Reduction of bilirubin ditaurate by the intestinal bacterium Clostridium perfringens.

Koníčková, Renata; Jirásková, Alena; Zelenka, Jaroslav; Lešetický, L.; Štícha, Martin; Vı́tek, Libor

doi:10.18388/abp.2012_2153

Cited by 15 publications

(10 citation statements)

References 12 publications

(16 reference statements)

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“…The broad specificity of anaerobic bacterial enzymes found in the human gastrointestinal tract for bile pigments has been previously demonstrated 13 and it has been suggested that bilirubin reducing enzymes serve for the disposal of electrons produced by fermentolytic processes performed by these bacteria, however, the mechanisms of biliverdin/bilirubin metabolism are poorly understood.…”

Section: Discussionmentioning

confidence: 99%

Unprecedented Microbial Conversion of Biliverdin into Bilirubin-10-sulfonate

Shiels

Vidimce

Pearson

et al. 2019

Sci Rep

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Biliverdin (BV) possesses antioxidant and anti-inflammatory properties, with previous reports identifying protection against oxidant and inflammatory injury in animal models. Recent reports indicate that intra-duodenal administration of BV results in the formation of an uncharacterised metabolite, which is potently absorbed into the blood and excreted into the bile. This compound may be responsible for protection against inflammatory responses. This study aimed to identify novel, enterally-derived BV metabolites and determine the source of their metabolic transformation. Rat duodena and bacterial cultures of Citrobacter youngae were treated with BV and subsequently analysed via high performance liquid chromatography/high resolution tandem mass spectrometry to identify and characterise metabolites of BV. A highly abundant metabolite was detected in duodenal wash and bacterial culture supernatants with a 663.215 m/z (3 ppm mass accuracy) and a composition of C 33 N 4 O 9 H 36 S, which conformed to the predicted structure of bilirubin-10-sulfonate (BRS) and possessed a λ max of 440 nm. Bilirubin-10-sulfonate was then synthesized for comparative LCMS/MS analysis and matched with that of the biologically formed BV metabolite. This report confirms the formation of a previously undocumented metabolite of BV in mammals, indicating that a new metabolic pathway likely exists for BV metabolism requiring enteric bacteria, Citrobacter youngae . These data may have important implications with regard to understanding and harnessing the therapeutic efficacy of oral BV administration.

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Section: Discussionmentioning

confidence: 99%

Unprecedented Microbial Conversion of Biliverdin into Bilirubin-10-sulfonate

Shiels

Vidimce

Pearson

et al. 2019

Sci Rep

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“…The intestinal microbiota then converts it to stercobilin for excretion in stool (4). The absence of gut microflora required for the conversion of bilirubin to stercobilin, such as Clostridium ramosum, Clostridium perfringens, Clostridium difficile, and Bacteroides fragilis, results in higher bilirubin levels in the intestinal tract, which then leads to elevated enterohepatic circulation (5).…”

Section: Introductionmentioning

confidence: 99%

Changes in Intestinal Flora and Metabolites in Neonates With Breast Milk Jaundice

Shen

et al. 2020

Front. Pediatr.

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Background: Breast milk jaundice (BMJ) is the first cause of neonatal jaundice; however, its underlying mechanism is yet to be deciphered. We conducted a study to investigate intestinal flora in neonates with BMJ and used metabolomics to decipher the possible mechanisms by which intestinal flora induces jaundice. Methods: Microbiota collected from the feces of BMJ patients and jaundice-free breastfeeding newborns was used for 16S rRNA sequencing. In addition, differences in fecal metabolites were analyzed using gas chromatography mass spectrometry (GC/MS). The relationship between intestinal microbiota and the differences in fecal metabolites was then analyzed. Results: There was no significant difference in the richness and diversity of intestinal flora between BMJ and the control group; however, there were differences in the structure. At the phylum level, the relative abundance of Firmicutes was higher in the control group compared to the BMJ group, whereas Proteobacteria was higher in the infants with BMJ. Additionally, at the genus level, the relative abundance of Haemophilus was higher in the control group, whereas the relative abundances of Escherichia, Morganella, and Rothia were lower. More remarkably, the major differences in metabolites between the two groups were glyceric acid, succinic acid, and phenylalanine. Additionally, the abundance of Escherichia was positively correlated with succinic acid and cadaverine levels. Conclusions: The intestinal flora colonization status in BMJ patients is immature. This study reports for the first time that the study of intestinal flora, especially Escherichia, plays an important role in BMJ, and found that it may be associated with the regulation of succinic acid metabolic pathways.

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“…Intestinal bacterial species, including Bacteroides fragilis, Clostridium ramosum, Clostridium perfringens, and Clostridium difficile, have been shown to catabolize bilirubin to urobilinogen [29][30][31][32] , although we could not assign these bacterial species in our results (Fig. 1C).…”

Section: Discussionmentioning

confidence: 77%

Intestinal microbial metabolite stercobilin involvement in the chronic inflammation of ob/ob mice

Sanada

Suzuki

Nagata

et al. 2020

Sci Rep

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It is crucial that the host and intestinal microflora interact and influence each other to maintain homeostasis and trigger pathological processes. Recent studies have shown that transplantation of the murine intestinal content to recipient germ-free mice enables transmission of the donor's phenotypes, such as low level chronic inflammation associated with lifestyle-related diseases. These findings indicate that intestinal bacteria produce some molecules to trigger pathological signals. However, fecal microbial metabolites that induce obesity and the type II diabetic phenotype have not been fully clarified. Here, we showed that the intestinal bacterial metabolite stercobilin, a pigment of feces, induced proinflammatory activities including TNF-α and IL-1β induction in mouse macrophage RAW264 cells. Proinflammatory stercobilin levels were significantly higher in ob/ob mice feces than in the feces of control C57BL/6 J mice. Moreover, in this study, we detected stercobilin in mice plasma for the first time, and the levels were higher in ob/ob mice than that of C57BL/6 J mice. Therefore, stercobilin is potentially reabsorbed, circulated through the blood system, and contributes to low level chronic inflammation in ob/ob mice. Since, stercobilin is a bioactive metabolite, it could be a potentially promising biomarker for diagnosis. Further analyses to elucidate the metabolic rate and the reabsorption mechanism of stercobilin may provide possible therapeutic and preventive targets.www.nature.com/scientificreports www.nature.com/scientificreports/ NF-κB-RE vector (Promega) using X-tremeGENE HP DNA Transfection Reagent (Roche). Luciferase activities were evaluated using the Nano-Glo Luciferase assay kit.Bligh-dyer extraction of feces. Fecal extracts were prepared by the Bligh-Dyer extraction method.Briefly, 30 mg feces suspended in a tube containing 0.5 mg of tert-butylhydroquinone (tBHQ) and 650 µL of MeOH/CHCl 3 /H 2 O = 400/200/40 was microdestructed (3000 rpm, 4°C, 120 s ×2 sets) by MicroSmash MS-100R (TOMY, Japan) with a 5.0 ϕ zirconia (ZrO 2 ) bead. After remove the ZrO 2 bead, the tube was centrifuged, and the aqueous and organic phases were harvested in new tubes. Soluble metabolites were extracted again by adding 200 µL of MeOH/CHCl 3 = 100/100 to the residue, vortexed, centrifuged, combined with former ones, then dried by a centrifuge evaporator.Lc-MS. Fecal metabolites were analyzed using LC-MS consisting of AQUITY UPLC (Waters, Milford, MA) coupled with micrOTOFQII (Bruker Daltonics, Bremen, Germany). UPLC separation 39,40 was performed with a CSH C18 column (1.7 μm, 100-mm × 2.1-mm i.d., Waters) at 40°C, using solvent A (0.1% formic acid in water) and solvent B (MeCN containing 0.1% formic acid). Samples were eluted from the column using a linear gradient of 1% solvent B from 0 to 3 min to 80% solvent B at 20-24 min. The flow rate of the mobile phase was 0.4 ml/min. The TOF-MS was operated in positive and negative ion mode using an electrospray ionization source. The detector conditions were as follows: capi...

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Reduction of bilirubin ditaurate by the intestinal bacterium Clostridium perfringens.

Cited by 15 publications

References 12 publications

Unprecedented Microbial Conversion of Biliverdin into Bilirubin-10-sulfonate

Unprecedented Microbial Conversion of Biliverdin into Bilirubin-10-sulfonate

Changes in Intestinal Flora and Metabolites in Neonates With Breast Milk Jaundice

Intestinal microbial metabolite stercobilin involvement in the chronic inflammation of ob/ob mice

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