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1.
Gastroenterology ; 164(7): 1069-1085, 2023 06.
Article in English | MEDLINE | ID: mdl-36841488

ABSTRACT

The human gut microbiome has been linked to numerous digestive disorders, but its metabolic products have been much less well characterized, in part due to the expense of untargeted metabolomics and lack of ability to process the data. In this review, we focused on the rapidly expanding information about the bile acid repertoire produced by the gut microbiome, including the impacts of bile acids on a wide range of host physiological processes and diseases, and discussed the role of short-chain fatty acids and other important gut microbiome-derived metabolites. Of particular note is the action of gut microbiome-derived metabolites throughout the body, which impact processes ranging from obesity to aging to disorders traditionally thought of as diseases of the nervous system, but that are now recognized as being strongly influenced by the gut microbiome and the metabolites it produces. We also highlighted the emerging role for modifying the gut microbiome to improve health or to treat disease, including the "engineered native bacteria'' approach that takes bacterial strains from a patient, modifies them to alter metabolism, and reintroduces them. Taken together, study of the metabolites derived from the gut microbiome provided insights into a wide range of physiological and pathophysiological processes, and has substantial potential for new approaches to diagnostics and therapeutics of disease of, or involving, the gastrointestinal tract.


Subject(s)
Gastrointestinal Microbiome , Microbiota , Humans , Gastrointestinal Microbiome/physiology , Bile Acids and Salts/metabolism , Metabolome , Microorganisms, Genetically-Modified , Fatty Acids, Volatile
2.
Nat Commun ; 11(1): 3176, 2020 06 18.
Article in English | MEDLINE | ID: mdl-32555158

ABSTRACT

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

3.
Nat Commun ; 10(1): 2151, 2019 05 14.
Article in English | MEDLINE | ID: mdl-31089133

ABSTRACT

Performance on cognitive tasks during learning is used to measure knowledge, yet it remains controversial since such testing is susceptible to contextual factors. To what extent does performance during learning depend on the testing context, rather than underlying knowledge? We trained mice, rats and ferrets on a range of tasks to examine how testing context impacts the acquisition of knowledge versus its expression. We interleaved reinforced trials with probe trials in which we omitted reinforcement. Across tasks, each animal species performed remarkably better in probe trials during learning and inter-animal variability was strikingly reduced. Reinforcement feedback is thus critical for learning-related behavioral improvements but, paradoxically masks the expression of underlying knowledge. We capture these results with a network model in which learning occurs during reinforced trials while context modulates only the read-out parameters. Probing learning by omitting reinforcement thus uncovers latent knowledge and identifies context- not "smartness"- as the major source of individual variability.


Subject(s)
Models, Neurological , Reinforcement, Psychology , Animals , Behavior, Animal/physiology , Biological Variation, Population/physiology , Female , Ferrets , Male , Mice , Models, Animal , Rats
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