REVIEW URRENT C OPINION
The gut microbiota and the metabolic health of the host Susan A. Joyce a and Cormac G.M. Gahan a,b,c
Purpose of review It is clear that the metabolic activities of the gut microbiota significantly impact upon human health and disease. Recent findings Recent analyses have correlated alterations in microbial community structure with the onset of diabetes, obesity and cardiovascular disease as well as inflammatory conditions of the intestine. This work has demonstrated the influence of diet upon the microbiota in disease states and has identified a number of microbial metabolites that orchestrate the crucial aspects of the host–microbe dialog. The microbial production of short-chain fatty acids, trimethylamine, acetaldehyde and inflammatory mediators has been shown to significantly impact upon the metabolic health of the host through pathways that influence satiety, gut permeability and immune function. In the small intestine, microbial metabolism alters the host bile acid profile affecting the interactions with dedicated bile acid receptors (including FXR and TGR5) to influence both local and systemic cellular responses. Recent findings have, therefore, identified specific microbiota profiles and metabolites as predictors of disease risk as well as determining the microbial species (such as Akkermansia muciniphila and Bilophila wadsworthia) which correlate with health and disease. Summary This work identifies the microbiota as an important target for new diagnostic and therapeutic approaches in metabolic disease. Keywords bile acid, butyrate, inflammation, microbiota, obesity
INTRODUCTION The small intestine is the initial site of nutrient digestion and absorption, and is the point of uptake of vitamins and bile acids. The microbiota of the small intestine is less well studied than that of the large intestine and is relatively sparsely populated with a gradient of 103 (duodenum) to 108 (ileum) microorganisms per ml [1]. This relatively low biomass is attributed to low pH, the presence of bile acids and the impact of secretory immunoglobulin A and antimicrobial peptides (reviewed by [2]). Analysis of the small intestinal microbiota has revealed the presence of mucosaassociated Bacteroidetes and Clostridium XIVa and IV groups, with Enterobacteria established in the lumen [3]. Metatranscriptomic analysis of this microbial community revealed significant levels of expression of microbial pathways associated with carbohydrate and amino acid metabolism, with the majority of the activity associated with facultative anaerobes (Streptococcus species and coliforms) www.co-gastroenterology.com
[3]. Given the abundance of metabolic activity in this region of the gastrointestinal tract and the capacity for absorption of metabolites by small intestinal enterocytes, it is likely that microbe–host interactions in the small intestine play a significant (if underappreciated) role in the metabolic health of the host. Herein, we examine the impact of the gastrointestinal microbiota upon the metabolic health of the host and, in particular, highlight the potential influence of the small intestinal microbiota in health and disease.
a Alimentary Pharmabiotic Centre, bSchool of Microbiology and cSchool of Pharmacy, University College Cork, Cork, Ireland
Correspondence to Cormac G.M. Gahan, Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland. Tel: +353 21 4901363; e-mail: [email protected] Curr Opin Gastroenterol 2014, 30:120–127 DOI:10.1097/MOG.0000000000000039 Volume 30 Number 2 March 2014
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Gut microbiota and the health of the host Joyce and Gahan &&
KEY POINTS Deep sequencing of the microbiome has identified microbial fingerprints that are associated with disease risk in humans. Controlled animal studies are providing insights into the mechanisms by which particular metabolites and bacterial species influence the health of the host. Bile acid metabolism provides a signaling mechanism in the small intestine, which regulates both microbial and host processes including energy metabolism. The short-chain fatty acid butyrate has emerged as a significant mediator of health through effects upon inflammation and satiety.
adiposity during early-life development [11 ]. The effect was correlated with an alteration in community structure of the microbiota and was reflected in elevated bacterial production of short-chain fatty acids (SCFAs) [11 ]. A longitudinal birth cohort study in humans similarly demonstrated that early-life (
The gut microbiota and the metabolic health of the host Susan A. Joyce a and Cormac G.M. Gahan a,b,c
Purpose of review It is clear that the metabolic activities of the gut microbiota significantly impact upon human health and disease. Recent findings Recent analyses have correlated alterations in microbial community structure with the onset of diabetes, obesity and cardiovascular disease as well as inflammatory conditions of the intestine. This work has demonstrated the influence of diet upon the microbiota in disease states and has identified a number of microbial metabolites that orchestrate the crucial aspects of the host–microbe dialog. The microbial production of short-chain fatty acids, trimethylamine, acetaldehyde and inflammatory mediators has been shown to significantly impact upon the metabolic health of the host through pathways that influence satiety, gut permeability and immune function. In the small intestine, microbial metabolism alters the host bile acid profile affecting the interactions with dedicated bile acid receptors (including FXR and TGR5) to influence both local and systemic cellular responses. Recent findings have, therefore, identified specific microbiota profiles and metabolites as predictors of disease risk as well as determining the microbial species (such as Akkermansia muciniphila and Bilophila wadsworthia) which correlate with health and disease. Summary This work identifies the microbiota as an important target for new diagnostic and therapeutic approaches in metabolic disease. Keywords bile acid, butyrate, inflammation, microbiota, obesity
INTRODUCTION The small intestine is the initial site of nutrient digestion and absorption, and is the point of uptake of vitamins and bile acids. The microbiota of the small intestine is less well studied than that of the large intestine and is relatively sparsely populated with a gradient of 103 (duodenum) to 108 (ileum) microorganisms per ml [1]. This relatively low biomass is attributed to low pH, the presence of bile acids and the impact of secretory immunoglobulin A and antimicrobial peptides (reviewed by [2]). Analysis of the small intestinal microbiota has revealed the presence of mucosaassociated Bacteroidetes and Clostridium XIVa and IV groups, with Enterobacteria established in the lumen [3]. Metatranscriptomic analysis of this microbial community revealed significant levels of expression of microbial pathways associated with carbohydrate and amino acid metabolism, with the majority of the activity associated with facultative anaerobes (Streptococcus species and coliforms) www.co-gastroenterology.com
[3]. Given the abundance of metabolic activity in this region of the gastrointestinal tract and the capacity for absorption of metabolites by small intestinal enterocytes, it is likely that microbe–host interactions in the small intestine play a significant (if underappreciated) role in the metabolic health of the host. Herein, we examine the impact of the gastrointestinal microbiota upon the metabolic health of the host and, in particular, highlight the potential influence of the small intestinal microbiota in health and disease.
a Alimentary Pharmabiotic Centre, bSchool of Microbiology and cSchool of Pharmacy, University College Cork, Cork, Ireland
Correspondence to Cormac G.M. Gahan, Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland. Tel: +353 21 4901363; e-mail: [email protected] Curr Opin Gastroenterol 2014, 30:120–127 DOI:10.1097/MOG.0000000000000039 Volume 30 Number 2 March 2014
Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Gut microbiota and the health of the host Joyce and Gahan &&
KEY POINTS Deep sequencing of the microbiome has identified microbial fingerprints that are associated with disease risk in humans. Controlled animal studies are providing insights into the mechanisms by which particular metabolites and bacterial species influence the health of the host. Bile acid metabolism provides a signaling mechanism in the small intestine, which regulates both microbial and host processes including energy metabolism. The short-chain fatty acid butyrate has emerged as a significant mediator of health through effects upon inflammation and satiety.
adiposity during early-life development [11 ]. The effect was correlated with an alteration in community structure of the microbiota and was reflected in elevated bacterial production of short-chain fatty acids (SCFAs) [11 ]. A longitudinal birth cohort study in humans similarly demonstrated that early-life (
