scholarly journals Structural and functional characterization of BaiA, an enzyme involved in secondary bile acid synthesis in human gut microbe

2013 ◽  
Vol 82 (2) ◽  
pp. 216-229 ◽  
Author(s):  
Shiva Bhowmik ◽  
David H. Jones ◽  
Hsien‐Po Chiu ◽  
In‐Hee Park ◽  
Hsiu‐Ju Chiu ◽  
...  
Keyword(s):  
Bile Acid ◽  
Functional Characterization ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Human Gut ◽  
Secondary Bile Acid ◽  
Gut Microbe

scholarly journals Structure and functional characterization of a bile acid 7α dehydratase BaiE in secondary bile acid synthesis

2016 ◽  
Vol 84 (3) ◽  
pp. 316-331 ◽  
Author(s):  
Shiva Bhowmik ◽  
Hsien-Po Chiu ◽  
David H. Jones ◽  
Hsiu-Ju Chiu ◽  
Mitchell D. Miller ◽  
...  
Keyword(s):  
Bile Acid ◽  
Functional Characterization ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Secondary Bile Acid

scholarly journals Biogeography of microbial bile acid transformations along the murine gut

2020 ◽  
Vol 61 (11) ◽  
pp. 1450-1463 ◽  
Author(s):  
Solenne Marion ◽  
Lyne Desharnais ◽  
Nicolas Studer ◽  
Yuan Dong ◽  
Matheus D. Notter ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Bile Acid Pool Size ◽  
Host Signaling ◽  
Gut Microorganisms ◽  
Gut Microbial Community

Bile acids, which are synthesized from cholesterol by the liver, are chemically transformed along the intestinal tract by the gut microbiota, and the products of these transformations signal through host receptors, affecting overall host health. These transformations include bile acid deconjugation, oxidation, and 7α-dehydroxylation. An understanding of the biogeography of bile acid transformations in the gut is critical because deconjugation is a prerequisite for 7α-dehydroxylation and because most gut microorganisms harbor bile acid transformation capacity. Here, we used a coupled metabolomic and metaproteomic approach to probe in vivo activity of the gut microbial community in a gnotobiotic mouse model. Results revealed the involvement of Clostridium scindens in 7α-dehydroxylation, of the genera Muribaculum and Bacteroides in deconjugation, and of six additional organisms in oxidation (the genera Clostridium, Muribaculum, Bacteroides, Bifidobacterium, Acutalibacter, and Akkermansia). Furthermore, the bile acid profile in mice with a more complex microbiota, a dysbiosed microbiota, or no microbiota was considered. For instance, conventional mice harbor a large diversity of bile acids, but treatment with an antibiotic such as clindamycin results in the complete inhibition of 7α-dehydroxylation, underscoring the strong inhibition of organisms that are capable of carrying out this process by this compound. Finally, a comparison of the hepatic bile acid pool size as a function of microbiota revealed that a reduced microbiota affects host signaling but not necessarily bile acid synthesis. In this study, bile acid transformations were mapped to the associated active microorganisms, offering a systematic characterization of the relationship between microbiota and bile acid composition.

The characterization of bile acid synthesis by cultured hamster hepatocytes

1990 ◽  
Vol 18 (6) ◽  
pp. 1211-1212 ◽  
Author(s):  
RICHARD P. FRY ◽  
G. MARTIN BENSON ◽  
KATHLEEN M. BOTHAM ◽  
KEITH E. SUCKLING
Keyword(s):  
Bile Acid ◽  
Acid Synthesis ◽  
Bile Acid Synthesis

scholarly journals Computational modeling of the gut microbiota reveals putative metabolic mechanisms of recurrent Clostridioides difficile infection

2021 ◽  
Vol 17 (2) ◽  
pp. e1008782
Author(s):  
Michael A. Henson
Keyword(s):  
Bile Acid ◽  
Amino Acid ◽  
In Silico ◽  
Aromatic Amino Acid ◽  
Sequence Data ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Amino Acid Catabolism ◽  
Secondary Bile Acid ◽  
Clostridioides Difficile

Approximately 30% of patients who have Clostridioides difficile infection (CDI) will suffer at least one incident of reinfection. While the underlying causes of CDI recurrence are poorly understood, interactions between C. difficile and commensal gut bacteria are thought to play an important role. In this study, an in silico pipeline was used to process 16S rRNA gene amplicon sequence data of 225 stool samples from 93 CDI patients into sample-specific models of bacterial community metabolism. Clustered metabolite production rates generated from post-diagnosis samples generated a high Enterobacteriaceae abundance cluster containing disproportionately large numbers of recurrent samples and patients. This cluster was predicted to have significantly reduced capabilities for secondary bile acid synthesis but elevated capabilities for aromatic amino acid catabolism. When applied to 16S sequence data of 40 samples from fecal microbiota transplantation (FMT) patients suffering from recurrent CDI and their stool donors, the community modeling method generated a high Enterobacteriaceae abundance cluster with a disproportionate large number of pre-FMT samples. This cluster also was predicted to exhibit reduced secondary bile acid synthesis and elevated aromatic amino acid catabolism. Collectively, these in silico predictions suggest that Enterobacteriaceae may create a gut environment favorable for C. difficile spore germination and/or toxin synthesis.

scholarly journals Computational Modeling of the Gut Microbiota Predicts Metabolic Mechanisms of Recurrent Clostridioides difficile Infection

2020 ◽  
Author(s):  
Michael A. Henson
Keyword(s):  
Bile Acid ◽  
Amino Acid ◽  
Bacterial Community ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Recurrent Infections ◽  
Amino Acid Catabolism ◽  
Secondary Bile Acid ◽  
Clostridioides Difficile ◽  
Model Predictions

AbstractApproximately 30% of patients who have a Clostridioides difficile infection (CDI) will suffer at least one incident of reinfection. While the underlying causes of CDI recurrence are poorly understood, interactions between C. difficile and other commensal gut bacteria are thought to play an important role. In this study, an in silico metagenomics pipeline was used to process taxa abundance data from 225 CDI patient stool samples into sample-specific models of bacterial community metabolism. The predicted metabolite production capabilities of each community were shown to provide improved recurrence prediction compared to direct use of taxa abundance data. More specifically, clustered metabolite synthesis rates generated from post-diagnosis samples produced a high Enterobacteriaceae cluster with disproportionate numbers of recurrent samples and patients. This cluster was predicted to have significantly reduced capabilities for secondary bile acid synthesis but elevated capabilities for aromatic amino acid catabolism. When applied to 40 samples from fecal microbiota transplantation (FMT) patients and their donors, community modeling generated a high Enterobacteriaceae cluster with a disproportionate number of pre-FMT samples. This cluster also was predicted to exhibit reduced secondary bile acid synthesis and elevated aromatic amino acid catabolism. Because clustering of CDI and FMT samples did not identify statistical differences in C. difficile abundances, these model predictions support the hypothesis that Enterobacteriaceae may create a gut environment favorable for C. difficile spore germination and toxin synthesis.ImportanceClostridioides difficile is an opportunistic human pathogen responsible for acute and sometimes chronic infections of the colon. Elderly individuals who are immunocompromised, frequently hospitalized and recipients of antibiotics are particular susceptible to infection. Approximately 30% of treated patients will suffer at least one episode of reinfection, commonly termed recurrence. The objective of the current study was to utilize computational metabolic modeling to investigate the hypothesis that recurrent infections are related to the composition of the gut bacterial community within each patient. Our model predictions suggest that patients who have high compositions of the bacterial family Enterobacteriaceae during antibiotic treatment are more likely to develop recurrent infections due to a metabolically-disrupted gut environment. Successful treatment of recurrent patients with transplanted fecal matter is predicted to correct this metabolic disruption, suggesting that interactions between C. difficile and Enterobacteriaceae are worthy of additional study.

scholarly journals Gut microbiome dysbiosis is associated with elevated toxic bile acids in Parkinson’s disease

2020 ◽  
Author(s):  
Peipei Li ◽  
Bryan A. Killinger ◽  
Ian Beddows ◽  
Elizabeth Ensink ◽  
Ali Yilmaz ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Bile Acid ◽  
Bile Acids ◽  
Gut Microbiome ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Cholesterol Homeostasis ◽  
Elevated Alkaline Phosphatase ◽  
Secondary Bile Acid

AbstractThe gut microbiome can impact brain health and is altered in Parkinson’s disease (PD) patients. Here, we investigate changes in the functional microbiome in the appendix of PD patients relative to controls by metatranscriptomic analysis. We find microbial dysbiosis affecting lipid metabolism, particularly an upregulation of bacteria responsible for secondary bile acid synthesis. Proteomic and transcript analysis corroborates a disruption in cholesterol homeostasis and lipid catabolism. Bile acid analysis reveals an increase in microbially-derived, toxic secondary bile acids. Synucleinopathy in mice induces similar microbiome alterations to those of PD patients. The mouse model of synucleinopathy has elevated DCA and LCA. An analysis of blood markers shows evidence of biliary abnormalities early in PD, including elevated alkaline phosphatase and bilirubin. Increased bilirubin levels are also evident before PD diagnosis. In sum, microbially-derived toxic bile acids are heightened in PD and biliary changes may even precede the onset of overt motor symptoms.

scholarly journals Endogenous Estrogens Lower Plasma PCSK9 and LDL Cholesterol But Not Lp(a) or Bile Acid Synthesis in Women

2012 ◽  
Vol 32 (3) ◽  
pp. 810-814 ◽  
Author(s):  
Lena Persson ◽  
Peter Henriksson ◽  
Eli Westerlund ◽  
Outi Hovatta ◽  
Bo Angelin ◽  
...  
Keyword(s):  
Bile Acid ◽  
Ldl Cholesterol ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Lower Plasma
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