Bile salt hydrolase catalyses formation of amine-conjugated bile acids

Nature · 2024 · 198 citations

• Biochemistry
• Biology
• Chemistry

; however, the bacterial gene(s) responsible for their production remain unknown. Herein, we report that bile salt hydrolase (BSH) possesses dual functions in bile acid metabolism. Specifically, we identified a previously unknown role for BSH as an amine N-acyltransferase that conjugates amines to bile acids, thus forming bacterial bile acid amidates (BBAAs). To characterize this amine N-acyltransferase BSH activity, we used pharmacological inhibition of BSH, heterologous expression of bsh and mutants in Escherichia coli and bsh knockout and complementation in Bacteroides fragilis to demonstrate that BSH generates BBAAs. We further show in a human infant cohort that BBAA production is positively correlated with the colonization of bsh-expressing bacteria. Lastly, we report that in cell culture models, BBAAs activate host ligand-activated transcription factors including the pregnane X receptor and the aryl hydrocarbon receptor. These findings enhance our understanding of how gut bacteria, through the promiscuous actions of BSH, have a significant role in regulating the bile acid metabolic network.

The Impact of Introducing Patient-Reported Inflammatory Bowel Disease Symptoms via Electronic Survey on Clinic Visit Length, Patient and Provider Satisfaction, and the Environment Microbiome

Inflammatory Bowel Diseases · 2021 · 2 citations

• Medicine
• Family medicine
• Internal medicine

Electronic health records have the potential to improve patient care while reducing the burden of documentation on clinicians. Smartforms are tools for standardized data collection within the Epic electronic health record. We developed an inflammatory bowel disease (IBD) Smartform and tested the impact of direct patient entry of symptom data via the internet or in-office tablet computers on visit length, patient and provider satisfaction, and changes in the tablet-associated microbiome. This research was determined to be exempt by the University of Pennsylvania Institutional Review Board. The IBD Smartform includes current patient symptom and historical data (eg, disease distribution). Patients can self-report current IBD symptoms before their scheduled clinic visits utilizing the Symptom Questionnaire, either via an electronic patient portal or at the office using a computer. Patients’ responses feed automatically into the IBD Smartform, allowing for immediate use in clinical notes by providers. In February 2015, the IBD Smartform was...

Bacterial colonization reprograms the neonatal gut metabolome

Nature Microbiology · 2020 · 126 citations

• Biology
• Microbiology
• Biochemistry

Fecal Microbiota Transplantation Is Highly Effective in Real-World Practice: Initial Results From the FMT National Registry

Gastroenterology · 2020 · 199 citations

• Medicine
• Internal medicine
• Biology

Mitochondrial dysfunction in inflammatory bowel disease alters intestinal epithelial metabolism of hepatic acylcarnitines

Journal of Clinical Investigation · 2020 · 91 citations

• Medicine
• Internal medicine
• Gastroenterology

As the interface between the gut microbiota and the mucosal immune system, there has been great interest in the maintenance of colonic epithelial integrity through mitochondrial oxidation of butyrate, a short-chain fatty acid produced by the gut microbiota. Herein, we showed that the intestinal epithelium could also oxidize long-chain fatty acids, and that luminally delivered acylcarnitines in bile could be consumed via apical absorption by the intestinal epithelium, resulting in mitochondrial oxidation. Finally, intestinal inflammation led to mitochondrial dysfunction in the apical domain of the surface epithelium that may reduce the consumption of fatty acids, contributing to higher concentrations of fecal acylcarnitines in murine Citrobacter rodentium-induced colitis and human inflammatory bowel disease. These results emphasized the importance of both the gut microbiota and the liver in the delivery of energy substrates for mitochondrial metabolism by the intestinal epithelium.