Identification of bilirubin reduction products formed by Clostridium perfringens isolated from human neonatal fecal flora

Vı́tek, Libor; Majer, Filip; Muchová, Lucie; Zelenka, Jaroslav; Jirásková, Alena; Branný, Pavel; Malina, Jiří; Ubik, Karel

doi:10.1016/j.jchromb.2006.01.032

Cited by 42 publications

(39 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Stercobilin (C 33 H 46 N 4 O 6 , PubChem CID 5280818) is an oxidative product of stercobilinogen (C 33 H 48 N 4 O 6 , PubChem CID 9548718) by bacterial action in the colon (Vitek et al 2006). Although these two compounds differ in mass by two H atoms, the high mass accuracy of FT-ICR makes possible distinguishing isotope peaks of stercobilin from stercobilinogen.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Depletion of stercobilin in fecal matter from a mouse model of autism spectrum disorders

et al. 2017

View full text Add to dashboard Cite

Introduction Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders lacking a clinical biomarker for diagnosis. Emerging evidence shows that intestinal microflora from ASD subjects can be distinguished from controls, suggesting metabolite differences due to the action of intestinal microbes may provide a means for identifying potential biomarkers for ASD. Objectives The aim of this study was to determine if quantitative differences in levels of stercobilin and stercobilinogen, metabolites produced by biological action of intestinal microflora, exist in the fecal matter between an ASD mouse model population and controls. Methods Pairs of fecal samples were collected from two mouse groups, an ASD model group with Timothy syndrome 2 (TS2-NEO) and a gender-matched control group. After centrifugation, supernatant was spiked with an 18O-labeled stercobilin isotopomer and subjected to solid phase extraction for processing. Extracted samples were spotted on a stainless steel plate and subjected to matrix-assisted laser desorption and ionization mass spectrometry using dihydroxybenzoic acid as the matrix (n = 5). Peak areas for bilins and 18O-stercobilin isotopomers were determined in each fecal sample. Results A 40–45% depletion in stercobilin in TS2-NEO fecal samples compared with controls was observed with p < 0.05; a less dramatic depletion was observed for stercobilinogen. Conclusions The results show that stercobilin depletion in feces is observed for an ASD mouse model vs. controls. This may help to explain recent observations of a less diverse microbiome in humans with ASD and may prove helpful in developing a clinical ASD biomarker.

show abstract

Section: Resultsmentioning

confidence: 99%

“…The metabolic products within the box are produced by the action of Clostridium perfringens (Vitek et al 2006). …”

Section: Figurementioning

confidence: 99%

Depletion of stercobilin in fecal matter from a mouse model of autism spectrum disorders

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Though a physiologic function for bile-secreted β-glucuronidases is not well described, secreted enzymes may function to increase the concentration of unconjugated bilirubin during bile transit down the GI tract by utilizing the high concentration of conjugated bilirubins. Further, the concentration of β-glucuronidase can be increased by populations of coliform bacteria and to a much greater extent by Clostridia species, both of which actively secrete β-glucuronidases, implicating these bacteria in initial bilirubin breakdown within the GI tract [6], [45]. Intestinal epithelia expression of UGT1A1, the enzyme responsible for biotransformation of bilirubin by conjugating the molecule with glucuronic acid, decreases from the ileum to the cecum, suggesting a driving force toward conjugated bilirubin diminishes as intestinal contents approach the colon [46].…”

Section: Discussionmentioning

confidence: 99%

A Product of Heme Catabolism Modulates Bacterial Function and Survival

2013

View full text Add to dashboard Cite

Bilirubin is the terminal metabolite in heme catabolism in mammals. After deposition into bile, bilirubin is released in large quantities into the mammalian gastrointestinal (GI) tract. We hypothesized that intestinal bilirubin may modulate the function of enteric bacteria. To test this hypothesis, we investigated the effect of bilirubin on two enteric pathogens; enterohemorrhagic E. coli (EHEC), a Gram-negative that causes life-threatening intestinal infections, and E. faecalis, a Gram-positive human commensal bacterium known to be an opportunistic pathogen with broad-spectrum antibiotic resistance. We demonstrate that bilirubin can protect EHEC from exogenous and host-generated reactive oxygen species (ROS) through the absorption of free radicals. In contrast, E. faecalis was highly susceptible to bilirubin, which causes significant membrane disruption and uncoupling of respiratory metabolism in this bacterium. Interestingly, similar results were observed for other Gram-positive bacteria, including B. cereus and S. aureus. A model is proposed whereby bilirubin places distinct selective pressure on enteric bacteria, with Gram-negative bacteria being protected from ROS (positive outcome) and Gram-positive bacteria being susceptible to membrane disruption (negative outcome). This work suggests bilirubin has differential but biologically relevant effects on bacteria and justifies additional efforts to determine the role of this neglected waste catabolite in disease processes, including animal models.

show abstract

“…In the intestinal tract, conjugated bilirubin glucuronosides are cleaved by β-glucuronidase originating from either intestinal bacteria or intestinal epithelial cells. Bilirubin remaining within the intestines undergoes a series of reduction steps involving the intestinal microflora, leading to the formation of urobilinoids [43,44]. Bilirubin remaining within the intestines undergoes a series of reduction steps involving the intestinal microflora, leading to the formation of urobilinoids [43,44].…”

Section: Insights Into Bilirubin Metabolismmentioning

confidence: 99%

Looking to the horizon: the role of bilirubin in the development and prevention of age-related chronic diseases

et al. 2015

View full text Add to dashboard Cite

Bilirubin, the principal tetrapyrrole, bile pigment and catabolite of haem, is an emerging biomarker of disease resistance, which may be related to several recently documented biological functions. Initially believed to be toxic in infants, the perception of bilirubin has undergone a transformation: it is now considered to be a molecule that may promote health in adults. Data from the last decade demonstrate that mildly elevated serum bilirubin levels are strongly associated with reduced prevalence of chronic diseases, particularly cardiovascular diseases (CVDs), as well as CVD-related mortality and risk factors. Recent data also link bilirubin to other chronic diseases, including cancer and Type 2 diabetes mellitus, and to all-cause mortality. Therefore, there is evidence to suggest that bilirubin is a biomarker for reduced chronic disease prevalence and a predictor of all-cause mortality, which is of important clinical significance. In the present review, detailed information on the association between bilirubin and all-cause mortality, as well as the pathological conditions of CVD, cancer, diabetes and neurodegenerative diseases, is provided. The mechanistic background concerning how bilirubin and its metabolism may influence disease prevention and its clinical relevance is also discussed. Given that the search for novel biomarkers of these diseases, as well as for novel therapeutic modalities, is a key research objective for the near future, bilirubin represents a promising candidate, meeting the criteria of a biomarker, and should be considered more carefully in clinical practice as a molecule that might provide insights into disease resistance. Clearly, however, greater molecular insight is warranted to support and strengthen the conclusion that bilirubin can prevent disease, with future research directions also proposed.

show abstract

Identification of bilirubin reduction products formed by Clostridium perfringens isolated from human neonatal fecal flora

Cited by 42 publications

References 33 publications

Depletion of stercobilin in fecal matter from a mouse model of autism spectrum disorders

Depletion of stercobilin in fecal matter from a mouse model of autism spectrum disorders

A Product of Heme Catabolism Modulates Bacterial Function and Survival

Looking to the horizon: the role of bilirubin in the development and prevention of age-related chronic diseases

Contact Info

Product

Resources

About