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Chou, C. J.

Publications and source records attributed to Chou, C. J..

2 recordsLinked to original sources

Application of computational data modeling to a large-scale population cohort assists the discovery of specific nutrients that influence beneficial human gut bacteria Faecalibacterium prausnitzii

Faecalibacterium prausnitzii (F. prausnitzii) is a bacterial taxon of the human gut with anti-inflammatory properties and negative associations with chronic inflammatory conditions. F. prausnitzii may be one of key species contributing to the effects of healthy eating habits, and yet little is known about the nutrients that enhance the growth of F. prausnitzii other than simple sugars and fibers. Here we combined dietary and microbiome data from the American Gut Project (AGP) to identify nutrients that may be linked to the relative abundance of F. prausnitzii. Using a machine learning approach in combination with univariate analyses, we identified that sugar alcohols, carbocyclic sugar and vitamins may contribute to F. prausnitzii growth. We next explored the effects of these nutrients on the growth of two F. prausnitzii strains in vitro and observed strain dependent growth patterns on the nutrient tested. In the context of a complex community using in vitro fermentation, none of the tested nutrients and nutrient combinations exerted a significant growth-promoting effect on F. prausnitzii due to high variability in batch responses. A positive association between F. prausnitzii and butyrate concentrations was observed. Future nutritional studies aiming to increase relative abundance of F. prausnitzii should explore a personalized approach accounting for strain-level genetic variations and community-level microbiome composition.

microbiology↗

Histone deacetylase inhibition by gut microbe-generated short chain fatty acids entrains intestinal epithelial circadian rhythms

Background and aimsThe circadian clock orchestrates ~24-hour oscillations of gastrointestinal (GI) epithelial structure and function that drive diurnal rhythms in the composition, localization, and metabolism of gut microbiota. Here, we use experimental and computational approaches in enteroids to reveal reciprocal effects of microbial metabolites on intestinal epithelial timekeeping by an epigenetic mechanism. MethodsWe cultured 3D PER2::LUCIFERASE and Bmal1-ELuciferase jejunal enteroids in media supplemented with sterile supernatants from the altered Schaedler Flora (ASF), a defined murine microbiota. Circadian oscillations of bioluminescent PER2 and Bmal1 were measured in enteroids cultured in the presence or absence of individual ASF supernatants. Separately, we applied machine learning to ASF metabolic profiles to identify phase-shifting metabolites. ResultsFiltrates from 3 of 7 ASF species (ASF360 Lactobacillus intestinalis, ASF361 Ligilactobacillus murinus, ASF502 Clostridium spp.) induced minimal alterations in circadian rhythms, whereas 4 ASF species (ASF356 Clostridium spp., ASF492 Eubacterium plexicaudatum, ASF500 Pseudoflavonifactor spp., ASF519 Parabacteroides goldsteinii) induced profound, concentration-dependent phase delays. Random forest classification identified short chain fatty acids (SCFA: butyrate, propionate, acetate, and isovalerate) production as a discriminating feature of "shifters", i.e., ASF taxa whose metabolites induce phase delay. Experiments with SCFAs confirmed machine learning predictions, with a median phase delay of 6.2 hours. Pharmacological or botanical HDAC inhibitors generated similar phase delays. Further, mithramycin A, an inhibitor of HDAC inhibition, abrogated SCFA-induced phase delays by 20% (P<0.05). Key findings were reproducible in human Bmal1-luciferase enteroids. ConclusionsGut microbe-generated SCFAs entrain intestinal epithelial circadian rhythms, in part, by an HDACi-dependent mechanism, with critical implications for understanding microbial and circadian network regulation of intestinal epithelial homeostasis.

cell biology↗