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 microbiome stabilizes circadian rhythms in the gut

Proceedings of the National Academy of Sciences · 2023 · 67 citations

• Biology
• Physiology
• Cell biology

flies. However, TF and loss of the microbiome influenced the composition of the gut cycling transcriptome, independently and together. Moreover, both interventions increased the amplitude of rhythmic gene expression, with effects of TF at least partly due to changes in histone acetylation. Contrary to expectations, timed feeding rendered animals more sensitive to stress. Analysis of microbiome function in circadian physiology revealed that germ-free flies reset more rapidly with shifts in the light:dark cycle. We propose that the microbiome stabilizes cycling in the host gut to prevent rapid fluctuations with changing environmental conditions.

Host immunity modulates the efficacy of microbiota transplantation for treatment of Clostridioides difficile infection

Nature Communications · 2021 · 95 citations

• Immunology
• Biology
• Microbiology

T cells, in FMT-mediated resolution of C. difficile infection. FMT non-responsive mice exhibit exacerbated inflammation, impaired engraftment of the FMT bacterial community and failed restoration of commensal bacteria-derived secondary bile acid metabolites in the large intestine. These data demonstrate that the host's inflammatory immune status can limit the efficacy of microbiota-based therapeutics to treat C. difficile infection.

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...

A Randomized Trial Comparing the Specific Carbohydrate Diet to a Mediterranean Diet in Adults With Crohn’s Disease

Gastroenterology · 2021 · 284 citations

• Medicine
• Internal medicine
• Gastroenterology

Dysbiosis-Induced Secondary Bile Acid Deficiency Promotes Intestinal Inflammation

Cell Host & Microbe · 2020 · 831 citations

• Biology
• Immunology
• Microbiology

Bacterial colonization reprograms the neonatal gut metabolome

Nature Microbiology · 2020 · 126 citations

• Biology
• Microbiology
• Biochemistry