In vitro modeling of bile acid processing by the human fecal microbiota
2018
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 (500μg/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.
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