“…Unfortunately, an oxalate-free diet is difficult to achieve and would probably be deficient in essential nutrients. Hence, other approaches to reducing urinary oxalate for management of stone disease have been explored.The discovery of oxalate-degrading bacteria within the human gastrointestinal tract has opened the way to a flurry of research regarding their potential role in reducing urinary excretion of oxalic acid (12,20,21,25,26,30,31,35,40,44,45). The first intestinal oxalate-degrading bacterium to be described was Oxalobacter formigenes, an obligate anaerobe which relies exclusively on oxalate metabolism for energy (2).…”

mentioning

confidence: 99%

“…Frc catalyzes the transfer of CoA from formate to oxalate, thus activating the oxalyl moiety for the thiamine-dependent decarboxylation mediated by Oxc. Several studies have established a direct correlation between the disappearance of O. formigenes from the intestinal microbiota and the appearance of hyperoxaluria symptoms, confirming its major role in maintaining oxalate homeostasis and making it the leading probiotic candidate for the management of kidney stone disease (21,25,26,30,44,45,49). However, the complicated growth requirements of O. formigenes, with the need to determine the optimal dietary oxalate level required to maintain its colonization, severely limited its administration (47).…”

mentioning

confidence: 99%

Oxalate-Degrading Activity in Bifidobacterium animalis subsp. lactis : Impact of Acidic Conditions on the Transcriptional Levels of the Oxalyl Coenzyme A (CoA) Decarboxylase and Formyl-CoA Transferase Genes

Turroni

Bendazzoli

Dipalo

et al. 2010

Oxalic acid occurs extensively in nature and plays diverse roles, especially in pathological processes. Due to its highly oxidizing effects, hyperabsorption or abnormal synthesis of oxalate can cause serious acute disorders in mammals and can be lethal in extreme cases. Intestinal oxalate-degrading bacteria could therefore be pivotal in maintaining oxalate homeostasis and reducing the risk of kidney stone development. In this study, the oxalate-degrading activities of 14 bifidobacterial strains were measured by a capillary electrophoresis technique. The oxc gene, encoding oxalyl-coenzyme A (CoA) decarboxylase, a key enzyme in oxalate catabolism, was isolated by probing a genomic library of Bifidobacterium animalis subsp. lactis BI07, which was one of the most active strains in the preliminary screening. The genetic and transcriptional organization of oxc flanking regions was determined, unraveling the presence of two other independently transcribed open reading frames, potentially responsible for the ability of B. animalis subsp. lactis to degrade oxalate. pH-controlled batch fermentations revealed that acidic conditions were a prerequisite for a significant oxalate degradation rate, which dramatically increased in cells first adapted to subinhibitory concentrations of oxalate and then exposed to pH 4.5. Oxalate-preadapted cells also showed a strong induction of the genes potentially involved in oxalate catabolism, as demonstrated by a transcriptional analysis using quantitative real-time reverse transcription-PCR. These findings provide new insights into the characterization of oxalate-degrading probiotic bacteria and may support the use of B. animalis subsp. lactis as a promising adjunct for the prophylaxis and management of oxalate-related kidney disease.Oxalate is a normal end product of amino acid metabolism and must be excreted, predominantly via the kidney, to maintain homeostasis (22). Oxalate is also present in a wide range of foods and drinks, and the normal dietary intake is variable, ranging from 70 to 920 mg per day (23). Because of its highly oxidizing effects and the capability to combine with cations to form insoluble salts, this organic dicarboxylate is extremely toxic for most forms of life. In humans, oxalate can cause a variety of pathological disorders, including hyperoxaluria, urolithiasis, cardiomyopathy, and renal failure (29,41,59). Hyperoxaluria is the single strongest promoter of kidney stone formation, whose medical management represents a burden to the individual patient as well as the health care system (49). The lack of new medications and the continued poor compliance with drug therapy have led to a growing interest in dietary manipulation and novel therapies aimed at preventing recurrent stone formation. Unfortunately, an oxalate-free diet is difficult to achieve and would probably be deficient in essential nutrients. Hence, other approaches to reducing urinary oxalate for management of stone disease have been explored.The discovery of oxalate-degrading bacteria within the human ...