In Vitro Modeling of Bile Acid Processing by the Human Fecal Microbiota

Bile acids, the products of concerted host and gut bacterial metabolism, have important signaling functions within the mammalian metabolic system and a key role in digestion. Given the complexity of the mega-variate bacterial community residing in the gastrointestinal tract, studying associations be...

Full description

Bibliographic Details
Main Authors: Glynn Martin, Sofia Kolida, Julian R. Marchesi, Elizabeth Want, James E. Sidaway, Jonathan R. Swann
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-06-01
Series:Frontiers in Microbiology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fmicb.2018.01153/full
_version_ 1818933831917371392
author Glynn Martin
Sofia Kolida
Julian R. Marchesi
Julian R. Marchesi
Julian R. Marchesi
Elizabeth Want
James E. Sidaway
Jonathan R. Swann
author_facet Glynn Martin
Sofia Kolida
Julian R. Marchesi
Julian R. Marchesi
Julian R. Marchesi
Elizabeth Want
James E. Sidaway
Jonathan R. Swann
author_sort Glynn Martin
collection DOAJ
description Bile acids, the products of concerted host and gut bacterial metabolism, have important signaling functions within the mammalian metabolic system and a key role in digestion. Given the complexity of the mega-variate bacterial community residing in the gastrointestinal tract, studying associations between individual bacterial genera and bile acid processing remains a challenge. Here, we present a novel in vitro approach to determine the bacterial genera associated with the metabolism of different primary bile acids and their potential to contribute to inter-individual variation in this processing. Anaerobic, pH-controlled batch cultures were inoculated with human fecal microbiota and treated with individual conjugated primary bile acids (500 μg/ml) to serve as the sole substrate for 24 h. Samples were collected throughout the experiment (0, 5, 10, and 24 h) and the bacterial composition was determined by 16S rRNA gene sequencing and the bile acid signatures were characterized using a targeted ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) approach. Data fusion techniques were used to identify statistical bacterial-metabolic linkages. An increase in gut bacteria associated bile acids was observed over 24 h with variation in the rate of bile acid metabolism across the volunteers (n = 7). Correlation analysis identified a significant association between the Gemmiger genus and the deconjugation of glycine conjugated bile acids while the deconjugation of taurocholic acid was associated with bacteria from the Eubacterium and Ruminococcus genera. A positive correlation between Dorea and deoxycholic acid production suggest a potential role for this genus in cholic acid dehydroxylation. A slower deconjugation of taurocholic acid was observed in individuals with a greater abundance of Parasutterella and Akkermansia. This work demonstrates the utility of integrating compositional (metataxonomics) and functional (metabonomics) systems biology approaches, coupled to in vitro model systems, to study the biochemical capabilities of bacteria within complex ecosystems. Characterizing the dynamic interactions between the gut microbiota and the bile acid pool enables a greater understanding of how variation in the gut microbiota influences host bile acid signatures, their associated functions and their implications for health.
first_indexed 2024-12-20T04:54:38Z
format Article
id doaj.art-f86156e4f74e42ae92dd99d0f5fcd861
institution Directory Open Access Journal
issn 1664-302X
language English
last_indexed 2024-12-20T04:54:38Z
publishDate 2018-06-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Microbiology
spelling doaj.art-f86156e4f74e42ae92dd99d0f5fcd8612022-12-21T19:52:46ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2018-06-01910.3389/fmicb.2018.01153300230In Vitro Modeling of Bile Acid Processing by the Human Fecal MicrobiotaGlynn Martin0Sofia Kolida1Julian R. Marchesi2Julian R. Marchesi3Julian R. Marchesi4Elizabeth Want5James E. Sidaway6Jonathan R. Swann7Department of Food and Nutritional Sciences, University of Reading, Reading, United KingdomOptiBiotix Health PLC, Innovation Centre, York, United KingdomDivision of Integrative Systems Medicine and Digestive Diseases, Imperial College London, London, United KingdomCentre for Digestive and Gut Health, Imperial College London, London, United KingdomSchool of Biosciences, Cardiff University, Cardiff, United KingdomDivision of Integrative Systems Medicine and Digestive Diseases, Imperial College London, London, United KingdomPhenotox Ltd., Macclesfield, United KingdomDivision of Integrative Systems Medicine and Digestive Diseases, Imperial College London, London, United KingdomBile acids, the products of concerted host and gut bacterial metabolism, have important signaling functions within the mammalian metabolic system and a key role in digestion. Given the complexity of the mega-variate bacterial community residing in the gastrointestinal tract, studying associations between individual bacterial genera and bile acid processing remains a challenge. Here, we present a novel in vitro approach to determine the bacterial genera associated with the metabolism of different primary bile acids and their potential to contribute to inter-individual variation in this processing. Anaerobic, pH-controlled batch cultures were inoculated with human fecal microbiota and treated with individual conjugated primary bile acids (500 μg/ml) to serve as the sole substrate for 24 h. Samples were collected throughout the experiment (0, 5, 10, and 24 h) and the bacterial composition was determined by 16S rRNA gene sequencing and the bile acid signatures were characterized using a targeted ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) approach. Data fusion techniques were used to identify statistical bacterial-metabolic linkages. An increase in gut bacteria associated bile acids was observed over 24 h with variation in the rate of bile acid metabolism across the volunteers (n = 7). Correlation analysis identified a significant association between the Gemmiger genus and the deconjugation of glycine conjugated bile acids while the deconjugation of taurocholic acid was associated with bacteria from the Eubacterium and Ruminococcus genera. A positive correlation between Dorea and deoxycholic acid production suggest a potential role for this genus in cholic acid dehydroxylation. A slower deconjugation of taurocholic acid was observed in individuals with a greater abundance of Parasutterella and Akkermansia. This work demonstrates the utility of integrating compositional (metataxonomics) and functional (metabonomics) systems biology approaches, coupled to in vitro model systems, to study the biochemical capabilities of bacteria within complex ecosystems. Characterizing the dynamic interactions between the gut microbiota and the bile acid pool enables a greater understanding of how variation in the gut microbiota influences host bile acid signatures, their associated functions and their implications for health.https://www.frontiersin.org/article/10.3389/fmicb.2018.01153/fullmetabonomicsmetataxonomicsbile acidmicrobiotamicrobiomedeconjugation
spellingShingle Glynn Martin
Sofia Kolida
Julian R. Marchesi
Julian R. Marchesi
Julian R. Marchesi
Elizabeth Want
James E. Sidaway
Jonathan R. Swann
In Vitro Modeling of Bile Acid Processing by the Human Fecal Microbiota
Frontiers in Microbiology
metabonomics
metataxonomics
bile acid
microbiota
microbiome
deconjugation
title In Vitro Modeling of Bile Acid Processing by the Human Fecal Microbiota
title_full In Vitro Modeling of Bile Acid Processing by the Human Fecal Microbiota
title_fullStr In Vitro Modeling of Bile Acid Processing by the Human Fecal Microbiota
title_full_unstemmed In Vitro Modeling of Bile Acid Processing by the Human Fecal Microbiota
title_short In Vitro Modeling of Bile Acid Processing by the Human Fecal Microbiota
title_sort in vitro modeling of bile acid processing by the human fecal microbiota
topic metabonomics
metataxonomics
bile acid
microbiota
microbiome
deconjugation
url https://www.frontiersin.org/article/10.3389/fmicb.2018.01153/full
work_keys_str_mv AT glynnmartin invitromodelingofbileacidprocessingbythehumanfecalmicrobiota
AT sofiakolida invitromodelingofbileacidprocessingbythehumanfecalmicrobiota
AT julianrmarchesi invitromodelingofbileacidprocessingbythehumanfecalmicrobiota
AT julianrmarchesi invitromodelingofbileacidprocessingbythehumanfecalmicrobiota
AT julianrmarchesi invitromodelingofbileacidprocessingbythehumanfecalmicrobiota
AT elizabethwant invitromodelingofbileacidprocessingbythehumanfecalmicrobiota
AT jamesesidaway invitromodelingofbileacidprocessingbythehumanfecalmicrobiota
AT jonathanrswann invitromodelingofbileacidprocessingbythehumanfecalmicrobiota