Glucocorticoids and gut bacteria: “The GALF Hypothesis” in the metagenomic era

David J. Morris, Jason M Ridlon

Research output: Contribution to journalReview article

Abstract

A new concept is emerging in biomedical sciences: the gut microbiota is a virtual ‘organ’ with endocrine function. Here, we explore the literature pertaining to the role of gut microbial metabolism of endogenous adrenocorticosteroids as a contributing factor in the etiology of essential hypertension. A body of literature demonstrates that bacterial products of glucocorticoid metabolism are absorbed into the portal circulation, and pass through the kidney before excretion into urine. Apparent mineralocorticoid excess (AME) syndrome patients were found to have congenital mutations resulting in non-functional renal 11β-hydroxysteroid dehydrogenase-2 (11β-HSD2) and severe hypertension often lethal in childhood. 11β-HSD2 acts as a “guardian” enzyme protecting the mineralocorticoid receptor from excess cortisol, preventing sodium and water retention in the normotensive state. Licorice root, whose active ingredient, glycerrhetinic acid (GA), inhibits renal 11β-HSD2, and thereby causes hypertension in some individuals. Bacterially derived glucocorticoid metabolites may cause hypertension in some patients by a similar mechanism. Parallel observations in gut microbiology coupled with screening of endogenous steroids as inhibitors of 11β-HSD2 have implicated particular gut bacteria in essential hypertension through the production of glycerrhetinic acid-like factors (GALFs). A protective role of GALFs produced by gut bacteria in the etiology of colorectal cancer is also explored.

Original languageEnglish (US)
Pages (from-to)1-13
Number of pages13
JournalSteroids
Volume125
DOIs
StatePublished - Jan 1 2017

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11-beta-Hydroxysteroid Dehydrogenases
Metagenomics
Glucocorticoids
Bacteria
Acids
Hypertension
Kidney
proctolin
Metabolism
Apparent Mineralocorticoid Excess Syndrome
Glycyrrhiza
Microbiology
Mineralocorticoid Receptors
Mineralocorticoids
Metabolites
Hydrocortisone
Colorectal Neoplasms
Screening
Sodium
Steroids

Keywords

  • 17α-Hydroxylase deficiency
  • 21-Dehydroxylase
  • Apparent mineralocorticoid excess
  • Clostridium
  • Corticosterone
  • Cortisol
  • Eggerthella
  • Essential hypertension
  • GALFs
  • Glycyrrhetinic acid
  • Gut microbiota
  • Kidney 11β-hydroxysteroid dehydrogenase
  • Steroid-17,20-desmolase

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology
  • Pharmacology
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Glucocorticoids and gut bacteria : “The GALF Hypothesis” in the metagenomic era. / Morris, David J.; Ridlon, Jason M.

In: Steroids, Vol. 125, 01.01.2017, p. 1-13.

Research output: Contribution to journalReview article

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abstract = "A new concept is emerging in biomedical sciences: the gut microbiota is a virtual ‘organ’ with endocrine function. Here, we explore the literature pertaining to the role of gut microbial metabolism of endogenous adrenocorticosteroids as a contributing factor in the etiology of essential hypertension. A body of literature demonstrates that bacterial products of glucocorticoid metabolism are absorbed into the portal circulation, and pass through the kidney before excretion into urine. Apparent mineralocorticoid excess (AME) syndrome patients were found to have congenital mutations resulting in non-functional renal 11β-hydroxysteroid dehydrogenase-2 (11β-HSD2) and severe hypertension often lethal in childhood. 11β-HSD2 acts as a “guardian” enzyme protecting the mineralocorticoid receptor from excess cortisol, preventing sodium and water retention in the normotensive state. Licorice root, whose active ingredient, glycerrhetinic acid (GA), inhibits renal 11β-HSD2, and thereby causes hypertension in some individuals. Bacterially derived glucocorticoid metabolites may cause hypertension in some patients by a similar mechanism. Parallel observations in gut microbiology coupled with screening of endogenous steroids as inhibitors of 11β-HSD2 have implicated particular gut bacteria in essential hypertension through the production of glycerrhetinic acid-like factors (GALFs). A protective role of GALFs produced by gut bacteria in the etiology of colorectal cancer is also explored.",
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